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Abstract Background Use of cannabis-based products is becoming more frequent, and it is important that healthcare professionals are informed and confident about them when making evidence-based decisions about their use. This study aimed to gain an international perspective on the attitudes, knowledge, and confidence of healthcare professionals about cannabis-based products. Methods An online questionnaire regarding these products was completed by 1580 healthcare professionals (neurologists, psychiatrists, general practitioners, pharmacists and nurses) from 16 countries across Asia, Europe, Oceania, South America, and the Middle East. Results Respondents expressed a high level of interest in cannabis-based products (median score 9 out of 10) and reported that they felt knowledgeable about them (median score 6 out of 7). They reported a high level of confidence when providing patients with information on cannabis-based products, returning median scores of 6 and 5 out of 7 for their legality and regulations, and their benefits and risks, respectively. Despite this, healthcare professionals sought further information on cannabis-based products across areas including legality, neurobiology, and scientific evidence. Finally, 59% (n = 930) of respondents considered robust clinical trial evidence as the most important factor to ensure patient safety in the context of these products. Few nominally significant differences emerged between healthcare professionals from different specialities or regions. Conclusion In conclusion, this large survey of attitudes held by healthcare professionals towards cannabis-based products revealed a high level of interest and a demand for more information. Limitations of this study include potential sample bias and limited external validity.

Abstract Background Gait impairment is a relevant problem in persons with multiple sclerosis (pwMS). The Multiple Sclerosis Walking Scale 12 (MSWS-12) is a valid Patient Reported Outcome Measure (PROM) to evaluate walking ability in pwMS. The aim of this study was to provide a linguistically valid translation of MSWS-12 into German language (MSWS-12/D) and to evaluate its psychometric properties. Methods The MSWS-12 was translated in a process modified from guidelines for the cross-cultural adaption of PROMs, and a pre-test was applied in a small sample of 20 pwMS to evaluate comprehensibility and acceptance. Psychometric properties (floor and ceiling effects, internal consistency, construct validity) were then assessed in 124 pwMS seen at academic MS centers. Construct validity was evaluated against Expanded Disability Status Scale (EDSS) and maximum gait speed in the Timed 25-Foot Walk (T25FW). Results Although the sample covered a wide spectrum of symptom severity, the majority had rather low levels of disability (EDSS median 2.0) and 6.5% scored EDSS of 0. In this sample, MSWS-12/D showed floor effects (36% with score 0) and for internal consistency, a Cronbach’s alpha of 0.98 was calculated. MSWS-12/D score showed a relevant correlation to EDSS (ρ = 0.73) and T25FW speed (r=-0.72). Conclusion We provide MSWS-12/D as a linguistically valid German version of MSWS-12. Psychometric properties (acceptance, floor and ceiling effects, internal consistency and construct validity) in pwMS were similar to those described for the original version. This indicates that MSWS-12/D can be applied as equivalent to the original version in German speaking pwMS. Results support the relevance of PROMs to capture patient perception of walking ability in addition to performance-based assessments such as maximum walking speed or maximum walking distance.

Background: The spectrum of disease-modifying therapies (DMTs) for people with multiple sclerosis (PwMS) has expanded over years, but data on treatment strategies is largely lacking. DMT switches are common clinical practice. Objective: To compare switchers and non-switchers, characterize the first DMT switch and identify reasons and predictors for switching the first DMT. Methods: Data on 2722 PwMS from the German MS Registry were retrospectively analyzed regarding sociodemographic/clinical differences between 1361 switchers (PwMS discontinuing the first DMT) and non-switchers matched according to age, sex, and observation period. Frequencies of first and second DMTs were calculated and switch reasons identified. Predictors for DMT switches were revealed using univariable and multivariable regression models. Results: Switchers and non-switchers differed significantly regarding time to first DMT, education, calendar period of the first DMT start (2014–2017 versus 2018–2021), first DMT class used [mild-to-moderate efficacy (MME) versus high-efficacy (HE) DMT], time on first DMT, and disease activity at first DMT start or cessation/last follow-up. The majority of PwMS started with MME DMTs (77.1%), with the most common being glatiramer acetate, dimethyl/diroximel fumarate, and beta-interferon variants. Switchers changed treatment more often to HE DMTs (39.6%), most commonly sphingosine-1-phosphate receptor modulators, anti-CD20 monoclonal antibodies, and natalizumab. Fewer PwMS switched to MME DMTs (35.9%), with the most common being dimethyl/diroximel fumarate, teriflunomide, or beta-interferon. Among 1045 PwMS with sufficient data (76.8% of 1361 switchers), the most frequent reasons for discontinuing the first DMT were disease activity despite DMT (63.1%), adverse events (17.1%), and patient request (8.3%). Predictors for the first DMT switch were MME DMT as initial treatment [odds ratio (OR) = 2.83 (1.76–4.61), p

In this work, an evanescent Bragg grating sensor inscribed in a few-mode planar polymer waveguide was integrated into microchannel structures and characterized by various chemical applications. The planar waveguide and the microchannels consisted of epoxide-based polymers. The Bragg grating structure was postprocessed by using point-by-point direct inscription technology. By monitoring the central wavelength shift of the reflected Bragg signal, the sensor showed a temperature sensitivity of −47.75 pm/K. Moreover, the functionality of the evanescent field-based measurements is demonstrated with two application examples: the refractive index sensing of different aqueous solutions and gas-phase hydrogen concentration detection. For the latter application, the sensor was additionally coated with a functional layer based on palladium nanoparticles. During the refractive index sensing measurement, the sensor achieved a sensitivity of 6.5 nm/RIU from air to 99.9% pure isopropyl alcohol. For the gas-phase hydrogen detection, the coated sensor achieved a reproducible concentration detection up to 4 vol% hydrogen. According to the reported experimental results, the integrated Bragg-grating-based waveguide sensor demonstrates high potential for applications based on the lab-on-a-chip concept.

Unreplicated field trials and genomic prediction are both used to enhance the efficiency in early selection stages of a hybrid maize breeding program. No results are available on the optimal experimental design when combining both approaches. Our objectives were to investigate the effect of the training set design on the accuracy of genomic prediction in unreplicated maize test crosses. We carried out a cross validation study on basis of an experimental data set consisting of 1436 hybrids evaluated for yield and moisture for which genotyping information of 461 SNP markers were available. Training set designs of different size, implementing within environment prediction, within year prediction, across year prediction, and combinations of data sources across years and environments were compared with respect to their prediction accuracy. Across year prediction did not reach prediction accuracies that are useful for genomic selection. Within year prediction across environments provided useful correlations between observed and predicted breeding values. The prediction accuracies did not improve when adding to the training set data from previous years. We conclude that using all data available from unreplicated tests of the current breeding cycle provides a good accuracy of predicting test crosses, whereas adding data from previous breeding cycles, in which the genotypes are less related to the tested material, has only limited value for increasing the prediction accuracy.

The crucial question for this exploration is: how could ordinary citizens (Gemeine), who had no chance of becoming members of the city-council, be incorporated into a common decision-making-process in the Late Middle Ages? In the background of this specific research-question lie the fundamental criteria for the ideal of urban peace and common good (gemein Gut) as an ideal vision of community. The following examples are primarily from Franconia, an area which had neither a unifying territory nor a supreme ruler. Instead, it was dominated by a multitude of different secular and spiritual rulers with many castles, monasteries and towns/citie. The town’s community was organized into neighborhoods, suburbs, quarters. Therefore, the quartermasters (Viertelsmeister) played an important role as speaker or representatives of the quarters or suburbs. The variety of possible duties for quartermasters were enormous. The quartermasters as representatives of the quarter communities were, for example, questioned by the council when it came to socio-politically sensitive issues. Mentioning the quartermasters and the community during the Peasants War is not coincidental but tells us a lot about the crisis of confidence of the city council by the citizens. A few hints should demonstrate the political influence of quartermasters in Franconian cities and towns as an example for future comparable research projects.

Abstract In 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry (GMSR) as a long-term data repository for MS healthcare research. By the establishment of a network of participating neurological centres of different healthcare sectors across Germany, GMSR provides observational real-world data on long-term disease progression, sociodemographic factors, treatment and the healthcare status of people with MS. This paper aims to illustrate the framework of the GMSR. Structure, design and data quality processes as well as collaborations of the GMSR are presented. The registry’s dataset, status and results are discussed. As of 08 January 2021, 187 centres from different healthcare sectors participate in the GMSR. Following its infrastructure and dataset specification upgrades in 2014, more than 196,000 visits have been recorded relating to more than 33,000 persons with MS (PwMS). The GMSR enables monitoring of PwMS in Germany, supports scientific research projects, and collaborates with national and international MS data repositories and initiatives. With its recent pharmacovigilance extension, it aligns with EMA recommendations and helps to ensure early detection of therapy-related safety signals.

Background: Multiple sclerosis patients often develop neurogenic lower urinary tract dysfunction with a potential risk of upper urinary tract damage. Diagnostic tools are urodynamics, bladder diary, uroflowmetry, and post-void residual, but recommendations for their use are controversial. Objective: We aimed to identify clinical parameters indicative of neurogenic lower urinary tract dysfunction in multiple sclerosis patients. Methods: 207 patients were prospectively assessed independent of the presence of lower urinary tract symptoms. We analyzed Expanded Disability Status Scale scores, uroflowmetry, post-void residual, rate of urinary tract infections, standardized voiding frequency, and voided volume in correlation with urodynamic findings. Results: We found a significant correlation between post-void residual (odds ratio (OR) 4.17, confidence interval (CI) 1.20–22.46), urinary tract infection rate (OR 3.91, CI 1.13–21.0), voided volume (OR 4.53, CI 1.85–11.99), increased standardized voiding frequency (OR 7.40, CI 2.15–39.66), and urodynamic findings indicative of neurogenic lower urinary tract dysfunction. Expanded Disability Status Scale shows no correlation. Those parameters (except post-void residual) are also associated with reduced bladder compliance, as potential risk for kidney damage. Conclusion: Therefore, bladder diary and urinary tract infection rate should be routinely assessed to identify patients who require urodynamics.

These/Ziel: Anhand weniger Beispiele aus dem frühen 15. sowie aus dem 17. und frühen 18. Jahrhundert kann die Ausreise von Bewohnern fränkischer Städte und Orte nach Thorn skizziert werden. Im Mittelpunkt steht die Würzburger Familie Lindwurm, näherhin ein Jost von Lindwurm, der am 4. Juli 1404 ein Empfehlungsschreiben des Würzburger Stadtrates ausgestellt bekam, das sich im Staatsarchiv in Thorn erhalten hat. Forschungsmethode: Literaturübersicht und Analyse von Archivquellen. Ergebnisse/Schlussfolgerungen: Die Motive für diesen Schritt bleiben leider letztlich unbekannt, eine Beziehung zum Deutschen Orden ist nicht erkennbar. Der Beitrag kann das große Thema der innereuropäischen Wanderungsbewegungen in einem Einzelbeispiel anschaulich machen.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options. The efficacy of tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies. To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters. Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of –2/–3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.

The combination of near-field microscopy along with nonlinear optical spectroscopic techniques is presented here. The scanning near-field imaging technique can be integrated with nonlinear spectroscopic techniques to improve spatial and axial resolution of the images. Additionally, ultrafast dynamics can be probed down to nano-scale dimension. The review shows some examples for this combination, which resulted in an exciton map and vibrational contrast images with sub-wavelength resolution. Results of two-color femtosecond time-resolved pump-probe experiments using scanning near-field optical microscopy (SNOM) on thin films of the organic semiconductor 3,4,9,10 Perylenetetracarboxylic dianhydride (PTCDA) are presented. While nonlinear Raman techniques have been used to obtain highly resolved images in combination with near-field microscopy, the use of femtosecond laser pulses in electronic resonance still constitutes a big challenge. Here, we present our first results on coherent anti-Stokes Raman scattering (fs-CARS) with femtosecond laser pulses detected in the near-field using SNOM. We demonstrate that highly spatially resolved images can be obtained from poly(3-hexylthiophene) (P3HT) nano-structures where the fs-CARS process was in resonance with the P3HT absorption and with characteristic P3HT vibrational modes without destruction of the samples. Sub-diffraction limited lateral resolution is achieved. Especially the height resolution clearly surpasses that obtained with standard microCARS. These results will be the basis for future investigations of mode-selective dynamics in the near-field.

Increasing investments in resource efficiency is considered essential for transitioning towards a sustainable model of economic growth. This article presents evidence on the complex incentives, trade-offs, and challenges associated with the economics and politics of resource efficiency investments, especially in light of the Sustainable Development Goals and the Paris Climate Agreement. By synthesising and evaluating a wide range of empirical evidence, practitioners’ insights, and policy perspectives, this article carefully examines the role of resource efficiency in reconciling environmental and economic objectives. It makes particular reference to the investment barriers and transitional implications of moving economies towards more circular and resource efficient pathways. In doing so, it provides a policy-oriented guide and toolbox to help overcome barriers, unlock the economic potential of resource efficiency, and highlight the challenges associated with the resource transition. Overall, this article brings together evidence, aiming to further develop and propose new strategies for improving the efficient use of natural resources to advance the sustainable development agenda.

A sensor for trinitrotoluene (TNT) detection was developed by using a combination of optical micro-ring technology and a receptor coating based on molecularly imprinted sol-gel layers. Two techniques for deposition of receptor layers were compared: Airbrush technology and electrospray ionization. A concentration of less than 5 ppb for TNT in the gas-phase, using electrospray deposition of the receptor layer, was detected. The cross-sensitivities to organic substances and further nitro-based explosives were compared. As a result, the sensitivity to TNT is about one order of magnitude higher in comparison to the explosives 2,4-dinitrotoluene (DNT) or 1,3-dinitrobenzene (DNB) and about four orders of magnitude higher than the organic substances phenol, ethanol, and acetone. The signal response of the sensor is fast, and the compact sensor design enables the deposition of different receptor layers on multiple optical micro-rings on one chip, which allows a more precise analysis and reduction of side effects and false alarms.

Various methods to determine the onset of the electromyographic activity which occurs in response to a stimulus have been discussed in the literature over the last decade. Due to the stochastic characteristic of the surface electromyogram (SEMG), onset detection is a challenging task, especially in weak SEMG responses. The performance of the onset detection methods were tested, mostly by comparing their automated onset estimations to the manually determined onsets found by well-trained SEMG examiners. But a systematic comparison between methods, which reveals the benefits and the drawbacks of each method compared to the other ones and shows the specific dependence of the detection accuracy on signal parameters, is still lacking. In this paper, several classical threshold-based approaches as well as some statistically optimized algorithms were tested on large samples of simulated SEMG data with well-known signal parameters. Rating between methods is performed by comparing their performance to that of a statistically optimal maximum likelihood estimator which serves as reference method. In addition, performance was evaluated on real SEMG data obtained in a reaction time experiment. Results indicate that detection behavior strongly depends on SEMG parameters, such as onset rise time, signal-to-noise ratio or background activity level. It is shown that some of the threshold-based signal-power-estimation procedures are very sensitive to signal parameters, whereas statistically optimized algorithms are generally more robust.