Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia

Aims - We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7–10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients. Methods and results - We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase–DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits. Conclusions - The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT

The globalizability of temporal discounting

Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns

The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis.

The objectives of this study are to review the long-term consequences of injuries to the anterior cruciate ligament and menisci, the pathogenic mechanisms, and the causes. of the considerable variability in outcome. Injuries of the anterior cruciate ligament and menisci are common in both athletes and the general population. At 10 to 20 years after the diagnosis, on average, 50% of those with a diagnosed anterior cruciate ligament or meniscus tear have ostecarthritis with associated pain and functional impairment: the young patient with an old knee. These individuals make up a substantial proportion of the overall ostecarthritis population. There is a lack of evidence to support a protective role of repair or reconstructive surgery of the anterior cruciate ligament or meniscus against ostecarthritis development. A consistent finding in a review of the literature is the often poor reporting of critical study variables, precluding data pooling or a meta-analysis. Osteoarthritis development in the injured joints is caused by intra-articular pathogenic processes initiated at the time of injury, combined with long-term changes in dynamic joint loading. Variation in outcome is reinforced by additional variables associated with the individual such as age, sex, genetics, obesity, muscle strength, activity, and reinjury. A better understanding of these variables may improve future prevention and treatment strategies. In evaluating medical treatment, we now expect large randomized clinical trials complemented by postmarketing monitoring. We should strive toward a comparable level of quality of evidence in surgical treatment of knee injuries. In instances in which a randomized clinical trial is not feasible, natural history and other observational cohort studies need to be as carefully designed and reported as the classic randomized clinical trial, to yield useful information

"The importance of the right material" : A multimodal critical discourse analysis of the outdoor clothing companies Fjällräven, Haglöfs and Houdini's sustainability communication on Instagram.

Klädföretagen Fjällräven, Haglöfs och Houdini är ledande inom den svenska friluftsbranschen och toppar Sustainable Brand Index lista över de, enligt konsumenterna, mest hållbara friluftsföretagen. Trots dessa topplaceringar går det inte att bortse från det motsägelsefulla i att företagen producerar kläder, som är skadliga för den natur de är ämnade att användas i – till en målgrupp som värnar om miljön. Med utgångspunkt i denna paradox är målet att i denna studie undersöka hur dessa företag kommunicerar hållbarhet på Instagram. För att genomföra detta har en multimodal kritisk diskursanalys använts. Med hjälp av denna har materialet (som består av Instagram-inlägg) kunnat analyseras såväl visuellt som lexikalt. Därtill undersöker den hur dessa element påverkar och påverkas av maktstrukturer, vilket i detta fall kan liknas med relationen mellan företag och konsument. Materialet som analyseras i denna studie består av sammanlagt 70 hållbarhetsrelaterade inlägg publicerade på Fjällrävens, Haglöfs och Houdinis officiella Instagram-konton under en ettårsperiod. Sammanfattningsvis visar analysen på att företagen kommunicerar hållbarhet genom de tre diskursiva temana hållbarhet genom material, hållbarhet genom kollektiva miljöåtgärder och hållbarhet genom information och utbildning. Studien kommer bland annat fram till att innebörden av begreppet hållbarhet beror på avsändarens ideologi, och därav får varierad betydelse beroende på vilken kontext det sätts in i. Utöver detta visar studien även att företagen tenderar att framställa sig själva som ett slags hållbarhetsideal. Dessutom påvisar studien även att miljöansvaret flyttas över till konsumenterna

"The importance of the right material" : A multimodal critical discourse analysis of the outdoor clothing companies Fjällräven, Haglöfs and Houdini's sustainability communication on Instagram.

Klädföretagen Fjällräven, Haglöfs och Houdini är ledande inom den svenska friluftsbranschen och toppar Sustainable Brand Index lista över de, enligt konsumenterna, mest hållbara friluftsföretagen. Trots dessa topplaceringar går det inte att bortse från det motsägelsefulla i att företagen producerar kläder, som är skadliga för den natur de är ämnade att användas i – till en målgrupp som värnar om miljön. Med utgångspunkt i denna paradox är målet att i denna studie undersöka hur dessa företag kommunicerar hållbarhet på Instagram. För att genomföra detta har en multimodal kritisk diskursanalys använts. Med hjälp av denna har materialet (som består av Instagram-inlägg) kunnat analyseras såväl visuellt som lexikalt. Därtill undersöker den hur dessa element påverkar och påverkas av maktstrukturer, vilket i detta fall kan liknas med relationen mellan företag och konsument. Materialet som analyseras i denna studie består av sammanlagt 70 hållbarhetsrelaterade inlägg publicerade på Fjällrävens, Haglöfs och Houdinis officiella Instagram-konton under en ettårsperiod. Sammanfattningsvis visar analysen på att företagen kommunicerar hållbarhet genom de tre diskursiva temana hållbarhet genom material, hållbarhet genom kollektiva miljöåtgärder och hållbarhet genom information och utbildning. Studien kommer bland annat fram till att innebörden av begreppet hållbarhet beror på avsändarens ideologi, och därav får varierad betydelse beroende på vilken kontext det sätts in i. Utöver detta visar studien även att företagen tenderar att framställa sig själva som ett slags hållbarhetsideal. Dessutom påvisar studien även att miljöansvaret flyttas över till konsumenterna

Pituitary function after high-dose 177Lu-DOTATATE therapy and long-term follow-up

INTRODUCTION: The pituitary gland has a high expression of somatostatin receptors (SSTRs) and is therefore a potential organ at risk for radiation-induced toxicity after 177Lu-DOTATATE treatment.OBJECTIVE: To study changes in pituitary function in patients with neuroendocrine tumors (NETs) treated with dosimetry-based 177Lu-DOTATATE to detect possible late toxicity.METHODS: 68 patients from a phase II clinical trial of dosimetry-based, individualized 177Lu-DOTATATE-therapy were included in this analysis. Patients had received a median of 5 (range 3-9) treatment cycles of 7.4 GBq/cycle. Median follow-up was 30 months (range 11-89). The GH/IGF1-axis, gonadotropins, adrenal and thyroid axes were analyzed from baseline and on a yearly basis thereafter. Percent changes in hormonal levels over time were analyzed statistically using a linear mixed model and described graphically using boxplots. The absorbed radiation dose to the pituitary was estimated based on post-therapeutic imaging, and the results analyzed vs % change in IGF1-levels over time.RESULTS: A statistically significant decrease in the levels of IGF1 was found (p<0.005), which was correlated to the number of treatment cycles (p=0.008) and absorbed radiation dose (p=0.03). A similar decrease, although non-significant, was seen in the gonadotropins in post-menopausal women, while in men there was an increase during the first years post-therapy, after which the levels returned to baseline. No change was observed in the adrenal nor thyroid axes.CONCLUSIONS: No signs of severe endocrine disorder were detected, although a significant decrease in the GH/IGF1-axis was found, where dosimetric analyses indicate radiation-induced damage to the pituitary gland as a probable cause

The Accuracy of Electoral Regulations : The Case of the Right to Vote by People with Cognitive Impairments

People with cognitive impairments are regularly denied access to the vote in democraticnations. At the same time, the accuracy of legal regulations is uncertain due to thevariety of legal classifications and the vague administrative procedures envisaged for theirimplementation. This article offers an extensive analysis of the accuracy of legal restrictionson the vote for people with cognitive impairments in all electoral democracies. The articleargues that the prospect of ever regulating the vote accurately, in the sense of avoidingboth misclassifications and arbitrary administration of restrictions, is difficult to envisage.In the face of the regulatory problems associated with the attempt to restrict the votefor people with cognitive impairment, it is concluded that enfranchisement of all adultcitizens would constitute an improvement