ReSeqLIMS: Laborinformations- und Managementsystem für die Hochdurchsatz-Resequenzierung

Die molekulare Typisierung von Mikroorganismen ist zur Erkennung von Infektionsausbrüchen und langfristiger evolutionärer Trends von immenser Bedeutung. Neben laborseitigen Anforderungen für die Hochdurchsatz-Resequenzierung stehen leistungsfähige Laborinformations- und Managementsysteme (LIMS) im Fokus. Die Webanwendung ReSeqLIMS wurde in einer Drei-Schichten-Architektur implementiert. Die Präsentationsschicht wurde mit Hilfe von JavaServerFaces (JSF), die Logikschicht mittels Java programmiert. Hibernate als Middleware garantiert Datenbankunabhängigkeit. Die Funktionalität kann in Module differenziert werden. Das Kundenmodul umfasst u.a. das Anwender- und Rechnungsmanagement. Die Integration der Arbeitsschritte in einen qualitätsüberwachten Workflow erfolgt im Labormodul. Gerätespezifische Parameter werden im Gerätemodul verwaltet. Das ReSeqLIMS ermöglicht die Steuerung des Datenflusses während der Laborprozesse und stellt die Resequenzierungsdaten für Downstream-Analysen bereit

Effects of subthalamic nucleus deep brain stimulation on emotional working memory capacity and mood in patients with Parkinson's disease

Background: In Parkinson’s disease (PD), cognitive symptoms and mood changes may be even more distressing for the patient than motor symptoms. Objective: Our aim was to determine the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on working memory (WM) and mood. Methods: Sixteen patients with PD were assessed with STN-DBS switched on (DBS-ON) and with dopaminergic treatment (Med-ON) compared to switched off (DBS-OFF) and without dopaminergic treatment (Med-OFF). The primary outcome measures were a Visual Analog Mood Scale (VAMS) and an emotional 2-back WM task at 12 months after DBS in the optimal DBS-ON/Med-ON setting compared to DBS-OFF/Med-OFF. Results: Comparison of DBS-OFF/Med-OFF to DBS-ON/Med-ON revealed a significant increase in alertness (meanoff/off =51.59±24.54; meanon/on =72.75; P=0.016) and contentedness (meanoff/off =38.73±24.41; meanon/on =79.01±17.66; P=0.001, n=16), and a trend for reduction in sedation (P=0.060), which was related to stimulation as shown in a subgroup of seven patients. The N-back task revealed a significant increase in accuracy with DBS-ON/Med-ON compared to DBS-OFF/Med- OFF (82.0% vs 76.0%, respectively) (P=0.044), regardless of stimulus valence. Conclusion: In line with previous studies, we found that patients rated themselves subjectively as more alert, content, and less sedated during short- term DBS-ON. Accuracy in the WM task increased with the combination of DBS and medication, possibly related to higher alertness of the patients. Our results add to the currently mixed results described for DBS on WM and suggest that there are no deleterious DBS effects on this specific cognitive domain

Progression events defined by home-based assessment of motor function in multiple sclerosis: protocol of a prospective study

Background: This study relates to emerging concepts of appropriate trial designs to evaluate effects of intervention on the accumulation of irreversible disability in multiple sclerosis (MS). Major starting points of our study are the known limitations of current definitions of disability progression by rater-based clinical assessment and the high relevance of gait and balance dysfunctions in MS. The study aims to explore a novel definition of disease progression using repeated instrumental assessment of relevant motor functions performed by patients in their home setting. Methods: The study is a prospective single-center observational cohort study with the primary outcome acquired by participants themselves, a home-based assessment of motor functions based on an RGB-Depth (RGB-D) camera, a camera that provides both depth (D) and color (RGB) data. Participants are instructed to perform and record a set of simple motor tasks twice a day over a one-week period every 6 months. Assessments are complemented by a set of questionnaires. Annual research grade assessments are acquired at dedicated study visits and include clinical ratings as well as structural imaging (MRI and optical coherence tomography). In addition, clinical data from routine visits is provided semiannually by treating neurologists. The observation period is 24 months for the primary endpoint with an additional clinical assessment at 27 month to confirm progression defined by the Expanded Disability Status Scale (EDSS). Secondary analyses aim to explore the time course of changes in motor parameters and performance of the novel definition against different alternative definitions of progression in MS. The study was registered at Deutsches Register für Klinische Studien (DRKS00027042). Discussion: The study design presented here investigates disease progression defined by marker-less home-based assessment of motor functions against 3-month confirmed disease progression (3 m-CDP) defined by the EDSS. The technical approach was chosen due to previous experience in lab-based settings. The observation time per participant of 24, respectively, 27 months is commonly conceived as the lower limit needed to study disability progression. Defining a valid digital motor outcome for disease progression in MS may help to reduce observation times in clinical trials and add confidence to the detection of progression events in MS

Neuropsychological Features of Patients with Spinocerebellar Ataxia (SCA) Types 1, 2, 3, and 6

A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic and semantic memory, and motor coordination. Severity of ataxia was assessed with the Scale for the Assessment and Rating of Ataxia (SARA), nonataxia symptoms with the Inventory of Non-Ataxia Symptoms. Depressive symptoms were evaluated with the Beck Depression Inventory. The SARA scores of our SCA patients (range 1–19.5) indicated an overall moderate ataxia, most pronounced in SCA6 and SCA1. Mean number of nonataxia symptoms (range 0–2.2) were most distinct in SCA1 and nearly absent in SCA6. SCA1 performed poorer than controls in 33% of all cognitive test parameters, followed by SCA2, SCA3, and SCA6 patients (17%). SCA 1–3 patients presented mainly attentional and executive dysfunctions while semantic and episodic memory functions were preserved. Attentional and executive functions were partly correlated with ataxia severity and fine motor coordination. All patients exhibited mildly depressed mood. Motor and dominant hand functions were more predictive for depressed mood than cognitive measures or overall ataxia. Besides motor impairments in all patients, SCA patients with extracerebellar pathology (SCA 1–3) were characterized by poor frontal attentional and executive dysfunction while mild cognitive impairments in predominantly cerebellar SCA6 patients appeared to reflect mainly cerebellar dysfunction. Regarding the everyday relevance of symptoms, (dominant) motor hand functioning emerged as a marker for the patient’s mood

Scale for the assessment and rating of ataxia (SARA): Übersetzung und kulturelle Anpassung an den deutschsprachigen Raum

BACKGROUND/OBJECTIVE: The scale for the assessment and rating of ataxia (SARA) is a feasible assessment for the classification and evaluation of therapeutic interventions. In order to provide access to the SARA in German, the aim of this work was to translate the SARA into German and to adapt it according to international guidelines for German-speaking countries. METHOD: The process involved six steps. The comprehensibility of the scale was assessed using interviews with potential users. RESULTS: A total of nine physiotherapists and six physicians working in various clinical settings were interviewed, seven of them worked in Germany and four each in Austria and Switzerland. The interviews led to a refined version of the translation. The comprehensibility testing revealed no country-specific differences. CONCLUSION: A German version of the SARA authorized by the co-author of the original publication, is now available. The results provide methodological insights into the translation process of observation-based standardized assessments

Disease progression of spinocerebellar ataxia types 1, 2, 3 and 6 before and after ataxia onset

OBJECTIVE: Our aim was to study the evolution of ataxia and neurological symptoms before and after ataxia onset in the most common spinocerebellar ataxias (SCAs), SCA1, SCA2, SCA3 and SCA6. We therefore jointly analysed the data of the EUROSCA and RISCA studies, which recruited ataxic and non-ataxic mutation carriers. METHODS: We used mixed effect models to analyse the evolution of Scale for the Rating and Assessment of Ataxia (SARA) scores, SCA Functional Index (SCAFI) and Inventory of Non-Ataxia Signs (INAS) counts. We applied multivariable modelling to identify factors associated with SARA progression. In the time interval 5 years prior to and after ataxia onset, we calculated sensitivity to change ratios (SCS) of SARA, SCAFI and INAS. RESULTS: 2740 visits of 677 participants were analysed. All measures showed non-linear progression that was best fitted by linear mixed models with linear, quadratic and cubic time effects. R(2) values indicating quality of the fit ranged from 0.70 to 0.97. CAG repeat was associated with faster progression in SCA1, SCA2 and SCA3, but not SCA6. 5 years prior to and after ataxia onset, SARA had the highest SCS of all measures with a mean of 1.21 (95% CI: 1.20, 1.21) in SCA1, 0.94 (0.93, 0.94) in SCA2 and 1.23 (1.22, 1.23) in SCA3. INTERPRETATION: Our data have important implications for the understanding of disease progression in SCA1, SCA2, SCA3 and SCA6 across the lifespan. Furthermore, our study provides information for the design of interventional trials, especially in pre-ataxic mutation carriers close to ataxia onset and patients in early disease stages

Late growth stages and post-growth diffusion in organic epitaxy: PTCDA on Ag(111)

The late growth stages and the post-growth diffusion of crystalline organic thin films have been investigated for 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) on Ag(111), a model system in organic epitaxy. In situ x-ray measurements at the anti-Bragg point during the growth show intensity oscillations followed by a time-independent intensity which is independent of the growth temperature. At T > 350 K, the intensity increases after growth up to a temperature-dependent saturation value due to a post-growth diffusion process. The time-independent intensity and the subsequent intensity recovery have been reproduced by models based on the morphology change as a function of the growth temperature. The morphology found after the post-growth diffusion processes has been studied by specular rod measurements.Comment: 9 pages, 8 figures, accepted for publication in Surface Scienc

Association Between Fatigue and Motor Exertion in Patients With Multiple Sclerosis - a Prospective Study

Background: Fatigue in multiple sclerosis (MS) is conceived as a multidimensional construct. Objectives: This study aims to describe the changes of balance and gait parameters after 6 min of walking (6 MW) as potential quantitative markers for perceptions of state fatigue and trait fatigue in MS. Methods: A total of 19 patients with MS (17 with fatigue) and 24 healthy subjects underwent static posturography, gait analysis, and ratings of perceived exertion before and after 6 MW. Results: 6 MW was perceived as exhaustive, but both groups featured more dynamic comfortable speed walking after 6 MW. Shorter stride length at maximum speed and increased postural sway after 6 MW indicated fatigability of balance and gait in MS group only. While most changes were related to higher levels of perceived exertion after 6 MW (state fatigue), higher fatigue ratings (trait fatigue) were only associated with less increase in arm swing at comfortable speed. Further analysis revealed different associations of trait fatigue and performance fatigability with disability and motor functions. Performance fatigability was most closely related to the Expanded Disability Status Scale, while for trait fatigue, the strongest correlations were seen with balance function and handgrip strength. Conclusions: Fatigability of performance was closely related to perceptions of exertion after 6 MW (state fatigue) and disability in MS but distinct from fatigue ratings, conceived as trait fatigue. Our study identified postural sway, arm swing during gait, and hand grip strength as unexpected potential motor indicators of fatigue ratings in MS

Prediction of high and low disease activity in early MS patients using multiple kernel learning identifies importance of lateral ventricle intensity

BACKGROUND: Lack of easy-to-interpret disease activity prediction methods in early MS can lead to worse patient prognosis. OBJECTIVES: Using machine learning (multiple kernel learning - MKL) models, we assessed the prognostic value of various clinical and MRI measures for disease activity. METHODS: Early MS patients (n = 148) with at least two associated clinical and MRI visits were investigated. T2-weighted MRIs were cropped to contain mainly the lateral ventricles (LV). High disease activity was defined as surpassing NEDA-3 Criteria more than once per year. Clinical demographic, MRI-extracted image-derived phenotypes (IDP), and MRI data were used as inputs for separate kernels to predict future disease activity with MKL. Model performance was compared using bootstrapped effect size analysis of mean differences. RESULTS: A total of 681 visits were included, where 81 (55%) patients had high disease activity in a combined end point measure using all follow-up visits. MKL model discrimination performance was moderate (AUC ≥ 0.62); however, modelling with combined clinical and cropped LV kernels gave the highest prediction performance (AUC = 0.70). CONCLUSIONS: MRIs contain valuable information on future disease activity, especially in and around the LV. MKL techniques for combining different data types can be used for the prediction of disease activity in a relatively small MS cohort

Neural Processes of Psychological Stress and Relaxation Predict the Future Evolution of Quality of Life in Multiple Sclerosis

Health-related quality of life (HRQoL) is an essential complementary parameter in the assessment of disease burden and treatment outcome in multiple sclerosis (MS) and can be affected by neuropsychiatric symptoms, which in turn are sensitive to psychological stress. However, until now, the impact of neurobiological stress and relaxation on HRQoL in MS has not been investigated. We thus evaluated whether the activity of neural networks triggered by mild psychological stress (elicited in an fMRI task comprising mental arithmetic with feedback) or by stress termination (i.e., relaxation) at baseline (T0) predicts HRQoL variations occurring between T0 and a follow-up visit (T1) in 28 patients using a robust regression and permutation testing. The median delay between T0 and T1 was 902 (range: 363-1,169) days. We assessed HRQoL based on the Hamburg Quality of Life Questionnaire in MS (HAQUAMS) and accounted for the impact of established HRQoL predictors and the cognitive performance of the participants. Relaxation-triggered activity of a widespread neural network predicted future variations in overall HRQoL (t = 3.68, p(family-wise error [FWE])-corrected = 0.008). Complementary analyses showed that relaxation-triggered activity of the same network at baseline was associated with variations in the HAQUAMS mood subscale on an alpha(FWE) = 0.1 level (t = 3.37, p(FWE) = 0.087). Finally, stress-induced activity of a prefronto-limbic network predicted future variations in the HAQUAMS lower limb mobility subscale (t = -3.62, p(FWE) = 0.020). Functional neural network measures of psychological stress and relaxation contain prognostic information for future HRQoL evolution in MS independent of clinical predictors