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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.

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.

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.

The floodplain areas along the Naryn River in Kyrgyzstan are essential as they hold the riparian (local) ecosystems because they provide firewood, pastureland, and areas for recreation and protection against erosion. Due to limited access to adequate, reliable, and sustainable energy services, the rural population usually derived their energy needs from multiple natural energy resources (i.e., firewood, charcoal, agricultural residues, animal dung, and wood branches). This is considered a common and predominant practice in rural Kyrgyzstan. This situation leads to a negative impact on local ecosystem services. In addition to that, the reliance on solid fuels contributes to indoor and outdoor air pollution, which is partially threatening the local ecosystem services. By contrast, the employment of renewable-based energy supply systems would substantially reduce the burden on the environment, which is mainly untapped. To integrate renewable energies, it is important to understand the energy behavior of floodplain communities. In that response, the presented article is the first attempt to capture the energy identity of the floodplain community of Kyrgyzstan based on a quantitative energy-based (on-site) household survey. Furthermore, the present research article synthesizes the driving factors that have a (direct or indirect) impact on the energy and local ecosystem services. In addition, the present article proposes a brief pathway for the sustainable energy transition. The article records the recommendation to integrate renewable energies to preserve the local ecosystems of Kyrgyzstan.

In both rural and urban areas, two-wheeler vehicles are the most common means of transportation, contributing to local air pollution and greenhouse gas emissions (GHG). Transitioning to electric two-wheeler vehicles can help reduce GHG emissions while also increasing the socioeconomic status of people in rural Kenya. Renewable energy systems can play a significant role in charging electric two-wheeled vehicles, resulting in lower carbon emissions and increased renewable energy penetration in rural Kenya. As a result, using the Conventional and Renewable Energy Optimization (CARNOT) Toolbox in the MATLAB/Simulink environment, this paper focuses on integrating and modeling electric two-wheeled vehicles (e-bikes) into an off-grid photovoltaic Water-Energy Hub located in the Lake Victoria Region of Western Kenya. Electricity demand data obtained from the Water-Energy Hub was investigated and analyzed. Potential solar energy surplus was identified and the surplus was used to incorporate the electric two-wheeler vehicles. The energy consumption of the electric two-wheeler vehicles was also measured in the field based on the rider’s driving behavior. The modeling results revealed an annual power consumption of 27,267 kWh, a photovoltaic (PV) electricity production of 37,785 kWh, and an electricity deficit of 370 kWh. The annual results show that PV generation exceeds power consumption, implying that there should be no electricity deficit. The results, however, do not represent the results in hourly resolution, ignoring the impact of weather fluctuation on PV production. As a result, in order to comprehend the electricity deficit, hourly resolution results are shown. A load optimization method was designed to efficiently integrate the electric 2-wheeler vehicle into the Water-Energy Hub in order to alleviate the electricity deficit. The yearly electricity deficit was decreased to 1 kWh and the annual electricity consumption was raised by 11% (i.e., 30,767 kWh), which is enough to charge four more electric two-wheeler batteries daily using the load optimization technique.

Walking dysfunction is common in people with multiple sclerosis (MS). Besides walking speed or endurance, one crucial feature of ambulatory function is the ability to adjust the gait pattern according to walking speed which relies on the integrity of spinal motor centres, their reciprocal connections to supraspinal networks and peripheral sensory input. To investigate the capacity of people with MS to modify their gait pattern in response to changes in walking speed. 3D gait analysis during free treadmill walking was performed in 35 people with MS and 20 healthy controls. Twelve kinematic parameters ranging from basic spatiotemporal measures to complex indicators of intralimb coordination were assessed at different absolute and relative walking speeds. Cadence, double-limb support time, trunk movements and especially measures of intralimb coordination demonstrated significantly less speed-dependent modifications in MS than in controls. These limitations were more prominent in subjects with stronger MS-related impairment (worse outcome in clinical walking tests, higher Expanded Disability Status Scale). The incapacity to modify specific elements of the walking pattern according to walking speed contributes to gait dysfunction in people with MS limiting activities of daily living. Gait modulation may serve as sensitive marker of walking function in MS. Clinicaltrials.gov, NCT01576354; first posted April 12, 2012.

Pheochromocytoma is a tumor arising from the adrenal medulla, most frequent benign and, due to the excretion of catecholamines, a rare cause of hypertension. The diagnosis of pheochromocytoma can be challenging because of its episodic nature, unspecific symptoms and rarity. Consequently, treatment can be delayed with serious consequences for the patient. We present a case report regarding a young man with episodes of severe hypertension over a period of at least 9 years. Ultimately, with a possible trigger effect from the intake of multiple energy drinks, the patient presented with severe hypertension, symptoms mimicking acute coronary syndrome, abnormal laboratory parameters and echocardiography suggestive of severe cardiomyopathy. The patient’s pheochromocytoma was incidentally identified in a computed tomography scan during the initial workup. Although a rare condition, pheochromocytoma should be considered as a differential diagnosis, especially in young patients presenting with unexplained hypertension, chest pain and cardiac dysfunction.

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.

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.

Myotonic Dystrophy Type 1 (DM1) is the most frequent hereditary, adult-onset muscular dystrophy. Nevertheless, DM1-associated cognitive-motor impairments have not been fully characterized so far. This study aimed at profiling cognitive and locomotor dysfunctions in these patients. In addition, cognitive-motor interactions were assessed using a dual-task paradigm. Comprehensive cognitive-motor impairment profiles were generated for 19 patients with DM1 and 19 healthy subjects by thorough clinical, biomechanical and neuropsychological examinations. Detailed gait analysis was performed using a 3D motion capture system, whereas cognitive function was assessed using a standardized neuropsychological test battery. Patients with DM1 showed impaired functional mobility, gait velocity and endurance. DM1-related gait pathology was mainly characterized by enhanced dynamic instability, gait variability, and restricted ankle dorsiflexion. Patients' cognitive impairments particularly concerned attentional functions. Dual-task conditions induced gait deviations that slightly differed between patients and controls. DM1-associated cognitive impairments correlated with reduced functional mobility and impaired ankle dorsiflexion. Patients with DM1 revealed significant impairments of walking function, balance and cognitive performance. Differential cognitive-motor interference and significant interactions between cognitive and motor dysfunctions point towards a prominent role of cognition in gait performance of patients with DM1.

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

Magnetic sphincter-augmentation (MSA) has been proven effective in the treatment of GERD. No consensus exists on whether crural closure should be performed. Our aim was to assess the impact of cruroplasty on reflux-control and quality of life. MSA-Patients treated between 03/2012-03/2017 were classified into those without hiatal hernia (“NHH”), those post-MSA (NHR) and those post-MSA/hiatal repair (HR). GERD-symptoms, PPI-intake, GERD-Health-related-Quality-of-Life (GERD-HRQL) and Alimentary Satisfaction were assessed. Sixty-eight patients underwent MSA, 26 patients had additional crural closure. PH-monitoring was negative in 80% of HR, 73% of NHR and 89% of NHH-patients. GERD-HRQL-total scores decreased significantly in all groups (p

Gait dysfunction is a common and relevant symptom in multiple sclerosis (MS). This study aimed to profile gait pathology in gait-impaired patients with MS using comprehensive 3D gait analysis and clinical walking tests. Thirty-seven patients with MS walked on the treadmill at their individual, sustainable speed while 20 healthy control subjects walked at all the different patient’s paces, allowing for comparisons independent of walking velocity. Kinematic analysis revealed pronounced restrictions in knee and ankle joint excursion, increased gait variability and asymmetry along with impaired dynamic stability in patients. The most discriminative single gait parameter, differentiating patients from controls with an accuracy of 83.3% (χ2 test; p = 0.0001), was reduced knee range of motion. Based on hierarchical cluster and principal component analysis, three principal pathological gait patterns were identified: a spastic-paretic, an ataxia-like, and an unstable gait. Follow-up assessments after 1 year indicated deterioration of walking function, particularly in patients with spastic-paretic gait patterns. Our findings suggest that impaired knee/ankle control is common in patients with MS. Personalised gait profiles and clustering algorithms may be promising tools for stratifying patients and to inform patient-tailored exercise programs. Responsive, objective outcome measures are important for monitoring disease progression and treatment effects in MS trials.

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.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Within the present study a novel concept for the demand-oriented power generation of a solid-biomass fueled combined heat and power (CHP) plant is investigated. The integration of a steam storage system into the plants process enables a decoupling of the steam (boiler) and the power generation (steam turbine). By buffering the steam, the power output of the turbine can be adjusted without changing the rated thermal capacity of the plant. Various available storage systems are selected and comparatively evaluated applying the adapted analytic hierarchy process (AHP). The technology assessment revealed that the combination of a steam accumulator and solid concrete storage represents the best suiting option. An initial model based simulation study is performed to identify the fundamental behaviour of this system, integrated in a biomass CHP plant. The operation principle is has proved their technical feasibility and seems to be applicable at a commercial scale. According to the modelling results flexible short term power generation in a time range of up to fifteen minutes is applicable. A load-range of almost the plants rated capacity can be achieved.

Accurate functional outcome measures are critical for both clinical trials and routine patient assessments. Many functional outcomes improve with test repetition, a phenomenon that can confound the findings of longitudinal assessments. In this viewpoint, we tackle the poorly considered issue of practice effects in prevailing clinical walking tests based on current literature, while also presenting the original data from our own work, in which we investigated practice effects in the timed 25-foot walk (T25FW), timed-up and go (TUG), and 2-minute walk test (2MWT). In these tests, performed on 3 consecutive days in 10 patients with multiple sclerosis and 40 healthy controls, we observed significant practice effects in several established walking outcomes, including a 9.0% improvement in patients’ TUG performance ( p = 0.0146). Pre-training in these walking tests prior to baseline measurement may mitigate practice effects, thereby improving the accuracy and value of their repeated use in research and clinical settings.

Treadmill-based gait analysis is widely used to investigate walking pathologies and quantify treatment effects on locomotion. Differential sensorimotor conditions during overground vs. treadmill walking necessitate initial familiarization to treadmill walking. Currently, there is no standardized treadmill acclimatization protocol and insufficient familiarization potentially confounds analyses. We monitored initial adaptations to treadmill walking in 40 healthy adults. Twenty-six walking parameters were assessed over 10 minutes with marker-based kinematic analysis and acclimatization profiles were generated. While 16 walking parameters demonstrated initial acclimatization followed by plateau performance, ten parameters remained stable. Distal lower limb control including ankle range of motion, toe trajectory and foot clearance underwent substantial adaptations. Moreover, intralimb coordination and gait variability also demonstrated acclimatization, while measures of symmetry and interlimb coordination did not. All parameters exhibiting a plateau after acclimatization did so within 6–7 minutes (425 strides). Older participants and those naïve to treadmill walking showed adaptations with higher amplitudes but over similar timescales. Our results suggest a minimum of 6 minutes treadmill acclimatization is required to reach a stable performance, and that this should suffice for both older and naïve healthy adults. The presented data aids in optimizing treadmill-based gait analysis and contributes to improving locomotor assessments in research and clinical settings.

Flexible power provision from biogas can significantly contribute to energy systems with high shares of renewables. However, the characteristics and demands for this flexibility are not clearly defined or measured. In this paper eight indicators are defined to shape “flexibility” and perform a downstream investigation of eight research projects focusing on flexible energy provision of biogas plants. The indicators are structured in three dimensions (1) velocity (ramps) by which the system can be modulated, (2) power range (bandwidth) and (3) duration for specific load conditions. Based on these indicators bottlenecks for the flexibility potential were identified. One crucial result shows that short-term flexibility of biogas plants is mainly driven by properties of the combined heat and power unit (velocity and bandwidth). The long-term flexibility depends mainly on gas storage, mode of operation and ability for modulation of the target gas production.

Locomotion relies on the fine-tuned coordination of different muscles which are controlled by particular neural circuits. Depending on the attendant conditions, walking patterns must be modified to optimally meet the demands of the task. Assessing neuromuscular control during dynamic conditions is methodologically highly challenging and prone to artifacts. Here we aim at assessing corticospinal involvement during different locomotor tasks using non-invasive surface electromyography. Activity in tibialis anterior (TA) and gastrocnemius medialis (GM) muscles was monitored by electromyograms (EMGs) in 27 healthy volunteers (11 female) during regular walking, walking while engaged in simultaneous cognitive dual tasks, walking with partial visual restriction, and skilled, targeted locomotion. Whereas EMG intensity of the TA and GM was considerably altered while walking with partial visual restriction and during targeted locomotion, dual-task walking induced only minor changes in total EMG intensity compared to regular walking. Targeted walking resulted in enhanced EMG intensity of GM in the frequency range associated with Piper rhythm synchronies. Likewise, targeted walking induced enhanced EMG intensity of TA at the Piper rhythm frequency around heelstrike, but not during the swing phase. Our findings indicate task- and phase-dependent modulations of neuromuscular control in distal leg muscles during various locomotor conditions in healthy subjects. Enhanced EMG intensity in the Piper rhythm frequency during targeted walking points toward enforced corticospinal drive during challenging locomotor tasks. These findings indicate that comprehensive time-frequency EMG analysis is able to gauge cortical involvement during different movement programs in a non-invasive manner and might be used as complementary diagnostic tool to assess baseline integrity of the corticospinal tract and to monitor changes in corticospinal drive as induced by neurorehabilitation interventions or during disease progression.

A mathematical model of a flat-plate solar collector was developed on the basis of the physical principles of optics and heat transfer in order to determine collector’s component temperatures as well as collector efficiency. In contrast to many available models, the targeted use of this dynamic model is the detailed, theoretical investigation of the thermal behaviour of newly developed or adjusted collector designs on component level, for example, absorber, casing, or transparent cover. The defined model is based on a multinode network (absorber, fluid, glazing, and backside insulation) containing the relevant physical equations to transfer the energy. The heat transfer network covers heat conduction, convection, and radiation. Furthermore, the collector optics is defined for the plane glazing and the absorber surface and also considers interactions between them. The model enables the variation of physical properties considering the geometric parameters and materials. Finally, the model was validated using measurement data and existing efficiency curve models. Both comparisons proved high accuracy of the developed model with deviation of up to 3% in collector efficiency and 1 K in component temperatures.

Gait dysfunction is common in patients with multiple sclerosis (PwMS). Treatment with prolonged-release fampridine (PR-fampridine) improves walking ability in some PwMS. Associated fampridine-induced changes in the walking pattern are still poorly understood but may provide a better understanding of the mechanisms underlying the beneficial drug effects. 61 PwMS were treated with PR-fampridine in a randomized, monocentric, double-blind and placebo-controlled clinical trial with crossover design (FAMPKIN). Drug-induced improvements in walking speed (Timed-25-Foot Walk; T25FW) and endurance (6-Minute Walk Test; 6MWT) were quantified. In this sub-study of the FAMPKIN trial, fampridine-induced changes in kinetic gait patterns were analyzed by pressure-based foot print analysis during treadmill walking. Vertical ground reaction forces were analyzed during different gait phases. Kinetic data of 44 PwMS was eligible for analysis. During double-blind treatment with PR-fampridine, patients performed significantly better in the T25FW and 6MWT than during placebo treatment (p < 0.0001 for both). At the group level (n = 44), there were no significant changes of gait kinetics under PR-fampridine vs. placebo. However, we found relevant changes of walking kinetics regarding forces during loading, single limb and pre-swing phase in a patient sub-group (n = 8). Interestingly, this sub-group demonstrated superior responsiveness to PR-fampridine in the clinical walking tests compared to those patients without any fampridine-induced changes in kinetics (n = 36). Our results demonstrate fampridine-induced changes in gait kinetics in a sub-group of PwMS. These gait pattern changes were accompanied by improved clinical walking performance under PR-fampridine. These results shed some light on the biomechanical changes in walking patterns underlying enhanced fampridine-induced gait performance.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. The increasing number of fluctuating renewable power producers in the electricity grid leads to several challenges in the grid's infrastructure and its operation. Biomass combustion plants, however, can be modified to increase the flexibility of power production by integrating steam storage devices. In this paper, the available storage systems are evaluated, considering the boundaries of the plants and the requirements of power grids and markets. An objective result is generated by conducting a Delphi study using energy experts. The Utility-Value-Analysis method is used to identify the most promising storage concept. Using this methodology, the resulting storage concept is found to be a combination of a steam accumulator and a solid storage.

Background Magnetic sphincter augmentation (MSA) is a modern treatment option for gastroesophageal reflux disease (GERD); however, laparoscopic fundoplication remains the gold standard. The aim of the study was to evaluate outcomes of MSA patients at a reflux center. Methods A retrospective review was performed of all patients that underwent MSA between March 2012 and November 2017. Out of 110 patients, 68 with a follow-up >3 months were included. Postoperative gastrointestinal symptoms, proton pump inhibitor (PPI) intake, GERD-Health-related Quality of Life (GERD-HRQL) and alimentary satisfaction (AS) were assessed. Postoperative esophageal functioning tests were performed in 50% of patients. Results Sixty-eight patients underwent MSA; hiatal repair was performed in 31 cases. The median OR time was 27 min, and no intraoperative complications occurred. The median follow-up was 13 months (IQR 4.2–45). Endoscopic dilatation was performed in 2 patients (3%) and device removal in another 2 cases. The postoperative GERD-HRQL score was significantly reduced (3 vs. 24; p

A 62-year-old female with a history of stroke due to cerebral arteriosclerosis suffered from recurrent fainting (

To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS). Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue. We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients’ perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders. Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS.

Study Design This is a focused review article. Objectives To identify important concepts in lower extremity (LE) assessment with a focus on locomotor outcomes and provide guidance on how existing outcome measurement tools may be best used to assess experimental therapies in spinal cord injury (SCI). The emphasis lies on LE outcomes in individuals with complete and incomplete SCI in Phase II-III trials. Methods This review includes a summary of topics discussed during a workshop focusing on LE function in SCI, conceptual discussion of corresponding outcome measures and additional focused literature review. Results There are a number of sensitive, accurate, and responsive outcome tools measuring both quantitative and qualitative aspects of LE function. However, in trials with individuals with very acute injuries, a baseline assessment of the primary (or secondary) LE outcome measure is often not feasible. Conclusion There is no single outcome measure to assess all individuals with SCI that can be used to monitor changes in LE function regardless of severity and level of injury. Surrogate markers have to be used to assess LE function in individuals with severe SCI. However, it is generally agreed that a direct measurement of the performance for an appropriate functional activity supersedes any surrogate marker. LE assessments have to be refined so they can be used across all time points after SCI, regardless of the level or severity of spinal injury. Sponsors Craig H. Neilsen Foundation, Spinal Cord Outcomes Partnership Endeavor.

Background: Prolonged-release fampridine (PR-fampridine, 4-aminopyridine) increases walking speed in the timed 25-foot walk test (T25FW) in some patients (timed-walk responders) with multiple sclerosis (MS). Objective: To explore the effects of PR-fampridine on different aspects of walking function and to identify associated gait modifications in subjects with MS. Methods: In this prospective, randomized, placebo-controlled, double-blind, phase II study (FAMPKIN; clinicaltrials.gov , NCT01576354), subjects received a 6-week course of oral placebo or PR-fampridine treatment (10 mg, twice daily) before crossing over. Using 3D-motion-analysis, kinematic and kinetic parameters were assessed during treadmill walking (primary endpoint). Clinical outcome measures included T25FW, 6-minute walk test (6MWT), and balance scales. Physical activity in everyday life was measured with an accelerometer device. Results: Data from 55 patients were suitable for analysis. Seventeen subjects were timed-walk responders under PR-fampridine. For the total study population and for responders, a significant increase in walking speed (T25FW) and distance (6MWT) was observed. Gait pattern changes were found at the single-subject level and correlated with improvements in the T25FW and 6MWT. Physical activity was increased in responders. Conclusion: PR-fampridine improves walking speed, endurance, and everyday physical activity in a subset of subjects with MS and leads to individual modifications of the gait pattern.

Uncontrolled muscle spasms often develop after spinal cord injury. Structural and functional maladaptive changes in spinal neuronal circuits below the lesion site were postulated as an underlying mechanism but remain to be demonstrated in detail. To further explore the background of such secondary phenomena, rats received a complete sacral spinal cord transection at S(2) spinal level. Animals progressively developed signs of tail spasms starting 1 week after injury. Immunohistochemistry was performed on S(3/4) spinal cord sections from intact rats and animals were sacrificed 1, 4 and 12 weeks after injury. We found a progressive decrease of cholinergic input onto motoneuron somata starting 1 week post-lesion succeeded by shrinkage of the cholinergic interneuron cell bodies located around the central canal. The number of inhibitory GABAergic boutons in close contact with Ia afferent fibers was greatly reduced at 1 week after injury, potentially leading to a loss of inhibitory control of the Ia stretch reflex pathways. In addition, a gradual loss and shrinkage of GAD65 positive GABAergic cell bodies was detected in the medial portion of the spinal cord gray matter. These results show that major structural changes occur in the connectivity of the sacral spinal cord interneuronal circuits below the level of transection. They may contribute in an important way to the development of spastic symptoms after spinal cord injury, while reduced cholinergic input on motoneurons is assumed to result in the rapid exhaustion of the central drive required for the performance of locomotor movements in animals and humans.

Rodents are frequently used to model damage and diseases of the central nervous system (CNS) that lead to functional deficits. Impaired locomotor function is currently evaluated by using scoring systems or biomechanical measures. These methods often suffer from limitations such as subjectivity, nonlinearity and low sensitivity, or focus on a few very restricted aspects of movement. Thus, full quantitative profiles of motor deficits after CNS damage are lacking. Here we report the detailed characterization of locomotor impairments after applying common forms of CNS damage in rodents. We obtained many objective and quantitative readouts from rats with either spinal cord injuries or strokes and from transgenic mice (Epha4−/−) during skilled walking, overground walking, wading and swimming, resulting in model-specific locomotor profiles. Our testing and analysis method enables comprehensive assessment of locomotor function in rodents and has broad application in various fields of life science research.

Minimum toe clearance (MTC) occurs during a highly dynamic phase of the gait cycle and is associated with the highest risk of unintentional contact with obstacles or the ground. Age, cognitive function, attention and visual feedback affect foot clearance but how these factors interact to influence MTC control is not fully understood. We measured MTC in 121 healthy individuals aged 20–80 under four treadmill walking conditions; normal walking, lower visual field restriction and two Stroop colour/word naming tasks of two difficulty levels. Competition for cognitive and attentional resources from the Stroop task resulted in significantly lower mean MTC in older adults, with the difficult Stroop task associated with a higher frequency of extremely low MTC values and subsequently an increased modelled probability of tripping in this group. While older adults responded to visual restriction by markedly skewing MTC distributions towards higher values, this condition was also associated with frequent, extremely low MTC values. We reveal task-specific, age-dependent patterns of MTC control in healthy adults. Age-related differences are most pronounced during heavy, distracting cognitive load. Analysis of critically-low MTC values during dual-task walking may have utility in the evaluation of locomotor control and fall risk in older adults and patients with motor control deficits.

Objective:To expand upon the limited knowledge of the long-term effects of prolonged-release (PR) fampridine in patients with multiple sclerosis (PwMS) regarding safety, walking improvements, and changes in drug responsiveness.Methods:Fifty-three PwMS who completed the FAMPKIN core study were included in this extension trial. Drug efficacy was assessed in an open-label and randomized double-blind, placebo-controlled study design with regular baseline assessments over a period of 2 years using the Timed 25-Foot Walk (T25FW), 6-Minute Walk Test (6MWT), and 12-item MS Walking Scale (MSWS-12) as outcome measures.Results:The data showed good tolerability and persisting efficacy of PR fampridine during long-term treatment in PwMS. Significant improvements in walking speed, endurance, and self-perceived ambulatory function were observed during open-label (T25FW: +11.5%; 6MWT: 10.7%; MSWS-12: 6.1 points) and double-blind controlled treatment with PR fampridine (T25FW: +13.1%; 6MWT: 11.9%; MSWS-12: 7.4 points). Several patients showed changes in drug responsiveness over time, resulting in an increased proportion of patients exceeding 10% or 20% improvements in walking measures after long-term treatment.Conclusions:Efficacy and tolerability data confirmed PR fampridine as a valuable long-term treatment for improving ambulatory function in gait-impaired PwMS. Similar results in open-label and double-blind phases reveal that the walking tests used are objective and reliable. The considerable proportion of patients in whom responsiveness to PR fampridine changed over time emphasizes the importance of regular reassessment of drug efficacy in clinical practice to optimize treatment. Such reassessments seem to be particularly important in patients with poor initial drug responses, as this group demonstrated enhanced responsiveness after long-term treatment.Clinicaltrials.gov identifier:NCT01576354.Classification of evidence:This study provides Class II evidence that PR fampridine significantly improved gait compared to placebo in a 2-week study in PwMS who had been using PR fampridine for 2 years.

The research project ‘Solar Heat in the Liquid Food Industry’ (part of the FORETA Research Network [1] ) focused on the development and optimisation of low-temperature heating systems for the liquid food industry. Its main objectives are in energy efficiency, waste heat recovery and the feasibility of a solar-thermal process heating system. Based on the particular simulation results the overall solar-thermal potentials for German breweries and dairies were determined. In this connection a literature review indicated that most of the potential studies on solar-thermal energy use in the industry or related to specific industrial sectors are based on the total use of low-temperature heat. In opposition to these results, the available and mainly limited roof area was found to be a more important aspect for the solar-thermal potential. Hence, the development of a methodology for a site- specific analysis was necessary. The interconnection of only a few defined evaluation criteria resulted in a more realistic estimation of the potential for a solar-thermal heat supply.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. The increasing share of fluctuating energy generation causes new challenges in the power grids. The demand for flexible power plants is increasing. Solid biomass fueled combined heat and power (CHP) plants are able to get modified into dispatchable power plants. In this paper, boundaries for this operation mode are summarized and several measures to achieve a flexible power generation in biomass CHP plants are concluded. The integration of high temperature storage system for buffering the plants steam seems to be the most promising, however the least investigated option. The tasks and necessary features of such storage systems were investigated and a review of available technologies and systems for the storage of steam made.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. With the expansion of renewable, but fluctuating power generation from wind and solar energy, the demand placed on the security and reliability of supply is increasing. To ensure grid stability in the future, controllable power production via biogas plants has great technical and economic potential. In order to demonstrate the operation of controllable electricity production, an existing industrial-scale biogas plant was modified to produce electricity in accordance to the demands of the electricity market. In the course of scientific monitoring, extensive instrumentation was installed at the demonstration plant, which allows detailed evaluation of the operation of the limited gas storage volume and the behavior of the combined heat and power units (CHPs) during flexible operation.

The ‘Network of Excellence in Renewable Energy Technologies for Development’ also known as "Network of Energy Excellence for Development" (NEED), comprises a consortium of five partner institutions from Botswana, Germany, Namibia and Zambia undertaking collaborative research aimed at kick-starting and institutionalizing the widespread exploitation of renewable energy resources in the Southern African region. Starting with three countries, namely Botswana, Namibia, and Zambia, the network is expected to gradually expand to cover the SADC region. The paper highlights the activity areas and concerns of the NEED project: establishing the dominant renewable energy technologies (RET); capacity building; harmonizing industry standards; institutionalizing policies and research strategies; and developing RET concepts for the dry and wet regions of Namibia and Botswana, respectively.

Therapy for relapsing-remitting multiple sclerosis with natalizumab (Tysabri; Biogen Idec) has been shown to be effective in the reduction of the clinical relapse rate and disability progression. However, real-life longitudinal data, including years before baseline, are rare.An observational single-center study was carried out. We analyzed data from 64 consecutive patients with multiple sclerosis.After 1 year of treatment (n = 64), score on the Expanded Disability Status Scale (EDSS) decreased by 0.47 points (P = 0.047) and the annualized relapse rate (ARR) decreased by 82% (P0.001). After 2 years (n = 41), EDSS score was still reduced by 0.28 (not significant) and ARR was reduced by 69% (P0.001). After 3 years (n = 23), EDSS score was reduced by 0.26 (not significant), and ARR was reduced by 77% (P0.001). Reduction of EDSS score and ARR did not depend on baseline ARR (1-2 vs2) or EDSS score and was not biased by exceptional high disease activity or relapses around baseline.These real-life data reinforce that natalizumab is effective over years, reduces ARR, and stabilizes EDSS score independent of baseline ARR, baseline EDSS score, or baseline treatment.

With a drag coefficient of cD = 0.26 the new Audi A8 4.2 FSI is ahead of its rivals. Low lift coefficients at the front and rear axles provide a dynamic driving experience and ensure supreme dynamic stability at high motorway speeds. The standard of wind noise represents a new milestone in the luxury saloon car class and emphasises the harmonious overall impression made by the new Audi A8 in this segment. Aerodynamics and aeroacoustics therefore make a significant contribution to efficient, dynamic and comfortable travel in the new Audi A8.

Small lesions of the adult central nervous system (CNS) often have a good prognosis with extensive functional recovery based in part on spontaneous neuritic sprouting and rearrangements of projections. This is well documented for the cortex, but these changes can also occur in the spinal cord. Nogo-A is a protein present in CNS myelin that inhibits neurite growth. Models of spinal cord injury (SCI) in rats and macaque monkeys demonstrate that treatment with function-blocking antibodies of Nogo-A results in an upregulation of growth-specific proteins, enhanced regenerative and compensatory sprouting of fibers, and the formation of new functional connections in the spinal cord. In animals with unilateral sensorimotor cortex lesions followed by Nogo-A antibody treatment, fibers from the intact corticofugal system crossed the midline, supplying innervation to the denervated brain stem or spinal cord. Behavioral tests showed marked improvements of functional recovery in the Nogo-A antibody treated spinal cord- or brain-injured animals. A Phase I clinical trial applying anti-Nogo-A antibody to subjects with acute SCI has been successfully conducted and a multicentric, multinational Phase II trial is currently in preparation.

Objective: Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions. Methods and Results: Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti–Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms. Interpretation: The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect. ANN NEUROL 2010;68:48 –57 Motor and sensory deficits are an immediate consequence of spinal cord injury (SCI), caused by damage to ascending and descending fiber tracts. In addition, signs and symptoms of spasticity, such as muscle hypertonia, hyperreflexia, clonus, and spontaneous muscle spasms, develop gradually over weeks and months in 65 to 78% of patients with spinal cord injury. 1–3 The pathophysiology of spasticity is not well understood, but secondary plastic changes in the spinal cord below the lesion, such as alterations in reflex pathways, changes in the excitability of motoneurons, and formation of inappropriate new connections, have been implicated. 4–6 Painful muscle spasms are a common manifestation of the spastic syndrome. 3

Study design: A retrospective analysis of prospectively collected data. Objective: A hemisection of the spinal cord is a frequently used animal model for spinal cord injury (SCI), the corresponding human condition, that is, the Brown-Sequard syndrome (BS), is relatively rare as compared with the central cord syndrome (CC). The time course of neurological deficit, functional recovery, impulse conductivity and rehabilitation length of stay in BS and CC subjects were compared. Setting: Nine European Spinal Cord Injury Rehabilitation Centers. Methods: Motor score, walking function, daily life activities, somatosensory evoked potentials and length of stay were evaluated 1 and 6 months after SCI, and were compared between age-matched groups of tetraparetic BS and CC subjects. Results: For all analyzed measures no difference in the time course of improvement was found in 15 matched pairs. Conclusion: In contrast to the assumption of a better outcome of subjects with BS, no difference was found between the two incomplete SCI groups. This is of interest with respect to the different potential mechanisms leading to a recovery of functions in these two SCI subgroups.

We studied the influence of levodopa (L-Dopa) on training effects in subjects with spinal cord injury (SCI). A low-dose of L-Dopa per day is known to enhance the effects of physical training after stroke. This is tested here in subjects suffering a SCI. Twelve subacute, incomplete SCI (iSCI) subjects (ASIA C and D) were randomized in a trial with a double-blind, crossover design to receive 6 weeks of L-Dopa (200 mg), followed by 6 weeks of placebo, or vice versa. Outcome measures were ASIA Motor-Score (AMS) reflecting motor recovery; walking ability, assessed by the Walking Index of Spinal Cord Injury (WISCI); and Activities of Daily Living (ADL), as monitored by the Spinal Cord Independence Measure (SCIM). Both placebo and L-Dopa, in combination with physiotherapy, produced a significant motor recovery after SCI. The combination of L-Dopa and physiotherapy had no greater effect on the outcome than placebo and physiotherapy. The possible reasons for the different effect of L-Dopa in stroke and iSCI subjects are discussed.

Temsirolimus showed clinical efficacy in refractory squamous cell carcinoma of the head and neck (SCCHN), who failed platinum and epidermal growth factor receptor inhibition. Tumor shrinkage in 39% and a progression-free survival rate of 40% at 12 weeks warrants future studies in SCCHN, which may define a novel treatment paradigm in SCCHN. However, no predictive molecular marker was identified. Background Squamous cell carcinoma of the head and neck (SCCHN) is a common disease, which has a poor prognosis after failure of therapy. Activation of the PI3K–AKT–mTOR axis is commonly detected in recurrent or metastatic SCCHN, and provided the rationale for the clinical phase II trial in pretreated SCCHN. Patients and methods The primary end point was the progression-free survival rate (PFR) at 12 weeks. Forty eligible patients have been recruited after failure of platinum chemotherapy and cetuximab. A preplanned futility analysis was successfully passed after ≥1 success was detected in 20 patients. Secondary objectives consisted of progression-free survival (PFS), disease control rate (DCR), overall survival (OS), safety and tolerability, and predictive biomarkers for KRAS, BRAF, PIK3CA mutations, and HPV status. Archived tumor tissue was analyzed for DNA sequence. Results A total of 40 patients were eligible. The PFR at 12 weeks was 40% (95% CI 25.0–54.6). The median PFS and OS were 56 days (95% CI 36–113 days) and 152 days (76–256 days), respectively. In 33 assessable patients, disease stabilization occurred in 57.6%, with tumor shrinkage in 13 patients (39.4%). Overall, the treatment was well tolerated. Fatigue (47.5%), anemia (25.0%), nausea (20.0%), and pneumonia (20.0%) were the most common adverse events. Neither PIK3CA mutations, nor HPV status were predictive for success with temsirolimus treatment. No mutations were found for KRAS or BRAF. Conclusion Tumor shrinkage and efficacy parameter indicate that inhibition of the PI3K–AKT–mTOR axis was a putative novel treatment paradigm for SCCHN. We could not identify parameters predictive for treatment success of temsirolimus, which underscores the need for refinement of the molecular analysis in future studies. Clinical trials number NCT01172769.

Encouraged by Dr. Davis' insightful comment on our article,1 we retrospectively quantified the long-term responsiveness to fampridine of the patients with multiple sclerosis in our sample cotreated with natalizumab over a period of 2 years. Of 17 patients (32%) treated with natalizumab at the screening visit, only 6 were still receiving treatment with natalizumab 2 years later; natalizumab was stopped in 5 patients and a further 6 discontinued the study. Monitoring the efficacy of fampridine over 2 years in the 6 patients concomitantly treated with natalizumab did not reveal an increased benefit with respect to walking function compared to the other study participants. Patients cotreated with natalizumab improved by 5.4% in maximal walking speed (vs 3.0% in the rest of the population) and by 0.4% in walking endurance (vs 4.6%) and demonstrated no difference in self-perceived walking ability (vs 6.5 points improvement in the rest of the population). This post hoc analysis is obviously limited by the small number of subjects. Dr. Davis' hypothesis and other potential mechanisms, discussed in our article,1 underlying the observed increased responsiveness to fampridine over time should be investigated in future studies with larger cohorts and of sufficient statistical power.