Phase Dependency of the Human Primary Motor Cortex and Cholinergic Inhibition Cancelation during Beta tACS

The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits

Driving human motor cortical oscillations leads to behaviorally relevant changes in local GABAA inhibition: a tACS-TMS study

Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention.SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool

The Beginning of the Early Upper Paleolithic in Poland

Research on the timing of Homo sapiens dispersals in Central Europe is pivotal for understanding the behavioral trajectories of human adaptation to low biomass environments and cold climates. Previous studies on the Early Upper Paleolithic of Poland described a different scenario from the European panorama characterized by the local development of a laminar/lamellar technology from the foregoing Middle Paleolithic and the coexistence of different Aurignacian variants after 35 ka BP. In this paper, we examine this technical diversity by reassessing and revising the chronological and technological information of the key Aurignacian sites in Poland. Our study reveals that the distinctive techno-typological features of the different Aurignacian types are most likely the result of the mixing of artifacts from different chronologies. In our view, Poland was visited intermittently by Homo sapiens since the Early Aurignacian. The deterioration of the climatic conditions during the second half of MIS 3 converted the Polish territories into a satellite area of the Aurignacian settlement system

Comparison of data-driven uncertainty quantification methods for a carbon dioxide storage benchmark scenario

A variety of methods is available to quantify uncertainties arising with\-in the modeling of flow and transport in carbon dioxide storage, but there is a lack of thorough comparisons. Usually, raw data from such storage sites can hardly be described by theoretical statistical distributions since only very limited data is available. Hence, exact information on distribution shapes for all uncertain parameters is very rare in realistic applications. We discuss and compare four different methods tested for data-driven uncertainty quantification based on a benchmark scenario of carbon dioxide storage. In the benchmark, for which we provide data and code, carbon dioxide is injected into a saline aquifer modeled by the nonlinear capillarity-free fractional flow formulation for two incompressible fluid phases, namely carbon dioxide and brine. To cover different aspects of uncertainty quantification, we incorporate various sources of uncertainty such as uncertainty of boundary conditions, of conceptual model definitions and of material properties. We consider recent versions of the following non-intrusive and intrusive uncertainty quantification methods: arbitary polynomial chaos, spatially adaptive sparse grids, kernel-based greedy interpolation and hybrid stochastic Galerkin. The performance of each approach is demonstrated assessing expectation value and standard deviation of the carbon dioxide saturation against a reference statistic based on Monte Carlo sampling. We compare the convergence of all methods reporting on accuracy with respect to the number of model runs and resolution. Finally we offer suggestions about the methods' advantages and disadvantages that can guide the modeler for uncertainty quantification in carbon dioxide storage and beyond

Voter models on weighted networks

We study the dynamics of the voter and Moran processes running on top of complex network substrates where each edge has a weight depending on the degree of the nodes it connects. For each elementary dynamical step the first node is chosen at random and the second is selected with probability proportional to the weight of the connecting edge. We present a heterogeneous mean-field approach allowing to identify conservation laws and to calculate exit probabilities along with consensus times. In the specific case when the weight is given by the product of nodes' degree raised to a power theta, we derive a rich phase-diagram, with the consensus time exhibiting various scaling laws depending on theta and on the exponent of the degree distribution gamma. Numerical simulations give very good agreement for small values of |theta|. An additional analytical treatment (heterogeneous pair approximation) improves the agreement with numerics, but the theoretical understanding of the behavior in the limit of large |theta| remains an open challenge.Comment: 21 double-spaced pages, 6 figure

Möglichkeiten der Bekämpfung des Falschen Mehltaus an Gurke (Pseudoperonospora cubensis) mit alternativen Präparaten

In organic cucumber production the infection with downy mildew (Pseudoperonospora cubensis) is one of the major problems. Use of biological control agents based on plant extracts and antagonistic micro organisms may be one possibility to control the disease. Plant extracts from Salvia officinalis and a plant belonging to the family Fabaceae (P1), as well as cultures of Brevibacillus brevis showed, in bioassays on potted cucumber plants, high potential to control the disease with efficacies between 55% and 100%. For S. officinalis extract the efficacy was close to 100% even at a concentration of 0.1325%. Initial trials under commercial growing conditions showed that the control of P. cubensis is better in protected than in open field production. In order to optimise the efficacy of the preparations for use in commercial cucumber production, further investigations on the mode of action, the active ingredients etc. are under way

High-intensity interval training improves bone remodeling, lipid profile, and physical function in multiple sclerosis patients

Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease due to an autoimmune chronic inflammatory response, yet the etiology is currently not completely understood. It is already known that physical activity plays an essential role in improving quality of life, especially in neuropathological conditions. The study was aimed to investigate the possible benefits of high-intensity interval training (HIIT) in bone and lipid metabolism markers, and neuromotor abilities in MS patients. 130 participants were recruited; 16 subjects with MS met the inclusion criteria and were included in the data analysis. The patients were randomly assigned to two groups: a Control group (CG) (34.88 +/- 4.45 yrs) that didn't perform any physical activity and the Exercise group (EG) (36.20 +/- 7.80 yrs) that performed HIIT protocol. The training program was conducted remotely by a kinesiologist. It was performed three times a week for 8 weeks. At the beginning (T0) and the end of the study (T1) physical function tests, bone remodelling markers, and lipid markers analyses were performed. After 8 weeks of training the wall squat (s) (T0 = 27.18 +/- 4.21; T1 = 41.68 +/- 5.38, p <= 0.01) and Time Up and Go test (s) (T0 = 7.65 +/- 0.43; T1 = 6.34 +/- 0.38 p <= 0.01) performances improved; lipid markers analysis showed a decrease in Total (mg/dl) (T0 = 187.22 +/- 15.73; T1 = 173.44 +/- 13.03, p <= 0.05) and LDL (mg/dl) (T0 = 108 +/- 21.08; T1 = 95.02 +/- 17.99, p < 0.05) cholesterol levels. Additionally, the levels of osteocalcin (g/L), a marker of bone formation increased (T0 = 20.88 +/- 4.22; T1 = 23.66 +/- 6.24, p < 0.05), 25-OH Vitamin D (g/L) improved after 8 weeks (T0 = 21.11 +/- 7.11; T1 = 27.66 +/- 7.59, p < 0.05). HIIT had an effect on lower limb strength and gait control, improved bone formation, and lipid management, in MS patients

Intraoperative Evaluation of Transmitral Pressure Gradients after Edge-to-Edge Mitral Valve Repair

Objective: Edge-to-edge repair of the mitral valve (MV) has been described as a viable option used for the surgical management of mitral regurgitation (MR). Based on the significant changes in MV geometry associated with this technique, we hypothesized that edge-to-edge MV repairs are associated with higher intraoperative transmitral pressure gradients (TMPG) compared to conventional methods. Methods: Patient records and intraoperative transesophageal echocardiography (TEE) examinations of 552 consecutive patients undergoing MV repair at a single institution over a three year period were assessed. After separation from cardiopulmonary bypass (CPB), peak and mean TMPG were recorded for each patient and subsequently analyzed. Results: 84 patients (15%) underwent edge-to-edge MV repair. Peak and mean TMPG were significantly higher compared to gradients in patients undergoing conventional repairs: 10.7±0.5 mmHg vs 7.1±0.2 mmHg; P<0.0001 and 4.3±0.2 mmHg vs 2.8±0.1 mmHg; P<0.0001. Only patients with mean TMPG ≥7 mmHg (n = 9) required prompt reoperation for iatrogenic mitral stenosis (MS). No differences in peak and mean TMPG were observed among edge-to-edge repairs performed in isolation, compared to those performed in combination with annuloplasty: 11.0±0.7 mmHg vs 10.3±0.6 mmHg and 4.4±0.3 mmHg vs 4.3±0.3 mmHg. There were no differences in TMPG between various types of annuloplasty techniques used in combination with the edge-to-edge repairs. Conclusions: Edge-to-edge MV repairs are associated with higher intraoperative peak and mean TMPG after separation from CPB compared to conventional repair techniques. Unless gradients are severely elevated, these findings are not necessarily suggestive of iatrogenic MS. Thus, in the immediate postoperative period mildly elevated TMPG can be expected and tolerated after edge-to-edge mitral repairs

Investigating the association between occupational exposure to asbestos and ovarian carcinoma: results from a pilot study in Germany

Background The aim of this pilot study was to assess the feasibility of a large-scale epidemiologic investigation elucidating the quantitative association between occupational exposure to asbestos and ovarian cancer in former German asbestos workers. Methods Between December 2017 and May 2018, a random sample of one thousand insured woman registered at the health service of a German trade association as formerly occupationally exposed to asbestos were invited to participate in a pilot study. Participation included a phone interview using a standardised questionnaire. The feasibility of the project was evaluated using a priori defined criteria. They included response, number of cases, eligibility of the questionnaire data for exact estimation of asbestos fibre-years, and availability of relevant medical documentation (imaging procedures, medical reports, and histologic materials). Results The response (17%) was clearly below the intended number of 60%. With six tumour suspects, of which two could be confirmed by medical documents, the number of cases was within the expected range of two to eleven cases. Exact asbestos fibre-year estimations could be performed for 29% of all interviewees, but only for one suspected case. Medical documentation could be collected for only few participants, while no histology reports could be obtained for all cases. Thus, only the feasibility criterion of the expected number of cases was fulfilled. Conclusion The results of the pilot study indicate that the planned project is feasible only to a very limited extent. For further planning of the study, measures to improve recruitment of participants are necessary

Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies

BACKGROUND: Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. METHODS: Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF25-75)) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. RESULTS: A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF25-75. Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (</=23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. CONCLUSIONS: Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents