Technocratic attitudes: a citizens’ perspective of expert decision-making

Despite repeated appointments of technocratic governments in Europe and increasing interest in technocracy, there is little knowledge regarding citizens’ attitudes towards technocracy and the idea of governance by unelected experts. This article revisits normative debates and hypothesises that technocracy and democracy stand in a negative relationship in the eyes of European citizens. It tests this alongside a series of hypotheses on technocratic attitudes combining country-level institutional characteristics with individual survey data. While findings confirm that individual beliefs about the merits of democracy influence technocratic attitudes, two additional important factors are also identified: first, levels of trust in current representative political institutions also motivate technocratic preferences; second, historical legacies, in terms of past party-based authoritarian regime experience, can explain significant cross-national variation. The implications of the findings are discussed in the broader context of citizen orientations towards government, elitism and the mounting challenges facing representative democracy

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Magmatic evolution of mafic granulites from Anakapalle, Eastern Ghats, India: implications for tectonic setting of a precambrian high-grade terrain

Maficgranulites showing intrusive relationships with enclosing pelitic, calcareous and quartzofeldspathic gneisses at Anakapalle, Eastern Ghats belt, share a common retrograde metamorphic history (decompression followed by near-isobaric cooling) and are, therefore, considered to be syn-metamorphic. Detail textural, phase chemical and bulk chemical analyses of the mafic granulites show that (a) these are melts derived through fractionation of a primary tholeiitic magma and (b) they crystallized at temperatures <1000°C and were thus in thermal equilibrium with the country rock granulites during peak metamorphism. Comparison with experimental data on similar bulk compositions constrains the depth of emplacement of the magmas at 30-35 km. Geochemical characteristics indicate that the mafic magmas are essentially similar to continental flood basalts and have thus been generated in an extensional set-up. The apparent clockwise trajectory recorded in the Anakapalle granulites was produced by extension of the crust of near-normal thickness with concommitant basic magmatism

Mid-crustal contact metamorphism around the Chimakurthy mafic-ultramafic complex, Eastern Ghats Belt, India

Pelitic rocks were thermally metamorphosed at the contact of the Chimakurthy mafic-ultramafic igneous complex, Eastern Ghats Belt, India. The rocks show progressive change in mineralogy from biotite-sillimanite-quartz-garnet-K-feldspar (association I, 150 m from the intrusive contact) to garnet-spinel-cordierite-K-feldspar-sillimanite (association II, 20-30m from the intrusive contact) to cordierite-K-feldspar-(cordierite-orthopyroxene-K-feldspar symplectite after osumilite)-spinel-FeTiAl oxides with/without garnet (associations III and IV, 5m from the intrusive contact), and finally to spinel-orthopyroxene-cordierite-K-feldspar (association V, xenoliths). Oxide mineral clots in associations III and IV resemble emery-type rocks. Initial mineral reactions involved biotite-dehydration melting with partial segregation of the melt. Down-temperature mineral reactions were largely diffusion controlled and preservation of symplectitic and coronitic textures in microdomains is common. Interpretation of reaction textures in relevant petrogenetic grids for the sytems KFMASH and FMAS and combined with geothermobarometry suggest that the pelitic rocks were thermally metamorphosed at c. 6 kbar pressure along a heating-cooling trajectory within the temperature interval between c. 750°C and c. 1000°C

Dysregulated PI3K Signaling in B Cells of CVID Patients

The altered wiring of signaling pathways downstream of antigen receptors of T and B cells contributes to the dysregulation of the adaptive immune system, potentially causing immunodeficiency and autoimmunity. In humans, the investigation of such complex systems benefits from nature’s experiments in patients with genetically defined primary immunodeficiencies. Disturbed B-cell receptor (BCR) signaling in a subgroup of common variable immunodeficiency (CVID) patients with immune dysregulation and expanded T-bethighCD21low B cells in peripheral blood has been previously reported. Here, we investigate PI3K signaling and its targets as crucial regulators of survival, proliferation and metabolism by intracellular flow cytometry, imaging flow cytometry and RNAseq. We observed increased basal but disturbed BCR-induced PI3K signaling, especially in T-bethighCD21low B cells from CVID patients, translating into impaired activation of crucial downstream molecules and affecting proliferation, survival and the metabolic profile. In contrast to CVID, increased basal activity of PI3K in patients with a gain-of-function mutation in PIK3CD and activated PI3K delta syndrome (APDS) did not result in impaired BCR-induced AKT-mTOR-S6 phosphorylation, highlighting that signaling defects in B cells in CVID and APDS patients are fundamentally different and that assessing responses to BCR stimulation is an appropriate confirmative diagnostic test for APDS. The active PI3K signaling in vivo may render autoreactive T-bethighCD21low B cells in CVID at the same time to be more sensitive to mTOR or PI3K inhibition

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations

Background: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. Objective: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts. Methods: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered. Results: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years. Conclusions: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations. (J Allergy Clin Immunol 2021;148:1332-41.