Post-Operative Radiotherapy for Soft Tissue Sarcoma of the Anterior Compartment of the Thigh: Should the Sartorius Muscle be Included?

Purpose: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh

Experiences of learning through collaborative evaluation from a masters programme in professional education

This paper presents findings from a collaborative evaluation project within a masters programme in professional education. The project aimed to increase knowledge of research methodologies and methods through authentic learning where participants worked in partnership with the tutor to evaluate the module which they were studying. The project processes, areas of the course evaluated and the data collection methods are outlined. The findings focus on key themes from evaluating the effectiveness of using a collaborative evaluation approach, including: enhanced student engagement; creativity of the collaborative evaluation approach; equality between the tutor and students; and enhanced research skills. Discussion focuses on the outcomes and effectiveness of the project and tutor reflections on adopting a collaborative approach. This paper highlights lessons from the project relevant to those interested in staff-student partnership approaches and those facilitating postgraduate learning and teaching programmes and educational research courses

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.This work was supported by Cancer Research UK (C1094/A11728 to CMLW and NGB for the RAPPER study, C26900/A8740 to GCB, and C8197/A10865 to AMD), the Royal College of Radiologists (C26900/ A8740 to GCB), the National Institute for Health Research (GCB; no grant number), Addenbrooke's Charitable Trust (GCB; no grant number), Institute of Cancer Research (National Institute for Health Research) Biomedical Research Centre (C46/A2131 to DPD and SG), the National Institute for Health Research Cambridge Biomedical Research Centre (NGB; no grant number), UK Medical Research Council (RG70550 to LD), the Joseph Mitchell Trust (AMD; no grant number), the Experimental Cancer Medicine Centre (CMLW; no grant number), Cancer Research UK Program grant Section of Radiotherapy (C33589/ A19727 to SLG), the United States National Institutes of Health (1R01CA134444 to BSR and HO, 2P30CA014520-34 to SB, and 1K07CA187546-01A1 to SLK), the American Cancer Society (RSGT-05- 200-01-CCE to BSR), the U.S. Department of Defense (PC074201 to BSR and HO), Mount Sinai Tisch Cancer Institute Developmental Fund Award (BSR; no grant number), the Instituto de Salud Carlos III (FIS PI10/00164 and PI13/02030 to AV and PI13/01136 to AC), Fondo Europeo de Desarrollo Regional (FEDER 2007–2013 to AV and AC; no grant number), Instituto de Salud Carlos III (FIS PI10/00164 and PI13/ 02030 to AV and PI13/01136 to AC), Xunta de Galicia and the European Social Fund (POS-A/2013/034 to LF), and the Alberta Cancer Board Research Initiative Program (103.0393.71760001404 to MP). AMD receives support from the REQUITE study, which is funded by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 601826. Laboratory infrastructure for the RAPPER study was funded by Cancer Research UK [C8197/A10123] and the Manchester Experimental Cancer Medicine Centre. The RAPPER cohort comprises individuals and data recruited into the RT01 and CHHiP UK radiotherapy trials. The RT01 trial was supported by the UK Medical Research Council. The CHHiP trial (CRUK/06/016) was supported by the Department of Health and Cancer Research UK (C8262/A7253); trial recruitment was facilitated within centers by the National Institute for Health Research Cancer Research Network. DPD and SLG acknowledge NHS funding to the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2016.07.02

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 nea

The Iceland Microcontinent and a continental Greenland-Iceland-Faroe Ridge

The breakup of Laurasia to form the Northeast Atlantic Realm was the culmination of a long period of tectonic unrest extending back to the Late Palaeozoic. Breakup was prolonged and complex and disintegrated an inhomogeneous collage of cratons sutured by cross-cutting orogens. Volcanic rifted margins formed, which are blanketed by lavas and underlain variously by magma-inflated, extended continental crust and mafic high-velocity lower crust of ambiguous and probably partly continental provenance. New rifts formed by diachronous propagation along old zones of weakness. North of the Greenland-Iceland-Faroe Ridge the newly forming rift propagated south along the Caledonian suture. South of the Greenland-Iceland-Faroe Ridge it propagated north through the North Atlantic Craton along an axis displaced ~ 150 km to the west of the northern rift. Both propagators stalled where the confluence of the Nagssugtoqidian and Caledonian orogens formed a transverse barrier. Thereafter, the ~ 400-km-wide latitudinal zone between the stalled rift tips extended in a distributed, unstable manner along multiple axes of extension that frequently migrated or jumped laterally with shearing occurring between them in diffuse transfer zones. This style of deformation continues to the present day. It is the surface expression of underlying magma-assisted stretching of ductile mid- and lower continental crust which comprises the Icelandic-type lower crust that underlies the Greenland-Iceland-Faroe Ridge. This, and probably also one or more full-crustal-thickness microcontinents incorporated in the Ridge, are capped by surface lavas. The Greenland-Iceland-Faroe Ridge thus has a similar structure to some zones of seaward-dipping reflectors. The contemporaneous melt layer corresponds to the 3–10 km thick Icelandic-type upper crust plus magma emplaced in the ~ 10–30-km-thick Icelandic-type lower crust. This model can account for seismic and gravity data that are inconsistent with a gabbroic composition for Icelandic-type lower crust, and petrological data that show no reasonable temperature or source composition could generate the full ~ 40-km thickness of Icelandic-type crust observed. Numerical modeling confirms that extension of the continental crust can continue for many tens of Myr by lower-crustal flow from beneath the adjacent continents. Petrological estimates of the maximum potential temperature of the source of Icelandic lavas are up to 1450 °C, no more than ~ 100 °C hotter than MORB source. The geochemistry is compatible with a source comprising hydrous peridotite/pyroxenite with a component of continental mid- and lower crust. The fusible petrology, high source volatile contents, and frequent formation of new rifts can account for the true ~ 15–20 km melt thickness at the moderate temperatures observed. A continuous swathe of magma-inflated continental material beneath the 1200-km-wide Greenland-Iceland-Faroe Ridge implies that full continental breakup has not yet occurred at this latitude. Ongoing tectonic instability on the Ridge is manifest in long-term tectonic disequilibrium on the adjacent rifted margins and on the Reykjanes Ridge, where southerly migrating propagators that initiate at Iceland are associated with diachronous swathes of unusually thick oceanic crust. Magmatic volumes in the NE Atlantic Realm have likely been overestimated and the concept of a monogenetic North Atlantic Igneous Province needs to be reappraised. A model of complex, piecemeal breakup controlled by pre-existing structures that produces anomalous volcanism at barriers to rift propagation and distributes continental material in the growing oceans fits other oceanic regions including the Davis Strait and the South Atlantic and West Indian oceans

Sketching women in court: The visual construction of co-accused women in court drawings

This paper explores the visual construction and representation of co-accused women offenders in court drawings. It utilises three case studies of female co-defendants who appeared in the England and Wales court system between 2003 and 2013. In doing so this paper falls into three parts. The first part considers the emergence of the sub-discipline, visual criminology and examines what is known about the visual representation of female offenders. The second part presents the findings of an empirical investigation, which involved engaging in a critical, reflexive visual analysis of a selection of court drawings of three female co-offenders. The third part discusses the ways in which the court artists' interpretation, the conventions of court sketching, and motifs of female offenders as secondary actors, drew on existing myths and prejudices by representing the women as listening, remorseless ‘others’

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome