Combining transplant professional's psychosocial donor evaluation and donor self-report measures to optimise the prediction of HRQoL after kidney donation:an observational prospective multicentre study

OBJECTIVES: Living donor kidney transplantation is currently the preferred treatment for patients with end-stage renal disease. The psychosocial evaluation of kidney donor candidates relies mostly on the clinical viewpoint of transplant professionals because evidence-based guidelines for psychosocial donor eligibility are currently lacking. However, the accuracy of these clinical risk judgements and the potential added value of a systematic self-reported screening procedure are as yet unknown. The current study examined the effectiveness of the psychosocial evaluation by transplant professionals and the potential value of donor self-report measures in optimising the donor evaluation. Based on the stress-vulnerability model, the predictive value of predonation, intradonation and postdonation factors to impaired longer term health-related quality of life (HRQoL) of kidney donors was studied. DESIGN: An observational prospective multicentre study. SETTING: Seven Dutch transplantation centres. PARTICIPANTS: 588 potential donors participated, of whom 361 donated. Complete prospective data of 230 donors were available. Also, 1048 risk estimation questionnaires were completed by healthcare professionals. METHODS: Transplant professionals (nephrologists, coordinating nurses, social workers and psychologists) filled in risk estimation questionnaires on kidney donor candidates. Furthermore, 230 kidney donors completed questionnaires (eg, on HRQoL) before and 6 and 12 months after donation. PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL, demographic and preoperative, intraoperative and postoperative health characteristics, perceived support, donor cognitions, recipient functioning and professionals risk estimation questionnaires. RESULTS: On top of other predictors, such as the transplant professionals’ risk assessments, donor self-report measures significantly predicted impaired longer term HRQoL after donation, particularly by poorer predonation physical (17%–28% explained variance) and psychological functioning (23%). CONCLUSIONS: The current study endorses the effectiveness of the psychosocial donor evaluation by professionals and the additional value of donor self-report measures in optimising the psychosocial evaluation. Consequently, systematic screening of donors based on the most prominent risk factors provide ground for tailored interventions for donors at risk

Short-term variations of Icelandic ice cap mass inferred from cGPS coordinate time series

As the global climate changes, understanding short-term variations in water storage is increasingly important. Continuously operating Global Positioning System (cGPS) stations in Iceland record annual periodic motion—the elastic response to winter accumulation and spring melt seasons—with peak-to-peak vertical amplitudes over 20 mm for those sites in the Central Highlands. Here for the first time for Iceland, we demonstrate the utility of these cGPS-measured displacements for estimating seasonal and shorter-term ice cap mass changes. We calculate unit responses to each of the five largest ice caps in central Iceland at each of the 62 cGPS locations using an elastic half-space model and estimate ice mass variations from the cGPS time series using a simple least squares inversion scheme. We utilize all three components of motion, taking advantage of the seasonal motion recorded in the horizontal. We remove secular velocities and accelerations and explore the impact that seasonal motions due to atmospheric, hydrologic, and nontidal ocean loading have on our inversion results. Our results match available summer and winter mass balance measurements well, and we reproduce the seasonal stake-based observations of loading and melting within the 1 math formula confidence bounds of the inversion. We identify nonperiodic ice mass changes associated with interannual variability in precipitation and other processes such as increased melting due to reduced ice surface albedo or decreased melting due to ice cap insulation in response to tephra deposition following volcanic eruptions, processes that are not resolved with once or twice-yearly stake measurements

Methods to assess the effect of meat processing on viability of Toxoplasma gondii: towards replacement of mouse bioassay by in vitro testing

Consumption of meat containing viable tissue cysts is considered one of the main sources of human infection with Toxoplasma gondii. In contrast to fresh meat, raw meat products usually undergo processing, including salting and mixing with other additives such as sodium acetate and sodium lactate, which affects the viability of T. gondii. However, the experiments described in the literature are not always performed in line with the current processing methods applied in industry. It was our goal to study the effect of salting and additives according to the recipes used by industrial producers. Mouse or cat bioassay is the ‘gold standard’ to demonstrate the presence of viable T. gondii. However, it is costly, time consuming and for ethical reasons not preferred for large-scale studies. Therefore, we first aimed to develop an alternative for mouse bioassay that can be used to determine the effect of processing on the viability of T. gondii tissue cysts. The assays studied were (i) a cell culture method to determine the parasite’s ability to multiply, and (ii) a propidium monoazide (PMA) dye-based assay to selectively detect DNA from intact parasites. Processing experiments were performed with minced meat incubated for 20 h with low concentrations of NaCl, sodium lactate and sodium acetate. NaCl appeared to be the most effective ingredient with only one or two out of eight mice infected after inoculation with pepsin-digest of portions processed with 1.0, 1.2 and 1.6% NaCl. Results of preliminary experiments with the PMA-based method were inconsistent and did not sufficiently discriminate between live and dead parasites. In contrast, the cell culture method showed promising results, but further optimization is needed before it can replace or reduce the number of mouse bioassays needed. In future, standardised in vitro methods are necessary to allow more extensive testing of product-specific processing methods, thereby providing a better indication of the risk of T. gondii infection for consumers

A Framework for the Empirical Investigation of Mindfulness Meditative Development

Millions of people globally have learned mindfulness meditation with the goal of improving health and well-being outcomes in both clinical and non-clinical contexts. An estimated half of these practitioners follow mindfulness teachers’ recommendations to continue regular meditation after completion of initial instruction, but it is unclear whether benefits are strengthened by regular practice and whether harm can occur. Increasing evidence shows a wide range of experiences that can arise with regular mindfulness meditation, from profoundly positive to challenging and potentially harmful. Initial research suggests that complex interactions and temporal sequences may explain these experiential phenomena and their relations to health and well-being. We believe further study of the effects of mindfulness meditation is urgently needed to better understand the benefits and challenges of continued practice after initial instructions. Effects may vary systematically over time due to factors such as initial dosage, accumulation of ongoing practice, developing skill of the meditator, and complex interactions with the subjects’ past experiences and present environment. We propose that framing mindfulness meditation experiences and any associated health and well-being benefits within integrated longitudinal models may be more illuminating than treating them as discrete, unrelated events. We call for ontologically agnostic, collaborative, and interdisciplinary research to study the effects of continued mindfulness meditation and their contexts, advancing the view that practical information found within religious and spiritual contemplative traditions can serve to develop initial theories and scientifically falsifiable hypotheses. Such investigation could inform safer and more effective applications of mindfulness meditation training for improving health and well-being

InAs nanowire hot-electron Josephson transistor

At a superconductor (S)-normal metal (N) junction pairing correlations can "leak-out" into the N region. This proximity effect [1, 2] modifies the system transport properties and can lead to supercurrent flow in SNS junctions [3]. Recent experimental works showed the potential of semiconductor nanowires (NWs) as building blocks for nanometre-scale devices [4-7], also in combination with superconducting elements [8-12]. Here, we demonstrate an InAs NW Josephson transistor where supercurrent is controlled by hot-quasiparticle injection from normal-metal electrodes. Operational principle is based on the modification of NW electron-energy distribution [13-20] that can yield reduced dissipation and high-switching speed. We shall argue that exploitation of this principle with heterostructured semiconductor NWs opens the way to a host of out-of-equilibrium hybrid-nanodevice concepts [7, 21].Comment: 6 pages, 6 color figure

eHealth in Geriatric Rehabilitation: An International Survey of the Experiences and Needs of Healthcare Professionals.

While eHealth can help improve outcomes for older patients receiving geriatric rehabilitation, the implementation and integration of eHealth is often complex and time-consuming. To use eHealth effectively in geriatric rehabilitation, it is essential to understand the experiences and needs of healthcare professionals. In this international multicentre cross-sectional study, we used a web-based survey to explore the use, benefits, feasibility and usability of eHealth in geriatric rehabilitation settings, together with the needs of working healthcare professionals. Descriptive statistics were used to summarize quantitative findings. The survey was completed by 513 healthcare professionals from 16 countries. Over half had experience with eHealth, although very few (52 of 263 = 20%) integrated eHealth into daily practice. Important barriers to the use or implementation of eHealth included insufficient resources, lack of an organization-wide implementation strategy and lack of knowledge. Professionals felt that eHealth is more complex for patients than for themselves, and also expressed a need for reliable information concerning available eHealth interventions and their applications. While eHealth has clear benefits, important barriers hinder successful implementation and integration into healthcare. Tailored implementation strategies and reliable information on effective eHealth applications are needed to overcome these barriers

Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18–65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain

Absent B Cells, agammaglobulinemia, and Hypertrophic Cardiomyopathy in Folliculin-interacting Protein 1 Deficiency

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy or copy-number variants (CNVs) in 2 patients, expanding the variant spectrum of this novel inborn error of immunity. The results indicate that FNIP1 deficiency can be caused by complex genetic mechanisms and support the clinical utility of exome sequencing and CNV analysis in patients with broad phenotypes, including agammaglobulinemia and HCM. FNIP1 deficiency is a novel inborn error of immunity characterized by early and severe B-cell development defect, agammaglobulinemia, variable neutropenia, and HCM. Our findings elucidate a functional and relevant role of FNIP1 in B-cell development and metabolism and potentially neutrophil activity

Exploring, exploiting and evolving diversity of aquatic ecosystem models: A community perspective

Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly available through open-source policies, to standardize documentation and technical implementation of models, and to compare models through ensemble modelling and interdisciplinary approaches. We end with our perspective on how the field of aquatic ecosystem modelling might develop in the next 5–10 years. To strive for clarity and to improve readability for non-modellers, we include a glossary