Partizipative Wohnraumgestaltung Stiftung Behindertenbetriebe Uri: Projektbericht

Der Projektbericht erläutert das Projekt «Partizipative Wohnraumgestaltung Stiftung Behindertenbetriebe Uri». Das Projekt hat durch Erfassungssequenzen die Bedürfnisse der fünf Bewohner: innen der Wohngruppe Alpenrose bezüglich der Wohnraumgestaltung festgehalten und dadurch eine Umgestaltung der Wohnräume ermöglicht. Der Grundsatz der Partizipation lag im Fokus des Projekts. Das Endprodukt des Projekts beinhaltet mehrere umgestaltete Bereiche im Wohnraum der Wohngruppe Alpenrose, die sich an den Bedürfnissen der Bewohner: innen orientieren. Dazu wurde ein Erfassungsbogen mit unterschiedlichen Methoden erarbeitet, um die Bedürfnisse bedarfsgerecht zu erfassen. Dieser Erfassungsbogen steht der Institution nun weiter zur Verfügung. Menschen mit Beeinträchtigung haben den Anspruch auf Partizipation, Empowerment, Selbstbestimmung und sich in ihrem Lebensraum wohl und zu Hause zu fühlen. Hier bietet sich pädagogische Handeln an, dass dazu ermächtigt.+ Code Diss LU: hslusa pasp + Fussnote: Projekt-Arbeit, Hochschule Luzern – Soziale Arbeit, Studienrichtung Sozialpädagogik, 2023 + NL-Code: NLLUHSA20230

Aeolian sediment reconstructions from the Scottish Outer Hebrides: Late Holocene storminess and the role of the North Atlantic Oscillation

Northern Europe can be strongly influenced by winter storms driven by the North Atlantic Oscillation (NAO), with a positive NAO index associated with greater storminess in northern Europe. However, palaeoclimate reconstructions have suggested that the NAO-storminess relationship observed during the instrumental period is not consistent with the relationship over the last millennium, especially during the Little Ice Age (LIA), when it has been suggested that enhanced storminess occurred during a phase of persistent negative NAO. To assess this relationship over a longer time period, a storminess reconstruction from an NAO-sensitive area (the Outer Hebrides) is compared with Late Holocene NAO reconstructions. The patterns of storminess are inferred from aeolian sand deposits within two ombrotrophic peat bogs, with multiple cores and two locations used to distinguish the storminess signal from intra-site variability and local factors. The results suggest storminess increased after 1000 cal yrs BP, with higher storminess during the Medieval Climate Anomaly (MCA) than the LIA, supporting the hypothesis that the NAO-storminess relationship was consistent with the instrumental period. However the shift from a predominantly negative to positive NAO at c.2000 cal yrs BP preceded the increased storminess by 1000 years. We suggest that the long-term trends in storminess were caused by insolation changes, while oceanic forcing may have influenced millennial variability

Investigating the maximum resolution of µXRF core scanners: a 1800 year storminess reconstruction from the Outer Hebrides

Micro x-ray fluorescence (µXRF) core scanning is capable of measuring the elemental composition of lake sediment at sub-millimetre resolution, but bioturbation and physical mixing may degrade environmental signals at such fine scales. The aim of this research is to determine the maximum possible resolution at which meaningful environmental signals may be reconstructed from lake sediments using this method. Sediment from a coastal lake in the Outer Hebrides, Scotland, has been analysed using calibrated element measurements to reconstruct storminess since AD 200. We find that a Ca/K ratio in lake-core sediments reflects the presence of fine calcium carbonate shell fragments, a constituent of sand in the catchment that is washed and blown into the lake. Variations in this ratio are significantly correlated with instrumental records of precipitation and low pressures, suggesting it is a proxy for storminess. Furthermore, identification of a c. 60-year cycle supports a climatic influence on Ca/K, as this cycle is frequently identified in reconstructions of the North Atlantic Oscillation and North Atlantic sea-surface temperature. Comparison with weather records at different resolutions and spectral analysis indicate that µXRF data from Loch Hosta can be interpreted at sub-decadal resolutions (equivalent to core depth intervals of 3–5 mm in this location). Therefore, we suggest that sub-centimetre sampling using µXRF core scanning could be beneficial in producing environmental reconstructions in many lake settings where sediments are not varved

Phorbol-12-myristate-13-acetate is a potent enhancer of B cells with a granzyme B+ regulatory phenotype

IntroductionThe infusion of ex-vivo-generated regulatory B cells may represent a promising novel therapeutic approach for a variety of autoimmune and hyperinflammatory conditions including graft-versus-host disease.MethodsPreviously, we developed a protocol for the generation of a novel population of regulatory B cells, which are characterized by secretion of enzymatically active granzyme B (GraB cells). This protocol uses recombinant interleukin 21 (IL-21) and goat-derived F(ab)’2 fragments against the human B cell receptor (anti-BCR). Generally, the use of xenogeneic material for the manufacturing of advanced therapy medicinal products should be avoided to prevent adverse immune reactions as well as potential transmission of so far unknown diseases.ResultsIn the present work we demonstrated that phorbol-12-myristate-13-acetate (PMA/TPA), a phorbol ester with a particular analogy to the second messenger diacylglycerol (DAG), is a potent enhancer of IL-21-induced differentiation of pre-activated B cells into GraB cells. The percentage of GraB cells after stimulation of pre-activated B cells with IL-21 and PMA/TPA was not significantly lower compared to stimulation with IL-21 and anti-BCR.DiscussionGiven that PMA/TPA has already undergone encouraging clinical testing in patients with certain haematological diseases, our results suggest that PMA/TPA may be a safe and feasible alternative for ex-vivo manufacturing of GraB cells

Avian Intestinal Mucus Modulates Campylobacter jejuni Gene Expression in a Host-Specific Manner

Campylobacter jejuni is a leading cause of bacterial foodborne illness in humans worldwide. However, C. jejuni naturally colonizes poultry without causing pathology where it resides deep within mucus of the cecal crypts. Mucus may modulate the pathogenicity of C. jejuni in a species-specific manner, where it is pathogenic in humans and asymptomatic in poultry. Little is known about how intestinal mucus from different host species affects C. jejuni gene expression. In this study we characterized the growth and transcriptome of C. jejuni NCTC11168 cultured in defined media supplemented with or without mucus isolated from avian (chicken or turkey) or mammalian (cow, pig, or sheep) sources. C. jejuni showed substantially improved growth over defined media, with mucus from all species, showing that intestinal mucus was an energy source for C. jejuni. Seventy-three genes were differentially expressed when C. jejuni was cultured in avian vs. mammalian mucus. Genes associated with iron acquisition and resistance to oxidative stress were significantly increased in avian mucus. Many of the differentially expressed genes were flanked by differentially expressed antisense RNA asRNA, suggesting a role in gene regulation. This study highlights the interactions between C. jejuni and host mucus and the impact on gene expression, growth and invasion of host cells, suggesting important responses to environmental cues that facilitate intestinal colonization.IMPORTANCE Campylobacter jejuni infection of humans is an important health problem world-wide and is the leading bacterial cause of foodborne illnesses in U.S. The main route for exposure for humans is consumption of poultry meat contaminated during processing. C. jejuni is frequently found in poultry, residing within the mucus of the intestinal tract without causing disease. It is not clear why C. jejuni causes disease in some animals and humans, while leaving birds without symptoms. To understand its activity in birds, we characterized C. jejuni responses to poultry mucus to identify genes turned on in the intestinal tract of birds. We identified genes important for colonization and persistence within the poultry gut, turned on when C. jejuni was exposed to poultry mucus. Our findings are an important step in understanding how C. jejuni responds and interacts in the poultry gut, and may identify ways to reduce C. jejuni in birds

Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study

Background: The combination of BRAF and MEK inhibitors has become standard of care in the treatment of metastatic BRAF V600-mutated melanoma. Clinical factors for an early prediction of tumor response are rare. The present study investigated the association between the development of an early exanthema induced by vemurafenib or vemurafenib plus cobimetinib and therapy outcome. Methods: This multicenter retrospective study included patients with BRAF V600-mutated irresectable AJCC-v8 stage IIIC/D to IV metastatic melanoma who received treatment with vemurafenib (VEM) or vemurafenib plus cobimetinib (COBIVEM). The development of an early exanthema within six weeks after therapy start and its grading according to CTCAEv4.0 criteria was correlated to therapy outcome in terms of best overall response, progression-free (PFS), and overall survival (OS). Results: A total of 422 patients from 16 centers were included (VEM, n=299; COBIVEM, n=123). 20.4% of VEM and 43.1% of COBIVEM patients developed an early exanthema. In the VEM cohort, objective responders (CR/PR) more frequently presented with an early exanthema than non-responders (SD/PD); 59.0% versus 38.7%; p=0.0027. However, median PFS and OS did not differ between VEM patients with or without an early exanthema (PFS, 6.9 versus 6.0 months, p=0.65; OS, 11.0 versus 12.4 months, p=0.69). In the COBIVEM cohort, 66.0% of objective responders had an early exanthema compared to 54.3% of non-responders (p=0.031). Median survival times were significantly longer for patients who developed an early exanthema compared to patients who did not (PFS, 9.7 versus 5.6 months, p=0.013; OS, not reached versus 11.6 months, p=0.0061). COBIVEM patients with a mild early exanthema (CTCAEv4.0 grade 1-2) had a superior survival outcome as compared to COBIVEM patients with a severe (CTCAEv4.0 grade 3-4) or non early exanthema, respectively (p=0.047). This might be caused by the fact that 23.6% of patients with severe exanthema underwent a dose reduction or discontinuation of COBIVEM compared to only 8.9% of patients with mild exanthema. Conclusions: The development of an early exanthema within 6 weeks after treatment start indicates a favorable therapy outcome upon vemurafenib plus cobimetinib. Patients presenting with an early exanthema should therefore be treated with adequate supportive measures to provide that patients can stay on treatment

Past changes in the North Atlantic storm track driven by insolation and sea-ice forcing

Changes in the location of Northern Hemisphere storm tracks may cause significant societal and economic impacts under future climate change, but projections of future changes are highly uncertain and drivers of long-term changes are poorly understood. Here we develop a late Holocene storminess reconstruction from northwest Spain and combine this with an equivalent record from the Outer Hebrides, Scotland, to measure changes in the dominant latitudinal position of the storm track. The north-south index shows that storm tracks moved from a southern position to higher latitudes over the past 4000 yr, likely driven by a change from meridional to zonal atmospheric circulation, associated with a negative to positive North Atlantic Oscillation shift. We suggest that gradual polar cooling (caused by decreasing solar insolation in summer and amplified by sea-ice feedbacks) and mid-latitude warming (caused by increasing winter insolation) drove a steepening of the winter latitudinal temperature gradient through the late Holocene, resulting in the observed change to a more northern winter storm track. Our findings provide paleoclimate support for observational and modeling studies that link changes in the latitudinal temperature gradient and sea-ice extent to the strength and shape of the circumpolar vortex. Together this evidence now suggests that North Atlantic winter storm tracks may shift southward under future warming as sea-ice extent decreases and the mid- to high-latitude temperature gradient decreases, with storms increasingly affecting southern Europe

Characteristics of meiofauna in extreme marine ecosystems: a review

Extreme marine environments cover more than 50% of the Earth’s surface and offer many opportunities for investigating the biological responses and adaptations of organisms to stressful life conditions. Extreme marine environments are sometimes associated with ephemeral and unstable ecosystems, but can host abundant, often endemic and well-adapted meiofaunal species. In this review, we present an integrated view of the biodiversity, ecology and physiological responses of marine meiofauna inhabiting several extreme marine environments (mangroves, submarine caves, Polar ecosystems, hypersaline areas, hypoxic/anoxic environments, hydrothermal vents, cold seeps, carcasses/sunken woods, deep-sea canyons, deep hypersaline anoxic basins [DHABs] and hadal zones). Foraminiferans, nematodes and copepods are abundant in almost all of these habitats and are dominant in deep-sea ecosystems. The presence and dominance of some other taxa that are normally less common may be typical of certain extreme conditions. Kinorhynchs are particularly well adapted to cold seeps and other environments that experience drastic changes in salinity, rotifers are well represented in polar ecosystems and loriciferans seem to be the only metazoan able to survive multiple stressors in DHABs. As well as natural processes, human activities may generate stressful conditions, including deoxygenation, acidification and rises in temperature. The behaviour and physiology of different meiofaunal taxa, such as some foraminiferans, nematode and copepod species, can provide vital information on how organisms may respond to these challenges and can provide a warning signal of anthropogenic impacts. From an evolutionary perspective, the discovery of new meiofauna taxa from extreme environments very often sheds light on phylogenetic relationships, while understanding how meiofaunal organisms are able to survive or even flourish in these conditions can explain evolutionary pathways. Finally, there are multiple potential economic benefits to be gained from ecological, biological, physiological and evolutionary studies of meiofauna in extreme environments. Despite all the advantages offered by meiofauna studies from extreme environments, there is still an urgent need to foster meiofauna research in terms of composition, ecology, biology and physiology focusing on extreme environments

Correction to: Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study (Neurotherapeutics, (2021), 18, 2, (1127-1136), 10.1007/s13311-020-01004-3)

This article has been updated to add the author Richard S. Finkel. The original article has been corrected

The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion

Memory T cells exhibit superior responses to pathogens and tumors compared with their naive counterparts. Memory is typically generated via an immune response to a foreign antigen, but functional memory T cells can also be produced from naive cells by homeostatic mechanisms. Using a recently developed method, we studied CD8 T cells, which are specific for model (ovalbumin) and viral (HSV, vaccinia) antigens, in unimmunized mice and found a subpopulation bearing markers of memory cells. Based on their phenotypic markers and by their presence in germ-free mice, these preexisting memory-like CD44hi CD8 T cells are likely to arise via physiological homeostatic proliferation rather than a response to environmental microbes. These antigen-inexperienced memory phenotype CD8 T cells display several functions that distinguish them from their CD44lo counterparts, including a rapid initiation of proliferation after T cell stimulation and rapid IFN-γ production after exposure to proinflammatory cytokines. Collectively, these data indicate that the unprimed antigen-specific CD8 T cell repertoire contains antigen-inexperienced cells that display phenotypic and functional traits of memory cells