Efficacy and Safety of a New 20% Immunoglobulin Preparation for Subcutaneous Administration, IgPro20, in Patients With Primary Immunodeficiency

Subcutaneous human IgG (SCIG) therapy in primary immunodeficiency (PID) offers sustained IgG levels throughout the dosing cycle and fewer adverse events (AEs) compared to intravenous immunoglobulin (IVIG). A phase I study showed good local tolerability of IgPro20, a new 20% liquid SCIG stabilized with L-proline. A prospective, open-label, multicenter, single-arm, phase III study evaluated the efficacy and safety of IgPro20 in patients with PID over 15 months. Forty-nine patients (5–72 years) previously treated with IVIG received weekly subcutaneous infusions of IgPro20. The mean serum IgG level was 12.5 g/L. No serious bacterial infections were reported. There were 96 nonserious infections (rate 2.76/patient per year). The rate of days missed from work/school was 2.06/patient per year, and the rate of hospitalization was 0.2/patient per year. Ninety-nine percent of AEs were mild or moderate. No serious, IgPro20-related AEs were reported. IgPro20 effectively protected patients with PID against infections and maintained serum IgG levels without causing unexpected AEs

Post‐socialist language ideologies in action: Linking interview context and language ideology through stance

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136334/1/josl12225_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136334/2/josl12225.pd

Between Will and Thought: Individualism and Social Responsiveness in Amazonian Child Rearing

This essay provides an ethnographic account of how moral dispositions towards independence and social responsiveness are forged during infancy and toddlerhood among the Runa, an indigenous people in the Ecuadorian Amazon. I will show how two local concepts, munay (will) and yuyay (thought) shape children’s early experiences of the self and the self in relation to others. In particular, I will argue that, unlike middle class Anglo-Americans who repute paternal responsiveness to be necessary for a “healthy” child development, Runa adults strategically chose not to respond to children’s will in order to make them “thoughtful”. Such state of thoughtfulness, I argue, emerges from socialization practices which stress a child’s unique will while at the same time forcefully encourage the development of social responsiveness

Meiotic chromosomes and nucleolar behavior in testicular cells of the grassland spittlebugs Deois flavopicta, Mahanarva fimbriolata and Notozulia entreriana (Hemiptera, Auchenorrhyncha)

Spittlebugs annually infest pastures and cause severe damage, representing a serious problem for the tropical American beef cattle industry. Spittlebugs are an important biotic constraint to forage production and there is a lack of cytogenetic data for this group of insects. For these reasons, we conducted this work, in which the spermatogenesis and nucleolar behavior of Deois flavopicta, Mahanarva fimbriolata and Notozulia entreriana were studied. The males possessed testes in the shape of a “bunch of grapes”; a variable number of testicular lobes per individual and polyploid nuclei composed of several heteropycnotic bodies. A heteropycnotic area was located in the periphery of the nucleus (prophase I); the chiasmata were terminal or interstitial; metaphases I were circular or linear and anaphase showed late migration of the sex chromosome. The chromosome complement had 2n = 19, except for N. entreriana (2n = 15); the spermatids were round with heteropycnotic material in the center and elongated with conspicuos chromatin. The analysis of testes after silver nitrate staining showed polyploid nuclei with three large and three smaller nucleolar bodies. Early prophase cells had an intensely stained nucleolar body located close to the chromatin and another less evident body located away from the chromatin. The nucleolar bodies disintegrated during diplotene. Silver staining occurred in two autosomes, in terminal and subterminal locations, the latter probably corresponding to the nucleolus organizer regions (NORs). The spermatids were round with a round nucleolar body and silver staining was observed in the medial and posterior region of the elongated part of the spermatid head

Disruption of Mitochondrial DNA Replication in Drosophila Increases Mitochondrial Fast Axonal Transport In Vivo

Mutations in mitochondrial DNA polymerase (pol γ) cause several progressive human diseases including Parkinson's disease, Alper's syndrome, and progressive external ophthalmoplegia. At the cellular level, disruption of pol γ leads to depletion of mtDNA, disrupts the mitochondrial respiratory chain, and increases susceptibility to oxidative stress. Although recent studies have intensified focus on the role of mtDNA in neuronal diseases, the changes that take place in mitochondrial biogenesis and mitochondrial axonal transport when mtDNA replication is disrupted are unknown. Using high-speed confocal microscopy, electron microscopy and biochemical approaches, we report that mutations in pol γ deplete mtDNA levels and lead to an increase in mitochondrial density in Drosophila proximal nerves and muscles, without a noticeable increase in mitochondrial fragmentation. Furthermore, there is a rise in flux of bidirectional mitochondrial axonal transport, albeit with slower kinesin-based anterograde transport. In contrast, flux of synaptic vesicle precursors was modestly decreased in pol γ−α mutants. Our data indicate that disruption of mtDNA replication does not hinder mitochondrial biogenesis, increases mitochondrial axonal transport, and raises the question of whether high levels of circulating mtDNA-deficient mitochondria are beneficial or deleterious in mtDNA diseases

Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Ready Insights for the Future: Digital Dissemination of Agronomic and Environmental Knowledge Involved in the Agricultural Development of Central Brazil

Long-term agricultural development of a major region usually involves supportive national policy, infrastructure development, financial investment and favorable market factors. The remarkable growth of food production in the Savannah region of central Brazil, however, also reflects significant contributions from new technology developed in the area. Some of the early research under-girding the development of this region, locally known as the "cerrado," was conducted at a Brazilian research facility, now known as the CPAC (Agricultural Research Center for the Cerrado). Collaborative work was done there by local researchers and several US institutions, with the sustained and effective support of US government programs aimed at improving long-term world food production. Information about this unusual success story can be found scattered among the libraries of various institutions and agencies in differing languages and countries. Original objectives, methodology, findings and some of the anecdotal experiences of individuals involved may reside in research theses as well as in scientific journals and extension bulletins. Because this story began some four decades ago, some of it is found as personal remembrances and collected wisdom within the minds, and perhaps in the file cabinets, of now-retired persons. Current digital technological developments appear to offer unprecedented opportunities to organize and store such information in readily and widely accessible forms. Described as "subject-based digital repositories," these offer a means of collecting material and offering it world wide in a cost-efficient manner. Searchers with diverse interests ranging, as examples, from soil, agronomic and environmental sciences to international economics, policy or history would all have access to knowledge that could contribute to new insights about designs for long-term experiments or strategies for resource development. Research findings and raw data from this specific agricultural ecosystem may apply to similar regions under differing political jurisdictions to meet new challenges as the future unfolds. Such areas and topics could be well served by this repository of knowledge. We describe such a repository, currently being developed by Mann Agricultural Library at Cornell University in Ithaca, New York. It would focus on programs conducted by the Brazil Cerrados Agricultural Research Center/Cornell University/North Carolina State University cooperative research project during the 1970?s and 1980?s. This was a multi-university collaboration with EMBRAPA, a Brazilian public enterprise. This mutually beneficial project involved several institutions and dozens of researchers, and it contributed significantly to development of the productivity and influence of today's agriculture in the Brazilian Cerrados. Materials offered in this ?Brazil Cerrados digital repository? would include non-copyrighted text, citations to published documents, personal reflections about key methods and experiences, context photography with explanatory captions and specially-authored analyses or interpretations. Depending upon interests, even interactive virtual discussions could occur. This digital material will exist as a collection within Cornell University's Open Access Archive (http://dspace.library.cornell.edu/), which is powered by DSpace. A DSpace "community" will be created for Cerrados with "collections" added for organizing the material. Basic indexing (or metadata) will be created for each item deposited. The material may then be accessed via a direct URL or by searching within DSpace or the Cerrados "community" by author, title, or keyword. Browsing by author, title, and date is also allowed. The materials added to DSpace are also searchable via popular search engines such as Google, which will permit the information to be easily located and used by people around the world