An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme

© 2014 Massat et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Time-sequenced Multi-Radio-Frequency Observations of Cygnus X-3 in Flare

Multifrequency observations from the VLA, VLBA and OVRO Millimeter Array of a major radio outburst of Cygnus X-3 in 2001 September are presented, measuring the evolution of the spectrum of the source over three decades in frequency, over a period of six days. Following the peak of the flare, as the intensity declines the high-frequency spectrum at frequency nu steepens from nu^{-0.4} to nu^{-0.6}, after which the spectral index remains at this latter terminal value; a trend previously observed but hitherto not satisfactorily explained. VLBA observations, for the first time, track over several days the expansion of a sequence of knots whose initial diameters are approximately 8 milliarcseconds. The light-crossing time within these plasmons is of the same order as the time-scale over which the spectrum is observed to evolve. We contend that properly accounting for light-travel time effects in and between plasmons which are initially optically thick, but which after expansion become optically thin, explains the key features of the spectral evolution, for example the observed timescale. Using the VLBA images, we have directly measured for the first time the proper motions of individual knots, analysis of which shows a two-sided jet whose axis is precessing. The best-fit jet speed is roughly beta = 0.63 and the precession period is about 5 days, significantly lower than fitted for a previous flare. Extrapolation of the positions of the knots measured by the VLBA back to zero-separation shows this to occur approximately 2.5 days after the detection of the rise in flux density of Cygnus X-3.Comment: 23 pages, 10 figures, accepted by Ap

Developing Healthy Kids in Healthy Communities: Eight Evidence-based Strategies for Preventing High-risk Behaviour.

Australian youth engage in behaviour that threatens their health and wellbeing. National surveys report that about a third of young Australians have tried an illicit drug. High rates of substance use and risky sexual behaviour among young Australians suggest that effective prevention efforts based on empirical evidence need to be expanded. Church-associated organisations are an untapped resource that could be used to improve the health and welfare of young people. We describe eight evidence-based elements to consider in designing strategies to prevent high-risk behaviour in young people

Angular Momentum Evolution in Dark Matter Halos

We have analyzed high resolution N-body simulations of dark matter halos, focusing specifically on the evolution of angular momentum. We find that not only is individual particle angular momentum not conserved, but the angular momentum of radial shells also varies over the age of the Universe by up to factors of a few. We find that torques from external structure are the most likely cause for this distribution shift. Since the model of adiabatic contraction that is often applied to model the effects of galaxy evolution on the dark-matter density profile in a halo assumes angular momentum conservation, this variation implies that there is a fundamental limit on the possible accuracy of the adiabatic contraction model in modeling the response of DM halos to the growth of galaxies.Comment: 16 pages, 9 figures, accepted for publication in MNRA

Genomics: Think Global, Act Local

Long a slogan for environmentalists, “think global, act local” could be a new rallying cry for biologists. As genome-wide techniques advance and their costs drop, scientists are expanding into larger and larger territories—metagenomics, global proteomic approaches, and analyses of thousands of genomes. These massive data sets are opening up new possibilities for understanding some of the smallest details of the genome. Here, we look at four such cases—investigating the evolutionary role of insertions and deletions in the genome, connecting an orphan enzyme with its gene, mapping the fine details of chromatin structure, and characterizing global interactions between proteins and RNA—all of which depend on a combination of global thinking and local action

High Efficiency Megawatt Motor Preliminary Design

The High Efficiency Megawatt Motor (HEMM) is being designed to meet the needs of Electrified Aircraft Propulsion (EAP). A preliminary design has been completed and risk reduction activities are being conducted in three key areas: cryogenic cooler design, superconducting rotor coil design and manufacturing, and stator thermal management. The key objective of HEMM is to establish a motor technology which simultaneously attains high specific power (>16kW/kg ratio to electromagnetic weight) and high efficiency (>98%) by judicious application of high temperature superconducting wire and integrated thermal management. Another important feature is to achieve the performance goals with an eye to aircraft integration constraints. An electromagnetic analysis was performed which shows that the proposed HEMM design meets the performance objectives if key current capability and mechanical constraints are achieved. The risk reduction activities are the first assessment of the key design features. The HEMM technology could be applied to a range of aircraft types that require megawatt level electrical power

Is there evidence for accelerated polyethylene wear in uncemented compared to cemented acetabular components? A systematic review of the literature

Joint arthroplasty registries show an increased rate of aseptic loosening in uncemented acetabular components as compared to cemented acetabular components. Since loosening is associated with particulate wear debris, we postulated that uncemented acetabular components demonstrate a higher polyethylene wear rate than cemented acetabular components in total hip arthroplasty. We performed a systematic review of the peer-reviewed literature, comparing the wear rate in uncemented and cemented acetabular components in total hip arthroplasty. Studies were identified using MEDLINE (PubMed), EMBASE and the Cochrane Central Register of Controlled Trials. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search resulted in 425 papers. After excluding duplicates and selection based on title and abstracts, nine studies were found eligible for further analysis: two randomised controlled trials, and seven observational studies. One randomised controlled trial found a higher polyethylene wear rate in uncemented acetabular components, while the other found no differences. Three out of seven observational studies showed a higher polyethylene wear in uncemented acetabular component fixation; the other four studies did not show any differences in wear rates. The available evidence suggests that a higher annual wear rate may be encountered in uncemented acetabular components as compared to cemented components

Overdiagnosis in organised mammography screening in Denmark. A comparative study

<p>Abstract</p> <p>Background</p> <p>Overdiagnosis in cancer screening is the detection of cancer lesions that would otherwise not have been detected. It is arguably the most important harm. We quantified overdiagnosis in the Danish mammography screening programme, which is uniquely suited for this purpose, as only 20% of the Danish population has been offered organised mammography screening over a long time-period.</p> <p>Methods</p> <p>We collected incidence rates of carcinoma in situ and invasive breast cancer in areas with and without screening over 13 years with screening (1991-2003), and 20 years before its introduction (1971-1990). We explored the incidence increase comparing unadjusted incidence rates and used Poisson regression analysis to compensate for the background incidence trend, variation in age distribution and geographical variation in incidence.</p> <p>Results</p> <p>For the screened age group, 50 to 69 years, we found an overdiagnosis of 35% when we compared unadjusted incidence rates for the screened and non-screened areas, but after compensating for a small decline in incidence in older, previously screened women. Our adjusted Poisson regression analysis indicated a relative risk of 1.40 (95% CI: 1.35-1.45) for the whole screening period, and a potential compensatory drop in older women of 0.90 (95% CI: 0.88-0.96), yielding an overdiagnosis of 33%, which we consider the most reliable estimate. The drop in previously screened women was only present in one of the two screened regions and was small in absolute numbers.</p> <p>Discussion</p> <p>One in four breast cancers diagnosed in the screened age group in the Danish screening programme is overdiagnosed. Our estimate for Denmark is lower than that for comparable countries, likely because of lower uptake, lower recall rates and lower detection rates of carcinoma in situ.</p

3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR