Technische Universität Dresden: Qucosa
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Geschlechtsspezifische Ergebnisse des Dresdner Kinder- und Jugendkopfschmerzprogrammes DreKiP
No full textHintergrund: Mädchen und Frauen sind häufiger von Kopfschmerzen betroffen als Jungen und Männer. Der Einfluss des Geschlechts auf die Wirksamkeit von Kopfschmerztherapien ist bisher kaum untersucht. Wir prüften geschlechterspezifische Unterschiede im ambulanten multimodalen Dresdner Kinder- und Jugendkopfschmerzprogramm DreKiP. - Methoden: 140 Patienten mit primären Kopfschmerzen wurden in einem 15-stündigen strukturiertem Gruppenprogramm behandelt. Zu Beginn des Programms (T0) sowie 6 (T1) und 12 Monate (T2) nach dem Ende wurden Daten zu kopfschmerzbedingter Einschränkung der Alltagsfähigkeit (PedMIDAS), Kopfschmerzfrequenz, -intensität und schmerzbedingter Alltagseinschränkung (P-PDI) erhoben. Retrospektiv wurden diese Daten für Mädchen und Jungen getrennt analysiert. - Ergebnisse: Von 91 Patienten (9–19 Jahre, Median = 15; 71,4 % weiblich) lagen Daten für mindestens zwei Messzeitpunkte vor. Mädchen zeigten zu allen Zeitpunkten eine signifikant höhere Kopfschmerzfrequenz als Jungen (Mediane Kopfschmerztage/letzte 3 Monate zu T0: ♀ 43, ♂ 20; T1: ♀ 32, ♂ 12; T2: ♀ 28, ♂ 9) sowie eine numerisch höhere kopfschmerzbedingte Alltagseinschränkung. Es zeigten sich signifikante Effekte über die Zeit mit Abnahme der Kopfschmerzfrequenz (F (2,88) = 5,862; p = 0,004) und Verbesserung der Alltagsfunktion (F (2,92) = 5,340; p = 0,006). Eine geschlechtsspezifische Therapieantwort zeigte sich nicht. - Diskussion: Therapieinhalte des DreKiP zeigten bei Mädchen und Jungen mit primären Kopfschmerzen Effekte. Höhere Kopfschmerzfrequenzen und Alltagseinschränkung bei Mädchen können vor allem hormonelle, aber auch psychosoziale Ursachen haben und sollten in Edukationsmaßnahmen aufgegriffen werden.Background: Girls and women are more frequently affected by headache than boys and men. The influence of gender on the effectiveness of headache therapies has so far been hardly investigated. We examined gender differences in the outpatient multimodal Dresden Child and Adolescent Headache Program DreKiP. - Methods: We treated 140 patients with primary headache in a 15-hour structured group program. At baseline (T0) and six (T1) and twelve months (T2) after the end of the program, data on headache-related limitation of daily activities (PedMIDAS) as well as headache frequency, intensity, and pain-related disability (P-PDI) were collected. Retrospectively, these data were analyzed separately for girls and boys. - Results: For 91 patients (9–19 years, median = 15; 71.4 % female) data were available for at least two measurement time points. Girls showed significantly higher headache frequency than boys at all time points (median headache days/last three months at T0: ♀ 43, ♂ 20; T1: ♀ 32, ♂ 12; T2: ♀ 28, ♂ 9) as well as numerically higher headache-related limitation of daily life. There were significant effects over time with a decrease in headache frequency (F (2.88) = 5.862; p = 0.004) and improvement in daily functioning (F (2.92) = 5.340; p = 0.006). There was no gender-specific treatment response. - Discussion: The DreKiP therapy shows effects in girls and boys with primary headache. Higher headache frequencies and everyday life restrictions in girls may have hormonal but also psychosocial causes and should be addressed in educational measures
Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen
No full textBackground: Spinal muscular atrophy (SMA) is a genetic neuromuscular disease caused by mutations of the SMN1 gene. Deficient SMN protein causes irreversible degeneration of alpha motor neurons characterized by progressive muscle weakness and atrophy. Considering that SMA is a multi-systemic disorder and SMN protein was found to be expressed in cortical structures, the cognitive profile of adult patients with SMA has recently been of particular interest. With nusinersen, a novel, disease-modifying drug has been established, but its effects on neuropsychological functions have not been validated yet. Aim of this study was to investigate the cognitive profile of adult patients with SMA during treatment initiation with nusinersen and to reveal improvement or deterioration in cognitive performance. - Methods: This monocentric longitudinal study included 23 patients with SMA type 2 and 3. All patients were assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) before and after 14 months of treatment initiation with nusinersen. Additionally, motor function was evaluated by Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). - Results: Of the treatment-naive patients, only three were below the age- and education-matched cut-off for cognitive impairment in the ECAS total score. Significant differences between SMA type 2 and 3 were only detected in the domain of Language. After 14 months of treatment, patients showed significant improvement of absolute scores in all three ALS-specific domains, in the non-ALS-specific domain of Memory, in both subscores and in the ECAS total score. No associations were detected between cognitive and functional outcome measures. - Conclusions: In some adult patients with SMA abnormal cognitive performance in ALS-specific functions of the ECAS was evident. However, the presented results suggest no clinically significant cognitive changes during the observed treatment period with nusinersen
Extracellular Vesicles and Their Role in Lung Infections
No full textLung infections are one of the most common causes of death and morbidity worldwide. Both bacterial and viral lung infections cause a vast number of infections with varying severities. Extracellular vesicles (EVs) produced by different cells due to infection in the lung have the ability to modify the immune system, leading to either better immune response or worsening of the disease. It has been shown that both bacteria and viruses have the ability to produce their EVs and stimulate the immune system for that. In this review, we investigate topics from EV biogenesis and types of EVs to lung bacterial and viral infections caused by various bacterial species. Mycobacterium tuberculosis, Staphylococcus aureus, and Streptococcus pneumoniae infections are covered intensively in this review. Moreover, various viral lung infections, including SARS-CoV-2 infections, have been depicted extensively. In this review, we focus on eukaryotic-cell-derived EVs as an important component of disease pathogenesis. Finally, this review holds high novelty in its findings and literature review. It represents the first time to cover all different information on immune-cell-derived EVs in both bacterial and viral lung infections
Enhanced method for reinforcement learning based dynamic obstacle avoidance by assessment of collision risk
No full textNaturally inspired designs of training environments for reinforcement learning (RL) often suffer from highly skewed encounter probabilities, with a small subset of experiences being encountered frequently, while extreme experiences remain rare. Despite recent algorithmic advancements, research has demonstrated that such environments present significant challenges for reinforcement learning algorithms. In this study, we first demonstrate that traditional designs in training environments for RL-based dynamic obstacle avoidance show extremely unbalanced probabilities for obstacle encounters in a way that high-risk scenarios with multiple threatening obstacles are rare. To address this limitation, we propose a traffic-type-independent training environment that allows us to exert control over the difficulty of obstacle encounter experiences. This allows us to customarily shift obstacle encounter probabilities towards high-risk experiences, which are assessed via two metrics: The number of obstacles involved and an existing collision risk metric. - Our findings reveal that shifting the training focus towards higher-risk experiences, from which the agent learns, significantly improves the final performance of the agent. To validate the generalizability of our approach, we designed and evaluated two realistic use cases: a mobile robot and a maritime ship facing the threat of approaching obstacles. In both applications, we observed consistent results, underscoring the broad applicability of our proposed approach across various application contexts and independent of the agent’s dynamics. Furthermore, we introduced Gaussian noise to the sensor signals and incorporated different non-linear obstacle behaviors, which resulted in only marginal performance degradation. This demonstrates the robustness of the trained agent in handling environmental uncertainties
Minimizing Energy Cost in PV Battery Storage Systems Using Reinforcement Learning
No full textThis article addresses the development and tuning of an energy management for a photovoltaic (PV) battery storage system for the cost-optimized use of PV energy using reinforcement learning (RL). An innovative energy management concept based on the Proximal Policy Optimization algorithm in combination with recurrent Long Short-Term Memory neural networks is developed for data-based policy learning, a concept that has been rarely addressed in the literature so far. As a reference system for the simulation-based investigations, a PV battery storage system is modelled, parametrized and implemented with an interface for the RL algorithm. To demonstrate the generalization capability of the learned energy management, 98 training and 12 evaluation episodes, each with a length of one year, are generated from an empirical dataset of global radiation and load power time series. To improve the convergence speed and stability of the RL algorithm as well as the learned policy with regards to techno-economic metrics, an extensive hyperparameter study is conducted by training 216 control policies with different hyperparameter configurations. A simulation-based evaluation of the learned energy management against conventional rule-based and model-predictive energy managements shows that the RL-based concept can achieve slightly better results in terms of energy costs and the amount of energy fed into the grid than the commonly used model-predictive method
On the Protonation and Deuteration of Pyrroles: Dedication: in Memoriam to Prof. Dr. Jürgen Fabian (1936–2023)
No full textOther than triarylamines, which are protonated by strong acids both at their N-atom and aromatic rings, pyrrole and its N-substituted derivatives were exclusively protonated at the carbon atoms of their heteroaromatic rings. Whereas with the strong trifluoromethane sulfonic acid (TFS) stable pyrrolium salts were obtained, with the weaker trifluoroacetic acid (TFA) oligomers are formed. E.g., from the N-(tert-butyl)pyrrole a dimeric compound could be unambiguously identified and structural characterised by means of ¹H NMR measurements. Treatment of N-aryl substituted pyrroles with deuterated TFS revealed an H/D exchange not only at the pyrrole rings but also at their aryl moieties even
Real-world considerations regarding the use of the combination of levodopa, carbidopa, and entacapone (Stalevo®) in Parkinson's disease
No full textAn important aim in long-term levodopa therapy is to prolong the duration of symptomatic efficacy of each dose without increasing peak plasma concentrations above the threshold for the emergence of dyskinesias. One strategy is to enhance levodopa delivery to the brain by co-administering it with inhibitors of peripheral dopa-decarboxylase and catechol-O-methyltransferase (COMT). Levodopa, carbidopa and entacapone (LCE), available in a range of fixed-dose combinations as the branded formulation Stalevo® (Orion Pharma), has been developed to address this requirement and has been in general use for 20 years, having first been evaluated in randomized controlled trials. Experience with LCE has established that improved levodopa pharmacokinetics achieved with dual-enzyme inhibition are translated into improved clinical efficacy, including the possibility of reducing total levodopa dosage with no loss of therapeutic effect. The ease and tolerability of switching to LCE has been affirmed in the SIMCOM trial and by personal experience detailed in this review. Some 300,000 patient-years of safety data are available for LCE, including trial data for up to 5 years. Most adverse effects associated with LCE are attributable to the levodopa component rather than the enzyme inhibitors. The hepatotoxicity observed with the class comparator tolcapone has not been observed with entacapone, the COMT inhibitor in LCE, and there is no formal requirement to monitor liver function during LCE therapy. Other common side effects include diarrhoea, which is one of the more prominent non-dopaminergic adverse events, and urine discolouration, which is harmless but about which patients may require reassurance
Heat effects on clay-bearing building sandstone
No full textDamages due to fire occurred on many monuments and affected building sandstones. Changes in technical properties of heated sandstones are caused by changes in their structure and mineralogy. Therefore, a better knowledge of the changing processes in grain size scale is crucial to understand and assess property changes. The study presents results for the Cotta type Elbe Sandstone, a clay-bearing sandstone that is a widespread material for construction and sculpting. Uniaxial compressive strength and ultrasonic wave velocity as well as changes in colour, structures and mineralogical phases were determined for samples treated at temperatures of 300, 400, 500, 600, 700, 800 and 1250 °C and compared to the untreated material. The results show that minor clay components in the sandstone pores determine the uniaxial compressive strength in dependence of temperature and dry or wet state. Uniaxial compressive strength does not show a decrease even at high temperatures, whereas ultrasonic wave velocity is decreasing continuously with higher temperatures as for many other sandstones. The differing mechanical behaviour of the clay-bearing sandstone can be explained by the phase changes of kaolinite in the pore cement
Effect of Endovascular Treatment in HERMES Patients With Isolated Occlusion of the Intracranial Internal Carotid Artery
No full textBackground:
The optimal management of patients with symptomatic isolated internal carotid artery (ICA) occlusion is unknown. We aimed to assess whether endovascular treatment (EVT) compared with standard medical care was associated with improved functional outcomes in patients with acute symptomatic isolated intracranial ICA occlusion without involvement of the middle or anterior cerebral artery, that is, ICA‐I occlusion. Additionally, we aimed to compare ICA‐I with ICA‐L/T occlusion, which involves themiddle and anterior cerebral artery, respectively.
Methods:
We analyzed data from the highly effective reperfusion evaluated in multiple endovascular stroke trials (HERMES) collaboration, which performed an individual patient data meta‐analysis of 7 randomized controlled trials conducted between 2010 and 2017 assessing the benefit of EVT compared to medical management in patients with anterior circulation large vessel occlusion. We assessed the association between EVT and 90‐day good functional outcome (modified Rankin scale scores 0–2), National Institutes of Health Stroke Scale scores at 24 hours, symptomatic intracranial hemorrhage rates and mortality in patients with ICA‐I and ICA‐L/T occlusion.
Results:
We included 442 patients with intracranial ICA occlusion, of whom 38 (8.6%) had ICA‐I occlusion. In the ICA‐I group, the median age [interquartile range] was 69.5 [61.7–79.5] years, 42.1% were male, and median baseline National Institutes of Health Stroke Scale was 17 [15–20]. Compared with standard medical care alone, EVT resulted in higher good outcome rates in patients with ICA‐I (42.9% versus 25%; P=0.296) and ICA‐L/T occlusion (32.5% versus 14.4%; P<0.001), and significant improvement in National Institutes of Health Stroke Scale scores at 24 hours. Mortality and symptomatic intracranial hemorrhage rates were similar between the treatment groups for both occlusion types.
Conclusions:
A minority of patients with intracranial carotid occlusion presented with ICA‐I occlusion in the HERMES population. EVT in patients with ICA‐I occlusion and moderate‐to‐severe deficit was safe and tended to be similarly effective as compared to patients with ICA‐L/T occlusion
Joint inversion of groundwater flow, heat, and solute state variables
No full textCharacterization of karst systems and forecast of their state variables are essential for groundwater management and engineering in karst regions. These objectives can be met by the use of process-based discrete-continuum models (DCMs). However, results of DCMs may suffer from inversion nonuniqueness. It has been demonstrated that the joint inversion of observations regulated by different natural processes can tackle the nonuniqueness issue in groundwater modeling. However, this has not been tested for DCMs thus far. This research proposes a methodology for the joint inversion of hydro-thermo-chemo-graphs, applying to two small-scale sink-to-spring experiments at Freiheit Spring, Minnesota, USA. In order to address conceptual uncertainty, a multimodel approach was implemented, featuring seven mutually exclusive variants. Spring hydro-thermo-chemo-graphs, for all the variants simulated by MODFLOW-CFPv2, were jointly inverted using a weighted least squares algorithm. Subsequently, models were compared in terms of inversion and forecast performances, as well as parameter uncertainties. Results reveal the suitability of the DCM approach for simultaneous inversion and forecast of hydro-physico-chemical behavior of karst systems, even at a scale of meters and seconds. The estimated volume of the tracer conduit passage ranges from approximately 46–51 m3, which is comparable to the estimate from the flood-pulse method. Moreover, it was demonstrated that the thermograph and hydrograph contain more information about aquifer characteristics than the chemograph. However, this finding can be site-specific and should depend on the analysis scale, the considered conceptual models, and the hydrological state, which are potentially affected by minor unaccountable processes and features