We reviewed the clinical features and etiologies of Leigh disease in 66 patients from 60 pedigrees. Biochemical or molecular defects were identified in 50% of all pedigrees, and in 74% of the 19 ...pedigrees with pathologically proved Leigh disease. Isolated deficiency of respiratory chain complex I was found in 7 patients, though the complex was only assayed in 25 patients, making this the second most common biochemical abnormality after complex IV deficiency. Mutations at residue 8993 of mitochondrial DNA were found in only 2 patients. No correlation was found between the clinical features and etiologies. No defects were identified in the 8 patients with normal lactate concentrations in the cerebrospinal fluid.
Background
Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not ...recognized in current disease classification.
Methods
We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided.
Results
Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 × 10−13) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 × 10−25) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 × 10−15; rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 × 10−10) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 × 10−31). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10−9), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 × 10−4) and replication series (P = .03).
Conclusion
Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.
Two experiments were conducted to evaluate reproductive responses to supplemental high-linoleate safflower seeds in postpartum beef cows. In Exp. 1, 18 primiparous, crossbred beef cows (411 ± 24.3 kg ...of BW) were fed Foxtail millet hay starting 1 d postpartum at 1.68% of BW (DM basis) and a low-fat control (control: 63.7% cracked corn, 33.4% safflower seed meal, and 2.9% liquid molasses; DM basis) at 0.35% of BW (n = 9) or a supplement (linoleate) containing 95.3% cracked high-linoleate (79% 18:2n-6) safflower seeds and 4.7% liquid molasses (DM basis) at 0.23% of BW (n = 9). Beginning 1 d postpartum, blood was collected every 3 d for sera. Cows were slaughtered at 37 ± 3 d postpartum for collection of hypothalami, anterior pituitary glands, liver, ovarian follicles, and uterine tissue. By 37 ± 3 d postpartum, dietary treatment did not influence ovarian follicular development (P greater-than-or-equal 0.17), hypophyseal concentrations of LH (P = 0.14), or concentrations of IGF-I in liver (P = 0.15). In contrast, anterior pituitary glands from linoleate cows contained more FSH (P = 0.02) than control cows and linoleate cows had less IGF-I in the medial basal hypothalamus (P = 0.05), preoptic area (P = 0.06), and in follicular fluid (P less-than or equal to 0.03) from follicles less than 15 mm in diameter. In Exp. 2, twenty-four 3-yr-old multiparous beef cows (initial BW 473.9 ± 9.2 kg) were fed chopped bromegrass hay at 2.1% of initial BW starting 1 d postpartum and a low-fat supplement (control) fed at 0.6% of initial BW or a high-linoleate supplement (linoleate) fed at 0.4% of initial BW until 80 d postpartum. Cows were observed for estrus twice daily from d 30 to 80 postpartum and treated with GnRH between 40 and 45 d postpartum. Seven days after GnRH administration cows were given PGF₂α and were checked for estrus and artificially inseminated until 80 d postpartum. The magnitude of GnRH-induced release of LH (P = 0.82) or FSH (P = 0.86) did not differ between treatments. However, peak serum concentrations of estradiol during proestrus after treatment with PGF₂α were less (P = 0.04) in linoleate than control cows. In conclusion, fat supplementation with high-linoleate safflower seeds did not improve the development of ovarian follicles and detrimentally affected early postpartum fertility possibly because of a reduction in IGF-I concentrations in tissues essential to reproduction.
This paper describes the operation of the Coherent CAPTAIN-Mills (CCM) detector located at the Los Alamos Neutron Science Center at Los Alamos National Laboratory. CCM is a 10-ton liquid argon ...detector located 20 meters from a high flux neutron/neutrino source and is designed to search for sterile neutrinos (νs’s) and light dark matter (LDM). An engineering run was performed in fall 2019 to study the characteristics of the CCM120 detector by searching for coherent scattering signals consistent with νs’s and LDM resulting from the production and decays of π+ and π0 in the tungsten target. New parameter space in a leptophobic dark matter (DM) model was excluded for DM masses between ~2.0 and 30 MeV. The lessons learned from this run have guided the development and construction of the new CCM200 detector that will begin operations in 2021 and significantly improve on these searches.
In singleton gestations, 17 alpha-hydroxyprogesterone caproate (17P) has been shown to reduce the rate of recurrent preterm birth. This study was undertaken to evaluate whether 17P would reduce the ...rate of preterm birth in twin gestations.
We performed a randomized, double-blind, placebo-controlled trial in 14 centers. Healthy women with twin gestations were assigned to weekly intramuscular injections of 250 mg of 17P or matching placebo, starting at 16 to 20 weeks of gestation and ending at 35 weeks. The primary study outcome was delivery or fetal death before 35 weeks of gestation.
Six hundred sixty-one women were randomly assigned to treatment. Baseline demographic data were similar in the two study groups. Six women were lost to follow-up; data from 655 were analyzed (325 in the 17P group and 330 in the placebo group). Delivery or fetal death before 35 weeks occurred in 41.5% of pregnancies in the 17P group and 37.3% of those in the placebo group (relative risk, 1.1; 95% confidence interval CI, 0.9 to 1.3). The rate of the prespecified composite outcome of serious adverse fetal or neonatal events was 20.2% in the 17P group and 18.0% in the placebo group (relative risk, 1.1; 95% CI, 0.9 to 1.5). Side effects of the injections were frequent in both groups, occurring in 65.9% and 64.4% of subjects, respectively (P=0.69), but were generally mild and limited to the injection site.
Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with twin gestations. (ClinicalTrials.gov number, NCT00099164 ClinicalTrials.gov.).
This paper presents an analytical solution developed to estimate probabilities of "failure" or advective flux "exceedance" for the case of a spatially variable geosynthetic clay liner (GCL) situated ...over a spatially variable compacted soil liner (CSL). The risk of utilizing such a liner system is assessed relative to a regulatory compacted clay-based soil liner. The analytical solution developed is validated over a range of parameters against random field simulation using the Local Average Subdivision method, and the analytical solution is shown to be in good agreement with simulation. The analytical solution is then used to examine the "probability of exceedance" for a spatially variable GCL and CSL combined liner system. It is shown that the use of a GCL can potentially result in a low probability of exceedance when used with a spatially varying, high hydraulic conductivity CSL. The risk of exceedance generally decreases as the hydraulic conductivity of the CSL decreases. An example problem is presented to demonstrate the capabilities of the analytical solution.
Perennial grasses are candidates for biomass cropping systems that are focused on providing a wide range of ecosystem services in addition to sustainable bioenergy production. Switchgrass (Panicum ...virgatum L.) and big bluestem (Andropogon gerardii Vitman) are two of the dominant grasses of the tallgrass prairie and both are candidates for development of multifunctional diverse production systems. Breeding programs for both species are aimed at increasing biomass yield as a mechanism of improving economic sustainability without increasing production costs. The objective of this study was to determine if long-term selection for increased biomass yield in these two species has had any adverse impacts on biomass quality, or the ability to convert biomass into bioenergy. Check cultivars and improved breeding populations of both species were evaluated for a wide range of biomass quality traits at 13 locations in the North Central and Northeastern USA, and a subset of these populations were also subjected to more intensive and detailed fermentation analyses. In general, lignin and ferulates either remained constant or decreased following selection for increased biomass yield in the various genetic pedigrees. These changes resulted in some increases in predicted ethanol production and in vitro digestibility. Here, the prediction of increased digestibility was confirmed by higher glucose release by pretreatment and deconstruction of an advanced lowland population. However, bioreactor fermentations with two different biofuel-producing microbes showed no differences in ethanol production. Overall, these studies indicated that the improved switchgrass and big bluestem populations had greater biomass yields without significantly reducing biomass quality or conversion efficiency into ethanol, suggesting that selection can achieve increases in biomass productivity while maintaining consistent biomass quality.
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