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Objectives: Evaluation of the feasibility of SARS-CoV-2-specific T cell manufacturing for adoptive T cell transfer in COVID-19 patients at risk to develop severe disease.Methods: Antiviral SARS-CoV-2-specific T cells were detected in blood of convalescent COVID-19 patients following stimulation with PepTivator SARS-CoV-2 Select using Interferon-gamma Enzyme-Linked Immunospot (IFN-gamma ELISpot), SARS-CoV-2 T Cell Analysis Kit (Whole Blood) and Cytokine Secretion Assay (CSA) and were characterized with respect to memory phenotype, activation state and cytotoxic potential by multicolor flow cytometry, quantitative real-time PCR and multiplex analyses. Clinical-grade SARS-CoV-2-specific T cell products were generated by stimulation with MACS GMP PepTivator SARS-CoV-2 Select using CliniMACS Prodigy and CliniMACS Cytokine Capture System (IFN-gamma) (CCS). Functionality of enriched T cells was investigated in cytotoxicity assays and by multiplex analysis of secreted cytotoxic molecules upon target recognition.Results: Donor screening via IFN-gamma ELISpot allows for pre-selection of potential donors for generation of SARS-CoV-2-specific T cells. Antiviral T cells reactive against PepTivator SARS-CoV-2 Select could be magnetically enriched from peripheral blood of convalescent COVID-19 patients by small-scale CSA resembling the clinical-grade CCS manufacturing process and showed an activated and cytotoxic T cell phenotype. Four clinical-grade SARS-CoV-2-specific T cell products were successfully generated with sufficient cell numbers and purities comparable to those observed in donor pretesting via CSA. The T cells in the generated products were shown to be capable to replicate, specifically recognize and kill target cells in vitro and secrete cytotoxic molecules upon target recognition. Cell viability, total CD3(+) cell number, proliferative capacity and cytotoxic potential remained stable throughout storage of up to 72 h after end of leukapheresis.Conclusion: Clinical-gr

Atlantic salmon is often a focal species of restoration efforts throughout the north Atlantic and it is therefore an excellent case study for how best to design programmes to address and mitigate threats and correct population declines. This perspective is written to promote the work that has been accomplished towards restoration of Atlantic salmon populations and synthesize how we believe the lessons can be used effectively to support efforts by management agencies to restore populations. We reviewed where restoration is needed for Atlantic salmon, agreed on definitions for three levels of successful restoration, and then applied these criteria to 49 published papers focused on Atlantic salmon restoration. We identified 16 successful examples of restoration among 49 papers reviewed and discussed what interventions led to success versus failure. We then addressed key questions about when hatchery stocking should be used as part of a restoration measure and whether local restoration efforts are enough when these wide-ranging species encounter broad-scale changes in the north Atlantic, specifically related to issues of climate change and to marine survival. We advise to avoid restoration as much as possible by protecting and managing existing populations and when restoration is necessary, problems should be identified and addressed in partnership with river users. With appropriate resources and research to resolve ongoing mysteries, restoration of lost Atlantic salmon populations is absolutely feasible.

Assessing the process of vegetative state is difficult. There are no observational tools so far which are sensitive enough to register the subtle changes in vegetative states. Besides, it is necessary to distinguish between measurements of consciousness and of functions. The »Basel Vegetative State Assessment« (BAVESTA) has been developed since 2007; its reliability and validity were examined in this study. Its main purpose is to bridge the gap between tools measuring the level of consciousness and tools observing functional capacities of a patient. Method: BAVESTA has been developed with the collaboration of experts and potential users. It has been applied at the vegetative state REHAB centre Basel for five years, in order to assess its validity. BAVESTA has been implemented in 126 patients with different aetiopathogeneses, for process evaluation and comparison with four further, well-established tools. Analyses: Cronbach’s alpha, interrater-reliability, retest-reliability, concurrent and prognostic validity were examined. Results: BAVESTA has been proven to be a reliable and valid assessment tool. It is able to consistently measure the subtle changes during the process of rehabilitation in vegetative state patients. Discussion: The results support that BAVESTA is a reliable and valid observational assessment tool. The validation process was undertaken at a rehabilitation centre with a highly specialized ward on patients with vegetative state. Hence, it remains unclear whether BAVESTA is generally comprehensive for users outside this centre. Furthermore, clinical day-to-day difficulties resulted in a considerable amount of missing data. Conclusion: BAVESTA bridges the gap between assessment of consciousness and of functions. Further institutions should investigate its validity.

Introduction: Clinical assessments should meet the general psychometric properties of reliability and validity. Furthermore there are requirements in matters of diagnostic validity and usability. In regards to patients with severe brain damage, both issues can mainly be implemented by detecting and assessing returning abilities as early as possible, in order to use them for treatment planning. Main aim of this article is to investigate whether the newly developed and validated interprofessional Basel Vegetative State Assessment (BAVESTA) meets these practice criteria. Method: Data were collected as part of validity assessment of BAVESTA. Using the Glasgow Coma Scale as a reference, predictive parameters and measures of effect are calculated. Moreover, expert users were interviewed and results are presented in a descriptive way. Results: With a sensitivity of 0.84 and a specificity of 0.85, the BAVESTA can be regarded as suitable in differentiating between vegetative state and further states of remission such as the minimally conscious state. Expert users regard BAVESTA as eligible for mapping rehabilitative process of patients with severely impaired consciousness. They agree upon the fact that all relevant areas are covered by BAVESTA. Discussion: The BAVESTA displays high levels of differentiation, in regards to both sensitivity and specificity. However, measures of effect ought generally to be regarded with caution, as reference standards have not been developed for the area of rehabilitation. Considering time expenditure, BAVESTA is rated as only marginally feasible by expert users. It should be continued to investigate BAVESTA in regards to its diagnostic quality, integrating electrophysical diagnostic tools as reference standards.

Introduction: Valid measurement instruments are necessary to evaluate the rehabilitation progress of brain-injured patients with severe disorders of consciousness such as persistent vegetative state and minimally conscious state. Method: Instruments and validation studies were identified by searching the databases MEDLINE, DIMDI, PEDro, OT Seeker, CINAHL, PsychInfo and PsychIndex and German journals according to following inclusion criteria: 1) the instrument should cover behavioural change in the rehabilitation of patients with persistent vegetative state and minimally conscious state, 2) it should be available as German version and 3) data on at least one psychometric property must be reported. A critical appraisal of the psychometric quality was carried out based on the identified validation studies. Results: 13 out of 28 instruments met the inclusion criteria. From these six were used to detect functional changes in everyday life and seven recorded the state of consciousness. The Glasgow Coma Instrument, the Early Functional Ability Assessment, the Functional Independent Measure and the Barthel Index demonstrated good metric properties. For the other instruments only in a few properties were reported. Conclusion: The Glasgow Coma Scale can be recommended for the assessment of coma depth in acute care, and the Functional Independent Measure to evaluate the progress of rehabilitation. Because only a few instruments were appropriately tested on reliability and validity, further validation studies are necessary.

An increase of dissolved organic carbon and iron in freshwater bodies across the Northern Hemisphere caused by environmental and land use changes lead to water browning with negative impacts on lake ecosystems. Effects of browning on aquatic ecosystems are complex and include reduced light penetration, thermal stratification, lower macrophyte cover, lower primary productivity, and potential shifts in species composition. However, little is known about impacts of browning on lake fish communities. In this study I analysed data from 146 lakes in Sweden along a large water colour gradient (measured as absorbance at 420 nm) to find out how fish community biomass is influenced by water colour. Furthermore, I studied if variations in species composition or mean body size contribute to differences in community fish biomass between clear and brown lakes. Therefore, I tested the relationship between absorbance and community biomass, species biomass, total a bundance of fish individuals, mean fish body length, size diversity and species richness and the relationship between community composition and absorbance. The main result of my study was a negative relationship between fish community biomass and water colour, meaning a lower fish biomass in brown lakes tha n in clear lakes. The lower community biomass is likely explained by a lower biomass of several of the most common fish species, a lower total abundance of fish in dark lakes, and a lower number of species and differences in fish community composition. In contrast, I found no relationship between absorbance and fish body length, demonstrating that a lower biomass in brown lakes was not due to smaller fish. I also found that the variation in total fish abundance and biomass wa s high for clear lakes, but low for dark lakes. Also, values for highest biomass, highest number of individuals and number of species were much lower in darker lakes than in clear ones, explaining the lower community biomass with increa sed absorb

eingereicht von Stephanie Koch, in englischer Sprache, Universität Innsbruck, Masterarbeit, 2018, (VLID)2774559