Methods for integrated simulation: 10 concepts to integrate

This note summarises the current status of the work of EUROSIMs ans ASIMs Technical Committees "Data Driven System Simulation" - with main emphasis on Big Data integration in simulation. This overview suggests ten developed concepts and methods which should be considered, implemented and documented in modern simulation studies with Big Data

Analysis of inflammatory markers and tau deposits in an autopsy series of nine patients with anti-IgLON5 disease

Anti-IgLON5 disease is a rare neurological, probably autoimmune, disorder associated in many cases with a specific tauopathy. Only a few post-mortem neuropathological studies have been reported so far. Little is known about the pathogenic mechanisms that result in neurodegeneration. We investigated the neuropathology of anti-IgLON5 disease and characterized cellular and humoral inflammation. We included nine cases (six of them previously published). Median age of patients was 71 years (53-82 years), the median disease duration was 6 years (0.5-13 years), and the female to male ratio was 5:4. Six cases with a median disease duration of 9 years presented a prominent tauopathy. Five of them had a classical anti-IgLON5-related brainstem tauopathy and another presented a prominent neuronal and glial 4-repeat tauopathy, consistent with progressive supranuclear palsy (PSP). Three cases with short disease duration (median 1.25 years) only showed a primary age-related neurofibrillary pathology. Inflammatory infiltrates of T and B cells were mild to moderate and did not significantly differ between anti-IgLON5 disease cases with or without tauopathy. In contrast, we found an extensive neuropil deposition of IgG4 in the tegmentum of the brainstem, olivary nucleus, and cerebellar cortex that was most prominent in two patients with short disease duration without the typical IgLON5-related tauopathy. The IgG4 deposits were particularly prominent in the cerebellar cortex and in these regions accompanied by mild IgG1 deposits. Activated complement deposition (C9neo) was absent. Our study indicates that IgLON5-related tau pathology occurs in later disease stages and may also present a PSP-phenotype with exclusively 4-repeat neuronal and glial tau pathology. The prominent deposition of anti-IgLON5 IgG4 at predilection sites for tau pathology suggests that anti-IgLON5 antibodies precede the tau pathology. Early start of immunotherapy might prevent irreversible neuronal damage and progression of the disease, at least in a subgroup of patients

Formalized classification of the class Montio-Cardaminetea in Europe : towards a consistent typology of spring vegetation

The class Montio-Cardaminetea includes vegetation of springs with constant water flow. These habitats, which function as islands for highly specialized and sensitive biota, are endangered by ongoing landscape and climatic changes. Although a harmonized classification into vegetation units is necessary for effective habitat conservation, there is currently no synthetic classification of the class Montio-Cardaminetea. Here a large set of vegetation-plot records was obtained from national and private databases. The aim was to validate the EuroVegChecklist classification scheme, search for additional ecologically meaningful vegetation types and develop an automatic system for classifying new plots from Europe. We formally defined the cores of eight of the ten EuroVegChecklist alliances: Caricion remotae, Cratoneurion commutati, Lycopodo europaei-Cratoneurion commutati, Epilobio nutantis-Montion, Koenigio- Microjuncion, Mniobryo-Epilobion hornemanii, Philonotidion seriatae (Cardamino-Montion) and Swertio perennis-Anisothecion squarrosi, which were also reproduced by unsupervised classifications. Both unsupervised and semi-supervised classifications further suggested two alliances not previously recognized in the EuroVegChecklist: Anthelion julaceae (liverwort- dominated subalpine to alpine springs in highly oceanic regions in Britain) and Cratoneuro filicini-Calthion laetae (mesotrophic herb-rich subalpine and alpine springs). The unsupervised classifications mainly reflected the base saturation gradient, distinguishing between calcareous and non-calcareous springs. Therefore, it is suggested the order Montio-Cardaminetalia, which is broadly delimited in the EuroVegChecklist, be divided into two separate orders and the following three orders should be distinguished within the class Montio-Cardaminetea: Cardamino-Chrysosplenietalia (non-calcareous forest springs; Caricion remotae), Cardamino-Cratoneuretalia (calcareous springs; Cratoneurion commutati, Lycopodo europaei-Cratoneurion commutati) and Montio-Cardaminetalia (non-calcareous non-forest springs; all other alliances)