Design and methodology of the Swiss Transplant Cohort Study (STCS): a comprehensive prospective nationwide long-term follow-up cohort

In Switzerland, organ procurement is well organized at the national-level but transplant outcomes have not been systematically monitored so far. Therefore, a novel project, the Swiss Transplant Cohort Study (STCS), was established. The STCS is a prospective multicentre study, designed as a dynamic cohort, which enrolls all solid organ recipients at the national level. The features of the STCS are a flexible patient-case system that allows capturing all transplant scenarios and collection of patient-specific and allograft-specific data. Beyond comprehensive clinical data, specific focus is directed at psychosocial and behavioral factors, infectious disease development, and bio-banking. Between May 2008 and end of 2011, the six Swiss transplant centers recruited 1,677 patients involving 1,721 transplantations, and a total of 1,800 organs implanted in 15 different transplantation scenarios. 10% of all patients underwent re-transplantation and 3% had a second transplantation, either in the past or during follow-up. 34% of all kidney allografts originated from living donation. Until the end of 2011 we observed 4,385 infection episodes in our patient population. The STCS showed operative capabilities to collect high-quality data and to adequately reflect the complexity of the post-transplantation process. The STCS represents a promising novel project for comparative effectiveness research in transplantation medicin

WHY PHUBBING IS TOXIC FOR YOUR RELATIONSHIP: UNDERSTANDING THE ROLE OF SMARTPHONE JEALOUSY AMONG “GENERATION Y” USERS

Coined as “phubbing”, excessive use of smartphones in the romantic context has been shown to rep-resent a barrier to meaningful communication, causing conflict, lowering relationship satisfaction, and undermining individual well-being. While these findings project a dire picture of the future of romance, the mechanisms behind the detrimental influence of partner phubbing on relationship-relevant markers are still little understood. Considering prior evidence that partner phubbing leads to the loss of exclusive attention towards the other party, we argue that these are rather the feelings of jealousy partner phubbing is triggering that are responsible for the negative relational outcomes. Based on the analysis of qualitative and quantitative responses from “generation Y” users, we find that partner phubbing is associated with heightened feelings of jealousy, which is inversely related to couple’s relational cohesion. Moreover, jealousy plays a mediating role in the relationship between partner’s smartphone use and relational cohesion, acting as a mechanism behind this undesirable link. Challenging the frequently promoted euphoria with regard to permanent “connectedness”, our study contributes to a growing body of IS research that addresses dark sides of information technolo-gy use and provides corresponding implications for IS practitioners

Metastable Se6 as a ligand for Ag+: from isolated molecular to polymeric 1D and 2D structures

Attempts to prepare the hitherto unknown Se6 2+ cation by the reaction of elemental selenium and Ag[A] ([A]- = [Sb(OTeF5)6]-, [Al(OC(CF3)3)4]-) in SO2 led to the formation of [(OSO)Ag(Se6)Ag(OSO)][Sb(OTeF5)6]2 1 and [(OSO)2Ag(Se6)Ag(OSO)2][Al(OC(CF3)3)4]2 2a. 1 could only be prepared by using bromine as co-oxidant, however, bulk 2b (2a with loss of SO2) was accessible from Ag[Al(OC(CF3)3)4] and grey Se in SO2 (chem. analysis). The reactions of Ag[MF6] (M= As, Sb) and elemental selenium led to crystals of 1/∞{[Ag(Se6)]∞[Ag2(SbF6)3]∞} 3 and {1/∞[Ag(Se6)Ag]∞}[AsF6]2 4. Pure bulk 4 was best prepared by the reaction of Se4[AsF6]2, silver metal and elemental selenium. Attempts to prepare bulk 1 and 3 were unsuccessful. 1–4 were characterized by single-crystal X-ray structure determinations, 2b and 4 additionally by chemical analysis and 4 also by X-ray powder diffraction, FT-Raman and FT-IR pectroscopy. Application of the PRESTO III sequence allowed for the first time 109Ag MAS NMR investigations of 4 as well as AgF, AgF2, AgMF6 and {1/∞[Ag(I2)]∞}[MF6] (M= As, Sb). Compounds 1 and 2a/b, with the very large counter ions, contain isolated [Ag(Se6)Ag]2+ heterocubane units consisting of a Se6 molecule bicapped by two silver cations (local D3d sym). 3 and 4, with the smaller anions, contain close packed stacked arrays of Se6 rings with Ag+ residing in octahedral holes. Each Ag+ ion coordinates to three selenium atoms of each adjacent Se6 ring. 4 contains [Ag(Se6)+]∞ stacks additionally linked by Ag(2)+ into a two dimensional network. 3 features a remarkable 3-dimensional [Ag2(SbF6)3]- anion held together by strong Sb–F … Ag contacts between the component Ag+ and [SbF6]- ions. The hexagonal channels formed by the [Ag2(SbF6)3]- anions are filled by stacks of [Ag(Se6)+]∞ cations. Overall 1–4 are new members of the rare class of metal complexes of neutral main group elemental clusters, in which the main group element is positively polarized due to coordination to a metal ion. Notably, 1 to 4 include the commonly metastable Se6 molecule as a ligand. The structure, bonding and thermodynamics of 1 to 4 were investigated with the help of quantum chemical calculations (PBE0/TZVPP and (RI-)MP2/TZVPP, in part including COSMO solvation) and Born–Fajans–Haber-cycle calculations. From an analysis of all the available data it appears that the formation of the usually metastable Se6 molecule from grey selenium is thermodynamically driven by the coordination to the Ag+ ions

Impact of SARS-CoV-2-Related Hygiene Measures on Community-Acquired Respiratory Virus Infections in Lung Transplant Recipients in Switzerland

Background and Objectives: Community-acquired respiratory virus (CARV) infections pose a serious risk for lung transplant recipients (LTR) as they are prone to severe complications. When the COVID-19 pandemic hit Switzerland in 2020, the government implemented hygiene measures for the general population. We investigated the impact of these measures on the transmission of CARV in lung transplant recipients in Switzerland. Materials and Methods: In this multicenter, retrospective study of lung transplant recipients, we investigated two time periods: the year before the COVID-19 pandemic (1 March 2019–29 February 2020) and the first year of the pandemic (1 March 2020–28 February 2021). Data were mainly collected from the Swiss Transplant Cohort Study (STCS) database. Descriptive statistics were used to analyze the results. Results: Data from 221 Swiss lung transplant cohort patients were evaluated. In the year before the COVID-19 pandemic, 157 infections were diagnosed compared to 71 infections in the first year of the pandemic (decline of 54%, p < 0.001). Influenza virus infections alone showed a remarkable decrease from 17 infections before COVID-19 to 2 infections after the beginning of the pandemic. No significant difference was found in testing behavior; 803 vs. 925 tests were obtained by two of the three centers during the respective periods. Conclusions: We observed a significant decline in CARV infections in the Swiss lung transplant cohort during the first year of the COVID-19 pandemic. These results suggest a relevant impact of hygiene measures when implemented in the population due to the COVID-19 pandemic on the incidence of CARV infections

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratificatio

Macromolecular and elemental composition analysis and extracellular metabolite balances of Pichia pastoris growing at different oxygen levels

Background: Analysis of the cell operation at the metabolic level requires collecting data of different types and to determine their confidence level. In addition, the acquired information has to be combined in order to obtain a consistent operational view. In the case of Pichia pastoris, information of its biomass composition at macromolecular and elemental level is scarce particularly when different environmental conditions, such as oxygen availability or, genetic backgrounds (e.g. recombinant protein production vs. non production conditions) are compared. Results: P. pastoris cells growing in carbon-limited chemostat cultures under different oxygenation conditions (% O2 in the bioreactor inlet gas: 21%, 11% and 8%, corresponding to normoxic, oxygen-limiting and hypoxic conditions, respectively), as well as under recombinant protein (antibody fragment, Fab) producing and non-producing conditions, were analyzed from different points of view. On the one hand, the macromolecular and elemental composition of the biomass was measured using different techniques at the different experimental conditions and proper reconciliation techniques were applied for gross error detection of the measured substrates and products conversion rates. On the other hand, fermentation data was analyzed applying elemental mass balances. This allowed detecting a previously missed by-product secreted under hypoxic conditions, identified as arabinitol (aka. arabitol). After identification of this C5 sugar alcohol as a fermentation by-product, the mass balances of the fermentation experiments were validated. Conclusions: After application of a range of analytical and statistical techniques, a consistent view of growth parameters and compositional data of P. pastoris cells growing under different oxygenation conditions was obtained. The obtained data provides a first view of the effects of oxygen limitation on the physiology of this microorganism, while recombinant Fab production seems to have little or no impact at this level of analysis. Furthermore, the results will be highly useful in other complementary quantitative studies of P. pastoris physiology, such as metabolic flux analysis

Imaging of bronchial pathology in antibody deficiency: Data from the European Chest CT Group

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease

Being Tamil, being Hindu:Tamil migrants’ negotiations of the absence of Tamil Hindu spaces in the West Midlands and South West of England

This paper considers the religious practices of Tamil Hindus who have settled in the West Midlands and South West of England in order to explore how devotees of a specific ethno-regional Hindu tradition with a well-established UK infrastructure in the site of its adherents’ population density adapt their religious practices in settlement areas which lack this infrastructure. Unlike the majority of the UK Tamil population who live in the London area, the participants in this study did not have ready access to an ethno-religious infrastructure of Tamil-orientated temples and public rituals. The paper examines two means by which this absence was addressed as well as the intersections and negotiations of religion and ethnicity these entailed: firstly, Tamil Hindus’ attendance of temples in their local area which are orientated towards a broadly imagined Hindu constituency or which cater to a non-Tamil ethno-linguistic or sectarian community; and, secondly, through the ‘DIY’ performance of ethnicised Hindu ritual in non-institutional settings

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34+ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34+ cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34+ cells infused and younger age at GT affected positively the plateau of CD3+ transduced cells, lymphocytes and CD4+ CD45RA+ naive T cells, whereas the cell dose positively influenced the final plateau of CD15+ transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT034786