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This paper discusses an index based on the concept of mobility cultures for measuring the socio-ecological transformation of urban mobility, also referred to as the mobility transition. This index, termed the Mobility Transition Index, aims to enable municipal policymakers and planners to quantitatively assess progress in implementing the mobility transition. The uniqueness of the index lies in the consideration of both objective and subjective data, as well as the goal of incorporating as many open data sources as possible. In workshops with local experts of statistics and transport planning, the indicator set was discussed in terms of its applicability and the availability of additional data. Finally, a set of 78 measurement indicators and 16 core indicators for calculating the Mobility Transition Index emerged. Next, the index was calculated for three cities (Darmstadt, Frankfurt am Main, Wiesbaden), and discussed with experts again. The results demonstrate the potential of the index for analysing changes in urban mobility cultures. Furthermore, we identified a predominance of data related to the built environment and travel behaviour, but a lack of data for transport policy and planning, as well as for discourses and communication. We concluded that additionally to the necessity for collecting such data more extensively, a need arises for the critical examination of existing datasets and their contribution for the urban transformation of transport.

Only three fossils in the Pyraloidea (Insecta, Lepidoptera) have been confirmed to date, two adults and one larva. The first confirmed larva, in the subfamily Pyraustinae (Crambidae), was described from Baltic amber. Recently, another pyraloid larva from Dominican amber has come to our attention. We describe this second confirmed larval fossil as Penestola wichardi Solis, Léger & Neumann, sp. nov., based on larval morphological characters, such as setal patterns and the shape of their sclerotized bases or pinacula, and place it in the subfamily Spilomelinae (Crambidae).

Abstract Additive manufacturing of metals – and in particular building with laser-based powder bed fusion – is highly flexible and allows high-resolution features and feedstock savings. Meanwhile, though space stations in low Earth orbit are established, a set of visits to the Moon have been performed, and humankind can send out rovers to explore Venus and Mars, none of these milestone missions is equipped with technology to manufacture functional metallic parts or tools in space. In order to advance space exploration to long-term missions beyond low Earth orbit, it will be crucial to develop and employ technology for in-space manufacturing (ISM) and in-situ resource utilisation (ISRU). To use the advantages of laser-based powder bed fusion in these endeavours, the challenge of powder handling in microgravity must be met. Here we present a device capable of building parts using metallic powders in microgravity. This was proven on several sounding rocket flights, on which occasions Zr-based metallic glass parts produced by additive manufacturing in space were built. The findings of this work demonstrate that building parts using powder feedstock, which is more compact to transport into space than wire, is possible in microgravity environments. This thus significantly advances ISRU and ISM and paves the way for future tests in prolonged microgravity settings.

Summary: Background: Despite the high prevalence and major disability associated with fatigue and cognitive deficits after SARS-CoV-2 infection, little is known about long-term trajectories of these sequelae. We aimed to assess long-term trajectories of these conditions and to identify risk factors for non-recovery. Methods: We analyzed longitudinal data from the population-based COVIDOM/NAPKON-POP cohort in Germany. Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale (cutoff ≤ 30) and the Montreal Cognitive Assessment (MoCA, cutoff ≤ 25). Predictors of recovery from fatigue or cognitive deficits between assessments were identified through univariate and multivariable logistic regression models. The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584). Findings: Between 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% (95% confidence interval (CI) [20%, 23%]) had fatigue and 23% (95% CI [22%, 25%]) had cognitive deficits according to cutoff scores on the FACIT-Fatigue or MoCA. Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up (Hedges’ g [95% CI] = 0.73 [0.60, 0.87]) and 46% (95% CI [41%, 50%]) had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores (g [95% CI] = 1.12 [0.90, 1.33]) and 57% (95% CI [50%, 64%]) had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and

Abstract Background The efficacy of recanalization treatment in patients with ischemic stroke due to large vessel occlusion (LVO) is highly time dependent. We aimed to investigate the effects of an optimization of prehospital and intrahospital pathways on time metrics and efficacy of endovascular treatment in ischemic stroke due to LVO. Methods Patients treated with mechanical thrombectomy (MT) at the Hospital of St. John of God Vienna, Austria, between 2013 and 2020 were extracted from the Austrian Stroke Unit Registry. Study endpoints including time metrics, early neurological improvement and functional outcome measured by modified Rankin Scale (mRS) at 3 months were compared before and after optimization of prehospital and intrahospital pathways. Results Two hundred ninety-nine patients were treated with MT during the study period, 94 before and 205 after the workflow optimization. Workflow optimization was significantly associated with time metrics improvement (door to groin puncture time 45 versus 31 min; p

Background and Purpose It is unclear whether a particular stroke imaging modality offers an advantage for the acute stroke treatment. The aim of this study was to compare procedure times, efficacy and safety of thrombolysis and/or thrombectomy based on computed tomography (CT) versus magnetic resonance imaging (MRI) acute stroke imaging. Methods Data of stroke patients who received intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were extracted from a nationwide, prospective stroke unit registry and categorized according to initial imaging modality. Study endpoints included procedure times, symptomatic intracerebral hemorrhage (sICH), early neurological improvement, 3-month functional outcome by modified Rankin Scale (mRS) and mortality. Results Stroke patients (n=16,799) treated with IVT and 2,248 treated with MT were included. MRI-guided patients (n=2,599) were younger, had less comorbidities and higher rates of strokes with unknown onset as compared to CT-guided patients. In patients treated with IVT, no differences were observed regarding the rates of functional outcome by mRS 0–1 (adjusted odds ratio [OR], 0.87; 95% confidence interval [CI], 0.71 to 1.05), sICH (adjusted OR, 0.82; 95% CI, 0.61 to 1.08), and mortality (adjusted OR, 0.88; 95% CI, 0.63 to 1.22). Patients undergoing MT selected by MRI as compared to CT showed equal rates of functional outcome by mRS 0–2 (adjusted OR, 0.87; 95% CI, 0.65 to 1.16), sICH (adjusted OR, 0.9; 95% CI, 0.51 to 1.69), and mortality (adjusted OR, 0.62; 95% CI, 0.35 to 1.09). MRI-guided patients showed a significant intrahospital delay of about 20 minutes in both the IVT and the MT group. Conclusions This large non-randomized comparison study indicates that CT- and MRI-guided patient selection for IVT/MT may perform equally well in terms of functional outcome and safety.

Background and Purpose Studies on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with preexisting disability are limited. We aimed to compare the outcomes of MT versus best medical treatment (BMT) in these patients. Methods In the nationwide Austrian registry and Swiss monocentric registry, we identified 462 AIS patients with pre-stroke disability (modified Rankin Scale [mRS] score ≥3) and acute large vessel occlusion. The primary outcome was returning to pre-stroke mRS or better at 3 months. Secondary outcomes were early neurological improvement (National Institutes of Health Stroke Scale score improvement ≥8 at 24 to 48 hours), 3-month mortality, and symptomatic intracerebral hemorrhage (sICH). Multivariable regression models and propensity score matching (PSM) were used for statistical analyses. Results Compared with the BMT group (n=175), the MT group (n=175) had younger age, more severe strokes, and lower pre-stroke mRS, but similar proportion of receiving intravenous thrombolysis. MT was associated with higher odds of returning to baseline mRS or better at 3 months (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 1.39 to 4.47), early neurological improvement (aOR, 2.62; 95% CI, 1.41 to 4.88), and lower risk of 3-month mortality (aOR, 0.29; 95% CI, 0.18 to 0.49). PSM analysis showed similar findings. MT was not associated with an increased risk of sICH (4.0% vs. 2.1% in all patients; 4.2% vs. 2.4% in the PSM cohort). Conclusions MT in patients with pre-stroke mRS ≥3 might improve the 3-month outcomes and short-term neurological impairment, suggesting that pre-stroke disability alone should not be a reason to withhold MT, but that individual case-by-case decisions may be more appropriate.

Summary: Background: Reliable estimates of frequency, severity and associated factors of both fatigue and cognitive impairment after COVID-19 are needed. Also, it is not clear whether the two are distinct sequelae of COVID-19 or part of the same syndrome.'' Methods: In this prospective multicentre study, frequency of post-COVID fatigue and cognitive impairment were assessed in n = 969 patients (535 [55%] female) ≥6 months after SARS-CoV-2 infection with the FACIT-Fatigue scale (cut-off ≤30) and Montreal Cognitive Assessment (≤25 mild, ≤17 moderate impairment) between November 15, 2020 and September 29, 2021 at University Medical Center Schleswig-Holstein, Campus Kiel and University Hospital Würzburg in Germany. 969 matched non-COVID controls were drawn from a pre-pandemic, randomised, Germany-wide population survey which also included the FACIT-Fatigue scale. Associated sociodemographic, comorbid, clinical, psychosocial factors and laboratory markers were identified with univariate and multivariable linear regression models. Findings: On average 9 months after infection, 19% of patients had clinically relevant fatigue, compared to 8% of matched non-COVID controls (p

Neuroptera is one of the smaller ingroups of Holometabola, the ingroup of Insecta characterised by “complete” metamorphosis. Neuroptera comprises about 6000 species in the modern fauna, but appears to have been more diverse in the past. While adults distantly resemble certain moths or damselflies, the larval forms of Neuroptera are mostly fierce predators with prominent venom-injecting stylets. The most well-known of these larvae are probably those of antlions. Antlions and their closer relatives (silky lacewings, split-footed lacewings, ribbon-winged lacewings, spoon-winged lacewings, and owlflies) form a distinct monophyletic ingroup of Neuroptera, Myrmeleontiformia, hence the antlion-like forms. The fossil record of antlion-like larvae dates back far into the Cretaceous; many forms are known by exceptionally wellpreserved specimens entrapped in amber. The oldest fossil record of a neuropteran larva (not an antlion-like form) comes from Lebanese amber. Interestingly, the supposedly oldest record of an antlion-like larva is preserved in rock and comes from the famous Lower Cretaceous Crato Formation. We re-evaluate this fossil based on high-resolution composite photography. Due to the non-availability of many key characters, standard procedures for identifying the specimen to a more narrow ingroup remains challenging. Therefore, we used a morphometric approach. A combination of non-metric multidimensional scaling (NMDS), parallel coordinate plots and discriminant function analysis indicates that the fossil is a representative of the group Ascalaphidae (owlflies) + Myrmeleontidae (antlions). We discuss implications of this result for the fossil record of neuropteran larvae. These include the rather derived morphology of the oldest fossil larva of Myrmeleontiformia in contrast to previous expectations. Furthermore, fossils from soil dwellers can not only be expected to be found in amber, but also as compression fossils.

Background. Pericardial tamponade is a known life-threatening condition rarely reported in COVID-19 but has not been reported following asymptomatic SARS-CoV-2 infection. Its pathomechanism is still elusive. Case Summary. We report the case of a 66-year-old man with progressive shortness of breath and leg swelling due to new-onset heart failure and pericardial tamponade following asymptomatic SARS-CoV-2 infection. Ultrasound-guided placement of a pericardial drainage led to significant improvement of symptoms and revealed an exudative effusion. Throughout the diagnostic process, we were confronted with a systemic inflammatory syndrome suspicion of an induced autoimmune condition. After steroid pulse therapy and oral anticoagulation for subclavian vein thrombosis, the patient was discharged and followed in our outpatient clinic. Discussion. Patients with asymptomatic SARS-CoV-2 infection are at risk for developing life-threatening complications. Induced autoimmune conditions could be a potential explanation for late-onset pericardial tamponade in this population. A multimodal imaging approach is crucial in the diagnosis and characterization of cardiac inflammation. An interdisciplinary approach is essential. Awareness of uncommon cardiac complications following a SARS-CoV-2 infection is crucial for the initial assessment and the appropriate treatment of these patients.

The Siphloplecton jaegeri species group is established here for three extinct species, namely for the earlier described Siphloplecton jaegeri Demoulin, 1968, and for two new species from Eocene Baltic amber, Siphloplecton landolti sp. nov. and Siphloplecton studemannae sp. nov. Based on the well-preserved specimens of these species, a diagnosis is provided for the newly established species group. Representatives of the S. jaegeri species group are characterized by the presence of large, medially contiguous eyes, stout pointed setae along the outer margin of the foretibia, three intercalaries in the cubital field of the forewing, and elongated penis lobes, which are apically triangular or rounded, medially contiguous, and with a V-shaped cleft apically. Further new specimens of the S. jaegeri species group are documented that cannot be attributed to species level due to their poor preservation. Finally, a key to male adults of fossil species of Siphloplecton is given.

Throughout the last years, gut-resident Foxp3+ regulatory T (Treg) cells have been associated with a growing number of tissue-specific functions in the intestine, comprising various aspects of gut immunity and physiology. Treg cells have pivotal roles in intestinal tolerance induction and host defense by actively controlling immune responses towards harmless dietary antigens and commensal microorganisms as well as towards invading pathogens. In addition to these immune-related roles, it has become increasingly clear that intestinal Treg cells also exert important non-immune functions in the gut, such as promoting local tissue repair and preserving the integrity of the epithelial barrier. Thereby, intestinal Treg cells critically contribute to the maintenance of tissue homeostasis. In order to account for this functional diversity, gut-resident Treg cells have specifically adapted to the intestinal tissue microenvironment. In this Review, we discuss the specialization of Treg cells in the intestine. We survey the different populations of gut-resident Treg cells focussing on their unique functions, phenotypes and distinct transcription factor dependencies.

Toxic shock syndrome (TSS) is a rare inflammatory response syndrome associated with an infection by toxigenic strains of Staphylococcus aureus or group A ?-haemolytic Streptococcus. We report a rare case of menstrual TSS associated with usage of a menstrual cup. The diagnosis was established through case definition criteria and supported by vaginal cultural growth of Staphylococcus aureus with evidence of TSS toxin 1 (TSST-1). The patient received prophylactic intravaginal clindamycin in an individual approach to reduce the risk of recurrence. No relapse was reported in the 12 months following discharge.

RORγt+ group 3 innate lymphoid cells (ILC3s) maintain intestinal homeostasis through secretion of type 3 cytokines such as interleukin (IL)−17 and IL-22. However, CCR6- ILC3s additionally co-express T-bet allowing for the acquisition of type 1 effector functions. While T-bet controls the type 1 programming of ILC3s, the molecular mechanisms governing T-bet are undefined. Here, we identify c-Maf as a crucial negative regulator of murine T-bet+ CCR6- ILC3s. Phenotypic and transcriptomic profiling of c-Maf-deficient CCR6- ILC3s revealed a hyper type 1 differentiation status, characterized by overexpression of ILC1/NK cell-related genes and downregulation of type 3 signature genes. On the molecular level, c-Maf directly restrained T-bet expression. Conversely, c-Maf expression was dependent on T-bet and regulated by IL-1β, IL-18 and Notch signals. Thus, we define c-Maf as a crucial cell-intrinsic brake in the type 1 effector acquisition which forms a negative feedback loop with T-bet to preserve the identity of CCR6- ILC3s.

In this study, the attachment of microcapsules on the membrane surface and its influence on the flow field for a cross-flow membrane setup are investigated. The microcapsules were placed on the top layer of the membrane. The overall purpose of this modification was the prevention of membrane biofouling. Therefore, in a first step, the influence of such a combination on the fluid flow was investigated using computational fluid dynamics (CFD). Here, different properties, which are discussed as indicators for biofouling in the literature, were considered. In parallel, different fixation strategies for the microcapsules were experimentally tested. Two different methods to add the microcapsules were identified and further investigated. In the first method, the microcapsules are glued to the membrane surface, whereas in the second method, the microcapsules are added during the membrane fabrication. The different membrane modifications were studied and compared using CFD. Therefore, virtual geometries mimicking the real ones were created. An idealized virtual geometry was added to the comparison. Results from the simulation were fed back to the experiments to optimize the combined membrane. For the presented setup, it is shown that the glued configuration provides a lower transmembrane pressure than the configuration where microcapsules are added during fabrication.

The essential role of the intestinal microbiota in the well-functioning of host immunity necessitates the investigation of species-specific impacts on this interplay. Aim of this study was to examine the ability of defined Gram-positive and Gram-negative intestinal commensal bacterial species, namely Escherichia coli and Lactobacillus johnsonii, respectively, to restore immune functions in mice that were immunosuppressed by antibiotics-induced microbiota depletion. Conventional mice were subjected to broad-spectrum antibiotic treatment for 8 weeks and perorally reassociated with E. coli, L. johnsonii or with a complex murine microbiota by fecal microbiota transplantation (FMT). Analyses at days (d) 7 and 28 revealed that immune cell populations in the small and large intestines, mesenteric lymph nodes and spleens of mice were decreased after antibiotic treatment but were completely or at least partially restored upon FMT or by recolonization with the respective bacterial species. Remarkably, L. johnsonii recolonization resulted in the highest CD4+ and CD8+ cell numbers in the small intestine and spleen, whereas neither of the commensal species could stably restore those cell populations in the colon until d28. Meanwhile less efficient than FMT, both species increased the frequencies of regulatory T cells and activated dendritic cells and completely restored intestinal memory/effector T cell populations at d28. Furthermore, recolonization with either single species maintained pro- and anti-inflammatory immune functions in parallel. However, FMT could most effectively recover the decreased frequencies of cytokine producing CD4+ lymphocytes in mucosal and systemic compartments. E. coli recolonization increased the production of cytokines such as TNF, IFN-γ, IL-17, and IL-22, particularly in the small intestine. Conversely, only L. johnsonii recolonization maintained colonic IL-10 production. In summary, FMT appears to be most efficient in the restoration of antibiotics-induced collateral damages to the immune system. However, defined intestinal commensals such as E. coli and L. johnsonii have the potential to restore individual functions of intestinal and systemic immunity. In conclusion, our data provide novel insights into the distinct role of individual commensal bacteria in maintaining immune functions during/following dysbiosis induced by antibiotic therapy thereby shaping host immunity and might thus open novel therapeutical avenues in conditions of perturbed microbiota composition.

There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus) in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and systemic innate as well as adaptive immunity, exerting beneficial anti-inflammatory effects in intestinal as well as systemic compartments. Hence, VSL#3 might be considered a therapeutic immunomodulatory tool following antibiotic therapy.

HIV/AIDS remains the second most common cause of death in low and middle-income countries (LMICs), and only 34% of eligible patients in Africa received antiretroviral therapy (ART) in 2013. This study investigated the impact of ART decentralization on patient enrollment and retention in rural Malawi. We reviewed electronic medical records of patients registered in the Neno District ART program from August 1, 2006, when ART first became available, through December 31, 2013. We used GPS data to calculate patient-level distance to care, and examined number of annual ART visits and one-year lost to follow-up (LTFU) in HIV care. The number of ART patients in Neno increased from 48 to 3,949 over the decentralization period. Mean travel distance decreased from 7.3 km when ART was only available at the district hospital to 4.7 km when ART was decentralized to 12 primary health facilities. For patients who transferred from centralized care to nearer health facilities, mean travel distance decreased from 9.5 km to 4.7 km. Following a transfer, the proportion of patients achieving the clinic's recommended ≥4 annual visits increased from 89% to 99%. In Cox proportional hazards regression, patients living ≥8 km from a health facility had a greater hazard of being LTFU compared to patients

Adequate termination of an immune response is as important as the induction of an appropriate response. CD46, a regulator of complement activity, promotes T cell activation and differentiation towards a regulatory Tr1 phenotype. This Tr1 differentiation pathway is defective in patients with MS, asthma and rheumatoid arthritis, underlying its importance in controlling T cell function and the need to understand its regulatory mechanisms. CD46 has two cytoplasmic tails, Cyt1 and Cyt2, derived from alternative splicing, which are co-expressed in all nucleated human cells. The regulation of their expression and precise functions in regulating human T cell activation has not been fully elucidated.Here, we first report the novel role of CD46 in terminating T cell activation. Second, we demonstrate that its functions as an activator and inhibitor of T cell responses are mediated through the temporal processing of its cytoplasmic tails. Cyt1 processing is required to turn T cell activation on, while processing of Cyt2 switches T cell activation off, as demonstrated by proliferation, CD25 expression and cytokine secretion. Both tails require processing by Presenilin/γSecretase (P/γS) to exert these functions. This was confirmed by expressing wild-type Cyt1 and Cyt2 tails and uncleavable mutant tails in primary T cells. The role of CD46 tails was also demonstrated with T cells expressing CD19 ectodomain-CD46 C-Terminal Fragment (CTF) fusions, which allowed specific triggering of each tail individually.We conclude that CD46 acts as a molecular rheostat to control human T cell activation through the regulation of processing of its cytoplasmic tails.