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Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.
Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.
Methods/Design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.
Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.
Trial registered at: NCT01384006
Bücherschau
(2004)
he most basic behavioural states of animals can be described as active or passive. While high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which a combination of automatic radiotracking and machine learning is used to distinguish between active and passive behaviour in small vertebrates fitted with lightweight transmitters (<0.4 g).
We used a dataset containing >3 million signals from very-high-frequency (VHF) telemetry from two forest-dwelling bat species (Myotis bechsteinii [n = 52] and Nyctalus leisleri [n = 20]) to train and test a random forest model in assigning either active or passive behaviour to VHF-tagged individuals. The generalisability of the model was demonstrated by recording and classifying the behaviour of tagged birds and by simulating the effect of different activity levels with the help of humans carrying transmitters. The model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F1 0.96–0.98).
We provide an ecological case-study demonstrating the potential of this automated monitoring tool. We used the trained models to compare differences in the daily activity patterns of two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night-time activity of M. bechsteinii was relatively constant. These results show that subtle differences in the timing of species' activity can be distinguished using our method.
Our approach can classify VHF-signal patterns into fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radiotracking method, we provide the trained random forest models together with an R package that includes all necessary data processing functionalities. In combination with state-of-the-art open-source automated radiotracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
The most basic behavioural states of animals can be described as active or passive. However, while high-resolution observations of activity patterns can provide insights into the ecology of animal species, few methods are able to measure the activity of individuals of small taxa in their natural environment. We present a novel approach in which the automated VHF radio-tracking of small vertebrates fitted with lightweight transmitters (< 0.2 g) is used to distinguish between active and passive behavioural states.
A dataset containing > 3 million VHF signals was used to train and test a random forest model in the assignment of either active or passive behaviour to individuals from two forest-dwelling bat species (Myotis bechsteinii (n = 50) and Nyctalus leisleri (n = 20)). The applicability of the model to other taxonomic groups was demonstrated by recording and classifying the behaviour of a tagged bird and by simulating the effect of different types of vertebrate activity with the help of humans carrying transmitters. The random forest model successfully classified the activity states of bats as well as those of birds and humans, although the latter were not included in model training (F-score 0.96–0.98).
The utility of the model in tackling ecologically relevant questions was demonstrated in a study of the differences in the daily activity patterns of the two bat species. The analysis showed a pronounced bimodal activity distribution of N. leisleri over the course of the night while the night-time activity of M. bechsteinii was relatively constant. These results show that significant differences in the timing of species activity according to ecological preferences or seasonality can be distinguished using our method.
Our approach enables the assignment of VHF signal patterns to fundamental behavioural states with high precision and is applicable to different terrestrial and flying vertebrates. To encourage the broader use of our radio-tracking method, we provide the trained random forest models together with an R-package that includes all necessary data-processing functionalities. In combination with state-of-the-art open-source automated radio-tracking, this toolset can be used by the scientific community to investigate the activity patterns of small vertebrates with high temporal resolution, even in dense vegetation.
Wir untersuchen Zusammenhänge zwischen der Artenzusammensetzung, dem Artenreichtum und den Umweltbedingungen der Schwermetallrasen und Trockenrasen der Bottendorfer Hügel in Nord-Thüringen. In diesem Gebiet wachsen primäre und sekundäre Schwermetallrasen und verschiedene Trockenrasengesellschaften auf nicht-schwermetallhaltigen Böden mit einer artenreichen Xerothermrasen-Flora. Anhand von 206 Aufnahmen unterscheiden wir neun Pflanzengesellschaften aus sechs Verbänden der Klassen Koelerio-Corynephoretea (Sedo-Veronicion, Alysso-Sedion) und Festuco-Brometea (Festucion pallentis, Koelerio-Phleion, Festucion valesiacae, Cirsio-Brachypodion). Vier Trockenrasengesellschaften, in denen die Metallophyten Armeria maritima subsp. halleri und Minuartia verna subsp. hercynica häufig Vorkommen, werden als spezielle Subassoziationen (armerietosum halleri) von vier Assoziationen (Teucrio-Festucetum, Thymo-Festucetum, Filipendulo-Helictotrichetum, Adonido-Brachypodietum) neu beschrieben. In einer DCA mit angezeigten Umweltvektoren bilden die Gesellschaften klare Gruppen. Das Teucrio-Festucetum armerietosum und Thymo-Festucetum armerietosum sind in der DCA mit den Gehalten des Bodens an Kupfer und Blei sowie dem C/N-Verhältnis des Bodens eng korreliert, das Adonido-Brachypodietum teucrietosum und Festuco-Stipetum teucrietosum mit dem pH und Karbonatgehalt des Bodens. Der Artenreichtum an Gefäßpflanzen, Moosen und Flechten nimmt bis pH 7,5 zu und dann ab. Der Artenreichtum steigt mit dem Karbonatgehalt und der Leitfähigkeit des Bodens und nimmt mit dem C/N-Verhältnis des Bodens ab. Der Artenreichtum der Gefäßpflanzen nimmt mit dem Kupfergehalt des Bodens ab, während die Wahrscheinlichkeit des Vorkommens der Metallophyten mit dem Kupfer- und Zinkgehalt steigt. - Unsere Studie zeigt, dass Bodenfaktoren wie der pH und der Karbonatgehalt für die Zusammensetzung und den Artenreichtum der Vegetation auf kontaminierten Böden ebenso wichtig sind wie der Gehalt an Schwermetallen. Schwermetallrasen können daher Trockenrasen auf nicht-schwermetallhaltigen Böden floristisch sehr ähnlich sein.
Die Steppenrasen des NSG „Badraer Lehde–Großer Eller“ werden hier erstmalig beschrieben und analysiert. 156 Originalaufnahmen wurden über eine Clusteranalyse in sieben Assoziationen und zwei ranglose Gesellschaften innerhalb der Verbände Alysso-Sedion, Seslerio-Festucion pallentis, Festucion valesiacae, Xerobromion und Cirsio-Brachypodion gegliedert. Die Auswertung alter Luftbilder zeigt, dass die beiden ranglosen Gesellschaften junge Steppenrasen auf ehemaligen Ackerflächen darstellen, während die Assoziationen überwiegend alte Steppenrasen repräsentieren. Der erste floristische Gradient nach einer NMDS in der Vegetation wird durch Variablen erklärt, die die Temperatur und die Wasserversorgung der Standorte anzeigen. Der zweite floristische Gradient kann durch das Alter der Flächen erklärt werden. Alte Steppenrasen enthalten signifikant mehr gefährdete Pflanzenarten als junge Steppenrasen, während sich der Gesamtartenreichtum zwischen jungen und alten Beständen nicht signifikant unterscheidet. Ein CSR-Strategietypenspektrum zeigt in einer Gesellschaft auf ehemaligen Ackerflächen eine höhere Bedeutung der C-Strategie, sonst aber kaum Unterschiede zwischen den Syntaxa. Die beiden Xerobromion-Assoziationen sind besonders artenreich und enthalten überdurchschnittlich viele gefährdete Pflanzenarten. Eine Gesellschaft auf ehemaligen Ackerflächen enthält durchschnittlich viele und die andere fast keine gefährdeten Arten. Der Artenreichtum der Gefäßpflanzen ist am stärksten positiv mit der Bodengründigkeit, der Deckung der Krautschicht und dem Ellenberg-Zeigerwert für Bodenreaktion und negativ mit dem Zeigerwert für Temperatur korreliert. Unsere Studie zeigt die hohe Bedeutung des NSG für den Trockenrasenschutz. Diese beruht vor allem auf der allgemein hohen Artenvielfalt und Diversität an Gesellschaften sowie auf der sehr hohen Zahl gefährdeter Arten.
Reintroductions of plant species are increasingly popular in conservation practice. Steppe grasslands contain many rare and endangered plant species that are potential objects for such reintroductions. Most reintroduction projects, however, can only target a restricted number of species, which raises the question of how species should be prioritised. Here, we present a method to select priority species for reintroduction based on species' characteristics that are widely used in conservation practice. We first determined the local species pool containing those vascular plant species that occurred both in our target region (Thuringia, Germany) and target habitat (steppe grasslands), yielding 369 species. With the help of an a priori filter that selected currently endangered species with limited distribution, 136 potential target species were determined. These potential target species had experienced stronger decline, had a narrower phytosociological amplitude and were more likely to be species of the Festuco-Brometea class and the Festucetalia valesiacae order than non-target species. Potential target species were then ranked by a points system based on ten conservation-relevant characteristics of the species from the categories "threat and protection status", "distribution and decline", and "habitat affiliation". In the ranking, six steppe grassland plant species (Astragalus exscapus, Bothriochloa ischaemum, Prunella laciniata, Pulsatilla pratensis subsp. nigricans, Scorzonera purpurea, and Seseli hippomarathrum) achieved the highest scores. An additional seven species not specifically characteristic for steppe grasslands also scored highly. A post hoc evaluation of these 13 highest scoring species based on additional conservation criteria left five species (Astragalus exscapus, Linum leonii, Orchis morio, Pulsatilla pratensis subsp. nigricans and Scorzonera purpurea) as species with highest priority for reintroductions and another five species as highly suitable for reintroductions. Associations between the ranking order and different ranking criteria revealed that a species’ threat and rarity in Thuringia and its protection status had the highest representation in the ranking, followed by threat in Germany, regional decline and habitat affiliation. In contrast, international threat and responsibility of Thuringia for its conservation had only low representation in the ranking, probably because these characteristics applied to only a few species. The ranking list gives a selection of species for reintroductions, which combined with additional information based on comprehensive local and floristic knowledge, allows the identification of the species with the highest priority. Our method can be transferred to other regions or habitat types.