Meeting Overview: Interferon Lambda - Disease Impact and Therapeutic Potential

A meeting entitled, Interferon Lambda: Disease Impact and Translational Potential, was held on the campus of the National Institutes of Health in Bethesda, Maryland, on October 25-26, 2018. To our knowledge, this was the first meeting that focused exclusively on interferon lambda (IFN-λ). The meeting\u27s purpose was to enhance interdisciplinary communication and promote new collaborations. The gathering brought together an international group of scientists from a wide range of disciplines. Sessions included: IFN-λ Biology, Therapy and Genetic Variation; IFN-λ and Hepatitis C Virus Infection; IFN-λ in Other Infections; and IFN-λ - Hepatic Fibrosis and Cancer. The next meeting on IFN-λ is planned for 2020

Middle Eastern Americans and Socioeconomic Class in American Politics

The Middle-Eastern American's experience in the US underwent a dramatic shift after the terrorist attacks of September 11th

Three-dimensional relationship between high-order root-mean-square wavefront error, pupil diameter, and aging

We report root-mean-square (RMS) wavefront error (WFE) for individual aberrations and cumulative highorder (HO) RMS WFE for the normal human eye as a function of age by decade and pupil diameter in 1 mm steps from 3 to 7 mm and determine the relationship among HO RMS WFE, mean age for each decade of life, and luminance for physiologic pupil diameters. Subjects included 146 healthy individuals from 20 to 80 years of age. Ocular aberration was measured on the preferred eye of each subject (for a total of 146 eyes through dilated pupils; computed for 3, 4, 5, 6, and 7 mm pupils; and described with a tenth-radial-order normalized Zernike expansion. We found that HO RMS WFE increases faster with increasing pupil diameter for any given age and pupil diameter than it does with increasing age alone. A planar function accounts for 99% of the variance in the 3-D space defined by mean log HO RMS WFE, mean age for each decade of life, and pupil diameter. When physiologic pupil diameters are used to estimate HO RMS WFE as a function of luminance and age, at low luminance 9 cd/m2 HO RMS WFE decreases with increasing age. This normative data set details (1) the 3-D relationship between HO RMS WFE and age for fixed pupil diameters and (2) the 3-D relationship among HO RMS WFE, age, and luminance for physiologic pupil diameters

IL-4 engagement of the type 1 IL-4 receptor complex enhances mouse eosinophil migration to eotaxin-1 in vitro

Background Previous work from our laboratory demonstrated that IL-4Rα expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes/macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effect(s) of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function. Methods Standard Transwell chemotaxis assay was used to assay migration of mouse eosinophils and signal transduction was assessed by Western blotting. Results Here we determined that (i) mouse eosinophils express both type I and type II IL-4 receptors, (ii) in contrast to human eosinophils, mouse eosinophils do not chemotax to IL-4 or IL-13 although (iii) pre-treatment with IL-4 but not IL-13 enhanced migration to eotaxin-1. This IL-4-mediated enhancement was dependent on type I IL-4 receptor expression: γC-deficient eosinophils did not show enhancement of migratory capacity when pre-treated with IL-4. In addition, mouse eosinophils responded to IL-4 with the robust tyrosine phosphorylation of STAT6 and IRS-2, while IL-13-induced responses were considerably weaker. Conclusions The presence of IL-4 in combination with eotaxin-1 in the allergic inflammatory milieu could potentiate infiltration of eosinophils into the lungs. Therapies that block IL-4 and chemokine receptors on eosinophils might be more effective clinically in reducing eosinophilic lung inflammation

Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Rα, IL-13Rα1, and γc regulates relative cytokine sensitivity

Interleukin (IL)-4 and -13 are related cytokines sharing functional receptors. IL-4 signals through the type I (IL-4Rα/common γ-chain [γc]) and the type II (IL-4Rα/-13Rα1) IL-4 receptors, whereas IL-13 utilizes only the type II receptor. In this study, we show that mouse bone marrow–derived macrophages and human and mouse monocytes showed a much greater sensitivity to IL-4 than to IL-13. Lack of functional γc made these cells poorly responsive to IL-4, while retaining full responsiveness to IL-13. In mouse peritoneal macrophages, IL-4 potency exceeds that of IL-13, but lack of γc had only a modest effect on IL-4 signaling. In contrast, IL-13 stimulated greater responses than IL-4 in fibroblasts. Using levels of receptor chain expression and known binding affinities, we modeled the assemblage of functional type I and II receptor complexes. The differential expression of IL-4Rα, IL-13Rα1, and γc accounted for the distinct IL-4–IL-13 sensitivities of the various cell types. These findings provide an explanation for IL-13's principal function as an “effector” cytokine and IL-4's principal role as an “immunoregulatory” cytokine

Lateral Marsh Edge Erosion as a Source of Sediments for Vertical Marsh Accretion

With sea level rise accelerating and sediment inputs to the coast declining worldwide, there is concern that tidal wetlands will drown. To better understand this concern, sources of sediment contributing to marsh elevation gain were computed for Plum Island Sound estuary, MA, USA. We quantified input of sediment from rivers and erosion of marsh edges. Maintaining elevation relative to the recent sea level rise rate of 2.8 mm yr−1 requires input of 32,299 MT yr−1 of sediment. The input from watersheds is only 3,210 MT yr−1. Marsh edge erosion, based on a comparison of 2005 and 2011 LiDAR data, provides 10,032 MT yr−1. This level of erosion is met by \u3c0.1% of total marsh area eroded annually. Mass balance suggests that 19,070 MT yr−1 should be of tidal flat or oceanic origin. The estuarine distribution of 14C and 13C isotopes of suspended particulate organic carbon confirms the resuspension of ancient marsh peat from marsh edge erosion, and the vertical distribution of 14C‐humin material in marsh sediment is indicative of the deposition of ancient organic carbon on the marsh platform. High resuspension rates in the estuarine water column are sufficient to meet marsh accretionary needs. Marsh edge erosion provides an important fraction of the material needed for marsh accretion. Because of limited sediment supply and sea level rise, the marsh platform maintains elevation at the expense of total marsh area

Electroconvulsive Therapy - Guidelines for Health Authorities in British Columbia

The purpose of these guidelines for electroconvulsive therapy (ECT Guidelines) is to standardize the delivery of electroconvulsive therapy services across British Columbia. There will be differences in the way care is delivered according to local resources, but good basic care must be available wherever ECT is provided. These guidelines cover patient and family education, clinical applications of ECT by physicians, nurses, and anesthetists, as well as suggestions for charting, professional education, and quality assurance programs. Disclaimer: This document appears here with permission from the UBC Department of Psychiatry and the BC Ministry of Health. The material is only current to the date of initial publication. New, more accurate, information may be available. For completeness, please investigate the most recent details on this topic

Mating system of the Eurasian badger, Meles meles, in a high density population

Badgers are facultatively social, forming large groups at high density. Group-living appears to have high reproductive costs for females, and may lead to increased levels of inbreeding. The extent of female competition for reproduction has been estimated from field data, but knowledge of male reproductive success and the extent of extra-group paternity remains limited. Combining field data with genetic data (16 microsatellite loci), we studied the mating system of 10 badger social groups across 14 years in a high-density population. From 923 badgers, including 425 cubs, we were able to assign maternity to 307 cubs, with both parents assigned to 199 cubs (47%) with 80% confidence, and 14% with 95% confidence. Age had a significant effect on the probability of reproduction, seemingly as a result of a deficit of individuals aged two years and greater than eight years attaining parentage. We estimate that approximately 30% of the female population successfully reproduced in any given year, with a similar proportion of the male population gaining paternity across the same area. While it was known there was a cost to female reproduction in high density populations, it appears that males suffer similar, but not greater, costs. Roughly half of assigned paternity was attributed to extra-group males, the majority of which were from neighbouring social groups. Few successful matings occurred between individuals born in the same social group (22%). The high rate of extra-group mating, previously unquantified, may help reduce inbreeding, potentially making philopatry a less costly strategy

Role of Anopheles (Cellia) rufipes (Gough, 1910) and other local anophelines in human malaria transmission in the northern savannah of Cameroon: a crosssectional survey

Background As part of a study to determine the impact of insecticide resistance on the effectiveness of longlasting insecticide treated nets (LLINs) in the north of Cameroon, the unexpectedly high density and anthropophilic behaviour of Anopheles rufipes lead us to investigate this species bionomics and role in human malaria parasite transmission. Methods For four consecutive years (2011–2014), annual cross-sectional sampling of adult mosquitoes was conducted during the peak malaria season (September-October) in three health districts in northern Cameroon. Mosquitoes sampled by human landing catch and pyrethrum spray catch methods were morphologically identified, their ovaries dissected for parity determination and Anopheles gambiae siblings were identified by molecular assay. Infection with P. falciparum and blood meal source in residual fauna of indoor resting anopheline mosquitoes were determined by enzyme-linked-immunosorbent assays. Results Anopheles gambiae (sensu lato) (s.l.) comprised 18.4% of mosquitoes collected with An. arabiensis representing 66.27% of the sibling species. The proportion of An. rufipes (2.7%) collected was high with a humanbiting rate ranging between 0.441 and 11.083 bites/person/night (b/p/n) and an anthropophagic rate of 15.36%. Although overall the members of An. gambiae complex were responsible for most of the transmission with entomological inoculation rates (EIR) reaching 1.221 infective bites/person/night (ib/p/n), An. arabiensis and An.coluzzii were the most implicated. The roles of An. funestus, An. pharoensis and An. paludis were minor. Plasmodium falciparum circumsporozoite protein rate in Anopheles rufipes varied from 0.6 to 5.7% with EIR values between 0.010 and 0.481 ib/p/n Conclusions The study highlights the epidemiological role of An. rufipes alongside the members of the An.gambiae complex, and several other sympatric species in human malaria transmission during the wet season in northern Cameroon. For the first time in Cameroon, An. rufipes has been shown to be an important local malaria vector, emphasising the need to review the malaria entomological profile across the country as pre-requisite to effective vector management strategies

Role of Anopheles (Cellia) rufipes (Gough, 1910) and other local anophelines in human malaria transmission in the northern savannah of Cameroon: a crosssectional survey

Background As part of a study to determine the impact of insecticide resistance on the effectiveness of longlasting insecticide treated nets (LLINs) in the north of Cameroon, the unexpectedly high density and anthropophilic behaviour of Anopheles rufipes lead us to investigate this species bionomics and role in human malaria parasite transmission. Methods For four consecutive years (2011–2014), annual cross-sectional sampling of adult mosquitoes was conducted during the peak malaria season (September-October) in three health districts in northern Cameroon. Mosquitoes sampled by human landing catch and pyrethrum spray catch methods were morphologically identified, their ovaries dissected for parity determination and Anopheles gambiae siblings were identified by molecular assay. Infection with P. falciparum and blood meal source in residual fauna of indoor resting anopheline mosquitoes were determined by enzyme-linked-immunosorbent assays. Results Anopheles gambiae (sensu lato) (s.l.) comprised 18.4% of mosquitoes collected with An. arabiensis representing 66.27% of the sibling species. The proportion of An. rufipes (2.7%) collected was high with a humanbiting rate ranging between 0.441 and 11.083 bites/person/night (b/p/n) and an anthropophagic rate of 15.36%. Although overall the members of An. gambiae complex were responsible for most of the transmission with entomological inoculation rates (EIR) reaching 1.221 infective bites/person/night (ib/p/n), An. arabiensis and An.coluzzii were the most implicated. The roles of An. funestus, An. pharoensis and An. paludis were minor. Plasmodium falciparum circumsporozoite protein rate in Anopheles rufipes varied from 0.6 to 5.7% with EIR values between 0.010 and 0.481 ib/p/n Conclusions The study highlights the epidemiological role of An. rufipes alongside the members of the An.gambiae complex, and several other sympatric species in human malaria transmission during the wet season in northern Cameroon. For the first time in Cameroon, An. rufipes has been shown to be an important local malaria vector, emphasising the need to review the malaria entomological profile across the country as pre-requisite to effective vector management strategies