488 research outputs found
Adjuvant statin therapy for oesophageal adenocarcinoma: the STATâROC feasibility study
Background Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. Methods For this multicentre, doubleâblind, parallelâgroup, randomized, placeboâcontrolled feasibility trial, adults with OAC (including Siewert IâII lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40âmg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1âyear. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. Results A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower lowâdensity lipoprotein cholesterol levels by 3âmonths (adjusted mean difference â0·83 (95 per centâc.i. â1·4 to â0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12âmonths' followâup. Adverse events were similar between the groups. Qualityâofâlife data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the nonârandomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. Conclusion This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (www.isrctn/com)
The political process of constructing a sustainable London Olympics sports development legacy
This study attempts to develop a research agenda for understanding the process of constructing a sustainable Olympic sports development legacy. The research uses a social constructivist perspective to examine the link between the 2012 London Olympic Games and sustainable sports development. The first part of the paper provides justification for the study of sport policy processes using a constructivist lens. This is followed by a section which critically unpacks sustainable sports development drawing on Mosseâs (1998) ideas of process-oriented research and Searleâs conceptualisation of the construction of social reality. Searleâs (1995) concepts of the assignment of function, collective intentionality, collective rules, and human capacity to cope with the environment are considered in relation to the events and discourses emerging from the legacy vision(s) associated with the 2012 London Olympic Games. The paper concludes by proposing a framework for engaging in process oriented research and highlights key elements, research questions, and methodological issues. The proposed constructivist approach can be used to inform policy, practice, and research on sustainable Olympic sports development legacy
CEM03 and LAQGSM03 - new modeling tools for nuclear applications
An improved version of the Cascade-Exciton Model (CEM) of nuclear reactions
realized in the code CEM2k and the Los Alamos version of the Quark-Gluon String
Model (LAQGSM) have been developed recently at LANL to describe reactions
induced by particles and nuclei for a number of applications. Our CEM2k and
LAQGSM merged with the GEM2 evaporation/fission code by Furihata have
predictive powers comparable to other modern codes and describe many reactions
better than other codes; therefore both our codes can be used as reliable event
generators in transport codes for applications. During the last year, we have
made a significant improvements to the intranuclear cascade parts of CEM2k and
LAQGSM, and have extended LAQGSM to describe photonuclear reactions at energies
to 10 GeV and higher. We have produced in this way improved versions of our
codes, CEM03.01 and LAQGSM03.01. We present a brief description of our codes
and show illustrative results obtained with CEM03.01 and LAQGSM03.01 for
different reactions compared with predictions by other models, as well as
examples of using our codes as modeling tools for nuclear applications.Comment: 12 pages, 10 figures, to be published in Journal of Physics:
Conference Series: Proc. Europhysics Conf. on New Trends in Nuclear Physics
Applications and Technologies (NPDC19), Pavia, Italy, September 5-9, 200
A Green Function for Metric Perturbations due to Cosmological Density Fluctuations
We study scalar perturbations to a Robertson-Walker cosmological metric in
terms of a pseudo-Newtonian potential, which emerges naturally from the
solution of the field equations. This potential is given in terms of a Green
function for matter density fluctuations of arbitrary amplitude whose time and
spatial dependence are assumed known. The results obtained span both the
linearized and Newtonian limits, and do not explicitly depend on any kind of
averaging procedure, but make the valid assumption that the global expansion
rate is that of a Friedmann-Robertson-Walker model. In addition, we discuss the
similarity to diffusive processes in the evolution of the potential, and
possible applications.Comment: 19 pages, REVTeX. SU-ITP-9233, submitted to Physical Review
Thermal Diffusion and Quench Propagation in YBCO Pancake Coils Wound with ZnO-and Mylar Insulations
The thermal diffusion properties of several different kinds of YBCO
insulations and the quench properties of pancake coils made using these
insulations were studied. Insulations investigated include Nomex, Kapton, and
Mylar, as well as insulations based on ZnO, Zn2GeO4, and ZnO-Cu. Initially,
short stacks of YBCO conductors with interlayer insulation, epoxy, and a
central heater strip were made and later measured for thermal conductivity in
liquid nitrogen. Subsequently, three different pancake coils were made. The
first two were smaller, each using one meter total of YBCO tape present as four
turns around a G-10 former. One of these smaller coils used Mylar insulation
co-wound with the YBCO tape, the other used YBCO tape onto which ZnO based
insulation had been deposited. One larger coil was made which used 12 total
meters of ZnO-insulated tape and had 45 turns. The results for all short sample
and coil thermal conductivities were ~1-3 Wm-1K-1. Finally, quench propagation
velocity measurements were performed on the coils (77 K, self field) by
applying a DC current and then using a heater pulse to initiate a quench.
Normal zone propagation velocity (NZP) values were obtained for the coils both
in the radial direction and in the azimuthal direction. Radial NZP values
(0.05-0.7 mm/s) were two orders of magnitude lower than axial values (~14-17
mm/s). Nevertheless, the quenches were generally seen to propagate radially
within the coils, in the sense that any given layer in the coil is driven
normal by the layer underneath it.Comment: 58 pages, 5 tables, 16 fig
Altered Skeletal Muscle Lipase Expression and Activity Contribute to Insulin Resistance in Humans
International audienceOBJECTIVE: Insulin resistance is associated with elevated content of skeletal muscle lipids, including triacylglycerols (TAGs) and diacylglycerols (DAGs). DAGs are by-products of lipolysis consecutive to TAG hydrolysis by adipose triglyceride lipase (ATGL) and are subsequently hydrolyzed by hormone-sensitive lipase (HSL). We hypothesized that an imbalance of ATGL relative to HSL (expression or activity) may contribute to DAG accumulation and insulin resistance. RESEARCH DESIGN AND METHODS: We first measured lipase expression in vastus lateralis biopsies of young lean (n = 9), young obese (n = 9), and obese-matched type 2 diabetic (n = 8) subjects. We next investigated in vitro in human primary myotubes the impact of altered lipase expression/activity on lipid content and insulin signaling. RESULTS: Muscle ATGL protein was negatively associated with whole-body insulin sensitivity in our population (r = -0.55, P = 0.005), whereas muscle HSL protein was reduced in obese subjects. We next showed that adenovirus-mediated ATGL overexpression in human primary myotubes induced DAG and ceramide accumulation. ATGL overexpression reduced insulin-stimulated glycogen synthesis (-30%, P < 0.05) and disrupted insulin signaling at Ser1101 of the insulin receptor substrate-1 and downstream Akt activation at Ser473. These defects were fully rescued by nonselective protein kinase C inhibition or concomitant HSL overexpression to restore a proper lipolytic balance. We show that selective HSL inhibition induces DAG accumulation and insulin resistance. CONCLUSIONS: Altogether, the data indicate that altered ATGL and HSL expression in skeletal muscle could promote DAG accumulation and disrupt insulin signaling and action. Targeting skeletal muscle lipases may constitute an interesting strategy to improve insulin sensitivity in obesity and type 2 diabetes
Definitive chemoradiation in patients with inoperable oesophageal carcinoma
We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m-2 day-1 is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m-2 day-1, reduced to 225 mg m-2 day-1 during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery
- âŠ