Evaluation and classification of severity for 176 genes on an expanded carrier screening panel

Background

Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity-related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG).

Methods

Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene.

Results

Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four.

Conclusion

This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait-based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation.

     

Correction to: Globally regional life cycle analysis of automotive lithium-ion nickel manganese cobalt batteries

Mitigation and Adaptation Strategies for Global Change - The article Globally regional life cycle analysis of automotive lithium-ion nickel manganese cobalt batteries written by Jarod C. Kelly,...     

The value of echocardiography and Doppler in the prediction of fetal demise after laser coagulation for TTTS: A systematic review and meta-analysis

This study aimed to investigate the value of echocardiography and Doppler before fetoscopic laser coagulation for twin-twin transfusion syndrome (TTTS) in the prediction of intrauterine fetal demise (IUFD). We performed a systematic review and meta-analysis to compare preoperative parameters between fetuses with and without demise after laser surgery. Eighteen studies were included. Recipient twins have an increased risk of demise in case of preoperative absent/reversed flow (A/REDF) in the umbilical artery (odds ratio [OR] 2.76, 95% confidence interval [CI], 1.78-4.28), absent or reversed a-wave in the ductus venosus (OR 2.32, 95% CI, 1.70-3.16), or a middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) (OR 7.59, 95% CI, 2.56-22.46). In donors, only A/REDF in the umbilical artery (OR 3.40, 95% CI, 2.68-4.32) and absent or reversed a-wave in the ductus venosus (OR 1.66, 95% CI, 1.12-2.47) were associated with IUFD. No association was found between donor-IUFD and preoperative myocardial performance index (MPI). Two studies found an association between abnormal MPI and recipient demise. With this study, we have identified a set of preoperative Doppler parameters predictive of fetal demise after laser surgery. More research is needed to assess the utility of preoperative echocardiographic parameters such as the MPI in predicting IUFD.     

Differences in diet composition and foraging patterns between sexes of the Magellanic penguin (Spheniscus magellanicus) during the non-breeding period as revealed by δ13C and δ15N values in feathers and bone

In diving seabirds, sexual dimorphism in size often results in sex-related differences of foraging patterns. Previous research on Magellanic penguins, conducted during the breeding season, failed to reveal consistent differences between the sexes on foraging behavior, despite sexual dimorphism. In this paper, we tested the hypothesis that male and female Magellanic penguins differ in diet and foraging patterns during the non-breeding period when the constraints imposed by chick rearing activities vanish. We used stable isotope ratios of carbon and nitrogen in feather and bone to characterize the diet and foraging patterns of male and female penguins in the South Atlantic at the beginning of the 2009–2010 and 2010–2011 post-breeding seasons (feathers) and over several consecutive breeding and migratory seasons (bone). The mean δ¹³C and δ¹⁵N values of feathers showed no differences between the sexes in any of the three regions considered or in the diet composition between the sexes from identical breeding regions; however, Bayesian ellipses showed a higher isotopic niche width in males at the beginning of the post-breeding season. Stable isotope ratios in bone revealed the enrichment of males with δ¹³C compared with females across the three regions considered. Furthermore, the Bayesian ellipses were larger for males and encompassed those of females in two of the three regions analyzed. These results suggest a differential use of winter resources between the sexes, with males typically showing a larger diversity of foraging/migratory strategies. The results also show that dietary differences between male and female Magellanic penguins may occur once the constraints imposed by chick rearing activities cease at the beginning of the post-breeding season.     

Estimating the safety performance of urban intersections in Lisbon,Portugal

According to official statistics, a large percentage of crashes in Portugal are reported on urban roads. For instance, from 2004 to 2007, about 70% of all injury accidents and 43% of the fatalities occurred inside urban agglomerations. This important safety problem has also been observed on the urban network of Lisbon. Understanding this significant problem, the Government of the Portuguese Republic via its research grant agency – The Foundation for Science and Technology – funded a project whose primary objective consists of developing tools that would help estimating the safety performance of various components of the urban highway system in Lisbon. This paper documents one component of the safety tools that were developed and describes the steps that were taken to develop predictive models for estimating the safety performance of signalized and unsignalized intersections of Lisbon. Several crash predictive models were developed using the Poisson-gamma modeling framework. Two types of models were estimated: flow-only and models with covariates. They were estimated using crash and other related data collected at 44 three-legged and 50 four-legged intersections for the years 2004–2007, inclusively. It was found that some highway geometric design characteristics were associated with the crashes occurring at urban three- and four-legged intersections in Lisbon.     

Analysis of the circumstances of accidents and impact of transformations on the accidents in a beverage delivery company

The aim of the study was to analyze the narratives in accident files to document the circumstances of accidents in a beverage delivery company, in particular, in regard with the activities performed at the time of the accident and the deviations reported. A second aim was to understand the impact of the transformations introduced by the company on accident patterns. Narrative material from 546 files covering a 7-year period was analyzed. Special attention was given to collecting information on the activities conducted at the time of the accident, including location, foot support base, operation, and material involved. The analysis allowed specifying elements that have good potential for improving handling situations and decreasing accident risks. Three categories of deviation were analyzed: situations reported as particular or difficult, unforeseen events, and dysfunction reported in the activity itself. Results show that several external factors play an important role in the occurrence of accidents. Most of these factors are beyond risk analysis of handling situations. The impact of the transformations on the number, seriousness, and causes of accidents was dramatic. Analysis shows that current investigative risk tools are insufficient in helping management predict how decisions will affect safety. The discussion situates the results within the various theories of musculoskeletal mechanisms of injury.