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,...     

Variation in pelagic larval growth of Atlantic billfishes: the role of prey composition and selective mortality

Atlantic blue marlin (Makaira nigricans) and sailfish (Istiophorus platypterus) larvae were collected from 10 monthly cruises (June–October 2003 and 2004) across the Straits of Florida to test (1) whether growth differed between the more productive western region near the Florida shelf, and the less productive eastern region toward the Bahamas, and (2) whether growth was related to prey consumption. Examination of larval sagittal otoliths revealed that instantaneous growth and daily growth during the first 2–3 weeks of life did not vary significantly between the two regions for either species. However, recent growth during the last two full days prior to collection was greater in the west for blue marlin larvae. Recent growth of blue marlin larvae <9 mm SL (primarily zooplanktivorous) was significantly related to prey composition (faster growth when higher proportions of Farranula copepods were consumed). Western larvae grew faster and had higher proportions of Farranula in their guts. Trends for sailfish larvae were not significant. In both species, comparison of early growth between <9 and ≥9 mm SL size groups indicated that growth trajectories diverged around 5–8 mm SL, the time when billfish larvae become capable of piscivory. Significantly faster growth of larger (older) larvae suggests that mortality was selective for fast growers and that the transition to piscivory may be a critical point in the early life of billfish.     

Population structure of two deep-sea hydrothermal vent gastropods from the Juan de Fuca Ridge, NE Pacific

The gastropods Lepetodrilus fucensis and Depressigyra globulus are abundant faunal components of animal communities at deep-sea hydrothermal vents along the Juan de Fuca Ridge in the NE Pacific. The population structure and recruitment pattern of both species were studied using modal decomposition of length–frequency distributions. Gastropod populations were collected from Axial Volcano and Endeavour Segment in 2002 and 2003. Polymodal size–frequency distributions, particularly at Axial Volcano vent sites, suggest a discontinuous recruitment pattern for D. globulus. In contrast, there were no distinct peaks visible in the distributions of L. fucensis, suggesting a continuous recruitment pattern for this species. For both species, distributions were positively skewed towards the smaller length–classes, implying post-settlement mortality is high. However, variations in growth, due to short- and long-term variability in environmental conditions in the hydrothermal vent habitat, as well as biological interactions, may also be influencing the distribution and abundance of subsequent life-history stages. Using maximum shell lengths from populations of known ages, the growth rate of L. fucensis was estimated as 9.6 μm day⁻¹, indicating adulthood would be reached in ∼1 year. Our results suggest that, despite occupying the same habitat, abundance and population structure are regulated by different biotic and abiotic processes in L. fucensis and D. globulus.     

Sex and status in a cooperative breeding fish: behavior and androgens

Among taxonomically widespread cooperatively breeding vertebrates, those with non-breeding helpers-at-the-nest provide an excellent opportunity to understand the proximate mechanisms underlying care and allocare. In this study, we examined androgen levels in relation to care behavior in a cooperatively breeding cichlid fish, Neolamprologus pulcher, from Lake Tanganyika. We concentrated on androgens, as these hormones have been linked to the defense behavior, and the defense of young is a common form of parental care in fishes. N. pulcher dominant female breeders performed the most care and also displayed the highest levels of plasma testosterone (T) compared with other individuals within the social group. We also found that dominant male breeders provided a similar amount of care as did the subordinate helpers, but breeding males had the highest levels of 11-ketotestosterone (11KT), an important androgen in fish. Breeders had higher levels of both androgens (T and 11KT) compared to helpers. There was a weak but significant positive correlation between T levels and the frequency of care regardless of sex and status. Our results suggest that androgens may promote defense of young and are in contrast to the commonly reported trade-off between androgen and parental care.     

In situ push-pull method to determine ground water denitrification in riparian zones

To quantify ground water denitrification in discrete locations of riparian aquifers, we modified and evaluated an in situ method based on conservative tracers and 15N-enriched nitrate. Ground water was "pushed" (i.e., injected) into a mini-piezometer and then "pulled" (i.e., extracted) from the same mini-piezometer after an incubation period. This push-pull method was applied in replicate mini-piezometers at two Rhode Island riparian sites, one fresh water and one brackish water. Conservative tracer pretests were conducted to determine incubation periods, ranging from 5 to 120 h, to optimize recovery of introduced plumes. For nitrate push-pull tests, we used two conservative tracers, sulfur hexafluoride and bromide, to provide insight into plume recovery. The two conservative tracers behaved similarly. The dosing solutions were amended with 15N-enriched nitrate that enabled us to quantify the mass of denitrification gases generated during the incubation period. The in situ push-pull method detected substantial denitrification rates at a site where we had previously observed high denitrification rates. At our brackish site, we found high rates of ground water denitrification in marsh locations and minimal denitrification in soils fringing the marsh. The push-pull method can provide useful insights into spatial and temporal patterns of denitrification in riparian zones. The method is robust and results are not seriously affected by dilution or degassing from ground water to soil air. In conjunction with measurements of ground water flow-paths, this method holds promise for evaluating the influence of site and management factors on the ground water nitrate removal capacity of riparian zones.     

A NEW METHOD FOR ESTIMATING PRODUCTIVITY IN STANDING WATERS USING FREE OXYGEN MEASUREMENTS1

ABSTRACT: Continuous measures of net productivity at discrete depths in standing waters may be obtained using diurnal free oxygen measurements and estimates of the vertical mixing. If oxygen concentration and vertical mixing are known in a laterally homogeneous water body, the only unknown term in the oxygen mass-balance equation is net productivity. If this is represented by a Fourier series, the equation may be solved and Fourier coefficients selected so that the sum of square errors between the oxygen measurements and predictions of the equation is minimized; the Fourier series then describes the diurnal variation of net productivity.     

Improved protection for children in forward-facing restraints during side impacts

OBJECTIVE: This study aims to determine the potential for improved child occupant protection in side impacts that can be obtained using rigid and semi-rigid anchorage systems and the addition of energy-absorbing padding in the side structures of child restraints. METHODS: This study uses a comprehensive set of simulated side impacts to evaluate the potential for improved side impact protection in forward-facing child restraints. Factors investigated included methods of anchoring the restraint to the vehicle, energy-absorbing materials in the side structure of restraints, and design features of the restraints such as side wing geometry and seat belt routing. RESULTS: The results show clearly that completely rigid lower attachment of restraints offers the potential for great reductions in head injury risk, which anchorage systems employing a combination of a rigid anchorage bar and webbing attached to a child restraint cannot match. The addition of energy absorbing material in the side structure of restraint systems is effective when the head is fully contained within an adequately designed side wing structure. For restraints anchored by seat belts and loop style semi rigid anchorage straps, belt routing has the potential to significantly affect occupant head excursion. CONCLUSIONS: The results suggest that current child restraint standards and consumer testing protocols do not adequately encourage best practice design of child restraints for side impact protection.     

Application of capillary electrophoresis combined with a modified BCR sequential extraction for estimating of distribution of selected trace metals in PM2.5 fractions of urban airborne particulate matter

The capillary electrophoresis (CE) method combined with a sequential extraction was applied to determine the distribution of Fe, Zn, Cu, Mn and Cd in urban ambient air PM2.5 samples. PM2.5 was collected on Teflon filters with dichotomous sampler, and the modified extraction procedure following the BCR leaching procedure was used to chemically fractionate metals into "easily exchangeable" with water, "acid extractable" with 0.11 mol/l acetic acid, "reducible" with 0.1 mol/l hydroxylamine hydrochloride acidified to pH 2.0 with nitric acid, and "oxidisable" with oxidation by 8.8 mol/l hydrogen peroxide (H2O2) followed by extraction with 1.0 mol/l ammonium acetate. Based on the obtained results it was concluded that the application of the studied methodology provides chemical fractionation data that reflect the general sources and potential health hazards of the studied metals.