Tissue Cytokine Responses in Canine Visceral Leishmaniasis

To elucidate the local tissue cytokine response of dogs infected with Leishmania chagasi, cytokine mRNA levels were measured in bone marrow aspirates from 27 naturally infected dogs from Brazil and were compared with those from 5 uninfected control animals. Interferon-γ mRNA accumulation was enhanced in infected dogs and was positively correlated with humoral (IgG1) but not with lymphoproliferative responses to Leishmania antigen in infected dogs. Increased accumulation of mRNA for interleukin (IL)4, IL-10, and IL-18 was not observed in infected dogs, and mRNA for these cytokines did not correlate with antibody or proliferative responses. However, infected dogs with detectable IL-4 mRNA had significantly more severe symptoms. IL-13 mRNA was not detectable in either control or infected dogs. These data suggest that clinical symptoms are not due to a deficiency in interferon-γ production. However, in contrast to its role in human visceral leishmaniasis, IL-10 may not play a key immunosuppressive role in dogs

A 100 kHz pulse shaping 2D-IR spectrometer based on dual Yb:KGW amplifiers

A high-speed, high-sensitivity and compact two-dimensional infrared (2D-IR) spectrometer based on 100 kHz Yb:KGW regenerative amplifier technology is described and demonstrated. The setup is three color, using an independent pump OPA and two separately tunable probe OPAs. The spectrometer uses 100 kHz acousto-optic pulse shaping on the pump beam for rapid 2D-IR acquisitions. The shot-to-shot stability of the laser system yields excellent signal-to-noise figures (∼10 μOD noise on 5000 laser shots). We show that the reduced bandwidth of the Yb:KGW amplifiers in comparison with conventional Ti:sapphire systems does not compromise the ability of the setup to generate high-quality 2D-IR data. Instrument responses of <300 fs are demonstrated and 2D-IR data presented for several systems of interest to physical chemists, showing spectral diffusion in NaSCN, amide I and II bands of a β sheet protein and DNA base-pair–backbone couplings. Overall, the increased data acquisition speed, intrinsic stability, and robustness of the Yb:KGW lasers are a significant step forward for 2D-IR spectroscopy

A nonlinear spring mechanism incorporating a bistable composite plate for vibration isolation

The High Static Low Dynamic Stiffness (HSLDS) concept is a design strategy for a nonlinear anti-vibration mount that seeks to increase isolation by lowering the natural frequency of the mount whilst maintaining the same static load bearing capacity. It has previously been proposed that an HSLDS mount could be implemented by connecting linear springs in parallel with the transverse flexure of a composite bistable plate — a plate that has two stable shapes between which it may snap. Using a bistable plate in this way will lead to lightweight and efficient designs of HSLDS mounts. This paper experimentally demonstrates the feasibility of this idea. Firstly, the quasi-static force–displacement curve of a mounted bistable plate is determined experimentally. Then the dynamic response of a nonlinear mass–spring system incorporating this plate is measured. Excellent agreement is obtained when compared to theoretical predictions based on the measured force–displacement curve, and the system shows a greater isolation region and a lower peak response to base excitation than the equivalent linear system

Comparison of Transcriptomic Changes in Survivors of Exertional Heat Illness with Malignant Hyperthermia Susceptible Patients

Exertional heat illness (EHI) is an occupational health hazard for athletes and military personnel–characterised by the inability to thermoregulate during exercise. The ability to thermoregulate can be studied using a standardised heat tolerance test (HTT) developed by The Institute of Naval Medicine. In this study, we investigated whole blood gene expression (at baseline, 2 h post-HTT and 24 h post-HTT) in male subjects with either a history of EHI or known susceptibility to malignant hyperthermia (MHS): a pharmacogenetic condition with similar clinical phenotype. Compared to healthy controls at baseline, 291 genes were differentially expressed in the EHI cohort, with functional enrichment in inflammatory response genes (up to a four-fold increase). In contrast, the MHS cohort featured 1019 differentially expressed genes with significant down-regulation of genes associated with oxidative phosphorylation (OXPHOS). A number of differentially expressed genes in the inflammation and OXPHOS pathways overlapped between the EHI and MHS subjects, indicating a common underlying pathophysiology. Transcriptome profiles between subjects who passed and failed the HTT (based on whether they achieved a plateau in core temperature or not, respectively) were not discernable at baseline, and HTT was shown to elevate inflammatory response gene expression across all clinical phenotypes

Mapping the planet’s critical natural assets

Sustaining the organisms, ecosystems and processes that underpin human wellbeing is necessary to achieve sustainable development. Here we define critical natural assets as the natural and semi-natural ecosystems that provide 90% of the total current magnitude of 14 types of nature’s contributions to people (NCP), and we map the global locations of these critical natural assets at 2 km resolution. Critical natural assets for maintaining local-scale NCP (12 of the 14 NCP) account for 30% of total global land area and 24% of national territorial waters, while 44% of land area is required to also maintain two global-scale NCP (carbon storage and moisture recycling). These areas overlap substantially with cultural diversity (areas containing 96% of global languages) and biodiversity (covering area requirements for 73% of birds and 66% of mammals). At least 87% of the world’s population live in the areas benefitting from critical natural assets for local-scale NCP, while only 16% live on the lands containing these assets. Many of the NCP mapped here are left out of international agreements focused on conserving species or mitigating climate change, yet this analysis shows that explicitly prioritizing critical natural assets and the NCP they provide could simultaneously advance development, climate and conservation goals.We thank all the participants of two working groups hosted by Conservation International and the Natural Capital Project for their insights and intellectual contributions. For further advice or assistance, we thank A. Adams, K. Brandon, K. Brauman, A. Cramer, G. Daily, J. Fisher, R. Gould, L. Mandle, J. Montgomery, A. Rodewald, D. Rossiter, E. Selig, A. Vogl and T. M. Wright. The two working groups that provided the foundation for this analysis were funded by support from the Marcus and Marianne Wallenberg Foundation to the Natural Capital Project (R.C.-K. and R.P.S.) and the Betty and Gordon Moore to Conservation International (R.A.N. and P.M.C.)

The first catalog of active galactic nuclei detected by the Fermi large area telescope

We present the first catalog of active galactic nuclei (AGNs) detected by the Large Area Telescope (LAT), corresponding to 11 months of data collected in scientific operation mode. The First LAT AGN Catalog (1LAC) includes 671 ?-ray sources located at high Galactic latitudes (|b|&gt;10°) that are detected with a test statistic greater than 25 and associated statistically with AGNs. Some LAT sources are associated with multiple AGNs, and consequently, the catalog includes 709 AGNs, comprising 300 BL Lacertae objects, 296 flat-spectrum radio quasars, 41 AGNs of other types, and 72 AGNs of unknown type. We also classify the blazars based on their spectral energy distributions as archival radio, optical, and X-ray data permit. In addition to the formal 1LAC sample, we provide AGN associations for 51 low-latitude LAT sources and AGN "affiliations" (unquantified counterpart candidates) for 104 high-latitude LAT sources without AGN associations. The overlap of the 1LAC with existing ?-ray AGN catalogs (LBAS, EGRET, AGILE, Swift, INTEGRAL, TeVCat) is briefly discussed. Various properties—such as ?-ray fluxes and photon power-law spectral indices, redshifts, ?-ray luminosities, variability, and archival radio luminosities—and their correlations are presented and discussed for the different blazar classes. We compare the 1LAC results with predictions regarding the ?-ray AGN populations, and we comment on the power of the sample to address the question of the blazar sequenc

Prevalence of intellectual disability among eight-year-old children from selected communities in the United States, 2014

Background: Children with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups. Objective: Using empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators. Methods: We analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator. Results: Overall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0–16.5) among males and 7.7 (95% CI, 7.2–8.2) among females. ID prevalence was 17.7 (95% CI, 16.6–18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1–13.0), among Hispanic; 8.6 (95% CI, 7.1–10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5–8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES. Conclusions: ID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES