Clinical utility of two-dimensional Doppler echocardiographic techniques for estimating pulmonary to systemic blood flow ratios in children with left to right shunting atrial septal defect, ventricular septal defect or patent ductus arteriosus

Range gated two-dimensional Doppler echocardiographic methods were evaluated for quantifying pulmonary (QP) to systemic (QS) blood flow ratios. Twenty-one patients were studied, 4 with patent ductus arteriosus, 6 with atrial septal defect and 11 with ventricular septal defect. The Doppler pulmonary to systemic flow (QP:QS) estimation method involved calculating volume flow (liters/min) at a variety of intracardiac sites by using imaging information for flow area and Doppler outputs to calculate mean flow velocity as a function of time. Area volume flows were combined to yield QP:QS ratios. The sites sampled were main pulmonary artery, ascending aorta, mitral valve orifice and subpulmonary right ventricular outflow tract. The overall correlation between Doppler QP:QS estimates and those obtained at cardiac catheterization (n = 18) or radionuclide angiography (n = 3) was r = 0.85 (standard error of the estimate = 0.48:1). These preliminary results suggest that clinical application of this Doppler echocardiographic method should allow noninvasive estimation of the magnitude of cardiac shunts

The origin of the parrotfish species Scarus compressus in the Tropical Eastern Pacific: region-wide hybridization between ancient species pairs

BACKGROUND: In the Tropical Eastern Pacific (TEP), four species of parrotfishes with complex phylogeographic histories co-occur in sympatry on rocky reefs from Baja California to Ecuador: Scarus compressus, S. ghobban, S. perrico, and S. rubroviolaceus. The most divergent, S. perrico, separated from a Central Indo-Pacific ancestor in the late Miocene (6.6 Ma). We tested the hypothesis that S. compressus was the result of ongoing hybridization among the other three species by sequencing four nuclear markers and a mitochondrial locus in samples spanning 2/3 of the latitudinal extent of the TEP. RESULTS: A Structure model indicated that K = 3 fit the nuclear data and that S. compressus individuals had admixed genomes. Our data could correctly detect and assign pure adults and F1 hybrids with > 0.90 probability, and correct assignment of F2s was also high in some cases. NewHybrids models revealed that 89.8% (n = 59) of the S. compressus samples were F1 hybrids between either S. perrico × S. ghobban or S. perrico × S. rubroviolaceus. Similarly, the most recently diverged S. ghobban and S. rubroviolaceus were hybridizing in small numbers, with half of the admixed individuals assigned to F1 hybrids and the remainder likely > F1 hybrids. We observed strong mito-nuclear discordance in all hybrid pairs. Migrate models favored gene flow between S. perrico and S. ghobban, but not other species pairs. CONCLUSIONS: Mating between divergent species is giving rise to a region-wide, multispecies hybrid complex, characterized by a high frequency of parental and F1 genotypes but a low frequency of > F1 hybrids. Trimodal structure, and evidence for fertility of both male and female F1 hybrids, suggest that fitness declines sharply in later generation hybrids. In contrast, the hybrid population of the two more recently diverged species had similar frequencies of F1 and > F1 hybrids, suggesting accelerating post-mating incompatibility with time. Mitochondrial genotypes in hybrids suggest that indiscriminate mating by male S. perrico is driving pre-zygotic breakdown, which may reflect isolation of this endemic species for millions of years resulting in weak selection for conspecific mate recognition. Despite overlapping habitat use and high rates of hybridization, species boundaries are maintained by a combination of pre- and post-mating processes in this complex

Diversity of Murine Norovirus Strains Isolated from Asymptomatic Mice of Different Genetic Backgrounds within a Single U.S. Research Institute

Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute- the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U.S. Ten distinct murine norovirus strains were isolated from various tissues and feces of asymptomatic wild type sentinel mice as well as asymptomatic immunodeficient (RAG 2−/−) mice. The NIH MNV isolates showed little cytopathic effect in permissive RAW264.7 cells in early passages, but all isolates examined could be adapted to efficient growth in cell culture by serial passage. The viruses, although closely related in genome sequence, were distinguishable from each other according to facility location, likely due to the introduction of new viruses into each facility from separate sources or vendors at different times. Our study indicates that the murine noroviruses are widespread in these animal facilities, despite rigorous guidelines for animal care and maintenance

Mutations in CNNM4 Cause Jalili Syndrome, Consisting of Autosomal-Recessive Cone-Rod Dystrophy and Amelogenesis Imperfecta

The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL

Sleep patterns of elite youth team-sport athletes prior to and during international competition

Objective: To examine the effects of international competition on sleep patterns of elite youth team-sport athletes from two national squads compared to a baseline period. Methods: Fifty elite male youth rugby players from two squads were assessed two weeks before (HOME) and throughout two match-day cycles (matchday−1, matchday, matchday+1) of an international competition (COMP). Players were selected to represent their nation during the Six Nations Festival and completed daily self-reported sleep diaries before and during a competitive period. Linear mixed models were used to examine differences between HOME and COMP, and within camp days. Effect sizes±90% confidence intervals (ES±90%CI) were calculated to quantify the magnitude of pairwise differences. Results: Participants spent more time in bed (34.6±13.9 min; ES=0.26±0.19), slept for longer (35.4±12.7 min; ES=0.30±0.19), and woke up later (36.5±9.5 min; ES=0.41±0.20) in COMP compared to HOME, but maintained their regular bedtime (−1.8±11.2 min; ES=0.02±0.19), sleep onset latency (4.1±3.2 min; ES=0.17±0.25) and rating of sleep quality (0.30±0.17; ES=0.17±0.19). Conclusions: Elite youth team-sport athletes sleep for longer during a competition camp compared to home resulting from a delay in wake-up times. This highlights the opportunity for implementing interventions to improve sleep patterns in international-level team sport athletes in their daily environment