In silico modeling of oxygen-enhanced MRI of specific ventilation.

Specific ventilation imaging (SVI) proposes that using oxygen-enhanced 1H MRI to capture signal change as subjects alternatively breathe room air and 100% O2 provides an estimate of specific ventilation distribution in the lung. How well this technique measures SV and the effect of currently adopted approaches of the technique on resulting SV measurement is open for further exploration. We investigated (1) How well does imaging a single sagittal lung slice represent whole lung SV? (2) What is the influence of pulmonary venous blood on the measured MRI signal and resultant SVI measure? and (3) How does inclusion of misaligned images affect SVI measurement? In this study, we utilized two patient-based in silico models of ventilation, perfusion, and gas exchange to address these questions for normal healthy lungs. Simulation results from the two healthy young subjects show that imaging a single slice is generally representative of whole lung SV distribution, with a calculated SV gradient within 90% of that calculated for whole lung distributions. Contribution of O2 from the venous circulation results in overestimation of SV at a regional level where major pulmonary veins cross the imaging plane, resulting in a 10% increase in SV gradient for the imaging slice. A worst-case scenario simulation of image misalignment increased the SV gradient by 11.4% for the imaged slice

X-ray emitting young stars in the Orion Nebula

The Orion Nebula Cluster and the molecular cloud in its vicinity have been observed with the ACIS-I detector on board the Chandra X-ray Observatory with 23 hours exposure. We detect 1075 X-ray sources: 91% are spatially associated with known stellar members of the cluster, and 7% are newly identified deeply embedded cloud members. This provides the largest X-ray study of a pre-main sequence stellar population. We examine here the X-ray properties of Orion young stars as a function of mass. Results include: (a) the discovery of rapid variability in the O9.5 31 M_o star \theta^2A Ori, and several early B stars, inconsistent with the standard model of X-ray production in small wind shocks; (b) support for the hypothesis that intermediate-mass mid-B through A type stars do not themselves produce significant X-ray emission; (c) confirmation that low-mass G- through M-type T Tauri stars exhibit powerful flaring but typically at luminosities considerably below the `saturation' level; (d) confirmation that the presence or absence of a circumstellar disk has no discernable effect on X-ray emission; (e) evidence that T Tauri plasma temperatures are often very high with T >= 100 MK, even when luminosities are modest and flaring is not evident; and (f) detection of the largest sample of pre-main sequence very low mass objects showing high flaring levels and a decline in magnetic activity as they evolve into L- and T-type brown dwarfs.Comment: 82 pages, 16 figures, 6 tables. To appear in the Astrophysical Journal. For a version with high quality images and electronic tables, see ftp://ftp.astro.psu.edu/pub/edf/orion1

Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial

<p>Abstract</p> <p>Background</p> <p>Several uncontrolled studies of hyperbaric treatment in children with autism have reported clinical improvements; however, this treatment has not been evaluated to date with a controlled study. We performed a multicenter, randomized, double-blind, controlled trial to assess the efficacy of hyperbaric treatment in children with autism.</p> <p>Methods</p> <p>62 children with autism recruited from 6 centers, ages 2–7 years (mean 4.92 ± 1.21), were randomly assigned to 40 hourly treatments of either hyperbaric treatment at 1.3 atmosphere (atm) and 24% oxygen ("treatment group", n = 33) or slightly pressurized room air at 1.03 atm and 21% oxygen ("control group", n = 29). Outcome measures included Clinical Global Impression (CGI) scale, Aberrant Behavior Checklist (ABC), and Autism Treatment Evaluation Checklist (ATEC).</p> <p>Results</p> <p>After 40 sessions, mean physician CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0008), receptive language (p < 0.0001), social interaction (p = 0.0473), and eye contact (p = 0.0102); 9/30 children (30%) in the treatment group were rated as "very much improved" or "much improved" compared to 2/26 (8%) of controls (p = 0.0471); 24/30 (80%) in the treatment group improved compared to 10/26 (38%) of controls (p = 0.0024). Mean parental CGI scores significantly improved in the treatment group compared to controls in overall functioning (p = 0.0336), receptive language (p = 0.0168), and eye contact (p = 0.0322). On the ABC, significant improvements were observed in the treatment group in total score, irritability, stereotypy, hyperactivity, and speech (p < 0.03 for each), but not in the control group. In the treatment group compared to the control group, mean changes on the ABC total score and subscales were similar except a greater number of children improved in irritability (p = 0.0311). On the ATEC, sensory/cognitive awareness significantly improved (p = 0.0367) in the treatment group compared to the control group. Post-hoc analysis indicated that children over age 5 and children with lower initial autism severity had the most robust improvements. Hyperbaric treatment was safe and well-tolerated.</p> <p>Conclusion</p> <p>Children with autism who received hyperbaric treatment at 1.3 atm and 24% oxygen for 40 hourly sessions had significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness compared to children who received slightly pressurized room air.</p> <p>Trial Registration</p> <p>clinicaltrials.gov NCT00335790</p

Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1,131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (pvalue=4.82e-08, OR=2.12), and two known loci: UNC13A, led by rs1297319 (pvalue=1.27e-08, OR=1.50) and HLA-DQA2 led by rs17219281 (pvalue=3.22e-08, OR=1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n≥3) as compared to controls (n=0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g. DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis

Host Decoy Trap (HDT) with cattle odour is highly effective for collection of exophagic malaria vectors

Background: As currently implemented, malaria vector surveillance in sub-Saharan Africa targets endophagic and endophilic mosquitoes, leaving exophagic (outdoor blood feeding) mosquitoes underrepresented. We evaluated the recently developed host decoy trap (HDT) and compared it to the gold standard, human landing catch (HLC), in a 3x3 Latin square study design outdoors in western Kenya. HLCs are considered to represent the natural range of Anopheles biting-behaviour compared to other sampling tools, and therefore, in principle, provide the most reliable profile of the biting population transmitting malaria. The HDT incorporates the main host stimuli that attract blood meal seeking mosquitoes and can be baited with the odours of live hosts. Results: Numbers and species diversity of trapped mosquitoes varied significantly between HLCs and HDTs baited with human (HDT-H) or cattle (HDT-C) odour, revealing important differences in behaviour of Anopheles species. In the main study in Kisian, the HDT-C collected a nightly mean of 43.2 (95% CI; 26.7-69.8) Anopheles, compared to 5.8 (95% CI; 4.1-8.2) in HLC, while HDT-H collected 0.97 (95% CI; 0.4-2.1), significantly fewer than the HLC. Significantly higher proportions of An. arabiensis were caught in HDT-Cs (0.94 ± 0.01; SE) and HDT-Hs (0.76 ± 0.09; SE) than in HLCs (0.45 ± 0.05; SE) per trapping night. The proportion of An. gambiae s.s. was highest in HLC (0.55 ±0.05; SE) followed by HDT-H (0.20 ± 0.09; SE) and least in HDT-C (0.06 ± 0.01; SE). An unbaited HDT placed beside locales where cattle are usually corralled overnight caught mostly An. arabiensis with proportions of 0.97 ± 0.02 and 0.80 ± 0.2 relative to the total anopheline catch in the presence and absence of cattle, respectively. A mean of 10.4 (95% CI; 2.0-55.0) Anopheles/night were trapped near cattle, compared to 0.4 (95% CI; 0.1-1.7) in unbaited HDT away from hosts. Conclusions: The capability of HDTs to combine host odours, heat and visual stimuli to simulate a host provides the basis of a system to sample human- and cattle-biting mosquitoes. HDT-C is particularly effective for collecting An. arabiensis outdoors. The HDT offers the prospect of a system to monitor and potentially control An. arabiensis and other outdoor-biting mosquitoes more effectively

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In silico modeling of oxygen-enhanced MRI of specific ventilation.

Specific ventilation imaging (SVI) proposes that using oxygen-enhanced 1H MRI to capture signal change as subjects alternatively breathe room air and 100% O2 provides an estimate of specific ventilation distribution in the lung. How well this technique measures SV and the effect of currently adopted approaches of the technique on resulting SV measurement is open for further exploration. We investigated (1) How well does imaging a single sagittal lung slice represent whole lung SV? (2) What is the influence of pulmonary venous blood on the measured MRI signal and resultant SVI measure? and (3) How does inclusion of misaligned images affect SVI measurement? In this study, we utilized two patient-based in silico models of ventilation, perfusion, and gas exchange to address these questions for normal healthy lungs. Simulation results from the two healthy young subjects show that imaging a single slice is generally representative of whole lung SV distribution, with a calculated SV gradient within 90% of that calculated for whole lung distributions. Contribution of O2 from the venous circulation results in overestimation of SV at a regional level where major pulmonary veins cross the imaging plane, resulting in a 10% increase in SV gradient for the imaging slice. A worst-case scenario simulation of image misalignment increased the SV gradient by 11.4% for the imaged slice