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This paper describes and discusses findings gained in a teacher training reform project at the University of Hamburg in Germany. In a newly implemented structure, pre-service teachers partake in an integrated model of courses that prepare them to deal with multilingualism in the subject classroom. For the first four semesters of the new model, a complex evaluation tool was employed in a pre-post design to better understand student competence development, curricular components of the teaching degree and student beliefs about multilingualism. This paper sheds light on the professional beliefs that pre-service teachers have about linguistic diversity and multilingual learners. The overall results show generally positive beliefs about multilingual learners, multilingualism in schools, and language support for multilingual learners. Moreover, the data show that multilingual pre-service teachers have more positive beliefs, female participants have more positive beliefs, and that there is a significant interdependence between beliefs and relevant opportunities to learn. Comparing the pre-test and the post-test data using explorative factor analysis, it can be shown that students’ beliefs are far more structured and follow a clear five-dimensional pattern in the post test, whereas the pre-test data can be described as diffuse and unstructured.

Background In cystic fibrosis (CF) patients, the upper airways display the same ion channel defect as evident in the lungs, resulting in chronic inflammation and infection. Recognition of the sinonasal area as a site of first and persistent infection with pathogens, such as Pseudomonas aeruginosa , reinforces the “one-airway” hypothesis. Therefore, we assessed the effect of systemic antibiotics against pulmonary pathogens on sinonasal inflammation. Methods Nasal lavage fluid (NLF) from 17 CF patients was longitudinally collected prior to and during elective intravenous (i.v.) antibiotic treatment to reduce pathogen burden and resulting inflammation (median treatment time at time of analysis: 6 days). Samples were assessed microbiologically and cytologically. Cytokine and chemokine expression was measured by Cytometric Bead Array and ELISA (interleukin (IL)-1β, IL-6, IL-8, MPO, MMP9, RANTES and NE). Findings were compared with inflammatory markers from NLF obtained from 52 healthy controls. Results Initially, the total cell count of the NLF was significantly higher in CF patients than in controls. However after i.v. antibiotic treatment it decreased to a normal level. Compared with controls, detection frequencies and absolute concentrations of MPO, IL-8, IL-6 and IL-1β were also significantly higher in CF patients. The detection frequency of TNF was also higher. Furthermore, during i.v. therapy sinonasal concentrations of IL-6 decreased significantly ( P  = 0.0059), while RANTES and MMP9 levels decreased 10-fold and two-fold, respectively. PMN-Elastase, assessed for the first time in NFL, did not change during therapy. Conclusions Analysis of NLF inflammatory markers revealed considerable differences between controls and CF patients, with significant changes during systemic i.v. AB treatment within just 6 days. Thus, our data support further investigation into the collection of samples from the epithelial surface of the upper airways by nasal lavage as a potential diagnostic and research tool.

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.

Our knowledge about the underlying pathomechanisms of craniocervical junction abnormalities (CCJA) in dogs mostly derives from measurements based on tomographic imaging. These images are static and the positioning of the dogs’ head does not reflect the physiological in vivo position of the craniocervical junction (CCJ). Aberrant motion patterns and ranges of motion (ROM) in sound individuals of CCJA predisposed breeds may be a pathogenetic trigger. To further extend our limited knowledge of physiological motion of the CCJ, this prospective, comparative study investigates the in vivo motion patterns and ROM of the CCJ in walk and trot in sound Cavalier King Charles Spaniels and Chihuahuas. The Labrador retriever is used as a reference breed without predisposition for CCJA. This is the first detailed description of CCJ movement of trotting dogs. Biplanar fluoroscopy images, recorded in walking and trotting dogs, were matched to a virtual reconstruction of the skull and cranial cervical spine utilising Scientific Rotoscoping. Kinematic data reveal the same motion patterns among all breeds and gaits with individual temporal and spatial differences in each dog. A stride cycle-dependent lateral rotation of the cranial cervical spine and axial rotation of the atlantoaxial joint in trot in dogs is described for the first time. The ROM of the atlantoaxial and atlantooccipital joints in walk and trot were not statistically significantly greater in the CCJA-predisposed breeds CKCS and Chihuahua. ROM values of all translational and rotational degrees of freedom were larger in walk than trot, although this is only statistically significant for the atlantoaxial joint. Until proven otherwise, a more species-specific than breed-specific general motion pattern of the CCJ in walking and trotting, clinically sound dogs must be assumed. Species-specific anatomic properties of the CCJ seem to supersede breed-specific anatomical differences in clinically sound dogs.

According to previous research, borderline personality disorder (BPD) is associated with high cost-of-illness. However, there is still a shortage of cost-of-illness-studies assessing costs from a broad societal perspective, including direct and indirect costs. Further, there are considerable differences in the results among the existing studies. In the present study, 167 German men and women seeking specialized outpatient treatment for BPD were included. We assessed societal cost-of-illness bottom-up through structured face-to-face interviews and encompassed a wide range of cost components. All costs were calculated for the 2015 price level. Cost-of-illness amounted to € 31,130 per patient and year preceding disorder-specific outpatient treatment. € 17,044 (54.8%) were direct costs that were mostly related to hospital treatment. Indirect costs amounted to € 14,086 (45.2%). Within indirect costs, costs related to work disability were the most crucial cost driver. The present study underlines the tremendous economic burden of BPD. According to the present study, both the direct and indirect costs are of significant importance for the societal costs associated with BPD. Besides the need for more disorder-specific treatment facilities for men and women with BPD, we assume that education and employment are topics that should be specifically targeted and individually supported at an early stage of treatment.Trial Registration: German Clinical Trial Registration, DRKS00011534, Date of Registration: 11/01/2017, retrospectively registered.

A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease.

Background Grapevine trunk diseases (GTDs) such as Esca are among the most devastating threats to viticulture. Due to the lack of efficient preventive and curative treatments, Esca causes severe economic losses worldwide. Since symptoms do not develop consecutively, the true incidence of the disease in a vineyard is difficult to assess. Therefore, an annual monitoring is required. In this context, automatic detection of symptoms could be a great relief for winegrowers. Spectral sensors have proven to be successful in disease detection, allowing a non-destructive, objective, and fast data acquisition. The aim of this study is to evaluate the feasibility of the in-field detection of foliar Esca symptoms over three consecutive years using ground-based hyperspectral and airborne multispectral imaging. Results Hyperspectral disease detection models have been successfully developed using either original field data or manually annotated data. In a next step, these models were applied on plant scale. While the model using annotated data performed better during development, the model using original data showed higher classification accuracies when applied in practical work. Moreover, the transferability of disease detection models to unknown data was tested. Although the visible and near-infrared (VNIR) range showed promising results, the transfer of such models is challenging. Initial results indicate that external symptoms could be detected pre-symptomatically, but this needs further evaluation. Furthermore, an application specific multispectral approach was simulated by identifying the most important wavelengths for the differentiation tasks, which was then compared to real multispectral data. Even though the ground-based multispectral disease detection was successful, airborne detection remains difficult. Conclusions In this study, ground-based hyperspectral and airborne multispectral approaches for the detection of foliar Esca symptoms are presented. Both sensor systems seem to be suitable for the in-field detection of the disease, even though airborne data acquisition has to be further optimized. Our disease detection approaches could facilitate monitoring plant phenotypes in a vineyard.

Background Signal transduction via the Signal Transducer and Activator of Transcription 1 (STAT1) pathway is indispensable for mediating the intracellular effects of interferon-α (IFN-α), interferon-γ (IFN-γ) and other cytokines in the brain and, thereby, crucial for antiviral and antibacterial responses during potential life-threatening CNS infections. However, the role of STAT1 signaling beyond the known IFN-α and IFN-γ effects in immediate antimicrobial defense is highly context-dependent, and studies in the existing literature using STAT1-targeted mouse models under normal physiological conditions remain scarce. Methods Here, we characterized a STAT1 targeted-disruption mouse model in the absence of infectious stimuli by employing established behavioral testing paradigms and immunohistochemical stainings, as well as bulk hippocampal transcriptomic and proteomic analyses. Results While we found neither overt behavioral alterations nor immunohistochemical changes with respect to microglial phagocytosis or proliferation, significant alterations were detected in gene and protein expression profiles implicated in neuroinflammatory processes and neuroprotection. Conclusion In summary, this study highlights the complex and context-dependent role of STAT1-mediated signaling even in the absence of any detectable behavioral and neuropathological changes.

This manuscript presents practical recommendations for managing acute attacks and implementing preventive immunotherapies for neuromyelitis optica spectrum disorders (NMOSD), a rare autoimmune disease that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. The pillars of NMOSD therapy are attack treatment and attack prevention to minimize the accrual of neurological disability. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenicity. Recent advances in understanding NMOSD have led to the development of new therapies and the completion of randomized controlled trials. Four preventive immunotherapies have now been approved for AQP4-IgG-positive NMOSD in many regions of the world: eculizumab, ravulizumab - most recently-, inebilizumab, and satralizumab. These new drugs may potentially substitute rituximab and classical immunosuppressive therapies, which were as yet the mainstay of treatment for both, AQP4-IgG-positive and -negative NMOSD. Here, the Neuromyelitis Optica Study Group (NEMOS) provides an overview of the current state of knowledge on NMOSD treatments and offers statements and practical recommendations on the therapy management and use of all available immunotherapies for this disease. Unmet needs and AQP4-IgG-negative NMOSD are also discussed. The recommendations were developed using a Delphi-based consensus method among the core author group and at expert discussions at NEMOS meetings.

The Asian bush mosquito, Aedes japonicus japonicus (Theobald, 1901), a potential vector of several pathogens, has recently established in North America and Central Europe. In 2013, it was found on the Slovenian-Croatian border, and during the following years, it emerged in more and more counties of northwestern Croatia. Surveillance of Ae. j. japonicus and other invasive mosquito species was subsequently extended both spatially and temporally in Croatia and neighbouring Bosnia and Herzegovina and Serbia. Mosquito collections were conducted in 2017 and 2018, based on adult trapping through dry ice-baited CDC traps and BG-Lure-baited BG-Sentinel traps, larval sampling through dippers and nets, and ovitrapping. Aedes j. japonicus specimens from collected samples were subjected to population genetic analysis by comparing microsatellite signatures and nad4 DNA sequences between sampled locations and with data previously obtained from more western European distribution areas. Aedes j. japonicus immature stages were found at 19 sites in Croatia, two sites in Bosnia and Herzegovina and one site in Serbia. In Croatia, four new counties were found colonised, two in the east and two in the south of the previously known distribution area. A spread of 250 km could thus be documented within five years. The findings in Bosnia and Herzegovina and Serbia represent the first records of Ae. j. japonicus in these countries. Genetic analysis suggests at least two introduction events into the surveyed area. Among the locations analysed, Orahovica can be considered a genetic border. The individuals collected west of this point were found to be similar to samples previously collected in the border regions of Southeast Germany/Austria and Austria/Slovenia, while the specimens from more eastern Croatian localities, together with those from Bosnia and Herzegovina and Serbia, were genetically different and could not be assigned to a probable origin. Thus, introduction from Central Europe, possibly by vehicular traffic, into the study area is likely, but other origins, transportation routes and modes of entry appear to contribute. Further dispersal of Ae. j. japonicus to other parts of southeastern Europe is anticipated.