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In academic research virtually every field has increased its use of digital and computational technology, leading to new scientific discoveries, and this trend is likely to continue. Reliable and efficient scholarly research requires researchers to be able to validate and extend previously generated research results. In the digital era, this implies that digital objectsKahn and Wilensky 2006 used in research should be Findable, Accessible, Interoperable and Reusable (FAIR). These objects include (but are not limited to) data, software, models (for example, machine learning), representations of physical objects, virtual research environments, workflows, etc. Leaving any of these digital objects out of the FAIR process may result in a loss of academic rigor and may have severe consequences in the long term for the field, such as a reproducibility crisis. In this extended abstract, we focus on research software as a FAIR digital object (FDO).The FDO framework De Smedt et al. 2020 describes FDOs as being actionable units of knowledge, which can be aggregated, analyzed, and processed by different types of algorithms. Such algorithms must be implemented by software in one form or another. The framework also describes large software stacks supporting FDOs enabling responsible data science and increasing reproducibility. This implies that software is a key ingredient of the FDO framework, and should adhere to the FAIR principles. Software plays multiple roles: it is a DO itself, it is responsible for creating new FDOs (e.g., data) and it helps to make them available to the public (e.g., via repositories and registries). However there is a need to specify in more detail how non-data DOs, in particular software, fit in this framework.Different classes of digital objects have different intrinsic properties and ways to relate to other DOs. This means that while they, in principle, are subject to the high-level FAIR principles, there are also differences depending on their type and properties, requiring an adaptation so FAIR implementations are more aligned to the digital object itself. This holds true in particular to software. Software has intrinsic properties (executability, composite nature, development practices, continuous evolution and versioning, and packaging and distribution) and specific needs that must be considered by the FDO framework. For example, open source software is typically developed in the open on social coding platforms, where releases are distributed through package management systems, unlike data that is typically published in archival repositories. These social coding platforms do not provide long term archiving, permanent identifiers, or metadata, and package management systems, while somewhat better, similarly do not make a commitment to long term archiving, do not use identifiers that fit the scholarly publication system well, and provide metadata that may be missing key elements. The FAIR for research software (FAIR4RS, Chue Hong et al. 2021) working group has dedicated significant effort in building a community consensus around developing FAIR principles that are customized for research software, providing methods for researchers to understand and address these gaps.In this presentation we will highlight the importance of software for the FAIR landscape and why different (but related) FAIR principles are needed for software (vs those originally developed for data). Our goal here is to contribute to building an FDO landscape together, where we consider all different types of digital objects that are essential in today's research, and we are enthusiastic about contributing our expertise on research software in helping shape this landscape.

Starches are derived from three botanical sources, such as unripe mature banana fruits (Musa sapientum L.), cocoyam (Colocasia esculenta L. Schott), and bitter yam (Dioscorea dumetorum Pax) tubers, have been evaluated as polymers in the design of microspheres incorporating diclofenac sodium as a model drug. Using the ionic gelation process, the starches were pregelatinized and used as polymers in conjunction with sodium alginate to produce diclofenac sodium microspheres with 2% calcium chloride as a crosslinking agent. The morphology, swelling properties, Entrapment Efficiency (EE), and drug release properties of the microspheres were evaluated. Fitting the in-vitro dissolution data into multiple kinetic models yielded the drug release pathways. Spherical discrete microspheres with rough surfaces were obtained with diameters ranging from 580 µm to 670 µm and EEs ranging from 68.0% to 80.7% w/w. For more than 5 hours, diclofenac sodium was released in a controlled manner. The type and concentration of starch in the polymer blend affected drug release from the microspheres, with banana starch at a 4:1 ratio demonstrating the slowest dissolution rate. Drug release from microspheres is best described by the Korsmeyer-Peppas model, which implies that drug release is governed by both diffusion and erosion mechanisms. The finding shows that tropical starches could be used to develop diclofenac sodium microspheres with controlled release.

Abstract Introduction Various techniques for whole breast radiation therapy (WBRT) have been reported to increase dose to contralateral tissues. Heart dose is of critical importance as there is no apparent dose threshold below which there is no risk. The aim of this study was to compare planning techniques for WBRT that achieves the best target dosimetry and lowest organ at risk (OAR) dose. Methods Thirty early‐stage whole breast patient datasets, 15 each left‐ and right‐sided cases, were retrospectively selected. Five techniques were generated for each data set: three‐dimensional conformal radiation therapy (3DCRT), hybrid intensity modulated radiation therapy (HYI), hybrid volumetric modulated arc therapy (VMAT) – (HYV), reduced arc VMAT – bowtie (BT), and BT flattening filter free (FFF) – (BTFFF). Plan goals and OARs were evaluated and compared between techniques. Results BT had the highest median conformity index (CI) values (0.82, IQR: 0.80–0.85 left and 0.83, IQR 0.80–0.86 right). BT recorded lower mean heart doses (median value 1.19Gy, IQR: 0.90–1.55), and BTFFF recorded lower heart V2.5 Gy, V5 Gy; median 3.96% (IQR: 2.90–6.80) and 0.90% (IQR: 0.50–1.50) respectively for left‐sided patients. There was a statistically significant difference in all ipsilateral lung measures, (p

Abstract Background Whether restricted spirometry, i.e. low Forced Vital Capacity (FVC), predicts chronic cardiometabolic disease is not definitely known. In this international population-based study, we assessed the relationship between restricted spirometry and cardiometabolic comorbidities. Methods A total of 23,623 subjects (47.5% males, 19.0% current smokers, age: 55.1 ± 10.8 years) from five continents (33 sites in 29 countries) participating in the Burden of Obstructive Lung Disease (BOLD) study were included. Restricted spirometry was defined as post-bronchodilator FVC

The article presents selected issues within the field of space syntax, its theoretical assumptions, and application possibilities, taking into account, especially, works in the field of social and economic geography, and spatial management. The article attempts to present Polish works in the field of space syntax as related to the wider spectrum of its global applications. In Poland, the theory and research tools of space syntax are rarely used. It appears that there are two factors that influence the current marginalisation of space syntax. The first one is the relative complexity of the research procedure, which requires knowledge of specialist computer software. The second arises directly from the fact that, in reality, only occasional use of space syntax tools has been attempted within the Polish arena. This determines the actual lack of a native space syntax community that would support subsequent researchers who are ready to conduct such studies.

Schnitzler syndrome is a rare autoinflammatory disorder characterized by urticarial rash, joint pain, recurrent fever, leucocytosis, elevated C-reactive protein (CRP) and serum amyloid A (SAA), and monoclonal IgM or IgG gammopathy. According to the Strasbourg criteria, both urticarial rash and gammopathy are mandatorily required for the diagnosis of Schnitzler’s syndrome. However, incomplete variants lacking either skin symptoms or monoclonal gammopathy have also been described. Here, we report a case in which the diagnosis of Schnitzler-like syndrome was made despite the absence of gammopathy, based on neutrophilic dermal inflammation, episodic and excessive increase in inflammatory parameters, and prompt response to anakinra, a soluble IL1 receptor antagonist (sIL-1RA). In addition, we detected neutrophil epitheliotropism, which is highly suggestive of autoinflammatory disease. Using whole-exome sequencing, we were unable to find a causative pathogenic mutation but did find several mutations possibly related to the inflammatory processes in this patient. This and other cases highlight that the existing Strasbourg criteria are too strict to capture Schnitzler-like syndromes that may respond well and rapidly to IL1 inhibition. Recurrent episodes of disease with normalization of inflammatory symptoms in the interval, rapid response to anakinra, and neutrophilic epitheliotropism in a lesional skin biopsy may help confirm the diagnosis of Schnitzler-like syndrome.

The Covid19 pandemic and the accompanying measures between March 2020 and March 2022 had a strong impact on the sport system. The various restrictions on sports activities affected not only school sports, but also clubs and fitness centres, as well as competitive sports in general. At the same time, a considerable increase in unorganised outdoor sports activities and a shift in sport preferences could be observed. In order to assess and quantify the short- to medium-term changes in the sporting behaviour of the Swiss population due to the Covid 19 pandemic, the Federal Office of Sport commissioned a representative population survey. For this purpose, 2,130 people aged 15 and over were surveyed in the summer of 2022 in the three national languages German, French and Italian by means of an online questionnaire. To facilitate comparisons over time, the survey was based on the survey instrument of the "Sport Switzerland" studies (cf. Lamprecht et al., 2020), with additional questions on the assessment and management of the Covid19 pandemic. For the present paper, on the one hand, results on the changes in sports behaviour during the Covid19 pandemic will be presented and it will be shown how these changes affected sports activity in the different settings in the medium term. On the other hand, the consequences of these changes on social and regional differences in sports behaviour (cf. Lamprecht & Nagel, 2022) will be examined. Did the Covid19 pandemic and the accompanying measures in the field of sport tend to increase or rather level out the differences according to age, gender, social status and place of residence? Did the pandemic lead to a situation in which population groups who were only sparingly and irregularly active in sport were increasingly discouraged from taking part in sport, while those who were more active in sport found it easier to switch to other types of sport and settings? With regard to the regions, it will be investigated whether a connection can be found between compliance with the Corona measures and the changes in sports behaviour. Finally, the question will be raised as to how lasting the measured changes and shifts are likely to be and how an increase in social inequality in the field of sport could be countered. References Lamprecht, M., & Nagel, S. (2022). Sportsoziologie: Einführung. Nomos. Lamprecht, M., Bürgi, R., & Stamm, H. (2020). Sport Schweiz 2020: Sportaktivität und Sportinteresse der Schweizer Bevölkerung. Bundesamt für Sport BASPO.

Changes in sports behaviour and activities over the last decades are often attributed to developments of individualisation and differentiation in society. Existing empirical studies confirm that sporting activity is increasingly differentiated, with the proportion of regular sport-active people growing, as well as access improving for those previously less well represented, for example, women and older people. However, more men than women and more younger than older people are active in sports clubs (Lamprecht et al., 2020). This lecture will consider the extent to which social differences and inequalities in sporting behaviour have decreased in the Swiss population over recent decades. The underlying processes of exit and entry, age, cohort, and period effects are also examined. Mayer’s life course approach (1990; 2009) is the theoretical and methodological framework for the investigation of change processes in contemporary history, where “social structures and their changes can be partially reconstructed from individual trajectories” (Mayer, 1990, p.8). Changes in modern sport can therefore be reconstructed through personal longitudinal data and its aggregation. In 2019, this study gathered the trajectories of sport and physical activities of a total of 1,456 people living in Switzerland aged 15 to 76 years using a retrospective telephone survey. For the time-historical analyses, age cohorts of those born 1943 to 1950, 1951 to 1960, through to those born 1981 to 1990 were constructed. Information on sporting activities over the life course from childhood to the present from the periods 1950s to 2010s was then chronologically classified. The analyses confirm existing research that shows older people practice sport activities in clubs less frequently. This negative age effect in club sport can be seen across all age cohorts and time periods (all p < .001). Binary logistic regression analyses also indicate that this age effect is most pronounced, with an OR of 0.35, in the youngest age cohort born 1981 to 1990, whereas in the oldest cohort born 1943 to 1950, shows OR = 0.67. In recent decades, more child and adolescent girls have gained access to club sport, with a decline in the gender difference from approximately 22 percentage points in the 1950s/1960s to approximately 6 percentage points in the 2000s/2010s. A positive age effect can be observed in self-organised sporting activities. This is more pronounced in the younger age cohorts, OR = 2.72, than in the older, OR = 1.77. These historical analyses demonstrate that age differences in organisational forms of sport remain, but that gender differences in club sport have been minimised, particularly in childhood and adolescence. In addition, the effects have tended to become greater in recent years and changes in the forms of organisation tend to become more significant over time. References Lamprecht, M., Bürgi, R. & Stamm, H. (2020). Sport Schweiz 2020. Sportaktivität und Sportinteresse der Schweizer Bevölkerung. Bundesamt für Sport BASPO. Mayer, K. U. (Ed.). (1990). Lebensverläufe und sozialer Wandel. Kölner Zeitschrift für Soziologie und Sozialpsychologie, 31[Special issue]. Mayer, K. U. (2009). New directions in life course research. Annual Review of Sociology, 35, 413–433. https://doi.org/10.1146/annurev.soc.34.040507.134619

Despite the steady increase in the number of people active in sport over the past decades, certain population groups are still underrepresented in sport and especially in sport clubs, e.g. people with a low level of education and income, with a migration background or disabilities. In view of the diverse functions attributed to sport involvement, such as health promotion, transmission of norms and values, and social integration, analyses of social inequalities with regard to sport participation are of particular relevance. The symposium organized by the Research Committee for the Sociology of Sport aims, on the one hand, to highlight current developments and relevant factors with regard to the participation of different population groups in sport and, on the other hand, to present possibilities in the sense of diversity management of how sport organizations can facilitate access to sport. This will provide a knowledge base on the question of how to reduce barriers to access in sport and ensure greater equality. The first two presentations highlight developments with regard to social differences in the sport behavior of the Swiss population. Bürgi and Lamprecht analyze the effects of the Covid 19 pandemic and Klostermann et al. examine historical changes in sport behavior. The two other contributions look at specific target groups and the importance of structural conditions. Klenk et al. focus on the social participation of children with cognitive impairment in inclusive school sport. Buser and Nagel show how inclusive measures for people with a migration background are structurally anchored in soccer clubs.

ObjectiveTo analyze the impact of the COVID-19 pandemic on medical care and vaccination acceptance of vasculitis patients in Germany.MethodsA web-based national survey was developed by rheumatology centers and vasculitis patient advocacy groups. The survey was distributed nationwide by mail and flyers and could be accessed via a QR-code or weblink from December 2021 to April 2022. Descriptive statistics [mean, median, standard derivation (SD), 25%, 75% quantile] were calculated. 95% confidence intervals were presented for responses that were directly related to the impact of COVID-19 on parameters associated with vasculitis patient care.ResultsThe online survey was completed by 117 patients with small and large vessel vasculitis [granulomatosis with polyangiitis (n = 69), eosinophilic granulomatosis with polyangiitis (n = 16), microscopic polyangiitis (n = 12), giant cell arteritis (n = 17) and Takayasu's arteritis (n = 3)]. Prescheduled rheumatological appointments had been canceled due to the COVID-19 pandemic in 12.6% of the respondents [95% confidence interval (CI), 7.3–20.0%); in 9% (95% CI, 4.5–15.6%)] appointments had been replaced by digital services. Therapeutic regimens were changed (shifted, reduced, or discontinued) due to the pandemic in 15.5% (95% CI 9.5–22.2%). Vaccination coverages were generally high compared to patients with other rheumatic diseases and the general population. Highest vaccination coverage was observed against COVID-19 (98.1% 95% CI 93.9–99.6%).ConclusionVasculitis patients experienced changes in medical care during COVID-19 pandemic such as cancelation of prescheduled rheumatology appointments and modifications in therapeutic regimens. The overall acceptance rate for vaccination was comparatively high, particularly for vaccination against COVID-19.

Germline SAMD9 and SAMD9L mutations cause a spectrum of multisystem disorders that carry a markedly increased risk of developing myeloid malignancies with somatic monosomy 7. Here, we describe 16 siblings, the majority of which were phenotypically normal, from 5 families diagnosed with myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7; OMIM 252270) who primarily had onset of hematologic abnormalities during the first decade of life. Molecular analyses uncovered germline SAMD9L (n = 4) or SAMD9 (n = 1) mutations in these families. Affected individuals had a highly variable clinical course that ranged from mild and transient dyspoietic changes in the bone marrow to a rapid progression of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7. Expression of these gain-of-function SAMD9 and SAMD9L mutations reduces cell cycle progression, and deep sequencing demonstrated selective pressure favoring the outgrowth of clones that have either lost the mutant allele or acquired revertant mutations. The myeloid malignancies of affected siblings acquired cooperating mutations in genes that are also altered in sporadic cases of AML characterized by monosomy 7. These data have implications for understanding how SAMD9 and SAMD9L mutations contribute to myeloid transformation and for recognizing, counseling, and treating affected families.

Artykuł zawiera wyniki analizy konfiguracyjnej układu urbanistycznego Szadku (obszaru miasta lokacyjnego i jego bezpośredniego otoczenia) z zastosowaniem narzędzi składni przestrzeni (space syntax). Przedstawione badania ujawniły przestrzenie kluczowe dla funkcjonowania miasta w kontekście konfiguracyjnym. Są to m.in. dwa rdzenie integracji: jeden o charakterze pasmowym, położony na obszarze miasta lokacyjnego z przedłużeniem w kierunku struktur Nowego Miasta, drugi o charakterze węzłowym, istniejący na obszarze przypuszczalnego położenia struktur przedlokacyjnych tego miasta. Zidentyfikowane zostały także przestrzenie istotne dla utrzymania sprawności systemu miejskiego w kontekście ruchu pieszego.

As recognition of the vital importance of software for contemporary research is increasing, Research Software Engineering (RSE) is emerging as a discipline in its own right. We present an inventory of relevant research questions about RSE as a basis for future research and initiatives to advance the field, highlighting selected literature and initiatives. This work is the outcome of a RSE community workshop held as part of the 2020 International Series of Online Research Software Events (SORSE) which identified and prioritized key questions across three overlapping themes: people, policy and infrastructure. Almost half of the questions focus on the people theme, which addresses issues related to career paths, recognition and motivation; recruitment and retention; skills; and diversity, equity and inclusion. However, the people and policy themes have the same number of prioritized questions. We recommend that different types of stakeholders, such as RSE employers and policy makers, take responsibility for supporting or encouraging answering of these questions by organizations that have an interest. Initiatives such as the International Council of RSE Associations should also be engaged in this work.

IntroductionProgression of fibrotic interstitial lung disease (ILD) leads to irreversible loss of lung function and increased mortality. Based on an institutional ILD registry, we aimed to evaluate biomarkers derived from baseline patient characteristics, computed tomography (CT), and peripheral blood for prognosis of disease progression in fibrotic ILD patients.MethodsOf 209 subsequent ILD-board patients enregistered, 142 had complete follow-up information and were classified fibrotic ILD as defined by presence of reticulation or honeycombing using a standardized semi-quantitative CT evaluation, adding up typical ILD findings in 0–6 defined lung fields. Progression at 1 year was defined as relative loss of ≥10% in forced vital capacity, of ≥15% in diffusion capacity for carbon monoxide, death, or lung transplant. Two-thirds of the patients were randomly assigned to a derivation cohort evaluated for the impact of age, sex, baseline lung function, CT finding scores, and blood biomarkers on disease progression. Significant variables were included into a regression model, its results were used to derive a progression-risk score which was then applied to the validation cohort.ResultsIn the derivation cohort, age, monocyte count ≥0.65 G/L, honeycombing and traction bronchiectasis extent had significant impact. Multivariate analyses revealed the variables monocyte count ≥0.65 G/L (1 point) and combined honeycombing or traction bronchiectasis score [0 vs. 1–4 (1 point) vs. 5–6 lung fields (2 points)] as significant, so these were used for score development. In the derivation cohort, resulting scores of 0, 1, 2, and 3 accounted for 1-year progression rates of 20, 25, 46.9, and 88.9%, respectively. Similarly, in the validation cohort, progression at 1 year occurred in 0, 23.8, 53.9, and 62.5%, respectively. A score ≥2 showed 70.6% sensitivity and 67.9% specificity, receiver operating characteristic analysis for the scoring model had an area under the curve of 71.7%.ConclusionThe extent of honeycombing and traction bronchiectasis, as well as elevated blood monocyte count predicted progression within 1 year in fibrotic ILD patients.

Malnutrition (MN) is a common primary or secondary complication in gastrointestinal diseases. The patient’s nutritional status also influences muscle mass and function, which can be impaired up to the degree of sarcopenia. The molecular interactions in diseases leading to sarcopenia are complex and multifaceted, affecting muscle physiology, the intestine (nutrition), and the liver at different levels. Although extensive knowledge of individual molecular factors is available, their regulatory interplay is not yet fully understood. A comprehensive overall picture of pathological mechanisms and resulting phenotypes is lacking. In silico approaches that convert existing knowledge into computationally readable formats can help unravel mechanisms, underlying such complex molecular processes. From public literature, we manually compiled experimental evidence for molecular interactions involved in the development of sarcopenia into a knowledge base, referred to as the Sarcopenia Map. We integrated two diseases, namely liver cirrhosis (LC), and intestinal dysfunction, by considering their effects on nutrition and blood secretome. We demonstrate the performance of our model by successfully simulating the impact of changing dietary frequency, glycogen storage capacity, and disease severity on the carbohydrate and muscle systems. We present the Sarcopenia Map as a publicly available, open-source, and interactive online resource, that links gastrointestinal diseases, MN, and sarcopenia. The map provides tools that allow users to explore the information on the map and perform in silico simulations.

Ancestral sequence reconstruction is a technique that is gaining widespread use in molecular evolution studies and protein engineering. Accurate reconstruction requires the ability to handle appropriately large numbers of sequences, as well as insertion and deletion (indel) events, but available approaches exhibit limitations. To address these limitations, we developed Graphical Representation of Ancestral Sequence Predictions (GRASP), which efficiently implements maximum likelihood methods to enable the inference of ancestors of families with more than 10,000 members. GRASP implements partial order graphs (POGs) to represent and infer insertion and deletion events across ancestors, enabling the identification of building blocks for protein engineering. To validate the capacity to engineer novel proteins from realistic data, we predicted ancestor sequences across three distinct enzyme families: glucose-methanol-choline (GMC) oxidoreductases, cytochromes P450, and dihydroxy/sugar acid dehydratases (DHAD). All tested ancestors demonstrated enzymatic activity. Our study demonstrates the ability of GRASP (1) to support large data sets over 10,000 sequences and (2) to employ insertions and deletions to identify building blocks for engineering biologically active ancestors, by exploring variation over evolutionary time.

Sports clubs have been reporting several organizational problems in recent decades (e.g., recruitment and retention of members and volunteers). At the same time, certain sports clubs have professionalized their strategies, structures, processes, and staff. However, previous research has not analyzed whether the professionalization of sports clubs is related to their organizational problems. Therefore, this study conducts, in the first step, a cluster analysis based on three dimensions of professionalization to identify professionalization types among sports clubs. In the second step, it examines differences in organizational problems among the identified professionalization types. The main findings are that (1) sports clubs with paid staff report fewer problems with recruiting and retaining members but more problems with finances than sports clubs that rely on voluntary work, and (2) sports clubs with increased professionalization of human resources management (HRM) and strategy have fewer problems with recruiting and retaining board members and coaches than sports clubs with low professionalization of HRM and strategy. These results show that professionalized sports clubs have different, but not necessarily fewer, organizational problems.

Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (i.e., phagocytosis of apoptotic neutrophils by macrophages) as well as cell death-related release of damage-associated molecular patterns (DAMP) such as high mobility group box 1 (HMGB1) contribute to chronic non-resolving inflammation in GPA. DAMP have been shown to induce innate as well as adaptive cellular responses thereby creating a prerequisite for the development of pathogenic autoimmunity. In this review, we discuss factors contributing to as well as the impact of regulated cell death (RCD) accompanied by DAMP-release as early drivers of the granulomatous tissue inflammation and autoimmune responses in GPA.

Contrary to carbohydrate and fat metabolism, the influence of a single exercise dose on protein metabolism has not been adequately explored yet. We assessed the effects of different exercise intensities and durations on blood protein changes and their association with carbohydrate (CHO) and fat metabolism in six eligible trained subjects. Subjects performed maximal incremental (IE100: at 100%VO2max) and submaximal continuous exercise (CE) at 75%VO2max for 30 min (CE75) and at 50%VO2max for 90 min (CE50). Blood samples were collected at rest (R), end of exercise (EE), and 1 h after recovery to assess blood urea nitrogen (BUN), plasma amino acids (AA), glucose, lactate, FFA, and glycerol. In IE100 blood lactate, CHO-oxidation (g/min), energy expenditure (kcal/min), and RER were significantly increased during rest (p < 0.05). CE50 induced significantly higher BUN, FFA, glycerol, and fat oxidation (g/min) (p < 0.05). At recovery, the mean sum of the free AA pool (µmol/L) reduced by 8% (p < 0.03) during CE50. Values for CE75 were between IE100 and CE50. Beside lipolysis, also proteolysis (BUN) was an important source of fuel for low-to-moderate intensity CE50. An increased uptake of AA from the plasma bed during CE50 suggests the importance for oxidation and synthesis of other metabolic sources such as gluconeogenesis necessary for recovery. Therefore, one needs to be cautious of protein diet following prolonged cycle exercise training.

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.

Abstract Background One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA. Methods This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied. Discussion The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA. Trial registration ClinicalTrials.gov NCT03765788 . Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.

Abstract Background Vasculitides comprise a group of rare diseases which affect less than 5 in 10.000 individuals. Most types of vasculitis can become organ- and life-threatening and are characterized by chronicity, high morbidity and relapses, altogether resulting in significant morbidity and mortality. Previous studies have been either monocentric or mainly retrospective – studies with a prospective design mostly consisted of rather small cohorts of 100 to 200 patients. The aim of the Joint Vasculitis Registry in German-speaking countries (GeVas) is to record all patients who have been recently diagnosed with vasculitis or who have changed their treatment due to a relapse (inception cohort). In GeVas, data are collected prospectively in a multicenter design in Germany, Austria and Switzerland. By this approach, courses of vasculitis and their outcomes can be monitored over an extended period. Methods GeVas is a prospective, web-based, multicenter, clinician-driven registry for the documentation of organ manifestations, damage, long-term progress and other outcomes of various types of vasculitis. The registry started recruiting in June 2019. As of October 2020, 14 centers have been initiated and started recruiting patients in Germany. Involvement of sites in Austria and the German-speaking counties of Switzerland is scheduled in the near future. Discussion In June 2019, we successfully established a prospective multicenter vasculitis registry being the first of its kind in German-speaking countries. The participating centers are currently recruiting, and systematic analysis of long-term vasculitis outcomes is expected in the ensuing period. Trial registration German Clinical Trials Register (Deutsches Register Klinischer Studien): DRKS00011866 . Registered 10 May 2019.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.

The traditional view reflected in biblical Hebrew dictionaries and textbooks that heaven is construed as a mere cultural experience became problematic in at least two ways: firstly, the extension of the grammatical expression found in the biblical Hebrew exemplars becomes conventionalised in such a way that the original construal no longer constrains how the biblical Hebrew speakers think about the experience; and secondly, this released consequence influences recent publications on heaven. Consequently, most modern publications on heaven construed heaven as a relative design. This study argues that such inhibited way of expressing heaven reduces the structural schematisation as construed in the Hebrew Bible. Methodologically, this study proposes an experientialist-embodied approach towards the conceptualisation of heaven. The result, in theory, is a more effective schematisation in which different semantic structures were employed to express the experience. This is then applied towards understanding the spatial image schema of up versus down in the Hebrew Bible and offers a vantage point from which to investigate the whole network of the biblical Hebrew spatial cognition. Contribution: This article contributes to the understanding of the ancient Israelite conceptual system for ‘heaven’ in the Hebrew Bible.

Orientation: In business rescue, when pursuing the sale of the business to a third party, the business rescue practitioner (BRP) may use different bidding processes to interact with and select buyers. Research purpose: This study aimed to provide a framework to classify and describe the various bidding processes, including identifying the factors that would preserve value to the benefit of creditors and shareholders. Motivation for the study: Chapter 6 of the Companies Act is silent on the requirements regarding bidding processes. Therefore, the industry and legislator may benefit from guidance from industry experts. Research approach/design and method: Qualitative exploratory, using semi-structured interviews with 11 South African senior business rescue practitioners. Main findings: Three types of bidding processes were identified. In a sophisticated bidding process, information is communicated to buyers using a virtual data room. The second bidding process is less sophisticated; printed document packs are provided to bidders, and bids are submitted in tender boxes. Thirdly, the private bid-out process, where preferred bidders compete against each other in a closed envelope boardroom auction. The findings also revealed that deal certainty is more important in business rescue than ordinary mergers and acquisitions. Moreover, an equitable value, rather than a general market value, is often applied because of the bidding process. Lastly, the study identified a need for the pre-involvement of the BRP before a company files for business rescue, an aspect not currently allowed by the Companies Act. Practical/managerial implications: BRPs can benefit from the explication of the types and detailed steps of bidding processes. Moreover, the findings fill the void of limited guidance in the Companies Act. Contribution/value-add: The classification and description of the various bidding processes and key considerations in the context of a business rescue will assist BRPs in South Africa in preserving value under business rescue and guide the legislator in amending the Companies Act.