Our aim was to compare the accuracy of family- or disease-specific targeted haplotyping and direct mutation-detection strategies with the accuracy of genome-wide mapping of the parental origin of ...each chromosome, or karyomapping, by single-nucleotide polymorphism genotyping of the parents, a close relative of known disease status, and the embryo cell(s) used for preimplantation genetic diagnosis of single-gene defects in a single cell or small numbers of cells biopsied from human embryos following in vitro fertilization.
Genomic DNA and whole-genome amplification products from embryo samples, which were previously diagnosed by targeted haplotyping, were genotyped for single-nucleotide polymorphisms genome-wide detection and retrospectively analyzed blind by karyomapping.
Single-nucleotide polymorphism genotyping and karyomapping were successful in 213/218 (97.7%) samples from 44 preimplantation genetic diagnosis cycles for 25 single-gene defects with various modes of inheritance distributed widely across the genome. Karyomapping was concordant with targeted haplotyping in 208 (97.7%) samples, and the five nonconcordant samples were all in consanguineous regions with limited or inconsistent haplotyping results.
Genome-wide karyomapping is highly accurate and facilitates analysis of the inheritance of almost any single-gene defect, or any combination of loci, at the single-cell level, greatly expanding the range of conditions for which preimplantation genetic diagnosis can be offered clinically without the need for customized test development.
Human activities are transforming grassland biomass via changing climate, elemental nutrients, and herbivory. Theory predicts that food-limited herbivores will consume any additional biomass ...stimulated by nutrient inputs ('consumer-controlled'). Alternatively, nutrient supply is predicted to increase biomass where herbivores alter community composition or are limited by factors other than food ('resource-controlled'). Using an experiment replicated in 58 grasslands spanning six continents, we show that nutrient addition and vertebrate herbivore exclusion each caused sustained increases in aboveground live biomass over a decade, but consumer control was weak. However, at sites with high vertebrate grazing intensity or domestic livestock, herbivores consumed the additional fertilization-induced biomass, supporting the consumer-controlled prediction. Herbivores most effectively reduced the additional live biomass at sites with low precipitation or high ambient soil nitrogen. Overall, these experimental results suggest that grassland biomass will outstrip wild herbivore control as human activities increase elemental nutrient supply, with widespread consequences for grazing and fire risk.
Soft-tissue infections are common, generally of mild to modest severity, and are easily treated with a variety of agents. An etiologic diagnosis of simple cellulitis is frequently difficult and ...generally unnecessary for patients with mild signs and symptoms of illness. Here, Stevens et al present details of a study on practice guidelines for the diagnosis and management of Skin and Soft-Tissue Infections.
The Parker Solar Probe was launched on 2018 August 12 and completed its second orbit on 2019 June 19 with perihelion of 35.7 solar radii. During this time, the Energetic Particle Instrument-Hi ...(EPI-Hi, one of the two energetic particle instruments comprising the Integrated Science Investigation of the Sun, IS IS) measured seven proton intensity increases associated with stream interaction regions (SIRs), two of which appear to be occurring in the same region corotating with the Sun. The events are relatively weak, with observed proton spectra extending to only a few MeV and lasting for a few days. The proton spectra are best characterized by power laws with indices ranging from −4.3 to −6.5, generally softer than events associated with SIRs observed at 1 au and beyond. Helium spectra were also obtained with similar indices, allowing He/H abundance ratios to be calculated for each event. We find values of 0.016-0.031, which are consistent with ratios obtained previously for corotating interaction region events with fast solar wind ≤600 km s−1. Using the observed solar wind data combined with solar wind simulations, we study the solar wind structures associated with these events and identify additional spacecraft near 1 au appropriately positioned to observe the same structures after some corotation. Examination of the energetic particle observations from these spacecraft yields two events that may correspond to the energetic particle increases seen by EPI-Hi earlier.
To identify candidate genes for intellectual disability, we performed a meta-analysis on 2,637 de novo mutations, identified from the exomes of 2,104 patient-parent trios. Statistical analyses ...identified 10 new candidate ID genes: DLG4, PPM1D, RAC1, SMAD6, SON, SOX5, SYNCRIP, TCF20, TLK2 and TRIP12. In addition, we show that these genes are intolerant to nonsynonymous variation and that mutations in these genes are associated with specific clinical ID phenotypes.
The Solar Wind Electrons Alphas and Protons experiment on the Parker Solar Probe (PSP) mission measures the three-dimensional electron velocity distribution function. We derive the parameters of the ...core, halo, and strahl populations utilizing a combination of fitting to model distributions and numerical integration for ∼100,000 electron distributions measured near the Sun on the first two PSP orbits, which reached heliocentric distances as small as ∼0.17 au. As expected, the electron core density and temperature increase with decreasing heliocentric distance, while the ratio of electron thermal pressure to magnetic pressure (βe) decreases. These quantities have radial scaling consistent with previous observations farther from the Sun, with superposed variations associated with different solar wind streams. The density in the strahl also increases; however, the density of the halo plateaus and even decreases at perihelion, leading to a large strahl/halo ratio near the Sun. As at greater heliocentric distances, the core has a sunward drift relative to the proton frame, which balances the current carried by the strahl, satisfying the zero-current condition necessary to maintain quasi-neutrality. Many characteristics of the electron distributions near perihelion have trends with solar wind flow speed, βe, and/or collisional age. Near the Sun, some trends not clearly seen at 1 au become apparent, including anticorrelations between wind speed and both electron temperature and heat flux. These trends help us understand the mechanisms that shape the solar wind electron distributions at an early stage of their evolution.
To assess temporal trends in carpal tunnel syndrome (CTS) incidence, surgical treatment, and work-related lost time.
Incident CTS and first-time carpal tunnel release among Olmsted County, Minnesota, ...residents were identified using the medical records linkage system of the Rochester Epidemiology Project; 80% of a sample were confirmed by medical record review. Work-related CTS was identified from the Minnesota Department of Labor and Industry.
Altogether, 10,069 Olmsted County residents were initially diagnosed with CTS in 1981-2005. Overall incidence (adjusted to the 2000 US population) was 491 and 258 per 100,000 person-years for women vs men (p < 0.0001) and 376 per 100,000 for both sexes combined. Adjusted annual rates increased from 258 per 100,000 in 1981-1985 to 424 in 2000-2005 (p < 0.0001). The average annual incidence of carpal tunnel release surgery was 109 per 100,000, while that for work-related CTS was 11 per 100,000. An increase in young, working-age individuals seeking medical attention for symptoms of less severe CTS in the early to mid-1980s was followed in the 1990s by an increasing incidence in elderly people.
The incidence of medically diagnosed carpal tunnel syndrome (CTS) accelerated in the 1980s. The cause of the increase is unclear, but it corresponds to an epidemic of CTS cases resulting in lost work days that began in the mid-1980s and lasted through the mid-1990s. The elderly present with more severe disease and are more likely to have carpal tunnel surgery, which may have significant health policy implications given the aging population.
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