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Background Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects resulting in impaired neuromuscular transmission. Although effective treatments are available, CMS is probably underdiagnosed, and systematic clinico-genetic investigations are warranted. Methods We used a nationwide approach to collect Austrian patients with genetically confirmed CMS. We provide a clinical and molecular characterization of this cohort and aimed to ascertain the current frequency of CMS in Austria. Results Twenty-eight cases with genetically confirmed CMS were identified, corresponding to an overall prevalence of 3.1 per million (95% CI 2.0–4.3) in Austria. The most frequent genetic etiology was CHRNE (n = 13), accounting for 46.4% of the cohort. Within this subgroup, the variant c.1327del, p.(Glu443Lysfs*64) was detected in nine individuals. Moreover, causative variants were found in DOK7 (n = 4), RAPSN (n = 3), COLQ (n = 2), GMPPB (n = 2), CHAT (n = 1), COL13A1 (n = 1), MUSK (n = 1) and AGRN (n = 1). Clinical onset within the first year of life was reported in one half of the patients. Across all subtypes, the most common symptoms were ptosis (85.7%), lower limb (67.9%), upper limb (60.7%) and facial weakness (60.7%). The majority of patients (96.4%) received specific treatment, including acetylcholinesterase inhibitors in 20, adrenergic agonists in 11 and 3,4-diaminopyridine in nine patients. Conclusions Our study presents the first systematic characterization of individuals with CMS in Austria, providing prevalence estimates and genotype–phenotype correlations that may help to improve the diagnostic approach and patient management.

Ante la presencia del COVID-19, se identificó que en Paraguay la información de generación propia es escasa y en ocasiones, falsa; aun así, es diseminada por los medios de comunicación, a ello se suma que, en poblaciones rurales, la información sobre como el coronavirus afecta la salud es insuficiente y los comunicadores de estas zonas no están capacitados en la difusión de este tipo de noticias. La investigación se desarrolló en dos comunidades rurales y una comunidad indígena del distrito de Alto Vera, Itapúa, Paraguay. El objetivo principal fue elaborar un diagnóstico participativo para determinar la percepción de las comunidades de Poncho, Caraguata y Mberu Pirapo’i sobre la pandemia del COVID-19. Se aplicó una investigación con enfoque mixto, en lo cuantitativo se trabajó con un diseño no experimental, transaccional descriptivo, en lo cualitativo con grupos focales (personal de salud, líderes/referentes comunitarios y autoridades). Al concluir la investigación, se comprobó que la población accede a informaciones sobre el COVID-19 principalmente a través de medios radiales, seguido de la televisión y las redes sociales; sin embargo, no pueden confirmar si la información recibida a través de esta última es real o no. Además, se identificó una disminución en la implementación de medidas sanitarias en el área; la información obtenida es insumo necesario para establecer una estrategia comunicativa utilizando tecnologías existentes en la comunidad, a fin de permitir una comunicación fluida y real sobre la pandemia del COVID-19 a ser implementada en el área de estudio y con posibilidad de ser replicada.

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months.SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM).Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score.Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity.

ZusammenfassungSeit einiger Zeit stehen für die Behandlung der spinalen Muskelatrophie (SMA) Medikamente mit unterschiedlichen Wirkmechanismen zur Verfügung, die den Verlauf der Erkrankung erheblich beeinflussen können. Unbehandelt ist diese neuromuskuläre Erkrankung immer progredient und führt bei der schwersten Verlaufsform SMA Typ 1 meist innerhalb von 24 Monaten zum Tod. Der genetische Defekt liegt auf dem Survival-motor-neuron-1-Gen (SMN1-Gen). Dies führt zu einem Verlust von SMN1-Protein und damit zum Untergang von Motoneuronen. Bei allen Patienten liegt das SMN2-Gen, das nur etwa 10 % funktionstüchtiges Protein bilden kann, in unterschiedlicher Kopienanzahl vor und beeinflusst den klinischen Schweregrad der Erkrankung, wobei fließende Übergänge zwischen den einzelnen Typen zu beobachten sind. Das erste für die SMA zugelassene Medikament ist Spinraza®, ein Antisense-Oligonukleotid, das intrathekal verabreicht wird, das mRNA-Splicing verändert und so zu einer vermehrten Produktion von SMN2-Protein führt. Das zweite zugelassene Medikament ist Zolgensma®. Dabei handelt es sich um eine Genersatztherapie, bei der das SMN1-Gen mittels eines Virusvektors als Einmalinfusion in den Körper eingebracht wird, um dann funktionierendes SMN-Protein zu bilden. Kurz vor der Zulassung steht außerdem Risdiplam®, dies ist ein sogenanntes „small molecule“ und setzt wie Spinraza® am SMN2-Gen an. Der Vorteil besteht in der Möglichkeit der oralen Einnahme. In allen Studien zu diesen Medikamenten wurde gezeigt, dass ein möglichst früher, am besten präsymptomatischer Beginn die besten Ergebnisse in den motorischen Scores für die Patienten erbrachte. Ein Neugeborenen-Screening könnte die betroffenen Kinder noch vor Symptombeginn detektieren.

Transverse myelitis (TM) occurs isolated or within other acquired demyelinating syndromes (ADS) such as neuromyelitis optica spectrum disorders (NMOSD), multiple sclerosis (MS) or myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD).To describe and compare clinical and MRI features of children with ADS presenting with TM grouped according to antibody status and diagnosis of MS and NMOSD.Children with TM, radiological involvement of the myelon, MOG and aquaporin-4 antibody status were elegible.100 children were identified and divided into MOGAD (n=33), NMOSD (n=7), double seronegative TM (n=34), and MS (n=26). MOGAD children had mainly acute disseminated encephalomyelitis + TM/ longitudinally extensive TM (LETM) (42%) or isolated LETM (30%). In MOGAD, LETM was present in more than half of all children (55%) with predominant involvement of only the grey matter (73%). Leptomeningeal enhancement was highly predictive of MOGAD (16/30; p=0.003). In MS patients spinal MRI showed single (50%) or multiple short lesions (46%) with involvement of grey and white matter (68%). Double seronegative children presented with LETM (74%) and brain lesions were less frequent compared to the other groups (30%).Children with ADS presenting with TM reveal important radiological differences such as LETM with predominant involvement of spinal grey matter and leptomeningeal enhancement in MOGAD.

Background and ObjectiveThe spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody–associated disorder (MOGAD) comprises monophasic diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis (ON), and transverse myelitis and relapsing courses of these presentations. Persistently high MOG antibodies (MOG immunoglobulin G [IgG]) are found in patients with a relapsing disease course. Prognostic factors to determine the clinical course of children with a first MOGAD are still lacking. The objective of the study is to assess the clinical and laboratory prognostic parameters for a risk of relapse and the temporal dynamics of MOG‐IgG titers in children with MOGAD in correlation with clinical presentation and disease course.MethodsIn this prospective multicenter hospital-based study, children with a first demyelinating attack and complete data set comprising clinical and radiologic findings, MOG-IgG titer at onset, and clinical and serologic follow-up data were included. Serum samples were analyzed by live cell-based assay, and a titer level of ≥1:160 was classified as MOG-IgG–positive.ResultsOne hundred sixteen children (f:m = 57:59) with MOGAD were included and initially diagnosed with ADEM (n = 59), unilateral ON (n = 12), bilateral ON (n = 16), myelitis (n = 6), neuromyelitis optica spectrum disorder (n = 8) or encephalitis (n = 6). The median follow-up time was 3 years in monophasic and 5 years in relapsing patients. There was no significant association between disease course and MOG-IgG titers at onset, sex, age at presentation, or clinical phenotype. Seroconversion to MOG-IgG–negative within 2 years of the initial event showed a significant risk reduction for a relapsing disease course. Forty-two/one hundred sixteen patients (monophasic n = 26, relapsing n = 16) had serial MOG-IgG testing in years 1 and 2 after the initial event. In contrast to relapsing patients, monophasic patients showed a significant decrease of MOG-IgG titers during the first and second years, often with seroconversion to negative titers. During the follow-up, MOG-IgG titers were persistently higher in relapsing than in monophasic patients. Decrease in MOG-IgG of ≥3 dilution steps after the first and second years was shown to be associated with a decreased risk of relapses. In our cohort, no patient experienced a relapse after seroconversion to MOG-IgG–negative.DiscussionIn this study, patients with declining MOG-IgG titers, particularly those with seroconversion to MOG-IgG–negative, are shown to have a significantly reduced relapse risk.

Data de publicació electrònica: 23-03-2022 Background and purpose: The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the past 4 years, but treatment responses differ remarkably between individuals, and therapeutic decision-making remains challenging, underlining the persistent need for validated biomarkers. Methods: We applied untargeted proteomic analyses to determine biomarkers in cerebrospinal fluid (CSF) samples of SMA patients under treatment with nusinersen. Identified candidate proteins were validated in CSF samples of SMA patients by Western blot and enzyme-linked immunosorbent assay. Furthermore, levels of peripheral neurofilament heavy and light chain were determined. Results: Untargeted proteomic analysis of CSF samples of three SMA type 1 patients revealed the lysosomal protease cathepsin D as a candidate biomarker. Subsequent validation analysis in a larger cohort of 31 pediatric SMA patients (type 1, n = 12; type 2, n = 9; type 3, n = 6; presymptomatically treated, n = 4; age = 0-16 years) revealed a significant decline of cathepsin D levels in SMA patients aged ≥2 months at the start of treatment. Although evident in all older age categories, this decline was only significant in the group of patients who showed a positive motor response. Moreover, downregulation of cathepsin D was evident in muscle biopsies of SMA patients. Conclusions: We identified a decline of cathepsin D levels in CSF samples of SMA patients under nusinersen treatment that was more pronounced in the group of "treatment responders" than in "nonresponders." We believe that our results indicate a suitability of cathepsin D levels as a possible biomarker in SMA also in older patients, in combination with analysis of peripheral neurofilament light chain in adolescents or alone in adult patients. Funding: H.L. receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). This work was also supported by a grant of the French Muscular Dystrophy Association (AFM-Téléthon;#21466) to A.R. The work of B.W. is supported by the German Research Foundation (Wi945/17-1, SFB 1451 [project-ID 431549029–A01] and GRK1960 [project ID 233886668]), the European Research Council under the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 956185 (SMABEYOND), and the Center for Molecular Medicine Cologne (project No C18)

Resumen: Ante la presencia del COVID-19, se identificó que en Paraguay la información de generación propia es escasa y en ocasiones, falsa; aun así, es diseminada por los medios de comunicación, a ello se suma que, en poblaciones rurales, la información sobre como el coronavirus afecta la salud es insuficiente y los comunicadores de estas zonas no están capacitados en la difusión de este tipo de noticias. La investigación se desarrolló en dos comunidades rurales y una comunidad indígena del distrito de Alto Vera, Itapúa, Paraguay. El objetivo principal fue elaborar un diagnóstico participativo para determinar la percepción de las comunidades de Poncho, Caraguata y Mberu Pirapo’i sobre la pandemia del COVID-19. Se aplicó una investigación con enfoque mixto, en lo cuantitativo se trabajó con un diseño no experimental, transaccional descriptivo, en lo cualitativo con grupos focales (personal de salud, líderes/referentes comunitarios y autoridades). Al concluir la investigación, se comprobó que la población accede a informaciones sobre el COVID-19 principalmente a través de medios radiales, seguido de la televisión y las redes sociales; sin embargo, no pueden confirmar si la información recibida a través de esta última es real o no. Además, se identificó una disminución en la implementación de medidas sanitarias en el área; la información obtenida es insumo necesario para establecer una estrategia comunicativa utilizando tecnologías existentes en la comunidad, a fin de permitir una comunicación fluida y real sobre la pandemia del COVID-19 a ser implementada en el área de estudio y con posibilidad de ser replicada. Abstract: In view of the presence of COVID-19, it was identified that in Paraguay, selfgenerated information is scarce and sometimes false; even so, it is disseminated by the media, in addition to the fact that, in rural populations, information on how the coronavirus affects health is insufficient and communicators in these areas are not trained in the dissemination of this type of news. The research was carried out in two rural communities and one indigenous community in the district of Alto Vera, Itapúa, Paraguay. The main objective was to elaborate a participatory diagnosis to determine the perception of the communities of Poncho, Caraguata and Mberu Pirapo'i on the COVID-19 pandemic. A mixed approach research was applied: a non-experimental, transactional-descriptive design was used for the quantitative part, and a focus group (health personnel, community leaders/referents and authorities) for the qualitative part. At the conclusion of the research, it was found that the population accesses information on COVID-19 mainly through radio media, followed by television and social networks; however, they cannot confirm whether the information received through the latter is real or not. In addition, a decrease in the implementation of sanitary measures in the area was identified; the information obtained is necessary input to establish a communication strategy using existing technologies in the community, in order to allow a fluid and real communication about the COVID-19 pandemic to be implemented in the study area and with the possibility of being replicated.

Resumen: Cada año la Reserva para Parque Nacional San Rafael (RPNSR) se ve afectada por incendios forestales que ocasionan daños a extensas superficies tanto de bosques como pastizales naturales y otros componentes de la biodiversidad. Esto puede resultar en un inconveniente si no se toman las medidas correspondientes en la gestión de estos fenómenos. Por ello, el objetivo principal fue analizar la dinámica de los incendios forestales en la RPNSR, mediante un análisis multitemporal en el periodo 2007-2017, con el registro detallado de los focos de calor captados por el sensor MODIS y análisis con sistemas de información geográfica. Comparación y análisis con los datos de precipitaciones mensuales. Los mismos dieron como resultado que indistintamente del régimen pluviométrico dado a lo largo del periodo de análisis, se registraron ocurrencia de incendios. Con relación a la cantidad de focos de calor registrados mensualmente, los meses de mayor registro de focos de calor van de junio a noviembre, siendo los meses de julio y agosto los que más repetidamente presentan los picos más elevados. En base a estos resultados y analizando los antecedentes de acciones en gestión de incendios forestales, ya emprendidas por organizaciones e instituciones en la RPNSR, se propuso un Plan de Prevención y Control de Incendios Forestales con los puntos más resaltantes. Abstract: Every year the San Rafael National Park Reserve (RPNSR) is affected by forest fires that cause damage to extensive areas of both forests and natural grasslands and other components of biodiversity. This can result in an inconvenience if the corresponding measures are not taken in the management of these phenomena. Therefore, the main objective was to analyze the dynamics of forest fires in the RPNSR, through a multi-temporal analysis in the period 2007-2017, with the detailed recording of heat sources captured by the MODIS sensor and analysis with geographic information systems. Comparison and analysis with monthly rainfall data. The same ones gave as result that indistinctly of the pluviometric regime given throughout the period of analysis, fires were registered. In relation to the amount of heat sources registered monthly, the months of greater registry of heat sources go from June to November, being the months of July and August those that more repeatedly present the highest peaks. Based on these results and analyzing the history of actions in forest fire management already undertaken by organizations and institutions in the RPNSR, a Forest Fire Prevention and Control Plan was proposed with the most important points.

International audience; The ALF transcription factor paralogs, AFF1, AFF2, AFF3, and AFF4, are components of the transcriptional super elongation complex that regulates expression of genes involved in neurogenesis and development. We describe an autosomal dominant disorder associated with de novo missense variants in the degron of AFF3, a nine amino acid sequence important for its binding to ubiquitin ligase, or with de novo deletions of this region. The sixteen affected individuals we identified, along with two previously reported individuals, present with a recognizable pattern of anomalies, which we named KINSSHIP syndrome (KI for horseshoe kidney, NS for Nievergelt/Savarirayan type of mesomelic dysplasia, S for seizures, H for hypertrichosis, I for intellectual disability, and P for pulmonary involvement), partially overlapping the AFF4-associated CHOPS syndrome. Whereas homozygous Aff3 knockout mice display skeletal anomalies, kidney defects, brain malformations, and neurological anomalies, knockin animals modeling one of the microdeletions and the most common of the missense variants identified in affected individuals presented with lower mesomelic limb deformities like KINSSHIP-affected individuals and early lethality, respectively. Overexpression of AFF3 in zebrafish resulted in body axis anomalies, providing some support for the pathological effect of increased amount of AFF3. The only partial phenotypic overlap of AFF3-and AFF4-associated syndromes and the previously published transcriptome analyses of ALF transcription factors suggest that these factors are not redundant and each contributes uniquely to proper development.

Additional file 4: Supplementary Figure 4. Influence of age at LP on CSF parameters as detected by a pooled linear regression analysis of data from the pediatric and the adult cohort (r2=0.089 for CSF TP, p

Additional file 5: Supplementary Table 1. CSF findings during acute attacks and during remission in the ‘acute MY’ subgroup, the ‘acute ON’ subgroup and the ‘acute BRAIN’ subgroup (stratified results from Table 10).

Additional file 8: Supplementary Table 4. CSF findings in MOG-IgG-positive acute bilateral ON and in MOG-IgG-positive acute unilateral ON.

Additional file 2: Supplementary Figure 2. No marked differences in serum IgG, IgM, IgA and albumin levels between the ‘acute MY’, the ‘acute ON’ and the ‘acute BRAIN’ (B) subgroup, except for slightly higher median IgM values in the ‘acute BRAIN’ subgroup as compared to the acute ‘ON’ subgroup.

Additional file 1: Supplementary Figure 1. CSF white cell counts in the ‘acute MY subgroup’, the ‘acute BRAIN subgroup' and the ‘acute ON subgroup’.

Additional file 3: Supplementary Figure 3. Regression analysis of QAlb and CSF total protein, demonstrating a close relationship between the two parameters (r2=0.75, p

Additional file 7: Supplementary Table 3. CSF findings in MOG-IgG-positive acute longitudinally extensive transverse myelitis (LETM) and MOG-IgG-positive non-longitudinally extensive transverse myelitis (NETM).

Interspecific variation in life‐history traits and physiological limits can be linked to the environmental conditions species experience, including climatic conditions. As alpine environments are particularly vulnerable under climate change, we focus on the montane‐alpine fly Drosophila nigrosparsa. Here, we characterized some of its life‐history traits and physiological limits and compared these with those of other drosophilids, namely Drosophila hydei, Drosophila melanogaster, and Drosophila obscura. We assayed oviposition rate, longevity, productivity, development time, larval competitiveness, starvation resistance, and heat and cold tolerance. Compared with the other species assayed, D. nigrosparsa is less fecund, relatively long‐living, starvation susceptible, cold adapted, and surprisingly well heat adapted. These life‐history characteristics provide insights into invertebrate adaptations to alpine conditions which may evolve under ongoing climate change.

Background New-generation, cell-based assays have demonstrated a robust association of serum autoantibodies to full-length human myelin oligodendrocyte glycoprotein (MOG-IgG) with (mostly recurrent) optic neuritis, myelitis, and brainstem encephalitis, as well as with neuromyelitis optica (NMO)-like or acute-disseminated encephalomyelitis (ADEM)-like presentations. However, only limited data are yet available on cerebrospinal fluid (CSF) findings in MOG-IgG-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD). Objective To describe systematically the CSF profile in children with MOG-EM. Material and methods Cytological and biochemical findings (including white cell counts [WCC] and differentiation; frequency and patterns of oligoclonal bands; IgG/IgM/IgA and albumin concentrations and CSF/serum ratios; intrathecal IgG/IgM/IgA fractions; locally produced IgG/IgM/IgA concentrations; immunoglobulin class patterns; IgG/IgA/IgM reibergrams; Link index; measles/rubella/zoster [MRZ] reaction; other anti-viral and anti-bacterial antibody indices; CSF total protein; CSF l-lactate) from 108 lumbar punctures in 80 pediatric patients of mainly Caucasian descent with MOG-EM were analyzed retrospectively. Results Most strikingly, CSF-restricted oligoclonal IgG bands, a hallmark of multiple sclerosis (MS), were absent in 89% of samples (N = 96), and the MRZ reaction, the most specific laboratory marker of MS known so far, in 100% (N = 29). If present at all, intrathecal IgG synthesis was low, often transient and mostly restricted to acute attacks. Intrathecal IgM synthesis was present in 21% and exclusively detectable during acute attacks. CSF WCC were elevated in 54% of samples (median 40 cells/μl; range 6–256; mostly lymphocytes and monocytes; > 100/μl in 11%). Neutrophils were present in 71% of samples; eosinophils, activated lymphocytes, and plasma cells were seen only rarely (all N = 79) and at least once in 48% of all patients (N = 67) tested. CSF alterations were significantly more frequent and/or more pronounced in patients with acute spinal cord or brain disease than in patients with acute ON and varied strongly depending on attack severity. CSF l-lactate levels correlated significantly with the spinal cord lesions load (measured in vertebral segments) in patients with acute myelitis (p = 0.0099). An analysis of pooled data from the pediatric and the adult cohort showed a significant relationship of QAlb (p < 0.0005), CST TP (p < 0.0001), and CSF l-lactate (p < 0.0003) during acute attacks with age. Conclusion MOG-IgG-associated EM in children is characterized by CSF features that are distinct from those in MS. With regard to most parameters, no marked differences between the pediatric cohort and the adult cohort analyzed in Part 1 were noted. Our findings are important for the differential diagnosis of pediatric MS and MOG-EM and add to the understanding of the immunopathogenesis of this newly described autoimmune disease.

Antibodies against the myelin oligodendrocyte glycoprotein (MOG-Ab) can be detected in various pediatric acquired demyelinating syndromes (ADS). Here, we analyze the spectrum of neuroradiologic findings in children with MOG-Ab and a first demyelinating event. The cerebral and spinal MRI of 69 children with different ADS was assessed in regard to the distribution and characteristics of lesions. Children with acute disseminated encephalomyelitis (n = 36) or neuromyelitis optica spectrum disorder (n = 5) presented an imaging pattern characterized predominantly by poorly demarcated lesions with a wide supra- and infratentorial distribution. Younger children also tended to have poorly defined and widespread lesions. The majority of patients with an isolated optic neuritis (n = 16) only presented small non-specific brain lesions or none at all. A longitudinally extensive transverse myelitis mainly affecting the cervical, and less often so the thoracic, lumbar, and conus regions, was detected in 31 children. The three children of our cohort who were then finally diagnosed with multiple sclerosis had at onset already demarcated white matter lesions as well as transverse myelitis. In conclusion, children with MOG seropositive ADS present disparate, yet characteristic imaging patterns. These patterns have been seen to correlate to the disease entity as well as to age of symptom onset.

Objective:To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS).Methods:Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study.Results:Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG-ab cutoff titer ≥1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%.Conclusions:Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course.

Purpose: To compare therapy-induced reading and distance visual acuity (dVA) increases in neovascular age-related macular degeneration (nAMD) and uveitis-associated cystoid macular edema. Methods: This longitudinal study included 68 treatment-naive eyes: 39 subfoveal nAMD eyes with disrupted photoreceptor layers treated with monthly ranibizumab and 29 uveitis-associated cystoid macular edema eyes with intact photoreceptor layer treated with 1 triamcinolone injection. Patients were examined with high-definition optical coherence tomography, Early Treatment Diabetic Retinopathy Study dVA (logarithm of the minimum angle of resolution), reading acuity (logRADscore), and maximum reading speed (words per minute) over 3 months of therapy. Results: In uveitis-associated cystoid macular edema, logarithm of the minimum angle of resolution and logRADscore improved 1 day post treatment, from 0.49 ± 0.28 to 0.39 ± 0.3 (P = 0.018) and 0.71 ± 0.53 to 0.56 ± 0.49 (P = 0.012), respectively. In nAMD, logarithm of the minimum angle of resolution improved 1 week after anti–vascular endothelial growth factor therapy from 0.59 ± 0.29 to 0.49 ± 0.24 (P = 0.002), with no change in logRADscore. One month after treatment, logRADscore improved from 1.09 ± 0.65 to 0.90 ± 0.60 (P = 0.002). In uveitis-associated cystoid macular edema, the recovery course of reading and dVA was comparable, and in nAMD, reading acuity recovery was delayed. Irrespective of disease, a small reduction in dVA resulted in a larger reading acuity decrease. Conclusion: Cystoid macular edema resolution was associated with rapid synchronous reading and dVA improvement, whereas nAMD was followed by faster recovery of distance than reading acuity. In both conditions, reading acuity expressed by critical angular resolution was more suppressed by active disease and recovered relatively more than distance acuity. These discrepancies indicate that reading acuity might be a more sensitive measure for vision decrease in macular diseases than dVA. Reading acuity seems to be an important adjunct assessing intravitreal therapy efficacy.

In trophic studies on piscivorous birds, it is vital to know which kind of dietary sample provides the information of interest and how the prey can be identified reliably and efficiently. Often, noninvasively obtained dietary samples such as regurgitated pellets, feces, and regurgitated fish samples are the preferred source of information. Fish prey has usually been identified via morphological analysis of undigested hard parts, but molecular approaches are being increasingly used for this purpose. What remains unknown, however, is which dietary sample type is best suited for molecular diet analysis and how the molecular results compare to those obtained by morphological analysis. Pellets, feces, and regurgitated fish samples of Great Cormorants (Phalacrocorax carbo sinensis) were examined for prey using both morphological hard part analysis and molecular prey identification. The sample types and methods were compared regarding number of species detected (overall and per sample) as well as the prey species composition and its variability among individual samples. Via molecular analysis, significantly higher numbers of prey species were detected in pellets, feces, and fish samples. Of the three sample types, pellets contained the most comprehensive trophic information and could be obtained with the lowest sampling effort. Contrastingly, dietary information obtained from feces was least informative and most variable. For all sample types, the molecular approach outperformed morphological hard part identification regarding the detectable prey spectrum and prey species composition. We recommend the use of pellets in combination with molecular prey identification to study the diet of piscivorous birds.

Purpose: Quantification of short-term progression of active neovascular age-related macular degeneration and correlation with 1-year outcome. Methods: Sixty-five patients with newly diagnosed treatment-naive active subfoveal choroidal neovascularization (CNV), who had participated in clinical trials testing anti-vascular endothelial growth factor therapy, were retrospectively assessed. Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), Spectral Domain Optical Coherence Tomography (SD-OCT) and fluorescein angiography (FA) were performed twice during the pretreatment period. Changes in BCVA, central retinal thickness (CRT), average macular thickness (AMT) and leakage area were documented within this pretreatment period for all patients and for lesion type I (occult CNV, n = 42) and type II (classic CNV, n = 23). Three-month and 1-year BCVA were then correlated with the pretreatment period. Results: The pretreatment period was 19 ± 3 days (range: 2–108). Neither type I nor type II lesions showed a significant BCVA decrease or CRT/AMT increase during this period. On FA, mean leakage area increased significantly during the pretreatment period: in the pooled group from 5.50 ± 0.62 (screening) to 7.60 ± 0.86 mm2 (baseline) (p

We give another proof for the (-1)-enumeration of self-complementary plane partitions with at least one odd side-length by specializing a certain Schur function identity. The proof is analogous to Stanley's proof for the ordinary enumeration. In addition, we obtain enumerations of 180^o-symmetric rhombus tilings of hexagons with a barrier of arbitrary length along the central line.

Mit der Markteinfuhrung des neuen BMW-Sechszylinder-Reihenmotors im Jahr 2004 wurde ein Meilenstein hinsichtlich „effizienter Dynamik“ geschaffen. Einen entscheidenden Beitrag hierzu lieferte die Valvetronic, die einer unfassenden Weiterentwicklung unterzogen wurde. Neben Mechanik und Grundkonstruktion wurden die elektronischen Komponenten, die steuerungstechnischen Elemente und das Brennverfahren grundlegend uberarbeitet. Ein fachubergreifender Systemansatz stand im Mittelpunkt dieser hier vorgestellten Innovation.

Background Myelin oligodendrocyte glycoprotein (MOG) antibodies have been recently described in children with acute disseminating encephalomyelitis (ADEM), but the clinical and neuroradiological characterisation of this subgroup is lacking. Objective To compare the clinical and neuroradiological features of paediatric ADEM with and without MOG antibodies. Methods Clinical course, cerebrospinal fluid (CSF)-, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed. Results MOG antibodies (median 1:2560; range 1:160–1:20 480) were detected in 19 children with ADEM. The majority of children showed a decline of serum MOG-IgG titres over time. Children with MOG antibodies did not differ in their age at presentation, sex ratio, the presence of oligoclonal bands, clinical symptoms or initial severity, apart from a higher CSF cell count (p=0.038), compared with children without MOG antibodies. In addition, further relapsing demyelinating episodes associated with MOG antibodies were observed only in children with MOG antibodies. All 19 children with MOG antibodies had a uniform MRI pattern, characterised by large, hazy and bilateral lesions and the absence of atypical MRI features (eg, mainly small lesions, well-defined lesions), which was significantly different compared to that of children without MOG antibodies (p=0.003; and p=0.032, respectively). In addition, children with MOG antibodies had involvement of more anatomical areas (p=0.035) including the myelon characterised by a longitudinally extensive transverse myelitis (p=0.003), more often a complete resolution of lesions (p=0.036) and a better outcome (p=0.038). Conclusions Patients with ADEM with MOG antibodies in our cohort had a uniform MRI characterised by large, bilateral and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favourable clinical outcome in contrast to children lacking MOG antibodies.

We deal with unweighted and weighted enumerations of lozenge tilings of a hexagon with side lengths $a,b+m,c,a+m,b,c+m$, where an equilateral triangle of side length $m$ has been removed from the center. We give closed formulas for the plain enumeration and for a certain $(-1)$-enumeration of these lozenge tilings. In the case that $a=b=c$, we also provide closed formulas for certain weighted enumerations of those lozenge tilings that are cyclically symmetric. For $m=0$, the latter formulas specialize to statements about weighted enumerations of cyclically symmetric plane partitions. One such specialization gives a proof of a conjecture of Stembridge on a certain weighted count of cyclically symmetric plane partitions. The tools employed in our proofs are nonstandard applications of the theory of nonintersecting lattice paths and determinant evaluations. In particular, we evaluate the determinants $\det_{0\le i,j\le n-1}\big(\om \delta_{ij}+\binom {m+i+j}j\big)$, where $\om$ is any 6th root of unity. These determinant evaluations are variations of a famous result due to Andrews (Invent. Math. 53 (1979), 193--225), which corresponds to $\om=1$., Comment: 57 pages, AmS-LaTeX, uses TeXDraw

Objective: The aim of the study was to investigate whether there is a difference between body fat mass percentage measured by BIA and DXA method. Design: Transversal study, randomized. Setting: Lipid and Obesity Outpatient Clinic, Department of Pediatrics, University of Vienna, Austria. Subjects: Twenty-seven children and adolescents from the Lipid and Obesity Outpatient Clinic, Department of Pediatrics, University of Vienna, were included in the study (14 boys and 13 girls between 6 and 18 y; mean age 12.6 and 13.1 y). Methods: The body fat percentage was measured with BIA (bioelectrical impedance analyzer BIA 2000-M) and DXA (dual energy X-ray absorptiometry) methods on the same day. Results: The mean difference between the body fat mass percentage measured by BIA and DXA was 4.48 with a standard deviation of 2.93. The results measured by BIA were almost always lower than that by DXA by about 12%. The lower and upper limit of the difference in 95% confidence interval was −5.64 and −3.32. By paired t-test, these results were significantly different (P

When high voltage is applied to distilled water filled in two glass beakers which are in contact, a stable water connection forms spontaneously, giving the impression of a floating water bridge. A detailed experimental analysis reveals static and dynamic structures as well as heat and mass transfer through this bridge.

Facial nerve paralysis is a common disease in children. Most of the patients show complete recovery. This single-center cohort study exclusively included pediatric patients to investigate the outcome of all patients with facial nerve palsy.Hospital records of all the patients admitted to the Children's Hospital in Linz between January 2005 and December 2010 with facial nerve paralysis were reviewed. Patients with peripheral facial nerve palsy were invited for clinical reevaluation between July 2011 and October 2011. The House-Brackmann score was used for reassessment.Fifty-six patients agreed to return for an additional clinical reevaluation. Study participants were divided in two groups according to their House-Brackmann scores: group 1 (n = 44), with a score2 were considered good outcomes, and group 2 (n = 12), with a score ≥ 2 showed persistent mild to moderate dysfunction of the facial nerve and were considered moderate outcomes. The most important finding was the difference of the reported time to remission (P = 0.003) between the groups.The results of this study indicate that facial paralysis in children is not as benign as supposed. It is suggested that patients and their guardians be informed that a slight face asymmetry may persist, but functional recovery in general is excellent.

We prove a product formula for the remaining cases of the weighted enumeration of self–complementary plane partitions contained in a given box where adding one half of an orbit of cubes and removing the other half of the orbit changes the sign of the weight. We use nonintersecting lattice path families to express this enumeration as a Pfaffian which can be expressed in terms of the known ordinary enumeration of self–complementary plane partitions.

We compute 2-enumerations of certain halved alternating sign matrices. In one case the enumeration equals the number of perfect matchings of a halved Aztec diamond. In the other case the enumeration equals the number of perfect matchings of a halved fortress graph. Our results prove three conjectures by Jim Propp., Comment: 11 pages, AmS-LaTeX, uses TeXDraw

We compute the weighted enumeration of plane partitions contained in a given box with complementation symmetry where adding one half of an orbit of cubes and removing the other half of the orbit changes the weight by -1 as proposed by Kuperberg. We use nonintersecting lattice path families to accomplish this for transpose-complementary, cyclically symmetric transpose-complementary and totally symmetric self-complementary plane partitions. For symmetric transpose-complementary and self-complementary plane partitions we get partial results. We also describe Kuperberg's proof for the case of cyclically symmetric self-complementary plane partitions., Comment: 41 pages, AmS-LaTeX, uses TeXDraw; reference added

We prove a partition identity conjectured by Lassalle (Adv. in Appl. Math. 21 (1998), 457-472)., Comment: 3 pages, AMS-LaTeX

We compute the number of rhombus tilings of a hexagon with sides n, n, N, n, n, N, where two triangles on the symmetry axis touching in one vertex are removed. The case of the common vertex being the center of the hexagon solves a problem posed by Propp., Comment: 16 pages, AmS-LaTeX, uses TeXDraw

We compute the number of rhombus tilings of a hexagon with sides $a+2,b+2,c+2,a+2,b+2,c+2$ with three fixed tiles touching the border. The particular case $a=b=c$ solves a problem posed by Propp. Our result can also be viewed as the enumeration of plane partitions having $a+2$ rows and $b+2$ columns, with largest entry $\le c+2$, with a given number of entries $c+2$ in the first row, a given number of entries 0 in the last column and a given bottom-left entry., Comment: 7 pages, AmS-LaTeX, uses TeXDraw; revised version which is to appear in J. Combin. Theory Ser. A