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Most established clinical walking tests assess specific aspects of movement function (velocity, endurance, etc.) but are generally unable to determine specific biomechanical or neurological deficits that limit an individual's ability to walk. Recently, inertial measurement units (IMU) have been used to collect objective kinematic data for gait analysis and could be a valuable extension for clinical assessments (e.g., functional walking measures). This study assesses the reliability of an IMU-based overground gait analysis during the 2-min walk test (2mWT) in individuals with spinal cord injury (SCI). Furthermore, the study elaborates on the capability of IMUs to distinguish between different gait characteristics in individuals with SCI. Twenty-six individuals (aged 22-79) with acute or chronic SCI (AIS: C and D) completed the 2mWT with IMUs attached above each ankle on 2 test days, separated by 1 to 7 days. The IMU-based gait analysis showed good to excellent test-retest reliability (ICC: 0.77-0.99) for all gait parameters. Gait profiles remained stable between two measurements. Sensor-based gait profiling was able to reveal patient-specific gait impairments even in individuals with the same walking performance in the 2mWT. IMUs are a valuable add-on to clinical gait assessments and deliver reliable information on detailed gait pathologies in individuals with SCI.

Background Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events. Methods and Results Using Danish nationwide registries, all patients with first‐time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis‐to‐ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90‐day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5‐year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07–1.35), 1.29 (95% CI, 1.13–1.47), and 1.40 (95% CI, 1.28–1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04–1.44) in the late ablation group compared with the early ablation group. Conclusions In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early‐compared with late‐ablation patients., BACKGROUND: Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events. METHODS AND RESULTS: Using Danish nationwide registries, all patients with first-time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis-to-ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90-day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5-year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07-1.35), 1.29 (95% CI, 1.13-1.47), and 1.40 (95% CI, 1.28-1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04-1.44) in the late ablation group compared with the early ablation group. CONCLUSIONS: In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early-compared with late-ablation patients.

Background Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events. Methods and Results Using Danish nationwide registries, all patients with first‐time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis‐to‐ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90‐day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5‐year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07–1.35), 1.29 (95% CI, 1.13–1.47), and 1.40 (95% CI, 1.28–1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04–1.44) in the late ablation group compared with the early ablation group. Conclusions In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early‐compared with late‐ablation patients., BACKGROUND: Guidelines recommend prioritizing treatment with antiarrhythmic drugs before referral of patients with atrial fibrillation to ablation, delaying a potential subsequent ablation. However, delaying ablation may affect ablation outcomes. We sought to investigate the impact of duration from diagnosis to ablation on the risk of atrial fibrillation recurrence and adverse events. METHODS AND RESULTS: Using Danish nationwide registries, all patients with first-time ablation for atrial fibrillation were identified and included from 2010 to 2018. Patients were divided into 4 groups by diagnosis-to-ablation time: <1.0 year (early ablation), 1.0 to 1.9 years, 2.0 to 2.9 years, and >2.9 years (late ablation). The primary end point was atrial fibrillation recurrence after the 90-day blanking period, defined by admission for atrial fibrillation, cardioversions, use of antiarrhythmic drugs, or repeat atrial fibrillation ablations. The secondary end point was a composite end point of heart failure, ischemic stroke, or death, and each event individually. The study cohort consisted of 7705 patients. The 5-year cumulative incidence of atrial fibrillation recurrence in the 4 groups was 42.9%, 54.8%, 55.9%, and 58.4%, respectively. Hazard ratios were 1.20 (95% CI, 1.07-1.35), 1.29 (95% CI, 1.13-1.47), and 1.40 (95% CI, 1.28-1.53), respectively, with the early ablation group as reference. The hazard ratio for the combined secondary end point was 1.22 (95% CI, 1.04-1.44) in the late ablation group compared with the early ablation group. CONCLUSIONS: In patients undergoing ablation for atrial fibrillation, early ablation was associated with a significantly lower risk of atrial fibrillation recurrence. Furthermore, the associated risk of heart failure, ischemic stroke, or death was significantly lower in early-compared with late-ablation patients.

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.

In order to characterize the potential hazards of anthropogenic nanomaterials to humanity and the environment, as well as the successful implementation of SSbD approaches, it is imperative to have access to analytic tools that provide sensitive detection at low concentrations in complex media such as surface and waste water, sewage sludge, soil, biota, etc. against same element and particle backgrounds. The radiolabeling of nanomaterials provides these features for laboratory studies. We present an overview of our radiolabelling efforts with examples of their applications. We have developed a library of radiolabelling methods for the most common anthropogenic nanomaterials, including nanoplastics, that allow us to track nanomaterials in release, mobility and uptake studies including such complex systems as waste water treatment plants, plants, water organisms and soil. The labeling techniques are the synthesis of the nanoparticles using radioactive starting materials, the binding of the radiotracer to the nanoparticles, the activation of the nanoparticles using proton/neutron irradiation, the recoil labeling utilizing the recoil of a nuclear reaction to implant a radiotracer into the nanoparticle, and the in-diffusion of radiotracers into the nanoparticles at elevated temperatures. Using these methods we have produced [105/110mAg]Ag, [124/125/131I]CNTs, [48V]TiO2, [139/141Ce]CeO2, [7Be]MWCNT, [64Cu]SiO2, [64Cu]PS, etc. for accurate quantification in complex media at an environmentally relevant low concentrations range even with a background of the same element and without complicated sample preparations necessary. Using these approaches, we can go beyond mere quantification and gain mechanistic insights into nanomaterial behavior in the environment. For example, we have tracked the dissolution and internalization of CeO2 NP in freshwater shrimp, the dissolution of CdSe/ZnS quantum dots in waste water treatment or the size-dependent uptake of TiO2 in plants.

In order to characterize the potential hazards of anthropogenic nanomaterials to humanity and the environment, as well as the successful implementation of SSbD approaches, it is imperative to have access to analytic tools that provide sensitive detection at low concentrations in complex media such as surface and waste water, sewage sludge, soil, biota, etc. against same element and particle backgrounds. The radiolabeling of nanomaterials provides these features for laboratory studies. We present an overview of our radiolabelling efforts with examples of their applications. We have developed a library of radiolabelling methods for the most common anthropogenic nanomaterials, including nanoplastics, that allow us to track nanomaterials in release, mobility and uptake studies including such complex systems as waste water treatment plants, plants, water organisms and soil. The labeling techniques are the synthesis of the nanoparticles using radioactive starting materials, the binding of the radiotracer to the nanoparticles, the activation of the nanoparticles using proton/neutron irradiation, the recoil labeling utilizing the recoil of a nuclear reaction to implant a radiotracer into the nanoparticle, and the in-diffusion of radiotracers into the nanoparticles at elevated temperatures. Using these methods we have produced [105/110mAg]Ag, [124/125/131I]CNTs, [48V]TiO2, [139/141Ce]CeO2, [7Be]MWCNT, [64Cu]SiO2, [64Cu]PS, etc. for accurate quantification in complex media at an environmentally relevant low concentrations range even with a background of the same element and without complicated sample preparations necessary. Using these approaches, we can go beyond mere quantification and gain mechanistic insights into nanomaterial behavior in the environment. For example, we have tracked the dissolution and internalization of CeO2 NP in freshwater shrimp, the dissolution of CdSe/ZnS quantum dots in waste water treatment or the size-dependent uptake of TiO2 in plants.

Although small and medium-sized enterprises (SMEs) contribute considerably to Germany's carbon emissions, regional savings and cooperative banks - SMEs' most important financiers - hardly consider this aspect in lending to these businesses. However, given Germany's commitment to climate neutrality by 2045, suitable approaches for injecting climate finance into these SME lending processes are greatly required. Against this background, the paper at hand aims to introduce the specific case of regional banks into the debate on green finance and green banking and suggest future research in this context. In discussing the state of research on the peculiarities of regional savings and cooperative banks, we outline the resulting opportunities and limitations for climate impact assessments in SME lending. We argue that while the dual bottom-line orientation of regional banks in Germany precludes them from applying simple positive or negative screenings, their in-depth knowledge about local clients and circumstances enables them to be active and engaging partners for the green transformation of SMEs. Nonetheless, we explain why developing solutions to utilise this knowledge for climate finance by integrating climate impact assessments into routine lending processes remains a particularly challenging task.

Aims Overweight 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 results Through 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. Conclusion Following 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., Aims: Overweight 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 results: Through 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. Conclusion: Following 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.

we propose a Bayesian Logistic Smooth Transition Autoregressive (LSTAR) model with stochastic volatility (SV) to model inflation dynamics in a nonlinear fashion. Inflationary regimes are determined by smoothed money growth which serves as a transition variable that governs the transition between regimes. We apply this approach to quarterly data from the US, the UK and Canada and are able to identify well-known, high inflation periods in the samples. Moreover, our results suggest that the role of money growth is specific to the economy under scrutiny and it can help to improve forecasting accuracy. Finally, we analyze a variety of different model specifications and are able to confirm that adjusted money growth still has leading indicator properties on inflation regimes.

we propose a Bayesian Logistic Smooth Transition Autoregressive (LSTAR) model with stochastic volatility (SV) to model inflation dynamics in a nonlinear fashion. Inflationary regimes are determined by smoothed money growth which serves as a transition variable that governs the transition between regimes. We apply this approach to quarterly data from the US, the UK and Canada and are able to identify well-known, high inflation periods in the samples. Moreover, our results suggest that the role of money growth is specific to the economy under scrutiny and it can help to improve forecasting accuracy. Finally, we analyze a variety of different model specifications and are able to confirm that adjusted money growth still has leading indicator properties on inflation regimes.

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.

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.

The dissemination of solar district heating systems enables a more climate-friendly heat supply. However, the feasible dimensions of collector arrays and thermal storages as well as their distribution are often limited in urban areas and the plants suffer from high heat generation costs. Therefore, the objective of this thesis is the analysis of an improved hydraulic design with distributed solar thermal plants and suitable control strategies for an optimised utilisation of the solar heat., Die Verbreitung solarer Nahwärmesysteme ermöglicht eine klimafreundlichere Wärmeversorgung. Jedoch sind die möglichen Größen von Kollektorfeldern und thermischen Speichern sowie deren Verteilung in urbanen Gebieten oft eingeschränkt und die Anlagen leiden unter hohen Wärmegestehungskosten. Daher ist das Ziel dieser Arbeit die Analyse eines verbesserten hydraulischen Designs mit verteilten Solarthermieanlagen und angepassten Regelungsstrategien für eine optimierte Nutzung der Solarwärme.

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.

STUDY DESIGN Multicentre-observational study. OBJECTIVES The 6-minute walk test (6mWT) is an established assessment of walking function in individuals with spinal cord injury (SCI). However, walking 6 min can be demanding for severely impaired individuals. The 2-minute walk test (2mWT) could be an appropriate alternative that has already been validated in other neurological disorders. The aim of this study was to assess construct validity and test-rest reliability of the 2mWT in individuals with SCI. In addition, the influence of walking performance on sensitivity to change of the 2mWT was assessed. SETTING Swiss Paraplegic Center Nottwil, Switzerland; Balgrist University Hospital, Zürich, Switzerland. METHODS Fifty individuals (aged 18-79) with SCI (neurological level of injury: C1-L3, AIS: A-D) were assessed on two test days separated by 1 to 7 days. The first assessment consisted of a 2mWT familiarization, followed by a 2mWT and 10-meter walk test (10MWT) (including the Walking Index for Spinal Cord Injury (WISCI II)) in randomized order. The second assessment consisted of 2mWT and 6mWT in randomized order. Tests were separated by at least 30 min of rest. RESULTS The interclass correlation coefficient between the 2mWT assessed on the first and second test day was excellent (r = 0.980, p < 0.001). The 2mWT correlated very strongly with the 6mWT (r = 0.992, p < 0.001) and the 10MWT (r = 0.964, p < 0.001), and moderately with the WISCI II (r = 0.571, p < 0.001). Sensitivity to change was slightly affected by walking performance. CONCLUSION The 2mWT is a valid and reliable alternative to the 6mWT to measure walking function in individuals with SCI. TRIAL REGISTRATION NCT04555759.

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)

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 =

Polymeric solar thermal flat plate collectors promise lower costs compared to metal-based ones. In this context, drain back systems can make a meaningful contribution, as the setup of such systems complements the material characteristics of polymeric flat plate collectors. To assess the economic efficiency of drain back systems with polymeric collectors, this thesis aims for the determination of the levelised cost of heat and a comparison with conventional solar thermal systems., Solarthermische Kunststoffkollektoren versprechen niedrigere Kosten im Vergleich zu metallischen Flachkollektoren. In diesem Zusammenhang stellen Drain-Back-Systeme einen vielversprechenden Ansatz dar, da sie sich mit den Anforderungen von Kunststoffkollektoren wechselseitig ergänzen. Ziel dieser Arbeit ist die Beurteilung der Wirtschaftlichkeit auf Basis der Wärmegestehungskosten von Drain-Back-Systemen mit Kunststoffkollektoren im Vergleich zu konventionellen solarthermischen Systemen.

Polymeric solar thermal flat plate collectors promise lower costs compared to metal-based ones. In this context, drain back systems can make a meaningful contribution, as the setup of such systems complements the material characteristics of polymeric flat plate collectors. To assess the economic efficiency of drain back systems with polymeric collectors, this thesis aims for the determination of the levelised cost of heat and a comparison with conventional solar thermal systems., Solarthermische Kunststoffkollektoren versprechen niedrigere Kosten im Vergleich zu metallischen Flachkollektoren. In diesem Zusammenhang stellen Drain-Back-Systeme einen vielversprechenden Ansatz dar, da sie sich mit den Anforderungen von Kunststoffkollektoren wechselseitig ergänzen. Ziel dieser Arbeit ist die Beurteilung der Wirtschaftlichkeit auf Basis der Wärmegestehungskosten von Drain-Back-Systemen mit Kunststoffkollektoren im Vergleich zu konventionellen solarthermischen Systemen.

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.

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.

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.

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.

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%). While the overall kinematic pattern was comparable between walking conditions, controls showed significantly higher semitendinosus activity before heel-strike during targeted walking. This was accompanied by a shift of relative EMG intensity from 90-120Hz to lower frequencies of 20-60 Hz, previously associated with corticospinal control of muscle activity. Targeted walking in iSCI individuals 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 preclinical 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.

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.

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 d

Root architecture development determines the sites in soil where roots provide input of carbon and take up water and solutes. However, root architecture is difficult to determine experimentally when grown in opaque soil. Thus, root architectural models have been widely used and been further developed into functional-structural models that simulate the fate of water and solutes in the soil-root system. We present a root architectural model, CRootBox, as a flexible framework to model architecture and its interactions with static and dynamic soil environments. CRootBox is a C++-based root architecture model with Python binding, so that CRootBox can be included via a shared library into any Python code. Output formats include VTP, DGF, RSML and CSV. We further created a database of published root architectural parameters. The capabilities of CRootBox for the unconfined growth of single root systems, as well as the different parameter sets, are highlighted into a freely available web application. We demonstrate the use of CRootBox for 5 different cases (1) free growth of individual root systems (2) growth of root systems in containers as a way to mimic experimental setups, (3), field scale simulation, (4) root growth as affected by heterogeneous, static soil conditions, and (5) coupling CRootBox with Soil Physics with Python code to dynamically compute water flow in soil, root water uptake, and water flow inside roots. In conclusion, we present a fast and flexible functional-structural root model which is based on state-of-the-art computational science methods. Its aim is to facilitate modelling of root responses to environmental conditions as well as the impact of root on soil. In the future, we plan to extend this approach to the aboveground part of the plant.

Treadmill experiments suggest that left-dominant arm swing is common in healthy walking adults and is modulated by cognitive dual-tasking. Little is known about arm swing asymmetry in overground walking. We report directional (dASI) and non-directional arm swing symmetry indices (ndASI) from 334 adults (mean age 68.6 ± 5.9 y) walking overground at comfortable (NW) and fast (FW) speeds and while completing a serial subtraction task (DT). dASI and ndASI were calculated from sagittal shoulder range of motion data generated by inertial measurement units affixed to the wrist. Most (91%) participants were right-handed. Group mean arm swing amplitude was significantly larger on the left in all walking conditions. During NW, ndASI was 39.5 ± 21.8, with a dASI of 21.9 ± 39.5. Distribution of dASI was bimodal with an approximately 2:1 ratio of left:right-dominant arm swing. There were no differences in ndASI between conditions but dASI was smaller during DT compared to FW (15.2 vs 24.6; p = 0.009). Handedness was unrelated to ndASI, dASI or the change in ASI metrics under DT. Left-dominant arm swing is the norm in healthy human walking irrespective of walking condition or handedness. As disease markers, ndASI and dASI may have different and complementary roles.

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.

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.

Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex ‘take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the forelimb

Cervical incomplete spinal cord injuries often lead to severe and persistent impairments of sensorimotor functions and are clinically the most frequent type of spinal cord injury. Understanding the motor impairments and the possible functional recovery of upper and lower extremities is of great importance. Animal models investigating motor dysfunction following cervical spinal cord injury are rare. We analysed the differential spontaneous recovery of fore- and hindlimb locomotion by detailed kinematic analysis in adult rats with unilateral C4/C5 hemisection, a lesion that leads to the Brown-Séquard syndrome in humans. The results showed disproportionately better performance of hindlimb compared with forelimb locomotion; hindlimb locomotion showed substantial recovery, whereas the ipsilesional forelimb remained in a very poor functional state. Such a differential motor recovery pattern is also known to occur in monkeys and in humans after similar spinal cord lesions. On the lesioned side, cortico-, rubro-, vestibulo- and reticulospinal tracts and the important modulatory serotonergic, dopaminergic and noradrenergic fibre systems were interrupted by the lesion. In an attempt to facilitate locomotion, different monoaminergic agonists were injected intrathecally. Injections of specific serotonergic and noradrenergic agonists in the chronic phase after the spinal cord lesion revealed remarkable, although mostly functionally negative, modulations of particular parameters of hindlimb locomotion. In contrast, forelimb locomotion was mostly unresponsive to these agonists. These results, therefore, show fundamental differences between fore- and hindlimb spinal motor circuitries and their functional dependence on remaining descending inputs and exogenous spinal excitation. Understanding these differences may help to develop future therapeutic strategies to improve upper and lower limb function in patients with incomplete cervical spinal cord injuries

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.

Human arm swing looks and feels highly automated, yet it is increasingly apparent that higher centres, including the cortex, are involved in many aspects of locomotor control. The addition of a cognitive task increases arm swing asymmetry during walking, but the characteristics and mechanism of this asymmetry are unclear. We hypothesized that this effect is lateralized and a Stroop word-colour naming task-primarily involving left hemisphere structures-would reduce right arm swing only. We recorded gait in 83 healthy subjects aged 18-80 walking normally on a treadmill and while performing a congruent and incongruent Stroop task. The primary measure of arm swing asymmetry-an index based on both three-dimensional wrist trajectories in which positive values indicate proportionally smaller movements on the right-increased significantly under dual-task conditions in those aged 40-59 and further still in the over-60s, driven by reduced right arm flexion. Right arm swing attenuation appears to be the norm in humans performing a locomotor-cognitive dual-task, confirming a prominent role of the brain in locomotor behaviour. Women under 60 are surprisingly resistant to this effect, revealing unexpected gender differences atop the hierarchical chain of locomotor control.

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.

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.

In this analysis, Tropospheric Emission Spectrometer (TES) V004 nadir ozone (O3) profiles are validated with more than 4400 coinciding ozonesonde measurements taken across the world from the World Ozone and Ultraviolet Radiation Data Centre (WOUDC) during the period 2005–2010. The TES observation operator was applied to the sonde data to ensure a consistent comparison between TES and ozonesonde data, i.e. without the influence of the a priori O3 profile needed to regulate the retrieval. Generally, TES V004 O3 retrievals are biased high by 2–7 ppbv (7–15%) in the troposphere, consistent with validation results from earlier studies. Because of two degrees of freedom for signal in the troposphere, we can distinguish between upper and lower troposphere mean biases, respectively ranging from -0.4 to +13.3 ppbv for the upper troposphere and +3.9 to +6.0 ppbv for the lower troposphere. Focusing on the 464 hPa retrieval level, broadly representative of the free tropospheric O3, we find differences in the TES biases for the tropics (+3 ppbv, +7%), sub-tropics (+5 ppbv, +11%), and northern (+7 ppbv, +13%) and southern mid-latitudes (+4 ppbv, +10%). The relatively long-term record (6 yr) of TES–ozonesonde comparisons allowed us to quantify temporal variations in TES biases at 464 hPa. We find that there are no discernable biases in each of these latitudinal bands; temporal variations in the bias are typically within the uncertainty of the difference between TES and ozonesondes. Establishing these bias patterns is important in order to make meaningful use of TES O3 data in applications such as model evaluation, trend analysis, or data assimilation.

In this analysis, Tropospheric Emission Spectrometer (TES) V004 nadir ozone (O3) profiles are validated with more than 4400 coinciding ozonesonde measurements taken across the world from the World Ozone and Ultraviolet Radiation Data Centre (WOUDC) during the period 2005–2010. The TES observation operator was applied to the sonde data to ensure a consistent comparison between TES and ozonesonde data, i.e. without the influence of the a priori O3 profile needed to regulate the retrieval. Generally, TES V004 O3 retrievals are biased high by 2–7 ppbv (7–15%) in the troposphere, consistent with validation results from earlier studies. Because of two degrees of freedom for signal in the troposphere, we can distinguish between upper and lower troposphere mean biases, respectively ranging from -0.4 to +13.3 ppbv for the upper troposphere and +3.9 to +6.0 ppbv for the lower troposphere. Focusing on the 464 hPa retrieval level, broadly representative of the free tropospheric O3, we find differences in the TES biases for the tropics (+3 ppbv, +7%), sub-tropics (+5 ppbv, +11%), and northern (+7 ppbv, +13%) and southern mid-latitudes (+4 ppbv, +10%). The relatively long-term record (6 yr) of TES–ozonesonde comparisons allowed us to quantify temporal variations in TES biases at 464 hPa. We find that there are no discernable biases in each of these latitudinal bands; temporal variations in the bias are typically within the uncertainty of the difference between TES and ozonesondes. Establishing these bias patterns is important in order to make meaningful use of TES O3 data in applications such as model evaluation, trend analysis, or data assimilation.

Whereas large injuries to the brain lead to considerable irreversible functional impairments, smaller strokes or traumatic lesions are often associated with good recovery. This recovery occurs spontaneously, and there is ample evidence from preclinical studies to suggest that adjacent undamaged areas (also known as peri-infarct regions) of the cortex 'take over' control of the disrupted functions. In rodents, sprouting of axons and dendrites has been observed in this region following stroke, while reduced inhibition from horizontal or callosal connections, or plastic changes in subcortical connections, could also occur. The exact mechanisms underlying functional recovery after small- to medium-sized strokes remain undetermined but are of utmost importance for understanding the human situation and for designing effective treatments and rehabilitation strategies. In the present study, we selectively destroyed large parts of the forelimb motor and premotor cortex of adult rats with an ischaemic injury. A behavioural test requiring highly skilled, cortically controlled forelimb movements showed that some animals recovered well from this lesion whereas others did not. To investigate the reasons behind these differences, we used anterograde and retrograde tracing techniques and intracortical microstimulation. Retrograde tracing from the cervical spinal cord showed a correlation between the number of cervically projecting corticospinal neurons present in the hindlimb sensory-motor cortex and good behavioural recovery. Anterograde tracing from the hindlimb sensory-motor cortex also showed a positive correlation between the degree of functional recovery and the sprouting of neurons from this region into the cervical spinal cord. Finally, intracortical microstimulation confirmed the positive correlation between rewiring of the hindlimb sensory-motor cortex and the degree of forelimb motor recovery. In conclusion, these experiments suggest that following stroke to the forelimb

OBJECTIVES: 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. METHODS: An observational single-center study was carried out. We analyzed data from 64 consecutive patients with multiple sclerosis. RESULTS: 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% (P < 0.001). After 2 years (n = 41), EDSS score was still reduced by 0.28 (not significant) and ARR was reduced by 69% (P < 0.001). After 3 years (n = 23), EDSS score was reduced by 0.26 (not significant), and ARR was reduced by 77% (P < 0.001). Reduction of EDSS score and ARR did not depend on baseline ARR (1-2 vs >2) or EDSS score and was not biased by exceptional high disease activity or relapses around baseline. CONCLUSIONS: 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.

Cervical incomplete spinal cord injuries often lead to severe and persistent impairments of sensorimotor functions and are clinically the most frequent type of spinal cord injury. Understanding the motor impairments and the possible functional recovery of upper and lower extremities is of great importance. Animal models investigating motor dysfunction following cervical spinal cord injury are rare. We analysed the differential spontaneous recovery of fore- and hindlimb locomotion by detailed kinematic analysis in adult rats with unilateral C4/C5 hemisection, a lesion that leads to the Brown-Séquard syndrome in humans. The results showed disproportionately better performance of hindlimb compared with forelimb locomotion; hindlimb locomotion showed substantial recovery, whereas the ipsilesional forelimb remained in a very poor functional state. Such a differential motor recovery pattern is also known to occur in monkeys and in humans after similar spinal cord lesions. On the lesioned side, cortico-, rubro-, vestibulo- and reticulospinal tracts and the important modulatory serotonergic, dopaminergic and noradrenergic fibre systems were interrupted by the lesion. In an attempt to facilitate locomotion, different monoaminergic agonists were injected intrathecally. Injections of specific serotonergic and noradrenergic agonists in the chronic phase after the spinal cord lesion revealed remarkable, although mostly functionally negative, modulations of particular parameters of hindlimb locomotion. In contrast, forelimb locomotion was mostly unresponsive to these agonists. These results, therefore, show fundamental differences between fore- and hindlimb spinal motor circuitries and their functional dependence on remaining descending inputs and exogenous spinal excitation. Understanding these differences may help to develop future therapeutic strategies to improve upper and lower limb function in patients with incomplete cervical spinal cord injuries.

Das Modell ATOMIS (Assessment Tool for Metals in Soils) prognostiziert für die Schwermetalle Ni, Cu, Zn und Cd landnutzungsabhängig den Schwermetallhaushalt in landwirtschaftlich genutzten Oberböden. In dieser Arbeit wurde das Modell anhand von Messdaten aus einer intensiv ackerbaulich genutzten Region validiert und die Unsicherheit der Modellergebnisse abgeschätzt. Im Rahmen der Validierung wurde der Oberboden von 24 unterschiedlich bewirtschafteten Ackerstandorten in der Wetterau (Hessen) beprobt und hinsichtlich der Schwermetallgehalte und charakteristischer Bodeneigenschaften analysiert. Für diese Standorte liegen langfristige Dokumentationen zur Flächenbewirtschaftung (Düngemitteleinsatz etc.) vor, welche als Eingangsdaten in der Modellierung mit ATOMIS berücksichtigt werden. Die Validierung erfolgte durch den Vergleich der simulierten Schwermetallgesamtgehalte am Ende des Bilanzierungszeitraumes mit den gemessenen Daten aus Königswasser-Extrakten. Des Weiteren wurden die Zwischenergebnisse der im Modell implementierten Pedotransferfunktionen geprüft. Hierbei wurde die simulierte sorbierte Schwermetallfraktion mit gemessenen EDTA-extrahierbaren Werten verglichen. Die berechneten Bodenlösungskonzentrationen wurden den Analyseergebnissen aus Ca(NO3)2-Extrakten gegenübergestellt. Die Validierungsergebnisse zeigen, dass das Modell ATOMIS die Schwermetallgesamt-gehalte für alle Elemente im Größenbereich der Messwerte der untersuchten Standorte berechnet. Dabei sind die Unsicherheiten der Modellergebnisse mit Variationskoeffizienten von < 10 % bei Cu und < 20 % bei Ni, Zn und Cd als niedrig einzuschätzen. Die modellierte Änderung der Schwermetallgesamtgehalte (Schwermetall-Akkumulation) im simulierten Zeitraum ist jedoch meist sehr gering und wird teilweise durch die Modellunsicherheiten überdeckt. Bei der Validierung der sorbierten und gelösten Schwermetallfraktion sind sehr hohe Unsicherheiten in der Bilanzierung mit ATOMIS festzustellen (insbesondere für Ni, Cu un, ATOMIS (Assessment Tool for Metals in Soils) is a model that estimates site-specifically the long-term evolution of heavy metals (Ni, Cu, Zn, Cd) in top soils depending on land use and cultivation system. In this study, the model was validated on the basis of measured data from soils in an intensive agricultural used region called Wetterau (Hesse/Germany). Samples from the top soil were taken at 24 sites and analysed for heavy metal contents and characteristic soil properties. For the sample sites longtime management documentations (soil tillage, fertilization, etc.) were available. The validation of ATOMIS was accomplished by comparing the predicted total heavy metal contents with the measured values (aqua regia extracted) of the 24 sites. The model is based on two pedotransfer functions to calculate sorbed and solved heavy metal concentrations in the soil. These results were also considered in the validation process by comparing the simulations with measured contents in EDTA- and Ca(NO3)2 extracts. Furthermore, the uncertainties of the different model outputs were assessed. The results show good model predictions for total heavy metal contents depending on land management for almost all examined sites regarding Ni, Cu, Zn, and Cd. The uncertainty of the model results was very low. The coefficient of variation was less than 10 % for Cu and slightly higher (< 20 %) for Ni, Zn, and Cd. However the calculated rates for accumulation and decline of the metal contents in the soil were very low over the simulated time periods. In this way, the model uncertainties partially bracketed the changes of the metal contents in the calculated period. Consequently the considered time period was too short for some sites to achieve a clear concentration trend which limits the conclusions that can be drawn from the validation results. The validation of other heavy metal fractions showed high uncertainties of model results in predicting the potential exchangeable (sorbed) as well as so

A lateral hemisection injury of the cervical spinal cord results in Brown-Séquard syndrome in humans and rats. The hands/forelimbs on the injured side are rendered permanently impaired, but the legs/hindlimbs recover locomotor functions. This is accompanied by increased use of the forelimb on the uninjured side. Nothing is known about the cortical circuits that correspond to these behavioral adaptations. In this study, on adult rats with cervical spinal cord lateral hemisection lesions (at segment C3/4), we explored the sensory representation and corticospinal projection of the intact (ipsilesional) cortex. Using blood oxygenation level-dependent functional magnetic resonance imaging and voltage-sensitive dye (VSD) imaging, we found that the cortex develops an enhanced representation of the unimpaired forepaw by 12 weeks after injury. VSD imaging also revealed the cortical spatio-temporal dynamics in response to electrical stimulation of the ipsilateral forepaw or hindpaw. Interestingly, stimulation of the ipsilesional hindpaw at 12 weeks showed a distinct activation of the hindlimb area in the intact, ipsilateral cortex, probably via the injury-spared spinothalamic pathway. Anterograde tracing of corticospinal axons from the intact cortex showed sprouting to recross the midline, innervating the spinal segments below the injury in both cervical and lumbar segments. Retrograde tracing of these midline-crossing axons from the cervical spinal cord (at segment C6/7) revealed the formation of a new ipsilateral forelimb representation in the cortex. Our results demonstrate profound reorganizations of the intact sensory-motor cortex after unilateral spinal cord injury. These changes may contribute to the behavioral adaptations, notably for the recovery of the ipsilesional hindlimb.