Personal non-commercial use only

ABSTRACT. Objective. To develop a list of 5 tests or treatments used in rheumatology that have evidence indicating that they may be unnecessary and thus should be reevaluated by rheumatology healthcare providers and patients. Methods. Using the Delphi method, a committee of 16 rheumatologists from across Canada and an allied health professional generated a list of tests, procedures, or treatments in rheumatology that may be unnecessary, nonspecific, or insensitive. Items with high content agreement and perceived relevance advanced to a survey of Canadian Rheumatology Association (CRA) members. CRA members ranked these top items based on content agreement, effect, and item ranking. A methodology subcommittee discussed the items in light of their relevance to rheumatology, potential effect on patients, and the member survey results. Five candidate items selected were then subjected to a literature review. A group of patient collaborators with rheumatic diseases also reviewed these items. Results. Sixty-four unique items were proposed and after 3 Delphi rounds, this list was narrowed down to 13 items. In the member-wide survey, 172 rheumatologists responded (36% of those contacted). The respondent characteristics were similar to the membership at large in terms of sex and geographical distribution. Five topics (antinuclear antibodies testing, HLA-B27 testing, bone density testing, bone scans, and bisphosphonate use) with high ratings on agreement and effect were chosen for literature review. Conclusion. The list of 5 items has identified starting points to promote discussion about practices that should be questioned to assist rheumatology healthcare providers in delivering high-quality care

Immunogenic Eimeria tenella Glycosylphosphatidylinositol-Anchored Surface Antigens (SAGs) Induce Inflammatory Responses in Avian Macrophages

, but the ability of these proteins to stimulate immune responses in the chicken is unknown. infection. Concomitantly, treatment with rSAGs 4, 5 and 12 suppressed the expression of IL-12 and IFN-γ and elevated that of IL-10, suggesting that during infection these molecules may specifically impair the development of cellular mediated immunity. pathogenicity associated with the endogenous second generation stages

MAPK ERK Signaling Regulates the TGF-β1-Dependent Mosquito Response to Plasmodium falciparum

Malaria is caused by infection with intraerythrocytic protozoa of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Although a variety of anti-parasite effector genes have been identified in anopheline mosquitoes, little is known about the signaling pathways that regulate these responses during parasite development. Here we demonstrate that the MEK-ERK signaling pathway in Anopheles is controlled by ingested human TGF-β1 and finely tunes mosquito innate immunity to parasite infection. Specifically, MEK-ERK signaling was dose-dependently induced in response to TGF-β1 in immortalized cells in vitro and in the A. stephensi midgut epithelium in vivo. At the highest treatment dose of TGF-β1, inhibition of ERK phosphorylation increased TGF-β1-induced expression of the anti-parasite effector gene nitric oxide synthase (NOS), suggesting that increasing levels of ERK activation negatively feed back on induced NOS expression. At infection levels similar to those found in nature, inhibition of ERK activation reduced P. falciparum oocyst loads and infection prevalence in A. stephensi and enhanced TGF-β1-mediated control of P. falciparum development. Taken together, our data demonstrate that malaria parasite development in the mosquito is regulated by a conserved MAPK signaling pathway that mediates the effects of an ingested cytokine

MI 48084-5353 (formerly Technical Fellow at General Motors Research), [email protected]. John R. Hauser is the Kirin Professor of Marketing

Abstract Researchers and practitioners devote substantial effort to targeting banner advertisements, but less effort on how to communicate with consumers once targeted. Morphing enables a website to learn (actively and near optimally) which banner advertisements to serve to each cognitive-style segment in order to maximize click-through, brand consideration, and purchase. Cognitive-style segments are identified automatically from consumers' clickstreams. This paper describes the first large-sample random-assignment field-test of banner morphing -over 100,000 consumers viewing over 450,000 banners on CNET.com. On relevant webpages, CNET's click-through rates almost doubled relative to control banners. We supplement the CNET field test with a focused experiment on an automotive information-andrecommendation website. The focused experiment replaces automated learning with a longitudinal design to test the premise of morph-to-segment matching. Banners matched to cognitive styles, as well as the stage of the consumer's buying process and body-type preference, significantly increase click-through rates, brand consideration, and purchase likelihood relative to a control. Together the field and the focused experiments demonstrate that matching cognitive styles provide significant benefits above and beyond more-traditional targeting. Such improved banner effectiveness has strategic implications for allocations among media

MI 48084-5353 (formerly Technical Fellow at General Motors Research), [email protected]. John R. Hauser is the Kirin Professor of Marketing

Abstract Morphing enables a website to learn (actively and near optimally) which banner advertisements to serve to each cognitive-style segment in order to maximize outcome measures such as click-through, brand consideration, or purchase. Consumer segments are identified automatically from consumers' clickstream choices. Morphing works best on high-traffic websites with tens of thousands of visitors because large samples are necessary to reach steady state optimally. This paper describes the first large-sample random-assignment field test of banner morphing -over 100,000 consumers viewing over 450,000 banners on CNET.com. (Previously published morphing evaluations evaluated morphing website characteristics and were based on predictive simulations using only priming-study data.) On relevant webpages, CNET's clickthrough rates almost double relative to control banners. We supplement the CNET field test with a focused experiment on an automotive information-and-recommendation website. The focused experiment replaces automated learning with a longitudinal design which tests the premise of morph-to-segment matching. Banners matched to cognitive styles, as well as the stage of the consumer's buying process and body-type preference, significantly increase click-through rates, brand consideration, and purchase likelihood relative to a control

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Semiconductor Spintronics

Spintronics refers commonly to phenomena in which the spin of electrons in a solid state environment plays the determining role. In a more narrow sense spintronics is an emerging research field of electronics: spintronics devices are based on a spin control of electronics, or on an electrical and optical control of spin or magnetism. This review presents selected themes of semiconductor spintronics, introducing important concepts in spin transport, spin injection, Silsbee-Johnson spin-charge coupling, and spindependent tunneling, as well as spin relaxation and spin dynamics. The most fundamental spin-dependent nteraction in nonmagnetic semiconductors is spin-orbit coupling. Depending on the crystal symmetries of the material, as well as on the structural properties of semiconductor based heterostructures, the spin-orbit coupling takes on different functional forms, giving a nice playground of effective spin-orbit Hamiltonians. The effective Hamiltonians for the most relevant classes of materials and heterostructures are derived here from realistic electronic band structure descriptions. Most semiconductor device systems are still theoretical concepts, waiting for experimental demonstrations. A review of selected proposed, and a few demonstrated devices is presented, with detailed description of two important classes: magnetic resonant tunnel structures and bipolar magnetic diodes and transistors. In most cases the presentation is of tutorial style, introducing the essential theoretical formalism at an accessible level, with case-study-like illustrations of actual experimental results, as well as with brief reviews of relevant recent achievements in the field.Comment: tutorial review; 342 pages, 132 figure

Evaluating the diagnostic properties of the Whooley questionnaire as a case-finding instrument for depression among Chinese women during and after pregnancy

Purpose: There is a rising prevalence in undetected perinatal depression in many countries, more effort in screening and early identification of perinatal depression is needed. While the Whooley questionnaire is the recommended case-finding strategy for perinatal depression, there is no validated Chinese version. The aim was to evaluate the diagnostic accuracy and stability of the translated Chinese Whooley questionnaire against gold standard measurement during and early after pregnancy. Materials and Methods: This observational study recruited 131 pregnant women from an antenatal clinic in Hong Kong from September 2019 to May 2020. We translated the Whooley questionnaire in Chinese and evaluated self-reported responses against an interviewer-assessed diagnostic standard (DSM-IV criteria) in 107 women at 26–28 gestational weeks. We calculated sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio, with DSM-IV diagnosis as the gold standard. Results: The Chinese Whooley questions had a sensitivity of 79% (95% CI 54.4–93.9), a specificity of 97% (95% CI 90.4–99.3), a positive likelihood ratio of 23.2 (95% CI 7.4–72.1) and a negative likelihood ratio of 0.2 (95% CI 0.1–0.5) in identifying perinatal depression. Conclusion: The translated Chinese Whooley questionnaire has an acceptable diagnostic accuracy in identifying perinatal depression. It can be implemented in health services among Cantonesespeaking Chinese population

Electronic Structure of Crystalline 4He at High Pressures

Using inelastic X-ray scattering techniques, we have succeeded in probing the high-pressure electronic structure of helium crystal at 300 K which has the widest known electronic energy bandgap of all materials, that was previously inaccessible to measurements due to the extreme energy and pressure range. We observed rich electron excitation spectrum, including a cut-off edge above 23 eV, a sharp exciton peak showing linear volume dependence, and a series of excitations and continuum at 26 to 45 eV. We determined electronic dispersion along the {Gamma}-M direction over two Brillouin zones, and provided a quantitative picture of the helium exciton beyond the simplified Wannier-Frenkel description