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Energy is a pivotal element for overall development. Therefore, affordable and clean energy for all (Sustainable Development Goal 7) is one of the important elements. Despite a suitable approach, Kyrgyzstan lags behind to achieve its Sustainable Development Goals by 2030. Improving access to energy can significantly impact the progress of many other sustainable development targets. However, access to reliable, sustainable, and adequate energy is a crucial task in rural Kyrgyzstan. Taking into consideration the energy situation and the importance of the availability of energy services, the overarching aim of the presented article is to map the potential of improving rural energy services to foster overall sustainable development goals. The article presents the most relevant information about rural energy usage behaviour based on three primary pillars: energy demand, energy carrier, and energy sources. In addition, the presented research article synthesises the key driving factors which have a direct or indirect impact on the energy services in rural areas. The summarised data displays a deep insight into a variety of complex and dynamic household energy consumption patterns. The article provides a potential solution nexus to foster improved energy services in rural Kyrgyzstan and therefore to foster the overall sustainable development in Kyrgyzstan. The findings of the article help to formulate a strategy to design rural energy services for policy makers and stockholders.

Background Few studies address the appropriate duration of post-surgical antibiotic therapy for orthopedic infections; with or without infected residual implants. We perform two similar randomized-clinical trials (RCT) to reduce the antibiotic use and associated adverse events. Methods Two unblinded RCTs in adult patients (non-inferiority with a margin of 10%, a power of 80%) with the primary outcomes “remission” and “microbiologically-identical recurrences” after a combined surgical and antibiotic therapy. The main secondary outcome is antibiotic-related adverse events. The RCTs allocate the participants between 3 vs. 6 weeks of post-surgical systemic antibiotic therapy for implant-free infections and between 6 vs. 12 weeks for residual implant-related infections. We need a total of 280 episodes (randomization schemes 1:1) with a minimal follow-up of 12 months. We perform two interim analyses starting approximately after 1 and 2 years. The study approximatively lasts 3 years. Discussion Both parallel RCTs will enable to prescribe less antibiotics for future orthopedic infections in adult patients. Trial registration ClinicalTrial.gov NCT05499481. Registered on 12 August 2022. Protocol version: 2 (19 May 2022)

Additional file 1: Supplementary File 1. Protocol SALATIO Trials.

Additional file 3: Supplementary File 3. Internal Document and Proof of Funding.

Empirische Forschungsmethoden sind nicht allein Werkzeuge, sondern vielmehr Ausdruck allgemeiner erkenntnistheoretischer und forschungsmethodologischer Grundannahmen in Bezug auf die Rekonstruktion eines Forschungsgegenstands und Ausgestaltung des Forschungsprozesses, wodurch wiederum die Ergebnisse beeinflusst werden. Im Zentrum dieses Beitrags stehen Ansätze der in der qualitativen Zweit- und Fremdsprachenforschung verbreiteten Grounded Theory. Zwei methodologische Weiterentwicklungen, die Konstruktivistische Grounded Theory nach Kathy Charmaz und die postmodern ausgerichtete Situations­analyse nach Adele Clarke, werden v.a. hinsichtlich ihrer epistemologischen Grundannahmen sowie ihres methodischen Vorgehens miteinander verglichen, indem die beiden unterschiedli­chen Herangehensweisen bei der Interpretation desselben narrativen Interviews aus der DaZ-Professionsforschung einander gegenübergestellt werden. Der Vergleich zeigt, dass die Aufmerksamkeitslenkung im Forschungsprozess weitgehend von den ausgewählten For­schungsansätzen abhängt, insofern als diese nicht nur die Dateninterpretation prägen, sondern auch den Zugriff auf den Forschungsgegenstand bestimmen., Empirical research methods are not merely tools but rather an expression of general epistemological and methodological assumptions concerning the research topic and the research design. As such, they determine the character of the results. To identify how methodology influences research practices and outcomes, we focus on two recent versions of Grounded Theory, namely Kathy Charmaz' Constructivist Grounded Theory and Adele Clarke's postmodern Situational Analysis, which we discuss and compare especially with regard to their underlying epistemo­logical orientation and their procedures in data interpretation. To this end, we apply the two approaches to interpret a narrative interview with a student teacher in the field of second language provision. From this comparison, it becomes evident that the selected methodological approach crucially directs the researchers' attention in the research process by not only shaping the procedures in data interpretation but also by determining how a research topic is addressed in general terms.

Additional file 2: Supplementary File 2. Consent Form in English language. SALATIO Trials.

Stressful life events have a major impact on our mental health and are one of the foremost contributors to psychiatric disorders. Many symptoms of stress-related psychopathologies are at least partly driven by stress-induced impairments in effective emotion regulation abilities (Joormann and Gotlib, 2010; Campbell-Sills et al., 2011) and the predominant use of maladaptive strategies (Goldin et al., 2008; Moore et al., 2008). According to PASTOR (positive appraisal style theory of resilience), a positive appraisal style is the key resilience mechanism. Such resilience mechanisms may help individuals to regulate stress responses by fine-tuning them to optimal levels and terminating them if no longer necessary, thereby preventing stress-related dysfunctions (Kalisch et al., 2015). Stress-induced impairments in reappraisal likely result from the high cognitive demands that this strategy imposes on prefrontal cortex (PFC) functioning and in particular on working memory (Arnsten, 2015; Shields et al., 2016). Cognitive reappraisal has been shown to be supported by successful downregulation of the amygdala through dorsal and ventral PFC regions (Ochsner et al., 2012; Buhle et al., 2014). A recent meta-analysis revealed that across different experimental designs, including extinction, placebo treatment and emotion regulation, the ventromedial (vm)PFC controlled negative affect (Diekhof et al., 2011). Similar to extinction, the vmPFC may promote more implicit emotion regulation (Etkin et al., 2015). We propose that training cognitive reappraisal induces a shift toward a more automatic and implicit use of cognitive reappraisal. We hypothesize that this shift is accompanied by a decrease in dorsal and ventrolateral PFC involvement, whereas the pathway from the vmPFC to the amygdala is strengthened. Since habitual processes have been shown to be promoted under stress (Schwabe and Wolf, 2013; Wirz et al., 2018), cognitive reappraisal will be less sensitive to the detrimental effects of stress. We investigate this by means of a functional MRI experiment with four experimental groups (each N = 28). Half of the subjects will receive a 3-week long cognitive reappraisal training, whereas the other half will receive no such training. During the MRI session, subjects from the training and the no-training groups will be exposed to a laboratory stress or control condition and perform a cognitive emotion regulation task (CERT).

Background: Few studies address the appropriate duration of post-surgical antibiotic therapy for orthopedic infections; with or without infected residual implants. We perform two similar randomized-clinical trials (RCT) to reduce the antibiotic use and associated adverse events. Methods: Two unblinded RCTs in adult patients (non-inferiority with a margin of 10%, a power of 80%) with the primary outcomes "remission" and "microbiologically-identical recurrences" after a combined surgical and antibiotic therapy. The main secondary outcome are antibiotic-related adverse events. The RCTs allocate the participants between 3 vs. 6 weeks of post-surgical systemic antibiotic therapy for implant-free infections; and between 6 vs. 12 weeks for residual implant-related infections. We need a total of 280 episodes (randomization schemes 1:1) with a minimal follow-up 12 months. We perform two interim analyses starting approximately after 1 and 2 years. The study approximatively lasts 3 years. Discussion: Both parellel RCT will enable to prescribe less antibiotics for future orthopedic infections in adult patients. Trial registration: ClinicalTrial.gov NCT05499481. Registered on 12 August 2022. Protocol version: 2 (19 May 2022)

Despite the popularity of integrated conservation and development approaches to protected area management, adjacent communities increasingly face livelihood dilemmas. Yet understanding of how market processes and conservation enforcement interact to influence livelihood responses remains limited. Targeting eight villages in Nam Et-Phou Louey (NEPL) National Park in northern Lao PDR, we draw on survey data with 255 households, 93 semi-structured interviews, and meso-level data on village conditions to examine how residents navigate associated livelihood dilemmas. A cluster analysis reveals five livelihood types with divergent capacities to engage in market development and cope with enforcement pressures. We show how market linkages, historical conservation interventions, and local access conditions shape livelihoods and differences between villages. Our approach yields a nuanced picture of how global conservation efforts result in an uneven distribution of costs and benefits at local scales. Conservation measures must account for highly divergent capacities to cope with access loss and diversify livelihoods. Supplementary Information The online version contains supplementary material available at 10.1007/s10745-021-00267-4.

AimsOverweight is associated with increased risk of atrial fibrillation (AF), but the impact of overweight and AF recurrence after ablation is less clear. Despite this, an increasing number of AF ablations are carried out in overweight patients. We investigated the impact of body mass index (BMI) on AF recurrence rates after ablation.Methods and resultsThrough Danish nationwide registers, all patients undergoing first-time AF ablation between 2010 and 2018 were identified. Exposure of interest was BMI. The primary outcome was recurrent AF, defined from either any usage of antiarrhythmic medication, AF hospitalization, cardioversion, or re-ablation. A total of 9188 patients were included. Median age and interquartile range was 64 (60–75) in the normal-weight group and 60 (53–66) in the morbidly obese. There was an increase in comorbidity burden with increasing BMI, including a higher prevalence of heart failure, chronic obstructive pulmonary disease, diabetes, and hypertension. At 1- and 5-year follow ups, recurrence rates of AF increased incrementally by BMI categories. The hazard ratios and 95% confidence intervals of recurrent AF after ablation were 1.15 (1.07–1.23), 1.18 (1.09–1.28), and 1.26 (1.13–1.41) in overweight, obese, and morbidly obese, respectively, compared with normal-weight patients. Procedure duration and X-ray dose exposure also increased with increasing BMI.ConclusionFollowing AF ablation, recurrence rates of AF increased incrementally with increasing BMI. Therefore, aggressive weight management pre ablation in overweight patients could potentially provide substantial benefits and improve short- and long-term outcomes after ablation.

open access article Insulating glass flat-plate collectors can save cost by being produced quickly and automatically in insulated glass production facilities, and they can be filled with argon to reduce heat loss. During its lifetime, the collector is likely to lose argon because of gradual material degradation of the sealing. However, information on the influence of the argon concentration on the collector efficiency is limited. Therefore, the objective of this research work was to analyse this effect. A theoretical material property calculation of argon-air mixtures was carried out to determine the convective losses with variable argon concentrations. Thermal collector performance was measured experimentally using an outdoor solar tracker test rig. The results strongly suggest, that the influence of argon concentration on both the convective losses and the thermal efficiency is non-linear. The measurements revealed that an argon concentration of 90 % can increase average thermal performance by percentage points. An increase in argon concentration from 0 % to 50 % has almost twice the effect on average thermal efficiency as an increase from 50 % to 90 %. Concluding from these results, an argon leakage threshold of 2.5 percentage points per year is proposed to avoid disproportionate loss of efficiency over time.

In this paper, we augment a model of endogenous credit cycles by Matsuyama et al. (2016) with human capital to study its impact on the stability of income evolution and its distribution. Human capital is modelled as pure external effect of production, following a learning-by-producing approach. Agents have access to two different investment projects, which differ substantially in their next generations spillover effects. Some generate pecuniary externalities and technological spillovers through human capital formation whereas others fail to do so. Moreover, the latter are subject to financial frictions. Together with the interaction between those projects, endogenous credit cycles occur and a pattern of boom and bust cycles can be observed. We explore the impact of human capital on the systems stability by providing analytical results and numerical simulations, which confirm a strong interaction between credit market frictions and the importance of human capital in the production process. In general, we found that an increasing importance of human capital has an ambiguous effect on the income evolution. Especially during transition periods, we observe a destabilising effect while with high human capital importance, the income path is stabilised. Moreover, an increase of the importance of human capital favours investment projects with positive intergenerational spillovers, thus driving up the labour income of the young generation. Thus, our study reveals that human capital is an essential factor for economic stability under the presence of financial frictions and has substantial positive effects on the income distribution.

This paper proposes a home energy management system able to achieve optimized load scheduling for the operation of appliances within a given household. The system, based on the genetic algorithm, provides recommendations for the user to improve the way the energy needs of the home are handled. These recommendations not only take into account the dynamic pricing of electricity, but also the optimization for solar energy usage as well as user comfort. Historical data regarding the times at which the appliances have been used is leveraged through a statistical method to integrate the user’s preference into the algorithm. Based on real life appliance consumption data collected from a household in Morocco, three scenarios are established to assess the performance of the proposed system with each scenario having different parameters. Running the scenarios on the developed MATLAB script shows a cost saving of up to 63.48% as compared to a base scenario for a specific day. These results demonstrate that significant cost saving can be achieved while maintaining user comfort. The addition of supplementary shiftable loads (i.e., an electric vehicle) to the household as well as the limitations of such home energy management systems are discussed. The main contribution of this paper is the real data and including the user comfort as a metric in in the home energy management scheme.

The aim of this study was to develop the profile and competencies of a harmonised curriculum for a multi-country regional sector-specific higher education programme. The study, which was based on a case study of Renewable Energy involving six countries in Southern Africa, was based on established methodologies proposed by previous studies on harmonisation and profiling of higher education programmes. The study uses a general curriculum development approach leading to the definition of generic and specific competencies and feeding into a learning taxonomy to create alignment with specific learning outcomes at the intended qualification level. However, the approach extends the harmonisation concept to include industrialisation potential, which is crucial in the developing-country context. This allows for the exploitation of shared resources in sector-specific technology areas and supports the development of regional standards on technology and practice, as part of developing a sustainable regional economic sector. Twentytwo competencies, encompassing both generic and specific competencies, were defined. These competencies were grouped into six key competence areas, and later transformed into four clusters of competencies: core competencies, hard skills, soft skills and attitudes. These four clusters were then placed on a planetary system to represent the meta-profile for the qualification, which forms the framework for the future design of learning materials for the qualification. Received: 24 June 2019Accepted: 5 October 2020

The potential of combining biogas and photovoltaic (PV) power plants in hybrid systems in the German distribution grid is analyzed. The focus of the present research is on balancing the intermittent power supply from PV power plants with the controllable power production of combined heat and power (CHP) units of biogas plants within a period of seconds. To achieve an increase of the total energy feed-in of biogas and PV power plants to the electricity grid, a biogas plant energy management system is described. System parameters, such as the variable feed-in of PV power plants or power ramps of the start-up process of controllable biogas plant CHP unit, are described and adapted to the global installed capacity of PV power plant and biogas plants in the German distribution grid.

Background: Walking impairment is a common and highly disabling symptom in people with MS (PwMS). Ambulatory deterioration is poorly characterized in PwMS and reliable prognosis that may guide clinical decisions is elusive. This study aimed to objectively track the progression of clinical walking performance and kinematic gait patterns in PwMS over 4 years, thereby revealing potential prognostic markers for deterioration of ambulatory function. Methods: Twenty-two PwMS (48.8 ± 9.9 years, 14 females; expanded disability status scale [EDSS]: 4.5 ± 0.9 points) with gait impairments were recruited at the University Hospital Zurich, Switzerland. Gait function was monitored over a period of 4 years using a set of standardized clinical walking tests (timed 25-foot walk [T25FW], 6 min walk test [6MWT], 12-item MS walking scale [MSWS-12]) and comprehensive 3D kinematic gait analysis. Walking decline was assessed in the full patient cohort and in patient sub-groups that were built according to MS type (relapsing-remitting [RRMS], progressive [PMS]) and subjects' pathological gait signature (cluster groups 1–3). Results: In the total cohort (n = 22), we found a significant worsening in the 6MWT (BL vs. 4y: -41.1 m; P = 0.0053), while the performance in the T25FW, MSWS-12 and the EDSS remained unchanged over 4 years. Subjects with PMS (n = 12) showed a significant worsening in the EDSS (BL vs. 4y: +0.6 points; P = 0.0053), which was not observed in participants with RRMS (n = 10). Whereas deterioration of clinical walking function was not different between subjects with RRMS and PMS, we identified differences in clinical walking deterioration between PwMS with varying gait pattern pathologies: Subjects with spastic-paretic gait impairments (cluster 1; n = 9) demonstrated a marked worsening in the T25FW (BL vs. 4y: +2 s; P = 0.0020) and 6MWT (BL vs. 4y: -92.9 m; P < 0.0001) which was not seen in PwMS with an ataxia-like (cluster 2; n = 8) or unstable walking pattern (cluster 3; n = 5). Deterioration of clinical walking performance in cluster 1 was accompanied by a specific worsening of gait deficits that were characteristic of this cluster at baseline, a phenomenon not found in the other sub-groups. Accordingly, aggravation of cluster 1-specific gait impairments over 4 years predicted deterioration of the 6MWT in the total cohort (n = 22) with an accuracy of 90.9% (sensitivity: 90.9%; specificity: 90.9%; Nagelkerkes coefficient of determination R2: 0.721), unveiling key determinants of MS-related walking decline. Conclusions: Our findings highlight the potential of quantitative, functional outcomes for objective tracking of disease progression in PwMS. Gait pattern analysis can provide valuable information on the underlying pathomechanisms of gait deterioration and may represent a complementary prognostic tool for walking function in PwMS. Clinical trial: clinicaltrials.gov, NCT01576354, Multiple Sclerosis and Related Disorders, 63

Riparian forests are rare and valuable ecosystems in Central Asia, both due to their significance for biodiversity and to their provision of vital ecosystem services to local residents. However, the actual forest use behaviour is under-researched, official figures may not be trustworthy, and the question of over-use is up in the air. This paper sets out to shed light on riparian forest use behaviour by local residents using the example of Ak-Tal Village upon the Naryn River in Kyrgyzstan: Which economic use patterns do they practice (focusing on fuel wood and pasture)? Which other ecosystem services do they recognise? Is there forest over-exploitation? To answer these questions, this study builds on local knowledge, by applying the methods of focus group discussions and a household survey. Results show an extreme discrepancy between official wood consumption figures (50–60 m3 p.a.) and figures based on household wood consumption (310–404 m3 p.a.). The forest also serves as an important winter pasture over the seven months between October and April (stocking density 0.61 livestock units/ha), but payments for these ecosystem services are low, with annually 40 KGS/ha. Local residents are aware of additional material and nonmaterial ecosystem services of the riparian forest. Opinions diverge upon the question if there is forest over-exploitation, potentially because different stakeholders have different concepts of an optimal forest status. Consequently, optimal forest use behaviour can only be defined by the local users themselves, e.g., in a future stakeholder dialogue.

This paper considers Bayesian estimation of the threshold vector error correction (TVECM) model in moderate to large dimensions. Using the lagged cointegrating error as a threshold variable gives rise to additional difficulties that typically are solved by utilizing large sample approximations. By relying on Markov chain Monte Carlo methods, we are enabled to circumvent these issues and avoid computationally-prohibitive estimation strategies like the grid search. Due to the proliferation of parameters, we use novel global-local shrinkage priors in the spirit of Griffin and Brown (2010). We illustrate the merits of our approach in an application to five exchange rates vis-a-vis the US dollar by means of a forecasting comparison. Our findings indicate that adopting a non-linear modeling approach improves the predictive accuracy for most currencies relative to a set of simpler benchmark models and the random walk.

Within the present research study, a comparative evaluation of two different approaches for the development of a deep learning-based algorithm for the targeted detection of four selected electricity appliances in dairy farms is presented and discussed. Via a multilayer deep neural network based on the sequence-to-sequence (S2S) methodology, the algorithm allows to identify the state of the appliances according to the device-specific power signature by reading the daily load profile for the total power consumption. According to preliminary results, the multi-layer One-Directional Convolution Layer-Bidirectional GRU Recurrent Neural Network (1DConv-BRNN) model showed better performance, compared to a Long Short-Term Memory (LSTM)-based deep neural networks.

As robots become more advanced and capable, developing trust is an important factor of human-robot interaction and cooperation. However, as multiple environmental and social factors can influence trust, it is important to develop more elaborate scenarios and methods to measure human-robot trust. A widely used measurement of trust in social science is the investment game. In this study, we propose a scaled-up, immersive, science fiction Human-Robot Interaction (HRI) scenario for intrinsic motivation on human-robot collaboration, built upon the investment game and aimed at adapting the investment game for human-robot trust. For this purpose, we utilise two Neuro-Inspired Companion (NICO) - robots and a projected scenery. We investigate the applicability of our space mission experiment design to measure trust and the impact of non-verbal communication. We observe a correlation of 0.43 (p=0.02)between self-assessed trust and trust measured from the game and a positive impact of non-verbal communication on trust (p=0.0008) and robot perception for anthropomorphism (p=0.007) and animacy (p=0.00002). We conclude that our scenario is an appropriate method to measure trust in human-robot interaction and also to study how non-verbal communication influences a human's trust in robots.

Locomotor recovery after incomplete spinal cord injury (iSCI) is influenced by spinal and supraspinal networks. Conventional clinical gait analysis fails to differentiate between these components. There is evidence that corticospinal control is enhanced during targeted walking, where each foot must be continuously placed on visual targets in randomized order. This study investigates the potential of targeted walking in the functional assessment of corticospinal integrity. Twenty-one controls and 16 individuals with chronic iSCI performed normal and targeted walking on a treadmill while electromyograms (EMGs) and kinematics were recorded. Precision (% of accurate foot placements) in targeted walking was significantly lower in individuals with iSCI (82.9 ± 14.7%, controls: 94.9 ± 4.0%). Although the overall kinematic pattern was comparable between walking conditions, controls showed significantly higher semitendinosus (ST) activity before heel-strike during targeted walking. This was accompanied by a shift of relative EMG intensity from 90-120 Hz to lower frequencies of 20-60 Hz, previously associated with corticospinal control of muscle activity. Targeted walking in individuals with iSCI evoked smaller EMG changes, suggesting that the switch to more corticospinal control is impaired. Accordingly, mildly impaired iSCI individuals revealed higher adaptations to the targeted walking task than more-impaired individuals. Recording of EMGs during targeted walking holds potential as a research tool to reveal further insights into the neuromuscular control of locomotion. It also complements findings of pre-clinical studies and is a promising novel surrogate marker of integrity of corticospinal control in individuals with iSCI and other neurological impairments. Future studies should investigate its potential for diagnosis or tracking recovery during rehabilitation.

BACKGROUND Fampridine leads to significant walking improvements in many persons with multiple sclerosis (PwMS). However, a relevant proportion of PwMS does not respond to fampridine and predictors of initial drug responsiveness are unknown. METHODS Drug response to prolonged-release (PR)-fampridine was assessed in 55 PwMS using the timed 25-foot walk (T25FW), the 6-minute walk test (6MWT) and the 12-item multiple sclerosis walking scale (MSWS-12) as outcome parameters. Patients were treated with PR-fampridine and placebo each for 6 weeks in a randomised, double-blind, placebo-controlled trial with cross-over design (NCT01576354). Possible predictors of drug responsiveness were investigated by multiple correlation analysis and binary logistic regression models. An additional longitudinal analysis followed drug responses of 32 patients treated with PR-fampridine over 3 years to identify potential predictors of long-term drug responsiveness. RESULTS Severity of walking disability was positively correlated with enhanced responses to PR-fampridine. The strongest single predictor of drug responsiveness was poor 6MWT performance at baseline, which was positively correlated with enhanced drug response in the 6MWT (R=-0.541; P

The research work was funded by the Federal Ministry of Education and Research (BMBF) of the Federal Republic of Germany within the CLIENT II funding programme International Partnerships for Sustainable Innovations under the project “ÖkoFlussPlan” (Project ID 01LZ1802A-F). open access article The northern part of the globe is dominated by industrialisation and is well-developed. For many years, the southern part of the world (South Asia, Africa etc.) has been a target of research concentrating on access to energy (mainly electricity) in rural regions. However, the Central Asian region has not been a focus of energy research compared to South East Asia and Africa. Despite plentiful domestically available energy resources, the energy supply in Central Asia is very unevenly distributed between urban and rural areas. Almost half of the total population of Central Asia lives in rural areas and there is a lack of access to modern energy services to meet primary needs. To analyse the energy situation (i.e., electricity, heating, hot water consumption, cooking, etc.) in rural Central Asia, this paper reviews residential energy consumption trends in rural Central Asian regions as compared to urban areas. Furthermore, the paper illustrates the potential of renewable energies in Central Asia. To perform the study, a qualitative comparative analysis was conducted based on a literature review, data, and statistical information. In summary, the presented article discusses the rural energy situation analytically and provides in-depth insights of Central Asian energy infrastructure.

This review provides an overview of the precursor chemistry that has been developed around the phase-change material germanium-antimony-telluride, Ge2Sb2Te5 (GST). Thin films of GST can be deposited by employing either chemical vapor deposition (CVD) or atomic layer deposition (ALD) techniques. In both cases, the success of the layer deposition crucially depends on the proper choice of suitable molecular precursors. Previously reported processes mainly relied on simple alkoxides, alkyls, amides and halides of germanium, antimony, and tellurium. More sophisticated precursor design provided a number of promising new aziridinides and guanidinates.

Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions. We subsequently observed improved recovery of forelimb function after anti-Nogo-A treatment. Anterograde tracing of the corticospinal tract revealed enhanced axonal sprouting and arborisation within the spinal cord gray matter preferentially targeting pre-motor and motor spinal cord laminae on lesion level and above in the anti-Nogo-A-treated animals. An important additional effect of Nogo-A-neutralization was enhanced remyelination observed after lysolecithin-induced demyelination of spinal tracts. Whereas remyelinated fiber numbers in the lesion site were increased several fold, no effect of Nogo-A-inhibition was observed on oligodendrocyte precursor proliferation, migration, or differentiation. Enhancing remyelination and promoting axonal regeneration and plasticity represent important unmet medical needs in multiple sclerosis. Anti-Nogo-A antibodies hold promise as a potential new therapy for multiple sclerosis, in particular during the chronic phase of the disease when neurodegeneration and remyelination failure determine disability evolution.

In healthy subjects, changes in arm swing symmetry while walking are observed when a cognitive dual task is added, with a tendency toward left-dominant arm swing as cognitive load increases. We applied a modified Stroop word/color naming paradigm to investigate this effect in spinal cord injured (SCI) patients. Six patients with cervical SCI (cSCI), 6 with thoracic injuries (tSCI; all 12 patients American Spinal Injury Association [ASIA] Injury Score [AIS]D), and 12 healthy, matched controls underwent three-dimensional 3D gait analysis while walking normally at a comfortable speed (NW) and when performing an additional congruent (CS) and incongruent (IS) Stroop task. An arm swing symmetry index (ASI)-in which positive values indicate proportionally more movement on the left and vice versa-was calculated. Even in the baseline NW condition, all three subject groups showed larger arm movements on the left. In controls, ASI increased (NW, 13.7 ± 6.3; CS, 16.6 ± 6.4; IS, 19.6 ± 7.8) as the task became more demanding. A larger shift in tSCI patients (NW, 15.8 ± 6.0; CS, 23.4 ± 3.8; IS, 30.7 ± 4.4) was driven by a significant reduction in right wrist trajectory (p = 0.014), whereas cSCI patients showed a small reduction in mean ASI with high variability (NW, 14.2 ± 10.7; CS, 9.3 ± 13.5; IS, 6.0 ± 12.9). The effect of the IS task on ASI compared to baseline (NW) was significantly different between tSCI (+12.5 ± 6.3) and cSCI (-8.2 ± 6.0) patients (p = 0.011). Disruption of the long propriospinal connections coordinating arm and leg movements during walking may explain the heightened sensitivity to manipulation of cognitive load in tSCI, whereas the more robust automaticity in cSCI may be attributed to impaired supraspinal inputs in the context of preserved intraspinal pathways.