Le point de non-retour : Rekonstruktionsversuche der zerfallenden Identität in den Werken Georges Perecs

Georges Perec hat die Literatur der zweiten Hälfte des 20. Jahrhunderts in besonderer Weise geprägt. Aus der spielerischen Praxis der Autoren des Ouvroir de littérature potentielle (Oulipo) entwickelt Perec, im Zeichen seiner Erfahrung als Kind jüdischer Einwanderer und der Deportation seiner Familie, in seinen Texten eine existentielle Dimension. Es entsteht ein eigenes projet réaliste zwischen Sartres Konzept der littérature engagée und den Avantgardeströmungen von Nouveau Roman und Oulipo. Im Zentrum steht das Thema der prekären Identität. Wodurch ist Perecs Entwurf von Identität gekennzeichnet? Mit welchen narrativen Strategien und Verfahren realisiert er sich in seinen Werken? Welche Bedeutung hat die écriture für die Darstellung einer Identität, die bis an den Punkt einer irreversiblen Veränderung, den Point de non-retour, gelangt ist? Welche Möglichkeiten generiert die écriture, die Erfahrung der Diskontinuität zu überwinden? Vesna Stirnadel untersucht Konzeption und Inszenierung der zerfallenden Identität bei Georges Perec und nimmt dabei nicht nur autobiographische, sondern auch fiktionale, essayistische und dokumentarische Texte sowie Filme in den Blick

Le Point de non-retour - Rekonstruktionsversuche der zerfallenden Identität in den Werken Georges Perecs

Georges Perec hat die Literatur der zweiten Hälfte des 20. Jahrhunderts in besonderer Weise geprägt. Aus der spielerischen Praxis der Autoren des Ouvroir de littérature potentielle (Oulipo) entwickelt Perec, im Zeichen seiner Erfahrung als Kind jüdischer Einwanderer und der Deportation seiner Familie, in seinen Texten eine existentielle Dimension. Es entsteht ein eigenes projet réaliste zwischen Sartres Konzept der littérature engagée und den Avantgardeströmungen von Nouveau Roman und Oulipo. Im Zentrum steht das Thema der prekären Identität. Wodurch ist Perecs Entwurf von Identität gekennzeichnet? Mit welchen narrativen Strategien und Verfahren realisiert er sich in seinen Werken? Welche Bedeutung hat die écriture für die Darstellung einer Identität, die bis an den Punkt einer irreversiblen Veränderung, den Point de non-retour, gelangt ist? Welche Möglichkeiten generiert die écriture, die Erfahrung der Diskontinuität zu überwinden? Vesna Stirnadel untersucht Konzeption und Inszenierung der zerfallenden Identität bei Georges Perec und nimmt dabei nicht nur autobiographische, sondern auch fiktionale, essayistische und dokumentarische Texte sowie Filme in den Blick

A systematic review comparing the evidence for kidney function outcomes between oral antidiabetic drugs for type 2 diabetes.

Background: The development of kidney disease is a serious complication among people with type 2 diabetes mellitus, associated with substantially increased morbidity and mortality.  We aimed to summarise the current evidence for the relationship between treatments for type 2 diabetes and long-term kidney outcomes, by conducting a systematic search and review of relevant studies. Methods: We searched Medline, Embase and Web of Science, between 1st January 1980 and 15th May 2018 for published clinical trials and observational studies comparing two or more classes of oral therapy for type 2 diabetes. We included people receiving oral antidiabetic drugs. Studies were eligible that; (i) compared two or more classes of oral therapy for type 2 diabetes; (ii) reported kidney outcomes as primary or secondary outcomes; (iii) included more than 100 participants; and (iv) followed up participants for 48 weeks or more. Kidney-related outcome measures included were Incidence of chronic kidney disease, reduced eGFR, increased creatinine, 'micro' and 'macro' albuminuria. Results: We identified 15 eligible studies, seven of which were randomised controlled trials and eight were observational studies. Reporting of specific renal outcomes varied widely. Due to variability of comparisons and outcomes meta-analysis was not possible. The majority of comparisons between treatment with metformin or sulfonylurea indicated that metformin was associated with better renal outcomes. Little evidence was available for recently introduced treatments or commonly prescribed combination therapies. Conclusions: Comparative evidence for the effect of treatments for type 2 diabetes on renal outcomes, either as monotherapy or in combination is sparse

Heritability of Malaria in Africa

BACKGROUND: While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown. METHODS AND FINDINGS: We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively. CONCLUSION: Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas

Changing use of antidiabetic drugs in the UK: trends in prescribing 2000-2017.

OBJECTIVES: Guidelines for the use of drugs for type 2 diabetes mellitus (T2DM) have changed since 2000, and new classes of drug have been introduced. Our aim was to describe how drug choice at initiation and first stage of intensification have changed over this period, and to what extent prescribing was in accord with clinical guidelines, including adherence to recommendations regarding kidney function. DESIGN: Repeated cross-sectional study. SETTING: UK electronic primary care health records from the Clinical Practice Research Datalink. PARTICIPANTS: Adults initiating treatment with a drug for T2DM between January 2000 and July 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the proportion of each class of T2DM drug prescribed for initiation and first-stage intensification in each year. We also examined drug prescribing by kidney function and country within the UK. RESULTS: Of 280 241 people initiating treatment with T2DM drugs from 2000 to 2017, 73% (204 238/280 241) initiated metformin, 15% (42 288/280 241) a sulfonylurea, 5% (12 956/280 241) with metformin and sulfonylurea dual therapy and 7% (20 759/280 241) started other options. Clinicians have increasingly prescribed metformin at initiation: by 2017 this was 89% (2475/2778) of drug initiations. Among people with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2, the most common drug at initiation was a sulfonylurea, 58% (659/1135). In 2000, sulfonylureas were the predominant drug at the first stage of drug intensification (87%, 534/615) but by 2017 this fell to 30% (355/1183) as the use of newer drug classes increased. In 2017, new prescriptions for dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium/glucose cotransporter-2 inhibitors (SGLT2i) accounted for 42% (502/1183) and 22% (256/1183) of intensification drugs, respectively. Uptake of new classes differs by country with DPP4is and SGLT2is prescribed more in Northern Ireland and Wales than England or Scotland. CONCLUSIONS: Our findings show markedly changing prescribing patterns for T2DM between 2000 and 2017, largely consistent with clinical guidelines

Prevalence of chronic kidney disease in Asia: A systematic review and analysis

Introduction The burden of chronic kidney disease (CKD) is growing rapidly around the world. However, there is limited information on the overall regional prevalence of CKD, as well as the variations in national prevalence within Asia. We aimed to consolidate available data and quantify estimates of the CKD burden in this region. Methods We systematically searched MEDLINE, Embase and Google Scholar for observational studies and contacted national experts to estimate CKD prevalence in countries of Asia (Eastern, Southern and South Eastern Asia). CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 or the presence of proteinuria. For countries without reported data, we estimated CKD prevalence using agglomerative average-linkage hierarchical clustering, based on country-level risk factors and random effects meta-analysis within clusters. Published CKD prevalence data were obtained for 16 countries (of the 26 countries in the region) and estimates were made for 10 countries. Results There was substantial variation in overall and advanced (eGFR <30 mL/min/1.73 m 2) CKD prevalence (range: 7.0%-34.3% and 0.1%-17.0%, respectively). Up to an estimated 434.3 million (95% CI 350.2 to 519.7) adults have CKD in Asia, including up to 65.6 million (95% CI 42.2 to 94.9) who have advanced CKD. The greatest number of adults living with CKD were in China (up to 159.8 million, 95% CI 146.6 to 174.1) and India (up to 140.2 million, 95% CI 110.7 to 169.7), collectively having 69.1% of the total number of adults with CKD in the region. Conclusion The large number of people with CKD, and the substantial number with advanced CKD, show the need for urgent collaborative action in Asia to prevent and manage CKD and its complications

Comparative effects of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors added to metformin monotherapy: a propensity-score matched cohort study in UK primary care.

AIM: To assess the comparative effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on cardiometabolic risk factors in routine care. MATERIALS AND METHODS: Using primary care data on 10?631 new users of SUs, SGLT2 inhibitors or DPP-4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity-score matched cohorts and used linear mixed models to describe changes in glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), systolic blood pressure (BP) and body mass index (BMI) over 96?weeks. RESULTS: HbA1c levels fell substantially after treatment intensification for all drugs: mean change at week 12: SGLT2 inhibitors: -15.2?mmol/mol (95% confidence interval [CI] -16.9, -13.5); SUs: -14.3?mmol/mol (95% CI -15.5, -13.2); and DPP-4 inhibitors: -11.9?mmol/mol (95% CI -13.1, -10.6). Systolic BP fell for SGLT2 inhibitor users throughout follow-up, but not for DPP-4 inhibitor or SU users: mean change at week 12: SGLT2 inhibitors: -2.3?mmHg (95% CI -3.8, -0.8); SUs: -0.8?mmHg (95% CI -1.9, +0.4); and DPP-4 inhibitors: -0.9?mmHg (95% CI -2.1,+0.2). BMI decreased for SGLT2 inhibitor and DPP-4 inhibitor users, but not SU users: mean change at week 12: SGLT2 inhibitors: -0.7?kg/m2 (95% CI -0.9, -0.5); SUs: 0.0?kg/m2 (95% CI -0.3, +0.2); and DPP-4 inhibitors: -0.3?kg/m2 (95% CI -0.5, -0.1). eGFR fell at 12?weeks for SGLT2 inhibitor and DPP-4 inhibitor users. At 60?weeks, the fall in eGFR from baseline was similar for each drug class. CONCLUSIONS: In routine care, SGLT2 inhibitors had greater effects on cardiometabolic risk factors than SUs. Routine care data closely replicated the effects of diabetes drugs on physiological variables measured in clinical trials

Factors associated with choice of intensification treatment for type 2 diabetes after metformin monotherapy: a cohort study in UK primary care.

PURPOSE: To understand the patient characteristics associated with treatment choice at the first treatment intensification for type 2 diabetes. PATIENTS AND METHODS: This is a noninterventional study, using UK electronic primary care records from the Clinical Practice Research Datalink. We included adults treated with metformin monotherapy between January 2000 and July 2017. The outcome of interest was the drug prescribed at first intensification between 2014 and 2017. We used multinomial logistic regression to calculate the ORs for associations between the drugs and patient characteristics. RESULTS: In total, 14,146 people started treatment with an intensification drug. Younger people were substantially more likely to be prescribed sodium-glucose co-transporter-2 inhibitors (SGLT2is), than sulfonylureas (SUs): OR for SGLT2i prescription for those aged <30 years was 2.47 (95% CI 1.39-4.39) compared with those aged 60-70 years. Both overweight and obesity were associated with greater odds of being prescribed dipeptidyl peptidase-4 inhibitor (DPP4i) or SGLT2i. People of non-white ethnicity were less likely to be prescribed SGLT2i or DPP4i: compared with white patients, the OR of being prescribed SGLT2i among South Asians is 0.60 (95% CI 0.42-0.85), and for black people, the OR is 0.54 (95% CI 0.30-0.97). Lower socioeconomic status was also independently associated with reduced odds of being prescribed SGLT2is. CONCLUSION: Both clinical and demographic factors are associated with prescribing at the first stage of treatment intensification, with older and non-white people less likely to receive new antidiabetic treatments. Our results suggest that the selection of treatment options used at the first stage of treatment intensification for type 2 diabetes is not driven by clinical need alone

A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function.

INTRODUCTION: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. METHODS: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. RESULTS: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. CONCLUSION: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. TRIAL REGISTRATION: NCT02723786