Clinical Features of Rapidly Progressive Alzheimer's Disease

Objective: To characterize clinical features, CSF biomarkers and genetic polymorphisms of patients suffering from a rapidly progressing subtype of Alzheimer's dementia (rpAD). Methods: Retrospective analyses of 32 neuropathologically confirmed cases differentially diagnosed as AD out of a group with rapidly progressive dementia. CSF biomarkers (14-3-3, tau, beta-amyloid 1-42) and genetic markers (PRNP codon 129, apolipoprotein E, ApoE, polymorphism) were determined. Results: Median survival was 26 months, age at onset 73 years. Biomarkers: mean beta-amyloid 1-42: 266 pg/ml, median tau: 491 pg/ml, 14-3-3 positive: 31%. Genetic polymorphisms showed a predominance of methionine homozygosity at PRNP codon 129 and a low frequency of ApoE4 (38%, no homozygous patients). Thirty-five symptoms were studied. Frequent symptoms were myoclonus (75%), disturbed gait (66%) and rigidity (50%). Discussion: rpAD is associated with a diversity of neurological signs even able to mimic Creutz feldt-Jakob disease. Biomarkers and genetic profile differ from those seen in classical AD. The findings on biomarkers, symptomatology and genetics may aid the differential diagnostic process. Copyright (C) 2010 S. Karger AG, Base

Strengthening participation through decentralisation: findings on local economic development in Kyrgyzstan

"Decentralisation and local government reform are important elements of many developing countries' efforts to improve state governance. Nonetheless, local governments often appear to be very limited in their ability to meet the high expectations associated with decentralisation and the introduction of local self-government. Kyrgyzstan in Central Asia is a typical example of a country where decentralisation efforts have been on the political agenda for more than a decade but actual results are less than satisfactory. While there is widespread agreement among experts about the diagnosis as such, so far little research has been done on the exact reasons for this situation and their effects on the Kyrgyz Republic's development potential. To address this question, this study analyses one particular aspect of decentralisation in the Kyrgyz Republic, namely its impact on popular participation in the design and implementation of local economic development policies. Proceeding from this analysis, the study derives conclusions and recommendations for the Kyrgyz government and other official bodies, local NGOs and international donors." (author's abstract

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Aims Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. Methods and results This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Conclusion Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT0047058

dolls/puppets like mensch – dolls/puppets as artificial beings. Part 1.1

Die dritte Ausgabe der Zeitschrift denkste: puppe / just a bit of: doll (de:do), ein multi-disziplinäres Online-Journal für Mensch-Puppen-Diskurse, erscheint als Doppelheft, dessen gemeinsamer Themenschwerpunkt lautet: puppen/dolls like mensch – puppen als künstliche meschen. Mit diesem Fokus wird ein Thema aufgegriffen, das Menschen seit der Antike berührt und bis heute ihren Verstand und ihre Imagination, ihre Bedürfnisse und ihre Gefühle in Unruhe versetzt. In Mythologien, literarischen Fiktionen und Narrativen für Erwachsene und Kinder, in Werken der bildenden Künste, im Film, in mechanisch-technischen Anwendungen und Utopien, in den performativen Künsten, in der (Spiel-)Pädagogik und in den verschiedenen Bereichen der Popkultur wirft das Motiv der Puppe mit seinen unterschiedlichsten Ausdrucksformen immer auch existenzielle Fragen auf: Wer und was ist der Mensch? Die Puppe als künstlicher Mensch ist in gewisser Weise wie mensch, ohne Mensch zu sein. Als von Menschen geschaffene Abbilder, Vorbilder, Nachahmungen und Entwürfe des Menschen spiegeln und bestätigen Puppen vorhandene Lebenswelten und loten gleichzeitig Potenziale und Abgründe des Mensch-Seins zwischen Utopie und Dystopie, zwischen Neugier und Hingabe, zwischen Horror und Glückseligkeit, zwischen Macht und Ohnmacht aus. Puppen/dolls like mensch – der doppelte Wortsinn betont die gegebene Ambiguität der Puppen und die spannenden, ihnen innewohnenden Ambivalenzen. Im ersten Teilband (1.1) wird den Spuren und Erscheinungsformen des Puppenmo-tivs und der Puppe(n) – als literarisches Narrativ, als künstlerisches Motiv, als materialisiertes Objekt – vor allem im Kontext von bildender Kunst, Literatur, Fotografie, Theater und Androiden-technologien nachgegangen. Im zweiten Teilband (1.2) werden zum einen kinderliterarische und (spiel-)didaktische Texte akzentuiert, zum anderen sind hier verschiedene mediale und popkulturelle Formate aus den Bereichen Computerspiel, Comic-Film-Adaptation, Film (unterschiedlicher Genres) und dem Figurentheater versammelt sowie Thematisierungen der Verknüpfung von materiellen Artefakten und literarischen Narrativen. Rezensionen in Form von Essays über literarische Puppen-Narrative, eine Foto-Ausstellung und ein Ballett runden beide Ausgaben ab. Die zeitliche Spanne reicht vom Mittelalter bis in die Gegenwart und Zukunft und zeigt einmal mehr, wie über das Narrativ der Puppe uralte Menschheitsfragen in Traditionslinien eingebunden werden und sie auf faszinierende Weisen fortschreiben.The third edition of the journal denkste: puppe / just a bit of: doll (de: do), a multidisciplinary online journal for human-doll discourses, is a double issue whose shared thematic focus is: puppen/dolls like mensch – dolls/puppets as artificial beings. With this focus, we take up a topic that has concerned mankind since ancient times and has always upset their 'minds' and 'hearts’, their needs and feelings. In mythologies, literary fictions and narratives for adults as well as for children, in works of the visual arts, in film, in mechanical-technical applications and utopias, in the performative arts, in (play-)pedagogy and in the various fields of pop culture, the motif of the doll with its various forms of expression always raises existential questions: Who is man, what is human? The doll as an artificial human being is in a certain way like mensch without being human. As man-made images, as models, imitations and designs of humans, dolls/puppets reflect and confirm existing worlds and at the same time sound out the potentials and abysses of being human between utopia and dystopia, between curiosity and devotion, between horror and bliss, between power and powerlessness. Dolls/puppets like mensch – the double meaning of these words emphasizes the given ambiguity of the dolls/puppets and the intriguing ambivalences inherent in them. In the first part of volume (1.1) the traces and manifestations of the doll motif and of doll(s) – as literary narrative, as artistic motif, as materialized object – will be explored primarily in the context of the fine arts, of literature, photography, theater and android technologies. In the second part of the volume (1.2), on the one hand, children's literature and (play)didactic texts are accentuated; on the other hand, various media and pop-cultural formats from the fields of computer games, comic-film adaptations, films (of different genres) and puppet theater performances are gathered here, as well as issues that link material artifacts and literary narratives. Reviews in the form of essays on literary doll narratives, a photo exhibition and a ballet round off both editions. The time span extends from the Middle Ages to the present and future and shows once again how age-old questions regarding mankind and humanity are integrated into traditional lines and are carried on continuously in fascinating ways

Brain-derived proteins in the CSF, do they correlate with brain pathology in CJD?

BACKGROUND: Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Aβ(1–42 )were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed. METHODS: CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients. RESULTS: We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrP(c)) and Aβ(1–42 )levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions. CONCLUSION: Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins

Implicit motor sequence learning and working memory performance changes across the adult life span

Although implicit motor sequence learning is rather well understood in young adults, effects of aging on this kind of learning are controversial. There is first evidence that working memory (WM) might play a role in implicit motor sequence learning in young adults as well as in adults above the age of 65. However the knowledge about the development of these processes across the adult life span is rather limited. As the average age of our population continues to rise, a better understanding of age-related changes in motor sequence learning and potentially mediating cognitive processes takes on increasing significance. Therefore, we investigated aging effects on implicit motor sequence learning and WM. Sixty adults (18-71 years) completed verbal and visuospatial n-back tasks and were trained on a serial reaction time task. Randomly varying trials served as control condition. To further assess consolidation indicated by off-line improvement and reduced susceptibility to interference, reaction times (RTs) were determined 1 h after initial learning. Young and older but not middle-aged adults showed motor sequence learning. Nine out of 20 older adults (compared to one young/one middle-aged) exhibited some evidence of sequence awareness. After 1 h, young and middle-aged adults showed off-line improvement. However, RT facilitation was not specific to sequence trials. Importantly, susceptibility to interference was reduced in young and older adults indicating the occurrence of consolidation. Although WM performance declined in older participants when load was high, it was not significantly related to sequence learning. The data reveal a decline in motor sequence learning in middle-aged but not in older adults. The use of explicit learning strategies in older adults might account for the latter result

The significance of brain oscillations in motor sequence learning: Insights from Parkinson's disease

Motor sequence learning plays a pivotal role in various everyday activities. Motor-cortical beta oscillations have been suggested to be involved in this type of learning. In Parkinson's disease (PD), oscillatory activity within cortico-basal-ganglia circuits is altered. Pathologically increased beta oscillations have received particular attention as they may be associated with motor symptoms such as akinesia. In the present magnetoencephalography (MEG) study, we investigated PD patients and healthy controls (HC) during implicit motor sequence learning with the aim to shed light on the relation between changes of cortical brain oscillations and motor learning in PD with a particular focus on beta power. To this end, 20 PD patients (ON medication) and 20 age- and sex-matched HC were trained on a serial reaction time task while neuromagnetic activity was recorded using a 306-channel whole-head MEG system. PD patients showed reduced motor sequence acquisition and were more susceptible to interference by random trials after training on the task as compared to HC. Behavioral differences were paralleled by changes at the neurophysiological level. Diminished sequence acquisition was paralleled by less training-related beta power suppression in motor-cortical areas in PD patients as compared to HC. In addition, PD patients exhibited reduced training-related theta activity in motor-cortical areas paralleling susceptibility to interference. The results support the hypothesis that the acquisition of a new motor sequence relies on suppression of motor-cortical beta oscillations, while motor-cortical theta activity might be related to stabilization of the learned sequence as indicated by reduced susceptibility to interference. Both processes appear to be impaired in PD. Keywords: Implicit motor learning, Oscillatory beta activity, SRTT, Interference, Magnetoencephalography (MEG), Motor contro

Pre-stimulus beta power modulation during motor sequence learning is reduced in 'Parkinson's disease

Beta oscillations within motor-cortical areas have been linked to sensorimotor function. In line with this, pathologically altered beta activity in cortico-basal ganglia pathways has been suggested to contribute to the pathophysiology of Parkinson's disease (PD), a neurodegenerative disorder primarily characterized by motor impairment. Although its precise function is still discussed, beta activity might subserve an anticipatory role in preparation of future actions. By reanalyzing previously published data, we aimed at investigating the role of pre-stimulus motor-cortical beta power modulation in motor sequence learning and its alteration in PD. 20 PD patients and 20 healthy controls (HC) performed a serial reaction time task (SRTT) in which reaction time gain presumably reflects the ability to anticipate subsequent sequence items. Randomly varying patterns served as control trials. Neuromagnetic activity was recorded using magnetoencephalography (MEG) and data was reanalyzed with respect to task stimuli onset. Assuming that pre-stimulus beta power modulation is functionally related to motor sequence learning, reaction time gain due to training on the SRTT should vary depending on the amount of beta power suppression prior to stimulus onset. We hypothesized to find less pre-stimulus beta power suppression in PD patients as compared to HC associated with reduced motor sequence learning in patients. Behavioral analyses revealed that PD patients exhibited smaller reaction time gain in sequence relative to random control trials than HC indicating reduced learning in PD. This finding was indeed paralleled by reduced pre-stimulus beta power suppression in PD patients. Further strengthening its functional relevance, the amount of pre-stimulus beta power suppression during sequence training significantly predicted subsequent reaction time advantage in sequence relative to random trials in patients. In conclusion, the present data provide first evidence for the contribution of pre-stimulus motor-cortical beta power suppression to motor sequence learning and support the hypothesis that beta oscillations may subserve an anticipatory, predictive function, possibly compromised in PD.ISSN:2213-158

Mobility Data Mining: from Technical to Ethical (Dagstuhl Seminar 22022)

This report documents the program and the outcomes of Dagstuhl Seminar 22022 "Mobility Data Analysis: from Technical to Ethical" that took place fully remote and hosted by Schloss Dagstuhl from 10-12 January 2022. An interdisciplinary team of 23 researchers from Europe, the Americas and Asia in the fields of computer science, ethics and mobility analysis discussed interactions between their topics and fields to bridge the gap between the more technical aspects to the ethics with the objective of laying the foundations of a new Mobility Data Ethics research field