CD107a(+) (LAMP-1) Cytotoxic CD8(+) T-Cells in Lupus Nephritis Patients

Cytotoxic CD8(+) T-cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate the role of CD107a (LAMP-1) on cytotoxic CD8(+) T-cells in SLE-patients in particular with lupus nephritis. Peripheral blood of SLE-patients (n = 31) and healthy controls (n = 21) was analyzed for the expression of CD314 and CD107a by flow cytometry. Kidney biopsies of lupus nephritis patients were investigated for the presence of CD8(+) and C107a(+) cells by immunohistochemistry and immunofluorescence staining. The percentages of CD107a(+) on CD8(+) T-cells were significantly decreased in SLE-patients as compared to healthy controls (40.2 +/- 18.5% vs. 47.9 +/- 15.0%, p = 0.02). This was even more significant in SLE-patients with inactive disease. There was a significant correlation between the percentages of CD107a(+)CD8(+) T-cells and SLEDAI. The evaluation of lupus nephritis biopsies showed a significant number of CD107a(+)CD8(+) T-cells mainly located in the peritubular infiltrates. The intrarenal expression of CD107a(+) was significantly correlated with proteinuria. These results demonstrate that CD8(+) T-cells of patients with systemic lupus erythematosus have an altered expression of CD107a which seems to be associated with disease activity. The proof of intrarenal CD107a(+)CD8(+) suggests a role in the pathogenesis of lupus nephritis

Twenty-sixth Annual Bibliography (Contemporary German Literature Collection)

Bibliography of contemporary German literature volumes added the previous year to Washington University Libraries\u27 Contemporary German Literature Collection. These acquisitions generally include novels, poetry, short story collections, essays, autobiographical works, and literary and cultural periodicals from publishers in Germany, Austria, and Switzerland. This Collection serves as the research arm for the Department of Germanic Languages and Literature\u27s Max Kade Center for Contemporary German Literature. This bibliography is compiled by Washington University\u27s Department of Germanic Languages and Literatures in cooperation with the University Libraries. See also Contemporary German Literature Collection and Max Kade Center for Contemporary German Literature

Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus

Introduction: There is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL-17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134. Methods: Thirty-four patients (3 male, 31 female, mean age 41 +/- 15 years) fulfilling at least four of the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE and 24 healthy controls were enrolled. T-cells from the peripheral blood were analysed by fluorescence activated cell sorting (FACS) for their expression levels of CD80, CD134 and CCR6. In vitro stimulated CD3(+)IL17(+) cells were also investigated for the expression of these costimulatory markers. Finally, renal biopsies from SLE patients were evaluated for the presence of CD134 expressing T-cells. Results: Percentages of IL-17 expressing T-cells were significantly increased in patients with active disease as compared to healthy controls (1.46 +/- 0.58% versus 0.93 +/- 0.30%, P = 0.007). The percentage of IL-17 producing T-cells was correlated with disease activity as assessed by systemic lupus erythematosus disease activity index (SLEDAI) (r = 0.53, P = 0.003). In patients, most of the IL-17 producing T-cells were confined to the CCR6(+) T-cell subset (80 +/- 13%). Expression of CD80 and CD134 on the IL-17 producing T-cell subset was higher in SLE than in healthy controls (HC) (CD134: 71.78 +/- 14.51% versus 51.45 +/- 16.58%, P = 0.002; CD80: 25.5 +/- 14.99% versus 14.99 +/- 5.74%, P = 0.02). Also, patients with lupus nephritis expressed higher levels of CD134(+) on CD3(+)IL-17(+) cells as compared to HC (72.69 +/- 11.54% versus 51.45 +/- 16.58%, P = 0.006). Furthermore, renal biopsies of lupus nephritis patients showed infiltration of CD134(+) T cells. Conclusions: Percentages of IL-17 expressing T-cells correlate with disease activity. Further, these cells show increased expression of costimulatory markers such as CD134 and CD80. The presence of CD134(+) T-cells in renal biopsies of lupus nephritis patients suggest that these cells migrate to the kidney and might contribute to inflammatory processes through IL-17 secretion

A Recommendation and Risk Classification System for Connecting Rough Sleepers to Essential Outreach Services

Rough sleeping is a chronic problem faced by some of the most disadvantaged people in modern society. This paper describes work carried out in partnership with Homeless Link, a UK-based charity, in developing a data-driven approach to assess the quality of incoming alerts from members of the public aimed at connecting people sleeping rough on the streets with outreach service providers. Alerts are prioritised based on the predicted likelihood of successfully connecting with the rough sleeper, helping to address capacity limitations and to quickly, effectively, and equitably process all of the alerts that they receive. Initial evaluation concludes that our approach increases the rate at which rough sleepers are found following a referral by at least 15\% based on labelled data, implying a greater overall increase when the alerts with unknown outcomes are considered, and suggesting the benefit in a trial taking place over a longer period to assess the models in practice. The discussion and modelling process is done with careful considerations of ethics, transparency and explainability due to the sensitive nature of the data in this context and the vulnerability of the people that are affected.Comment: 10 pages, 5 figures, 5 table

Mitigating statistical bias within differentially private synthetic data

Increasing interest in privacy-preserving machine learning has led to new and evolved approaches for generating private synthetic data from undisclosed real data. However, mechanisms of privacy preservation can significantly reduce the utility of synthetic data, which in turn impacts downstream tasks such as learning predictive models or inference. We propose several re-weighting strategies using privatised likelihood ratios that not only mitigate statistical bias of downstream estimators but also have general applicability to differentially private generative models. Through large-scale empirical evaluation, we show that private importance weighting provides simple and effective privacy-compliant augmentation for general applications of synthetic data

Hospital admissions linked to SARS-CoV-2 infection in children and adolescents: cohort study of 3.2 million first ascertained infections in England

Objective To describe hospital admissions associated with SARS-CoV-2 infection in children and adolescents. Design Cohort study of 3.2 million first ascertained SARS-CoV-2 infections using electronic health care record data. Setting England, July 2020 to February 2022. Participants About 12 million children and adolescents (age <18 years) who were resident in England. Main outcome measures Ascertainment of a first SARS-CoV-2 associated hospital admissions: due to SARS-CoV-2, with SARS-CoV-2 as a contributory factor, incidental to SARS-CoV-2 infection, and hospital acquired SARS-CoV-2. Results 3 226 535 children and adolescents had a recorded first SARS-CoV-2 infection during the observation period, and 29 230 (0.9%) infections involved a SARS-CoV-2 associated hospital admission. The median length of stay was 2 (interquartile range 1-4) days) and 1710 of 29 230 (5.9%) SARS-CoV-2 associated admissions involved paediatric critical care. 70 deaths occurred in which covid-19 or paediatric inflammatory multisystem syndrome was listed as a cause, of which 55 (78.6%) were in participants with a SARS-CoV-2 associated hospital admission. SARS-CoV-2 was the cause or a contributory factor in 21 000 of 29 230 (71.8%) participants who were admitted to hospital and only 380 (1.3%) participants acquired infection as an inpatient and 7855 (26.9%) participants were admitted with incidental SARS-CoV-2 infection. Boys, younger children (<5 years), and those from ethnic minority groups or areas of high deprivation were more likely to be admitted to hospital (all P<0.001). The covid-19 vaccination programme in England has identified certain conditions as representing a higher risk of admission to hospital with SARS-CoV-2: 11 085 (37.9%) of participants admitted to hospital had evidence of such a condition, and a further 4765 (16.3%) of participants admitted to hospital had a medical or developmental health condition not included in the vaccination programme’s list. Conclusions Most SARS-CoV-2 associated hospital admissions in children and adolescents in England were due to SARS-CoV-2 or SARS-CoV-2 was a contributory factor. These results should inform future public health initiatives and research

Combined Coronary CT-Angiography and TAVI-Planning: A Contrast-Neutral Routine Approach for Ruling-Out Significant Coronary Artery Disease

Background: Significant coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). Assessment of CAD prior to TAVI is recommended by current guidelines and is mainly performed via invasive coronary angiography (ICA). In this study we analyzed the ability of coronary CT-angiography (cCTA) to rule out significant CAD (stenosis ≥ 50%) during routine pre-TAVI evaluation in patients with high pre-test probability for CAD. Methods: In total, 460 consecutive patients undergoing pre-TAVI CT (mean age 79.6 ± 7.4 years) were included. All patients were examined with a retrospectively ECG-gated CT-scan of the heart, followed by a high-pitch-scan of the vascular access route utilizing a single intravenous bolus of 70 mL iodinated contrast medium. Images were evaluated for image quality, calcifications, and significant CAD; CT-examinations in which CAD could not be ruled out were defined as positive (CAD+). Routinely, patients received ICA (388/460; 84.3%; Group A), which was omitted if renal function was impaired and CAD was ruled out on cCTA (Group B). Following TAVI, clinical events were documented during the hospital stay. Results: cCTA was negative for CAD in 40.2% (188/460). Sensitivity, specificity, PPV, and NPV in Group A were 97.8%, 45.2%, 49.6%, and 97.4%, respectively. Median coronary artery calcium score (CAC) was higher in CAD+-patients but did not have predictive value for correct classification of patients with cCTA. There were no significant differences in clinical events between Group A and B. Conclusion: cCTA can be incorporated into pre-TAVI CT-evaluation with no need for additional contrast medium. cCTA may exclude significant CAD in a relatively high percentage of these high-risk patients. Thereby, cCTA may have the potential to reduce the need for ICA and total amount of contrast medium applied, possibly making pre-procedural evaluation for TAVI safer and faster

Lernprozessbegleitende Diagnostik und Fachdidaktik: Gestufte digitale Lernhilfen als Professionalisierungskonzept für adaptiven Unterricht (DiLernProfis)

In inklusiven Settings sind Differenzierungen der Lerninhalte für ein adaptives Unterrichten unabdingbar. Diagnostische Erkenntnisse für die Planung, Durchführung und Reflexion von Unterricht sind von herausgehobener Bedeutung. In dem hier vorgestellten Verbundprojekt „DiLernProfis“ sollen die Praxen und Gelingensbedingungen der Verknüpfung von Diagnostik und adaptivem Unterricht analysiert werden. Dies erfolgt entlang der Konzeption und des Einsatzes von binnendifferenziert gestuften Lernhilfen, die in Form einer App für den naturwissenschaftlichen Unterricht erprobt werden. Dies erfolgt im Rahmen einer Fortbildung, die auf Lehrkräfteprofessionalisierung im Spannungsfeld von Diagnostik und Förderung zielt und in der die beteiligten Lehrpersonen als Community of Practice (CoP) organisiert sind. Die wissenschaftliche Begleitung des Projekts umfasst qualitative und quantitative Erhebungen. Die Befunde münden in einem zertifizierten Konzept zur Lehrpersonen-Professionalisierung. Dies umfasst lerndiagnostisch-adaptiven Unterricht in der Aus- und Weiterbildung zum Fachunterricht der Sekundarstufe. Der fachdidaktisch fundierte Praxistransfer wird über eine interdisziplinäre Community of Research (CoR) von universitären Fachdidaktiken des Forschungs- und Entwicklungszentrums (FuE-Zentrums) für inklusionssensible Lehrer*innenbildung sowie Lehrpersonenforscher*innen der Versuchsschulen „Oberstufen-Kolleg“ und „Laborschule“ gewährleistet

Rates of severe complications in patients undergoing colorectal surgery for deep endometriosis-a retrospective multicenter observational study.

INTRODUCTION Surgical experience and hospital procedure volumes have been associated with the risk of severe complications in expert centers for endometriosis in France. However, little is known about other certified units in Central European countries. MATERIAL AND METHODS This retrospective observational study included 937 women who underwent surgery for colorectal endometriosis between January 2018 and January 2020 in 19 participating expert centers for endometriosis. All women underwent complete excision of colorectal endometriosis by rectal shaving, discoid or segmental resection. Postoperative severe complications were defined as grades III-IV of the Clavien-Dindo classification system including anastomotic leakage, fistula, pelvic abscess and hematoma. Surgical outcomes of centers performing less than 40 (group 1), 40-59 (group 2) and ≥60 procedures (group 3) over a period of 2 years were compared. RESULTS The overall complication rate of grade III and IV complications was 5.1% (48/937), with rates of anastomotic leakage, fistula formation, abscess and hemorrhage in segmental resection, discoid resection and rectal shaving, respectively, as follows: anastomotic leakage 3.6% (14/387), 1.4% (3/222), 0.6% (2/328); fistula formation 1.6% (6/387), 0.5% (1/222), 0.9%; (3/328); abscess 0.5% (2/387), 0% (0/222) and 0.6% (2/328); hemorrhage 2.1% (8/387), 0.9% (2/222) and 1.5% (5/328). Higher overall complication rates were observed for segmental resection (30/387, 7.8%) than for discoid (6/222, 2.7%, P = 0.015) or shaving procedures (12/328, 3.7%, P = 0.089). No significant correlation was observed between the number of procedures performed and overall complication rates (rSpearman  = -0.115; P = 0.639) with a high variability of complications in low-volume centers (group 1). However, an intergroup comparison revealed a significantly lower overall severe complication rate in group 3 than in group 2 (2.9% vs 6.9%; P = 0.017) without significant differences between other groups. CONCLUSIONS A high variability in complication rates does exist in centers with a low volume of activity. Major complications may decrease with an increase in the volume of activity but this effect cannot be generally applied to all institutions and settings