Prenatal testing, cancer risk and the overdiagnosis dilemma

In March, US company Sequenom revealed that its MaterniT21 non-invasive prenatal test (NIPT) has detected potential cancer in some pregnant women (see BioNews 793). As well as receiving information about their fetus, around 40 of the 400,000 or so women who have had this test have been informed that they may have cancer. One example of this was Dr Eunice Lee, who had investigations following an abnormal NIPT result that identified a 7cm colorectal tumour, which was then surgically removed. This is a good thing, right? Women in the prime of their lives receiving information that may catch a cancer early. But, we suggest, it is not this simple. So-called liquid biopsies lead to ethical issues that go beyond the matter of using a test for one thing and finding out about something else. They are also a prime example of the problem of overdiagnosis. Before diving into this particular biopsy pool, we need to think carefully about what might be under the surface. Overdiagnosis is hard to define, but, loosely, an overdiagnosis is a correct diagnosis that doesn’t benefit a patient. It occurs when a test finds something that, if left alone, would regress, or never become symptomatic. Although in practical terms the line between false positives and overdiagnosis can be blurry, the conceptual distinction is this: an overdiagnosis is a correct diagnosis that doesn’t benefit, while a false positive is an incorrect test result: a finding that is not actually true. Both can lead to harm, such as having unnecessary medical interventions. They also consume valuable and often scarce health resources. We know neither the extent of overdiagnosis nor the false-positive rate for suspected cancer detection following NIPT. The latter will be measurable soon enough, but pinning down rates of overdiagnosis will be difficult.NHMR

Four New Planets Orbiting Metal-enriched Stars

Peer reviewe

Inter-laboratory comparison of fission track confined length and etch figure measurements in apatite

Apatite fission-track length and etch figure data are powerful tools for obtaining thermal history information, but both require human analysts making manual measurements and reproducibility is not assured. We report the results of an inter-laboratory study designed to clarify areas of congruence and divergence for these measurements and provide a basis for evaluating best practices to enhance intercompatibility of data sets. Four samples of megacrystic apatite from Durango, Mexico, with induced tracks, one unnannealed and three thermally annealed by varying amounts, were distributed internationally. In all, 55 analysts in 30 laboratory groups participated in the experiment. Relative mean track lengths among the samples were consistent across all analysts, but measurements for each sample showed scatter among labs and analysts considerably in excess of statistical expectation. Normalizing measurements of annealed samples using the unannealed sample improved consistency, as did normalizing for track angle using c-axis projection. Etch figure data also showed variability beyond statistical expectation, and consistency was improved by normalizing. Based on these data we recommend rigorous analyst training for length and etch figure measurement that includes measurement of standards, and that each analyst’s data on unknowns be normalized by that analyst’s own measurements on standards when using thermal history inverse modeling as part of the interpretation process

Dose rate conversion parameters: assessment of nuclear data

The dating of materials using stored dose methods requires accurate determination of the environmental dose rate. The calculation of dose rates from radionuclide concentrations requires conversion parameters derived from nuclear data (half life, decay energies and intensities, and branching ratios). With the substantial body of primary data, it is convenient to use data from evaluated libraries. These libraries show variations reflecting both newer data unavailable to earlier evaluations and the relative importance given to different data sets by the evaluators. Commonly used conversion parameters derive from the Evaluated Nuclear Structure Data File (ENSDF), either directly or from secondary publications, with new tabulations produced in recent years following revisions to this library. Other international evaluations of nuclear data include the NEA/OECD supported JEF2.2 and JEFF3.11 evaluations, and the Decay Data Evaluation Project (DDEP). A technique comparing different evaluations to identify data that can not be confidently used has been developed. These differences have been investigated with an evaluation of underlying nuclear data. Particular radionuclides of interest are discussed; 214Bi where recent evaluations depend on a single high precision data set, 228Ac where the decay scheme is incomplete and further measurements are required, and 40K where the mean beta energy has been calculated in the evaluations using an incorrect shape factor. Revised dose rate conversion factors have been produced, which are largely consistent with earlier values with the exception of the 40K beta parameter which is 4% higher than recent values but consistent with earlier calculations

Spatial variation in the effects of size and age on reproductive dynamics of common coral trout Plectropomus leopardus

The effects of size and age on reproductive dynamics of common coral trout Plectropomus leopardus populations were compared between coral reefs open or closed (no-take marine reserves) to fishing and among four geographic regions of the Great Barrier Reef (GBR), Australia. The specific reproductive metrics investigated were the sex ratio, the proportion of vitellogenic females and the spawning fraction of local populations. Sex ratios became increasingly male biased with length and age, as expected for a protogyne, but were more male biased in southern regions of the GBR (Mackay and Storm Cay) than in northern regions (Lizard Island and Townsville) across all lengths and ages. The proportion of vitellogenic females also increased with length and age. Female P. leopardus were capable of daily spawning during the spawning season, but on average spawned every 4·3 days. Mature females spawned most frequently on Townsville reserve reefs (every 2·3 days) and Lizard Island fished reefs (every 3·2 days). Females on Mackay reefs open to fishing showed no evidence of spawning over 4 years of sampling, while females on reserve reefs spawned only once every 2–3 months. No effect of length on spawning frequency was detected. Spawning frequency increased with age on Lizard Island fished reefs, declined with age on Storm Cay fished reefs, and declined with age on reserve reefs in all regions. It is hypothesized that the variation in P. leopardus sex ratios and spawning frequency among GBR regions is primarily driven by water temperature, while no-take management zones influence spawning frequency depending on the region in which the reserve is located. Male bias and lack of spawning activity on southern GBR, where densities of adult P. leopardus are highest, suggest that recruits may be supplied from central or northern GBR. Significant regional variation in reproductive traits suggests that a regional approach to management of P. leopardus is appropriate and highlights the need for considering spatial variation in reproduction where reserves are used as fishery or conservation management tools

Current-carrying cosmic string loops 3D simulation: towards a reduction of the vorton excess problem

The dynamical evolution of superconducting cosmic string loops with specific equations of state describing timelike and spacelike currents is studied numerically. This analysis extends previous work in two directions: first it shows results coming from a fully three dimensional simulation (as opposed to the two dimensional case already studied), and it now includes fermionic as well as bosonic currents. We confirm that in the case of bosonic currents, shocks are formed in the magnetic regime and kinks in the electric regime. For a loop endowed with a fermionic current with zero-mode carriers, we show that only kinks form along the string worldsheet, therefore making these loops slightly more stable against charge carrier radiation, the likely outcome of either shocks or kinks. All these combined effects tend to reduce the number density of stable loops and contribute to ease the vorton excess problem. As a bonus, these effects also may provide new ways of producing high energy cosmic rays.Comment: 11 pages, RevTeX 4 format, 8 figures, submitted to PR

Interconnected Self-Propagating Photopolymer Waveguides: An Alternative to Stereolithography for Rapid Formation of Lattice-Based Open-Cellular Materials

Recently, a new technique has been developed to create unique open-cellular materials with micro-scale truss, or lattice features ranging from tens to hundreds of microns. These materials are formed from a three-dimensional, interconnected array of self-propagating photopolymer waveguides. By utilizing this self-propagating effect, three-dimensional open-cellular polymer materials can be formed in seconds. In addition, intrinsic to the process is the ability to control specific micro-lattice parameters which ultimately affect the bulk material properties. Unlike stereolithography, this new fabrication technique is rapid (~ minutes to form an entire part) and relies on a single two-dimensional exposure surface to form three-dimensional structures (thickness > 25 mm possible). This combination of speed and planar scalability opens the possibility for large-scale mass manufacturing. The utility of these new materials range from lightweight energy absorbing structures to thermal management materials to bio-scaffolds.Mechanical Engineerin

A Glasgow tipple-transjugular intrahepatic portosystemic shunt insertion prior to Whipple resection

Abdominal surgery performed in patients with significant liver disease and portal hypertension is associated with high mortality rates, with even poorer outcomes associated with complex pancreaticobiliary operations. We report on a patient requiring portal decompression via transjugular intrahepatic portosystemic shunt (TIPS) prior to a pancreaticoduodenectomy. The 49-year-old patient presented with pain, jaundice and weight loss. At ERCP an edematous ampulla was biopsied, revealing high-grade dysplasia within a distal bile duct adenoma. Liver biopsy was performed to investigate portal hypertension, confirming congenital hepatic fibrosis (CHF). A TIPS was performed to enable a pancreaticoduodenectomy. Prophylactic TIPS can be performed for preoperative portal decompression for patients requiring pancreatic resection. A potentially curative resection was performed when abdominal surgery was initially thought impossible. Notably, CHF has been associated with the development of cholangiocarcinoma in only four previous instances, with this case being only the second reported distal bile duct cholangiocarcinoma