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British-Muslim Family Law as a Site of Citizenship
The Archbishop of Canterburyâs speech on âCivil and Religious Law in Englandâ, delivered a decade ago, attracted considerable public and academic attention. In the years that followed a âSharia debateâ emerged, where traces of (legal) orientalism became especially visible in an essentialist portrayal of âShariaâ as being in opposition to âthe Westâ. What was absent in this debate, which was conducted at the abstract level of compatibilityâincompatibility, EastâWest, lawâreligion, is an analysis of the actual practices of family law of Muslims in contemporary Britain. People marry, divorce, bring up their children and deal with inheritance by resorting to a variety of norms such as Muslim law, English family law and customary law. Drawing on legal pluralism scholarship and elements of Pierre Bourdieuâs theory of the field, this thesis investigates the emergence of British-Muslim family law as a site of citizenship. It is based on research focusing on solicitors offering Islamic legal services and advice in the UK and clients of such services. By focusing on the creative capacities of legal professionals as well as clients in navigating between English and Muslim family law, the thesis is an attempt to present an alternative narrative of British-Muslim family law, which may inform a different understanding to what is commonly perceived as âinformalâ legal practices threatening the cohesion of citizens in a the nation-state. The thesis argues that private practice in Islamic legal services is a particularly pertinent case for analysis. This is because solicitorsâ day-to-day practice in dealing with cases in between Muslim and English law challenges the presumed incompatibility of âMuslim and Englishâ family law, âthe foreign and the nativeâ, or âthe oriental and the occidentalâ
Solidarities outside the box
With constant news about growing Islamophobia and anti-Semitism, the rise of right-wing movements and parties across Europe and the world â the media is dominated by stories documenting and trying to understand our âage of angerâ as the essayist Pankai Mishra has called it in his recent book. Publicly displayed emotions of anger, anxiety and resentment have our attention. In a political climate shaped by uncertainty and competition, the social is increasingly understood in ethno-cultural-religious terms and the ability to live together in diversity is put in question. For example, a recent survey by the 2017 Aurora Humanitarian Index and reported in the Guardian found that âmore than half of Britons believe their culture is threatened by ethnic minorities living in the UKâ....
Disease severity in hospitalized COVID-19 patients: comparing routine surveillance with cohort data from the LEOSS study in 2020 in Germany
Introduction
Studies investigating risk factors for severe COVID-19 often lack information on the representativeness of the study population. Here, we investigate factors associated with severe COVID-19 and compare the representativeness of the dataset to the general population.
Methods
We used data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) of hospitalized COVID-19 patients diagnosed in 2020 in Germany to identify associated factors for severe COVID-19, defined as progressing to a critical disease stage or death. To assess the representativeness, we compared the LEOSS cohort to cases of hospitalized patients in the German statutory notification data of the same time period. Descriptive methods and Poisson regression models were used.
Results
Overall, 6672 hospitalized patients from LEOSS and 132,943 hospitalized cases from the German statutory notification data were included. In LEOSS, patients above 76 years were less likely represented (34.3% vs. 44.1%). Moreover, mortality was lower (14.3% vs. 21.5%) especially among age groups above 66 years. Factors associated with a severe COVID-19 disease course in LEOSS included increasing age, male sex (adjusted risk ratio (aRR) 1.69, 95% confidence interval (CI) 1.53â1.86), prior stem cell transplantation (aRR 2.27, 95% CI 1.53â3.38), and an elevated C-reactive protein at day of diagnosis (aRR 2.30, 95% CI 2.03â2.62).
Conclusion
We identified a broad range of factors associated with severe COVID-19 progression. However, the results may be less applicable for persons above 66 years since they experienced lower mortality in the LEOSS dataset compared to the statutory notification data.Peer Reviewe
Hospitalized patients dying with SARS-CoV-2 infectionâan analysis of patient characteristics and management in ICU and general ward of the LEOSS registry
BACKGROUND: COVID-19 is a severe disease with a high need for intensive care treatment and a high mortality rate in hospitalized patients. The objective of this study was to describe and compare the clinical characteristics and the management of patients dying with SARS-CoV-2 infection in the acute medical and intensive care setting. METHODS: Descriptive analysis of dying patients enrolled in the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS), a non-interventional cohort study, between March 18 and November 18, 2020. Symptoms, comorbidities and management of patients, including palliative care involvement, were compared between general ward and intensive care unit (ICU) by univariate analysis. RESULTS: 580/4310 (13%) SARS-CoV-2 infected patients died. Among 580 patients 67% were treated on ICU and 33% on a general ward. The spectrum of comorbidities and symptoms was broad with more comorbidities (â„ four comorbidities: 52% versus 25%) and a higher age distribution (>65 years: 98% versus 70%) in patients on the general ward. 69% of patients were in an at least complicated phase at diagnosis of the SARS-CoV-2 infection with a higher proportion of patients in a critical phase or dying the day of diagnosis treated on ICU (36% versus 11%). While most patients admitted to ICU came from home (71%), patients treated on the general ward came likewise from home and nursing home (44% respectively) and were more frequently on palliative care before admission (29% versus 7%). A palliative care team was involved in dying patients in 15%. Personal contacts were limited but more often documented in patients treated on ICU (68% versus 47%). CONCLUSION: Patients dying with SARS-CoV-2 infection suffer from high symptom burden and often deteriorate early with a demand for ICU treatment. Therefor a demand for palliative care expertise with early involvement seems to exist
Convalescent plasma treatment for SARS-CoV-2 infected high-risk patients: a matched pair analysis to the LEOSS cohort
Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration
Convalescent plasma treatment for SARS-CoV-2 infected high-risk patients: a matched pair analysis to the LEOSS cohort
Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.Open Access funding enabled and organized by Projekt DEAL.Forschungsnetzwerk der UniversitĂ€tsmedizin zu COVID-19German Centre for Infection Research (DZIF)Willy Robert Pitzer FoundationUniversitĂ€tsklinikum DĂŒsseldorf. Anstalt öffentlichen Rechts (8911
The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics
Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)
First results of the âLean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)â
Abstract
Purpose
Knowledge regarding patientsâ clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19.
Methods
Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models.
Results
We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66â85Â years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46â65Â years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25â2.42, pâ=â0.001; 66â85Â years: aOR 1.93, 95% CI 1.36â2.74, pââ85Â years: aOR 2.38, 95% CI 1.49â3.81, pâ<â0.001 vs. individuals aged 26â45Â years], male sex (aOR 1.23, 95% CI 1.01â1.50, pâ=â0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09â1.72, pâ=â0.007), and diabetes (aOR 1.33, 95% CI 1.04â1.69, pâ=â0.023) were associated with complicated stages of COVID-19 at diagnosis.
Conclusion
The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required
International Law and European Nationality Laws
This paper on international law and European nationality laws is based on the findings from country reports produced within the framework of the EUDO Citizenship Observatory as well as further correspondence with country experts who participated in this project. After a brief description of the history and sources of public international law on nationality, the domestic impact of international legal provisions in this field is being examined. To this end, the second part of this paper discusses the key factors which determine state receptivity towards international law on nationality. These include historical, regional and political factors, internal doctrinal preconditions, informal factors such as societal pressure as well as systems of reservations and the absence of independent review in international Treaty law. The regional influence of the European Convention on Nationality (ECN), as the most important multilateral instrument at present, is analysed in more detail in the last part of the paper including a description of common obstacles to ratification of the Convention.Research for the EUDO Citizenship Observatory Comparative Analyses has been jointly supported by the European Commission grant agreement JLS/2007/IP/CA/009 EUCITAC and by the British Academy Research Project CITMODES (both projects co-directed by the European University Institute and the University of Edinburgh)
Production and pathophysiological significance of sphingosine-1-phosphate in human dendritic cells
Dendritische Zellen (DCs) sind als Zielzellen des MV fĂŒr dessen Pathogenese von zentraler Bedeutung und fördern sowohl Dissemination und Transmission des Virus. Auf zellulĂ€rer Ebene findet sich eine Modulation des Sphingolipidmetabolismus in MV-infizierten DC-Kulturen. S1P selbst ist ein bioaktives Sphingolipid, das ĂŒber auto- und parakrine S1P-Rezeptorstimulation Funktion, Migration und Positionierung von Immunzellen, aber auch als intrazellulĂ€rer Botenstoff Calcium-Haushalt, Apoptose und Proliferation reguliert. Ăber die an der Vermittlung der intrazellulĂ€ren S1P-Effekte beteiligten Strukturen ist bisher weniger bekannt und der S1P-Metabolismus einzelner Zellen trotz Kompartiment-abhĂ€ngiger Schwankungen der S1P-Konzentrationen kaum adressiert. FĂŒr murine DCs konnte eine kontinuierliche S1P-Produktion und Sekretion nachgewiesen werden. Ob dies auch auf humane DCs zutrifft und pathophysiologisch im Rahmen einer MV-Infektion moduliert wird, ist bisher nicht bekannt. In dieser Arbeit wurde das Vorkommen S1Ps sowie dessen Metabolismus in humanen DCs quantitativ erfasst, und der Einfluss inflammatorischer, bakterieller und viraler (MV) Stimuli einbezogen. In Anbetracht der bekannten chemoattraktiven Potenz wurde nachfolgend der Beitrag S1Ps fĂŒr die DC-induzierte T-Zellmigration untersucht.
Es konnte gezeigt werden, dass beide SphK Isoenzyme und auch die irreversibel degradierende SPL in humanen unreifen DCs (iDCs) auf mRNA-Ebene exprimiert werden. S1P konnte intrazellulĂ€r nachgewiesen werden, eine mit Erythroyzten vergleichbare SpeicherkapazitĂ€t ist nicht anzunehmen. Unter bakteriell oder inflammatorisch vermittelter Ausreifung (mDCs) wurde eine Reduktion des S1P Gehalts in DCs beobachtet. Abweichend davon behielten insbesondere stark MV infizierte DC-Kulturen die hohen S1P-Spiegel unreifer DCs bei, was möglicherweise neben der modulierten Chemokinsynthese und OberflĂ€chenexpression ko-stimulatorischer MolekĂŒle einen weiteren Parameter ihrer inkompletten Reifung nach MV Infektion reflektiert. Da die VerĂ€nderungen zwischen MV-infizierten DCs und mDCs nur fĂŒr S1P, nicht aber fĂŒr andere Sphingolipidmetaboliten messbar waren, liegt ihnen wohl eine Regulation der Sphingosinkinasen oder S1P degradierender Enzyme zugrunde. Bei unverĂ€nderter Akkumulation der hierfĂŒr spezifischen mRNAs mĂŒsste dies auf Ebene der Translation, StabilitĂ€t oder AktivitĂ€t der Enzyme beruhen.
Die indirekte Messung des extrazellulĂ€ren S1Ps anhand der gegenlĂ€ufigen S1P1-Dichte lieĂ vermuten, dass in DCs synthetisiertes S1P extrazellulĂ€r wirken konnte. Es kann dabei autokrin auf DCs wirken, beispielsweise deren MotilitĂ€t oder Genexpression regulieren, ist aber auch Voraussetzung zum Aufbau eines S1P-Gradienten und damit parakriner Regulation lymphozytĂ€rer MigrationsvorgĂ€nge. Einen Beitrag S1Ps zur mDCs-induzierten T Zellchemotaxis konnte durch die erhobenen Daten mit hoher Wahrscheinlichkeit ausgeschlossen werden. BezĂŒglich der durch iDCs oder MV infizierte DCs induzierten T Zellchemotaxis konnte aufgrund experimenteller Limitationen keine abschlieĂende Aussage zur Beteiligung S1Ps getroffen werden. Die T-Zellmigration auf DCs erwies sich im 2 D-System als gerichtete Bewegung. Weder Ausreifung noch MV-Infektion der DCs hatten Auswirkungen auf die QuantitĂ€t der T-Zellmigration. Differentielle Expressionsmuster von Chemokinen in iDCs, mDCs und MV infizierten DCs sind jedoch bekannt und legen Variationen der Subset-Komposition innerhalb der migrierenden T Zellen nahe. Diese sollten gezielt in nachfolgenden Arbeiten untersucht werden.
Zusammenfassend weist die vorliegende Arbeit eine kontinuierliche Synthese S1Ps in DCs mit Stimulus-abhĂ€ngiger Fluktuation nach. Eine MV Infektion löst dabei einen zu inflammatorischen und bakteriellen Stimuli divergenten Effekt auf den S1P-Gehalt aus mit möglichen pathophysiologischen Konsequenzen. Eine Modulation der T Zellchemotaxis und damit der DC-T-Zell-Interaktion wĂ€re im Rahmen inflammatorischer, bakterieller oder viraler Szenarien denkbar. Unter inflammatorischen und bakteriellen Bedingungen trug S1P jedoch nicht zur T-Zellchemotaxis bei, fĂŒr MV blieb dies unklar. Dahingegen zeigten weitere Experimente der Arbeitsgruppe einen autokrin vermittelten Beitrag des intrazellulĂ€r produzierten S1Ps zur Migration MV-infizierter DCs im respiratorischen Epithel und identifizierten damit einen bisher unbekannten Einflussfaktor einer erfolgreichen MV-Transmission.As target for measles virus (MV) infection, dendritic cells (DCs) are central in MV pathogenesis also including viral dissemination and transmission. In this context, changes in sphingolipid metabolism and function of MV-infected DCs are described. Sphingosin-1-Phosphat (S1P) as a potent bioactive sphingolipid has pleiotropic functions in immunological processes. It regulates immune cell trafficking via autocrine or paracrine secretion and calcium homeostasis, apoptosis and proliferation via so far poorly defined intracellular signaling. Though compartment dependent S1P variations have been described, cell specific S1P metabolism remains mostly unclear. Little information is available in this regard for human DCs, especially under inflammatory, bacterial and viral (MV) conditions, while murine DCs were identified to continuously produce and secrete S1P.
In this study, the S1P pool in human DCs, its metabolism as well as its fluctuation in maturation and MV-infection were investigated. Considering its function as a chemoattractant, resulting consequences in T cell chemotaxis induced by DCs were addressed.
Sphingosinkinases (SphK1, SphK2), which generate, and S1P-Lyase (SPL), which irreversibly degrades S1P, were found to be expressed at the mRNA level in human immature DCs. Intracellular S1P was readily detected in immature DCs (iDCs), though they are unlikely to serve as S1P sores as described for erythrocytes. S1P concentrations decreased upon maturation triggered by cytokines (TNF α) or bacterial components (LPS). In contrast, S1P levels corresponding to those measured in iDCs were retained in MV-infected DC culture. In addition to the modulation of chemokine synthesis and surface expression of co-stimulatory molecules, retention of S1P levels may also reflect incomplete DC maturation induced by this virus. As fluctuations of the sphingolipid pool between maturing (mDCs) and infected DCs only affected levels of S1P but not its precursors, differential regulation of sphingosine kinases or degrading enzymes are most likely important in elevated S1P levels. As accumulation of mRNAs specific for SphK1, SphK2 and SPL was unaffected in MV-infected DC-cultures, regulation of the enzymes at translational, stability and/or activity level are likely to be operative.
Due to its S1P dependent internalization, S1P1 serves as a surrogate marker of extracellular S1P level. The decreased intracellular S1P concentrations in mDCs were paralleled by upregulated S1P1 expression making decreased S1P secretion likely. In MV infected DC culture secretion seems to be maintained at a level comparable to iDCs. Presuming continuous secretion of S1P, the detected S1P in DCs might contribute to S1P gradients among and within tissues, thus regulating lymphocyte migration. Findings obtained within this work do not support a role of S1P in T cell chemotaxis induced by mDCs. Experimental limitations precluded a final statement on a potential role of S1P in T cell chemotaxis induced by iDCs or MV-infected DCs. T cell chemotaxis induced by mDCs was highly directional in a two-dimensional system. At an overall quantitative basis, T cell chemotaxis induced by iDCs, mDCs or MV-infected DCs did not differ. As DCs are known to vary their chemokine expression depending on their differentiation status, it is, however, quite possible that the subset composition of the migrating T cell compartment differs; which has not been directly addressed in this work.
Altogether, this work revealed continuous production of S1P by human DCs with differentiation-dependent fluctuations. While intracellular S1P pools decreased with maturation induced by inflammatory conditions or LPS, these were fully retained upon MV infection. At a functional level, effects on T cell chemotaxis followed by differential interaction with DCs might be of pathogenetic advantage in inflammatory, bacterial or viral settings. However, S1P did not take part in T cell attraction by mDCs. Its contribution to T cell chemotaxis induced by MV infected DCs remains unsettled. However, further experiments in this research group revealed its importance in promoting migration in MV infected DCs by autocrine signaling, thus enabling efficient virus transmission