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A clinical case is described which occurred in the practice of the Department of Neurology 1 of the Mechnikov Dnipropetrovsk Regional Clinical Hospital. Using the patient’s case history as an example, some possible difficulties in a differential diagnosis of neurosyphilis and demyelinating diseases are shown, peculiarities of laboratory diagnosis of the former are highlighted and reviewed, and also the diagnostic importance of identification of antibody synthesis type during a cerebrospinal fluid analysis for detecting oligoclonal bands is explained. The article contains a brief overview of the works related to modern views on the place and role of the cerebrospinal fluid analysis for a diagnosis and a differential diagnosis of diseases of the nervous system, for studying the types of antibody synthesis in the blood serum and in the cerebrospinal fluid, as well as to some aspects of diagnosing syphilis.

To investigate mortality and causes of death associated with the use of paclitaxel-coated balloon (PCB) compared with plain balloon (PB) angioplasty in the treatment of femoropopliteal artery lesions in real-world clinical setting.This retrospective, single-center study included patients who underwent percutaneous femoropopliteal artery angioplasty without stenting between years 2014 and 2020. Patients were stratified into PCB and PB groups according to the index procedure. Those who had undergone any prior or subsequent intervention using drug-eluting technology were excluded from the PB group. Long-term survival was estimated up to 5 years using the Kaplan-Meier method, and risk factors for all-cause mortality were assessed in a multivariable analysis. Causes of death were retrieved from a national registry.The study included 139 patients treated with PB and 190 with PCB. Patients treated with PCB had a higher prevalence of chronic pulmonary disease (27% vs 17%; P = .02) and were less often on anticoagulant therapy (34% vs 48%; P = .01) compared with patients in the PB group. Those treated with PB were more likely to have chronic limb-threatening ischemia (CLTI; 82% vs 72%; P = .04). Ipsilateral perioperative amputation rate was significantly higher in the PB group (7% vs 1%; P = .01). There were no major differences in other 30-day outcomes between the groups and no differences in the rates of reinterventions and ipsilateral amputations during a mean follow-up time of 2.7 ± 1.9 years. Survival at 1 year in the PCB group was 83% ± 3% compared with 73% ± 4% in the PB group (P = .0001). The 5-year survival estimates were 56% ± 5% and 37% ± 5%, respectively. PCB use was independently associated with decreased risk of mortality (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.50-0.97). Independent risk factors for increased mortality were age (HR, 1.04 per year; 95% CI, 1.02-1.06), cardiac insufficiency (HR, 1.60; 95% CI, 1.12-2.27), chronic renal insufficiency (HR, 2.04; 95% CI, 1.47-2.85), anticoagulation therapy (HR, 1.65, 95% CI, 1.16-2.34), and CLTI (HR, 2.85; 95% CI, 1.51-5.39). In the PCB group, 63% of deaths were due to cardiovascular causes compared with 42% in the PB group (P .01).The use of PCB is safe, and there is no concern of increased mortality after the procedure based on the 5-year survival estimates.

Вже четвертий рік поспіль на Прикарпатті традиційно відкрився сезон науково-практичних конференцій з неврології в Україні. На базі Івано-Франківського національного медичного університету 10–11 березня 2016 року в с. Поляниця (м. Яремче Івано-Франківської області) проводилася науково-практична конференція з міжнародною участю «Сучасні аспекти клінічної неврології», яку організовує кафедра неврології та нейрохірургії університету.Надання результатів власних досліджень, їх обговорення, дискусія між провідними фахівцями сприяли виробленню консенсусу з ключових спірних питань профілактики, діагностики та лікування захворювань нервової системи, збагаченню новими ідеями і отриманню стимулу до подальшої наукової праці. Останній день був присвячений обговоренню клінічних випадків, що були репрезентовані у перший день конференції і наведені у стендовому форматі. Таким чином, лікарі впродовж 2 днів могли аналізувати обставини виникнення наведених випадків захворювань, оцінювати динаміку неврологічного статусу у взаємозв’язку з параклінічними методами обстеження пацієнтів, можливо, знайти помилки в проведеному лікуванні, яке не завжди було ефективним.І врешті-решт зробити висновок про діагноз, подальшу тактику ведення хворого.Тези та статті, отримані на адресу оргкомітету конференції, за інформаційної підтримки «Міжнародного неврологічного журналу» публікуються в цьому номері журналу.

Background Evidence for an association between the local food environment, diet and diet-related disease is mixed, particularly in the UK. One reason may be the use of more distal outcomes such as weight status and cardiovascular disease, rather than more proximal outcomes such as food purchasing. This study explores associations between food environment exposures and food and drink purchasing for at-home and out-of-home (OOH) consumption. Methods We used item-level food and drink purchase data for London and the North of England, UK, drawn from the 2019 Kantar Fast Moving Consumer Goods panel to assess associations between food environment exposures and household-level take-home grocery (n=2,118) and individual-level out-of-home (n=447) food and drink purchasing. Density, proximity and relative composition measures were created for both supermarkets and OOH outlets (restaurants and takeaways) using a 1 km network buffer around the population-weighted centroid of households’ home postcode districts. Associations between food environment exposure measures and frequency of take-home food and drink purchasing, total take-home calories, calories from fruits and vegetables, high fat, salt and sugar products, and ultra-processed foods (UPF), volume of take-home alcoholic beverages, and frequency of OOH purchasing were modelled using negative binomial regression adjusted for area deprivation, population density, and individual and household socio-economic characteristics. Results There was some evidence for an inverse association between distance to OOH food outlets and calories purchased from ultra-processed foods (UPF), with a 500 m increase in distance to the nearest OOH outlet associated with a 1.1% reduction in calories from UPF (IR=0.989, 95%CI 0.982–0.997, p=0.040). There was some evidence for region-specific effects relating to purchased volumes of alcohol. However, there was no evidence for an overall association between food environment exposures and take-home and OOH food and drink purchasing. Conclusions Despite some evidence for exposure to OOH outlets and UPF purchases, this study finds limited evidence for the impact of the food environment on household food and drink purchasing. Nonetheless, region-specific effects regarding alcohol purchasing indicate the importance of geographical context for research and policy.

The urban environment is characterised by many pressures caused by population growth, transport (and its related emissions), and the damage to green areas. Yet, there is a variety of ecosystem services available in urban areas, which may be deployed to ameliorate the current problems and foster their sustainability. This paper reviews the role of ecosystem services as tools for sustainability, based on an urban setting. It also describes a series of multi-country case studies, where an assessment of their functions using a set of benefits valuation approaches such as health benefits, economic benefits, social benefits and benefits to climate resilience, are provided, along with an appraisal of their role in up- keeping the overall quality of the urban environment in the studied areas. Policy recommendations aimed at enhancing the role of ecosystem services, and fostering sustainability in the sampled sites -and beyond-are provided.

Despite the potential curability and a positive prognosis of the course of myasthenia in geneal, the markers of quality of life in patients with this disease remain insufficiently studied and require further studying in order to optimize therapeutic approaches.Objective: to quantify the quality of life indicators in patients with myasthenia gravis, depending on the form and class of the disease.Material and methods. 182 patients with myasthenia gravi were examined, 147 (80.8%) of patients with a generalized form of the disease, 35 (19.2%) — with ocular, 128 (70.3%) women, 54 (men 29.7%). Clinical and neurological examination with the determination of the form and class of myasthenia gravis according to the classification of MGFA was performed. The assessment of quality of life was carried out according to the MG-QoL‑15 scale. Statistical processing was performed using non-parametric statistical methods due to the unnormal data distribution of the studied parameters.Results. In the total sample, the median quality of life indicators generally was reduced (21.5 (9.0; 33.0) points). In patients with an ocular form, the indicators of quality of life were generally not lowered, in contrast to patients with a generalized form, whose performance was significantly worse (p

The purpose of this work was to study comorbid conditions in patients with myasthenia gravis. Materials and methods: 182 patients with myasthenia gravis aged from 18 to 83 were examined. 147 (80.8%) of then were diagnosed to have generalized form of myasthenia and 35 (19.2%) had ocular form myasthenia. Clinical and neurological examination included present complaints, past medical history, social history, neurological examination. To evaluate the clinical form of myasthenia, the MGFA classification was used. For data processing, the methods of parametric and non-parametric statistics were applied. Among the patients there were 128 (70.3%) women and 54 (29.7%) men, the women to men ration was 2.37: 1. Median age was 52.0 (34.0; 65.0) years. The proportion of patients who, in their routine practice, had CT or MRI of the anterior mediastinal system, made up 74.2% of the total sample and did not differ significantly depending on the form, class or subclass of myasthenia. Results: Among patients with the class I of myasthenia gravis, there were no individuals who had thymoma and/or thymectomy, unlike the patients with generalized myasthenia. A significant proportion of thymic and/or thymectomy was recorded in patients with class II (28.9% and 25.0% respectively). The proportion of thymoma and thymectomy in the patients significantly differed based on the myasthenia form (significantly more in patients with generalized form compared to those with ocular form, p = 0.003 and p = 0.009, respectively). The proportion of thymoma and thymectomy history significantly differed among patients with different classes of generalized myasthenia (class II-IV (p = 0.008 and p = 0.018 respectively) and their subclasses (p = 0.006 and p = 0.009, respectively), while they were registered in each class and subclass of generalized myasthenia. Attention should be paid to the fact that the proportion of thymoma in the general sample was greater than the proportion of thymectomy (19.2% versus 15.9%). This suggests an inadequate level of surgical care for myasthenia patients, even to those who are shown with such treatment (patients with thymoma). The proportion of autoimmune diseases among patients with myasthenia class I (ocular form) significantly exceeded the corresponding level in patients with generalized myasthenia - 45.7% vs. 15.0% (p 0.05. One patient had from 0 to 6 concomitant diseases, on the average of 1.0 (0; 2.0) by the median value. Cardiovascular diseases, 34.1% (95% CI 27.2 - 41.0), rank the first place in the frequency of the concomitant diseases among the examined patients. The diseases of the gastrointestinal tract (namely, gastritis, ulcers of the stomach and duodenum, chronic holistic, chronic pancreatitis at the stage of remission, etc.) and autoimmune thyroiditis (20.9% (95% CI 15, 0-26.8) have the second highest rate, eye diseases (not related to the myasthenia) are (15.9% (95% CI 10.6 - 21.3)) ranked the third. No differences in the incidence of concomitant pathology, apart from autoimmune diseases, between forms, classes and subclasses of myasthenia were detected (p> 0.05). Conclusions. The proportion of visualization of the anterior mediastinum in patients with myasthenia gravis is far from being sufficient. This test is supposed to be done for absolutely all patients with myasthenia gravis for early detection of pathological changes of thymus. In the structure of the comorbidities in patients with myasthenia gravis cardiovascular, gastrointestinal and autoimmune thyroiditis have been found out to prevail. This should be taken into account when selecting treatment. Autoimmune thyroiditis was recorded in 45.7% of patients with ocular and in 20.9% of patients with generalized myasthenia that may indicate a systemic autoimmune disorder whose causative relationships require further in-depth study.

Summary Background Tolebrutinib is an oral, CNS-penetrant, irreversible inhibitor of Bruton’s tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are major drivers of inflammation in multiple sclerosis. We aimed to determine the dose-response relationship between tolebrutinib and the reduction in new active brain MRI lesions in patients with relapsing multiple sclerosis. Methods We did a 16-week, phase 2b, randomised, double-blind, placebo-controlled, crossover, dose-finding trial at 40 centres (academic sites, specialty clinics, and general neurology centres) in ten countries in Europe and North America. Eligible participants were adults aged 18–55 years with diagnosed relapsing multiple sclerosis (either relapsing-remitting or relapsing secondary progressive multiple sclerosis), and one or more of the following criteria: at least one relapse within the previous year, at least two relapses within the previous 2 years, or at least one active gadolinium-enhancing brain lesion in the 6 months before screening. Exclusion criteria included a diagnosis of primary progressive multiple sclerosis or a diagnosis of secondary progressive multiple sclerosis without relapse. We used a two-step randomisation process to randomly assign eligible participants (1:1) to two cohorts, then further randomly assign participants in each cohort (1:1:1:1) to four tolebrutinib dose groups (5, 15, 30, and 60 mg administered once daily as an oral tablet). Cohort 1 received tolebrutinib for 12 weeks, then matched placebo (ie, identical looking tablets) for 4 weeks; cohort 2 received 4 weeks of placebo followed by 12 weeks of tolebrutinib. Participants and investigators were masked for dose and tolebrutinib-placebo administration sequence; investigators, study team members, and study participants did not have access to unmasked data. MRI scans were done at screening and every 4 weeks over 16 weeks. The primary efficacy endpoint was the number of new gadolinium-enhancing lesions detected on the scan done after 12 weeks of tolebrutinib treatment (assessed at week 12 for cohort 1 and week 16 for cohort 2), relative to the scan done 4 weeks previously, and compared with the lesions accumulated during 4 weeks of placebo run-in period in cohort 2. Efficacy data were analysed in a modified intention-to-treat population, using a two-step multiple comparison procedure with modelling analysis. Safety was assessed for all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03889639), EudraCT (2018-003927-12), and WHO (U1111-1220-0572), and has been completed. Findings Between May 14, 2019, and Jan 2, 2020, we enrolled and randomly assigned 130 participants to tolebrutinib: 33 to 5 mg, 32 to 15 mg, 33 to 30 mg, and 32 to 60 mg. 129 (99%) completed the treatment regimen and 126 were included in the primary analysis. At treatment week 12, there was a dose-dependent reduction in the number of new gadolinium-enhancing lesions (mean [SD] lesions per patient: placebo, 1·03 [2·50]; 5 mg, 1·39 [3·20]; 15 mg, 0·77 [1·48]; 30 mg, 0·76 [3·31]; 60 mg, 0·13 [0·43]; p=0·03). One serious adverse event was reported (one patient in the 60 mg group was admitted to hospital because of a multiple sclerosis relapse). The most common non-serious adverse event during tolebrutinib treatment was headache (in one [3%] of 33 in the 5 mg group; three [9%] of 32 in the 15 mg group; one [3%] of 33 in the 30 mg group; and four [13%] of 32 in the 60 mg group). No safety-related discontinuations or treatment-related deaths occurred. Interpretation 12 weeks of tolebrutinib treatment led to a dose-dependent reduction in new gadolinium-enhancing lesions, the 60 mg dose being the most efficacious, and the drug was well tolerated. Reduction of acute inflammation, combined with the potential to modulate the immune response within the CNS, provides a scientific rationale to pursue phase 3 clinical trials of tolebrutinib in patients with relapsing and progressive forms of multiple sclerosis. Funding Sanofi.

Floods are among the devastating types of disasters in terms of human life, social and financial losses. Authoritative data from flood gauges are scarce in arid regions because of the specific type of dry climate that dysfunctions these measuring devices. Hence, social media data could be a useful tool in this case, where a wealth of information is available online. This study investigates the reliability of flood related data quality collected from social media, particularly for an arid region where the usage of flow gauges is limited. The data (text, images and videos) of social media, related to a flood event, was analyzed using the Machine Learning approach. For this reason, digital data (758 images and 1413 video frames) was converted into numeric values through ResNet50 model using the VGG-16 architecture. Numeric data of images, videos and text was further classified using different Machine Learning algorithms. Receiver operating characteristics (ROC) curve and area under curve (AUC) methods were used to evaluate and compare the performance of the developed machine learning algorithms. This novel approach of studying the quality of social media data could be a reliable alternative in the absence of real-time flow gauges data. A flash flood that occurred in the United Arab Emirates (UAE) from March 7–11, 2016 was selected as the focus of this study. Random forest showed the highest accuracy of 80.18% among the five other classifiers for images and videos. Precipitation/rainfall data were used to validate social media data, which showed a significant relationship between rainfall and the number of posts. The validity of the machine learning models was assessed using the area under the curve, precision-recall curve, root mean square error, and kappa statistics to confirm the validity and accuracy of the model. The data quality of YouTube videos was found to have the highest accuracy followed by Facebook, Flickr, Twitter, and Instagram. These results showed that social media data could be used when gauge data is unavailable.

У статті представлено результати дослідження тривожності та якості життя у 96 хворих на міастенію в залежності від імунологічного типу, тривалості та клінічної форми захворювання. Встановлено, що показники якості життя хворих на міастенію залежать від тяжкості перебігу захворювання та не залежать від імунологічного підтипу хвороби. Розвиток та ступінь тривожних порушень не залежить від імунологічного типу міастенії. Найвищі показники якості життя відзначаються у хворих з очною формою міастенії, а підвищений рівень ситуаційної тривожності достовірно знижує показники якості життя, Aim of the research: To investigate the level of anxiety in adult patients with myasthenia.Materials and methods. An in-depth clinical-neurological, immunological (detection of antibodies to acetylcholine and / or muscle-specific tyrosine kinase receptors) examination, testing according to MGQoL-15 scale, and Spielberg-Khanin anxiety scale of 96 patients (56 women and 40 men) with myasthenia (71 - with generalized, 25 - with an ophthalmologic form, respectively) were done.Results. Antibodies to acetylcholine receptors were detected in 57 (80.3 %) of 71 patients with generalized form and in 13 (52 %) of 25 patients with ophthalmic myasthenia, antibodies to muscle-specific tyrosine kinase in 6 (8.5 %) of 71 patients with generalized form. In the case of an ophthalmic form, these antibodies were not detected. In 8 (11.3 %) out of 71 patients with generalized myasthenia and in 12 (48.0 %) out of 25 patients with ophthalmic form of myasthenia antibodies to acetylcholine receptors and muscle-specific tyrosine kinase were not detected.When the MGQoL-15 scale was used, the average quality of life was 10.34 ± 9.4 points (ranging from 0 to 31).In assessing of situational anxiety, a moderate level of anxiety was detected in 44 patients, high – in 24 patients, while the low level of anxiety had 28 people. Patients with an ophthalmic form of myasthenia (class I by MGFA) are significantly more likely to have a low level of anxiety (p

Aim: to study the prevalence of myasthenia gravis among adults in certain regions of Ukraine, taking into account the type of settlement and place of residence. The biostatistical, medical-statistical and epidemiological methods was used in the study. A study of the prevalence of myasthenia gravis in Ukraine was conducted on a sample of ten regions of Ukraine. 757 cases of myasthenia gravis were studied in selected territories, of which 465 (61.43 %) were among urban residents, 292 (38.57 %) were among rural residents. The average annual prevalence of myasthenia gravis was 5.16 (95 % CI —4.79—5.53) per 100,000 population. An analysis of the prevalence of myasthenia gravis in each region showed that this indicator among rural residents was statistically signifi cantly higher than the prevalence of myasthenia gravis among urban residents in Vinnytsia, Zaporizhzhia and Kirovohrad regions (p < 0.05), and in Volyn, Ivano-Frankivsk, Mykolaiv and Chernivtsi regions — without statistically significant differences (p > 0.05). The highest prevalence of myasthenia gravis in rural residents compared with urban residents was in the Vinnytsia region with an excess of 5.63 times (p < 0.001). The city prevalences of myasthenia in the Dnipropetrovsk (+39.14 %; p = 0.001) and Poltava regions (+35.87 %; p = 0.048) signifi cantly exceeded the average city prevalence of myasthenia gravis in Ukraine. They were signifi cantly lower in Vinnytsia (–75.07 %; p < 0.001), Volyn (–51.49 %; p < 0.001), Ivano-Frankivsk (–42.58 %; p = 0.004) and Chernivtsi (–37.35 %; p = 0.046) regions. The chances of rural residents to have myasthenia gravis were signifi cantly higher compared to urban residents. In general, according to the data of mya sthenia gravis prevalence rate in the context of the place of residence, it was proved that living in rural areas is associated with the presence of myasthe nia gravis. Key words: myasthenia gravis, epidemiology, prevalence, incidence, urban residents, rural residents

Вивчено депресивні прояви у 96 хворих на міастенію. В результаті роботи встановлено, що частота розвитку депресивних порушень у хворих на міастенію збільшується з тривалістю перебігу хвороби. Депресивні прояви більш виражені у хворих на генералізовану міастенію порівняно з хворими з очною формою. Розвиток та ступінь депресивних проявів не залежить від імунологічного типу міастенії, Aim of the research: To study depressive manifestations in patients with myasthenia depending on the duration, clinical form and immunological type of the disease.Methods: A neurological examination, determination of antibodies to acetylcholine receptors and muscle-specific tyrosine-kinase, a Beck depression score of 96 patients with myasthenia was performed.Results: The average age of patients was 50.5±12.4 years, the average duration of the disease was 4.4±1.2 years. Antibodies to acetylcholine receptors were detected in 57 (80.3 %) of 71 patients with generalized form and in 13 (52 %) of 25 patients with ophthalmic myasthenia. In 6 (8.5 %) of 71 patients with generalized myasthenia, antibodies to muscle-specific tyrosine-kinase were detected. In 8 (11.3 %) out of 71 patients with a generalized form of myasthenia and 12 (48.0 %) out of 25 patients with an ocular form of myasthenia antibodies were not detected. Depressive manifestations in the form of mild (32 persons) and moderate (34 persons) depression were detected in 66 patients, the mean score on the Beck scale was 12.9±3.45 points). In patients with a generalized form of myasthenia, the incidence of mild to moderate depression does not significantly differ, with no significant difference in the average duration of the disease in these groups of patients. At the same time, in patients with generalized myasthenia without manifestations of depression, the average duration of the disease was significantly lower. The presence and degree of manifestations of depressive disorders does not depend on the presence of antibodies to the receptors of acetylcholine, antibodies to muscle-specific tyrosine-kinase or their absence.Conclusions: As a result of the work, it was found that the development of depressive disorders in patients with myasthenia increases with the duration of the disease. Depressive manifestations are more pronounced in patients with generalized myasthenia in compare to patients with ophthalmic form.The development and degree of depressive manifestations does not depend on the immune type of myasthenia

Проведено исследование эффективности различных схем применения лорноксикама, толперизона, габапентина для лечения острого болевого синдрома у 121 пациента с шейными радикулопатиями.Установлено, что лорноксикам достоверно снижает выраженность болевого синдрома у пациентов с доминированием как ноцицептивного, так и нейропатического компонента боли. При этом сочетанное применение лорноксикама и толперизона было более эффективным у пациентов без нейропатической боли, а сочетанное использование лорноксикама и габапентина — при нейропатической боли у пациентов с шейными радикулопатиями (в сравнении с монотерапией лорноксикамом).

The Batinah coastal plain in northern Oman has experienced a severe deterioration of groundwater quality due to seawater intrusion as a result of excessive groundwater abstraction for agricultural irrigation. Upgrading all farms to fully automated irrigation technology based on soil moisture sensors may significantly reduce the water demand and lead to recovering groundwater levels. This study compares the effects of smart irrigation technology, recharge dams, and a combination of both on seawater intrusion in the coastal aquifer of the Batinah. A groundwater flow and transport model is used to simulate the effect of reduced pumping rates on seawater intrusion for various intervention scenarios over a simulation period of 30 years, and an economic analysis based on cost-benefit analysis is conducted to estimate the potential benefits. Results indicate that a combination of smart irrigation and recharge dams may prevent further deterioration of groundwater quality over the next 30 years. In conjunction with increased efficiency, this combination also generates the highest gross profit. This outcome shows that the problem of seawater intrusion needs to be tackled by a comprehensive, integrated intervention strategy.

The International Water Research Alliance Saxony (IWAS) project (2009–2014) was dedicated to investigate global challenges concerning integrated water resources management (IWRM) in different model regions in Eastern Europe (region R1), Central and Southeast Asia (R2 and R3), the Middle East (R4) and Latin America (R5). This thematic issue compiles the most important scientific results of the second phase of the IWAS project which was introduced by Kalbus et al. (2012). The main results and lessons learned from the transdisciplinary IWRM project are presented in Seegert et al. (2014). The IWAS project was structured into the above-mentioned model regions (R1–5) and into cross-cutting topics: Q1—Model based scenario analysis, Q2—Technology development, Q3— Governance, and Q4—Capacity development (Fig. 1). The first cross-cutting topic Q1 was dedicated to modelbased scenario analysis of hydrological and climate related processes. Within the first project phase of IWAS a ToolBox for hydrological process simulation was developed and exemplary applied to the IWAS investigation regions (Kalbacher et al. 2012). The toolbox concept has been completed by invoking data integration as well as model visualization methods (Rink et al. 2014; Bilke et al. 2014). Within the second IWAS project phase, the toolbox has been extensively applied to several IWAS model regions: R1 (e.g. Fischer et al. 2014; Koerner et al. 2014; Pavlik et al. 2014), R2 (e.g. Karthe et al. 2014), R4 (e.g. Kloss et al. 2014; Graebe et al. 2013; Subagadis et al. 2014; Walther et al. 2014), R5 (e.g. Borges et al. 2014; Da Anunciacao et al. 2014; Goncalves et al. 2013) to address a variety of questions for surface water and groundwater management. More general works were Barfus and Bernhofer (2014) who applied global climate models (GCM) to different model regions and Pluntke et al. (2014) dealing with uncertainty in hydrological modeling due to data scarcity. The second cross-cutting topic Q2 was focused on technology development, implementation and transfer. Three work packages in Q2 were dealing with the Sewchar concept for sustainable sanitation systems (Fuehner et al. 2012), hydrothermal carbonization for treatment of domestic waste and sewage sludge (Poerschmann et al. 2014), and the development of multisensory systems for the detection of pathogens. The remaining transdisciplinary topics were dealing with aspects of governance (Q3) and capacity development (Q4). Dombrowsky et al. (2014) were discussing socioeconomic questions of water governance in transition countries as well as institutional and legal constraints for transboundary river basin management. Capacity development is an important method for the implementation of IWRM concepts (Leidel et al. 2014). As a result of the IWAS capacity development activities an E-learning platform has been established (Leidel et al. 2013, see http:// www.iwrm-education.de). IWAS Ukraine (R1) was dealing with a variety of IWRM aspects elaborating on socio-economic as well as natural science questions (Dombrowsky et al. 2014; Hagemann et al. 2014) discussing the role of water governance in transition countries as well as institutional and legal constraints on transboundary river basin management. A decision support concept was developed by Leidel et al. J. Seegert O. Kolditz (&) P. Krebs D. Borchardt Technische Universitat Dresden, Dresden, Germany e-mail: ees-editor@ufz.de

The level and features of fatigue development in patients with myasthenia gravis remain not well studied, but their research is promising in order to improve the therapeutic tactics, social, domestic, professional adaptation and, as a consequence, the quality of life of patients in general. The purpose of this work was to quantify the fatigue parameters in patients with myasthenia gravis depending on the form and class of the disease, as well as on the immunological type of the disease. Object and methods. 182 patients with myasthenia were examined (147 (80.8%) patients with a generalized form of the disease, 35 (19.2%) with ocular form). Clinical and neurological examination included complaints collection, history of disease and life, neurological examination. To evaluate the clinical form of myasthenia, the MGFA classification was used. For a quantitative assessment of fatigue, the Fatigue Severity Scale (FSS) was used. The assessment of the level of antibodies to acetylcholine receptors (AchR) and muscle-specific tyrosine kinase (MuSK) by ELISA was performed to all patients, as well as determination of antibodies to titin and SOX1 by indirect immunofluorescence method. In mathematical processing of data, methods of parametric and nonparametric statistics were used. Results and discussion. Among the surveyed patients by gender, women predominated 128 (70.3%), the number of men was 54 (29.7%), the ratio of women to men 2.37:1. Antibodies to acetylcholine receptors were detected in 68.1% of the patients in the general sample (in 73.5% patients with generalized form and in 45.7% - with an ocular form). Antibodies to muscle-specific tyrosine-kinase were detected in 16% of the total number of patients. These antibodies were not detected in patients with ocular myasthenia. Antibodies to titin were detected in almost a third of all subjects - 53 (29.1%). These antibodies were not detected in patients with ocular form of myasthenia gravis. Antibodies to SOX1 were not detected in patients with ocular myasthenia, but diagnosed in 5.5% patients with generalized form. The level of fatigue in patients increases with the increase of the MGFA class of the disease. The median fatigue rate in the general sample corresponded to a mild fatigue level (FSS:36- 44 points), and in patients with generalized myasthenia, it was consistent with moderate fatigue (FSS: 45-53 points). In patients with ocular myasthenia, median fatigue was significantly lower in comparison with the general sample and with the generalized form and did not reach the clinical value (p 0,05; ? = 0,08; p> 0,05, respectively), as well as the presence of antibodies to SOX1 (? = 0.06; p> 0.05). Fatigue significantly correlated with the clinical form of myasthenia (generalized) (? = -0,55; p

Analytical solutions to the one-dimensional heat transport equation for steady-state conditions can provide simple means to quantify groundwater surface water exchange. The errors in exchange flux calculations that are introduced when the underlying assumptions of homogeneous sediments and constant temperature boundary conditions are violated were systematically evaluated in a simulation study. Temperatures in heterogeneous sediments were simulated using a numerical model. Heterogeneity in the sediments was represented by discrete, binary geologic units. High contrasts between the hydraulic conductivities (K) of the geologic units were found to lead to large errors, while the influence of the structural arrangement of the units was smaller. The effects of transient temperature boundary conditions were investigated using an analytical equation. Errors introduced by transient boundary conditions were small for Darcy-velocities > 0.1 m d− 1 in the period near maximum and minimum annual surface water temperatures. For smaller fluxes, however, errors can be large. Assuming steady-state conditions and vertical flow in homogeneous sediments is acceptable at certain times of the year and for medium to high exchange fluxes, but pronounced geologic heterogeneity can lead to large errors.

Significant natural attenuation may occur on the passage of groundwater plumes through streambed sediments because of the transition from anaerobic to aerobic conditions and an increased microbial activity. Varying directions and magnitudes of water flow in the streambed may enhance or inhibit the supply of oxygen to the streambed and thus influence the redox zoning. In a field study at a small stream in the industrial area of Bitterfeld-Wolfen, we observed the variability of hydraulic gradients, streambed temperatures, redox conditions and monochlorobenzene (MCB) concentrations in the streambed over the course of 5 months. During the observation period, the hydrologic conditions changed from losing to gaining. Accordingly, the temperature-derived water fluxes changed from recharge to discharge. Redox conditions were highly variable between -170 and 368 mV in the shallow streambed at a depth of 0.1 m below the streambed surface. Deeper in the streambed, at depths of 0.3 m and 0.5 m, the redox conditions were more stable between -198 and -81 mV and comparable to those typically found in the aquifer. MCB concentrations in the streambed at 0.3 and 0.5 m depth increased with increasing upward water flux. The MCB concentrations in the shallow streambed at 0.1 m depth appeared to be independent of the hydrologic conditions suggesting that degradation of MCB may have occured. Copyright (C) 2010 John Wiley & Sons, Ltd.

Als Folge intensiver industrieller, bergbaulicher und urbaner Nutzung gibt es in Deutschland zahlreiche grosflachig kontaminierte Standorte. Diese so genannten Megasites stellen eine grose Herausforderung fur die Risikobewertung und Sanierung dar. An der Megasite Bitterfeld kommt es zudem zu Wechselwirkungen zwischen kontaminiertem Grundwasser und den lokalen Vorflutern. An einem 280 m langen Flussabschnitt wurden durch die Kombination integraler Pumpversuche, Kartierung der Flussbettsedimenttemperaturen und Analysen der Schadstoffkonzentrationen im Flussbettsediment die Schadstoffmassenstrome chlorierter Benzole abgeschatzt, die mit der Grundwasserstromung aus dem Aquifer und dem Flussbettsediment in den Vorfluter gelangen. Im Mittel gelangt am untersuchten Flussabschnitt eine Fracht von 617 mg d–1 Monochlorbenzen (MCB) und 157 mg d–1 Dichlorbenzen (DCB) aus dem Aquifer in den Vorfluter. Das Flussbettsediment des untersuchten Vorfluters stellt die dominante Schadstoffquelle dar. Wird das Flussbettsediment berucksichtigt, erhohen sich die Frachten in den Vorfluter in Abhangigkeit vom Standort auf Werte zwischen 2.355 und 4.323 mg d–1 MCB sowie zwischen 892 und 3.587 mg d–1 DCB.

Der Grundwasserzustrom in einen Vorfluter kann kleinraumige Heterogenitaten aufweisen, die durch die Struktur des angebundenen Aquifers hervorgerufen werden. Die raumlichen Muster des Grundwasserzustroms konnen durch Temperaturmessungen im Flussbett erfasst werden. Somit kann aus gemessenen Flussbett-Temperaturdaten auf die Heterogenitat der Durchlassigkeiten (kf -Werte) des Grundwasserleiters geschlossen werden. In einem Stromungs- und Warmetransportmodell wurde ein Fluss-Aquifer-System abgebildet und mit stochastischen kf -Feldern parametrisiert. Als Eingangsdaten fur die Generierung der kf -Felder dienten Mittelwert und Varianz von kf -Werten, die mit Direct-Push-Methoden gemessen wurden. Die simulierten Temperaturen im Flussbett deckten jedoch nicht die Spannweite der gemessenen Temperaturen ab. Deshalb wurde zusatzlich der Zusammenhang zwischen der Temperaturverteilung im Flussbett und der Varianz der kf -Werte des Aquifers genutzt, um die Varianz der kf -Werte so zu kalibrieren, dass die Verteilung der gemessenen Temperaturen im Modell wiedergegeben werden konnte. Diese Studie hat gezeigt, dass Methoden basierend auf Temperatur als Mess- und Kalibrierungsparameter eine wertvolle Erganzung zu herkommlichen Erkundungsmethoden darstellen.

T cell responses targeting myelin antigens are possibly involved in the pathogenesis of demyelinating diseases, such as multiple sclerosis (MS). Little is known about human T cell responses to 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase), the third most abundant myelin protein. We examined the primary peripheral T cell response to CNPase and characterized CNPase-specific CD4+ long-term T cell lines (TCL) from MS patients and healthy donors. The strongest primary responses were found in two MS patients with very active disease and were directed against CNP(343–373). We identified immunodominant epitope clusters in the regions CNP(343–373) and (356–388) that were recognized in the context of MS-associated HLA-DR2 and DR4 molecules. These data provide the immunological basis for further investigation of CNPase as a potential target self-antigen in MS.

The MHC class II molecule H2-A(s), expressed in the SJL mouse strain, is the principle restriction element of autoreactive CD4(+) T cells mediating experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. We deduced the H2-A(s) ligand motif from the analysis of naturally processed self peptides and from peptide binding studies. Major anchor residues were identified using various sets of substituted and truncated peptides, derived from natural peptide ligands and known H2-A(s) binders like myelin basic protein 81 - 99. The nine-residue H2-A(s) core binding motif comprises an arrangement of anchors in relative positions P1, P4, P6, P7, and P9. The P1 pocket is relatively unspecific and the P6 pocket favors hydrophobic-aliphatic side chains. The P1 pocket contributes little to peptide binding. Primary anchors were identified in P4, P7, and in particular in P9. The preferred anchor residues are Lys (P4), His/Arg (P7), and Pro (P9), respectively. Ala-polysubstituted peptides containing only one of these dominant anchor residues still retain the capacity to bind to H2-A(s). Thus, the presence of only one suitable anchor side chain in P4, P7, or P9 is sufficient for high-affinity peptide binding, at least in the absence of negatively charged side chains nearby. The identified ligand motif facilitates the analysis of immunogenic peptides interacting with H2-A(s) and will allow a better prediction of pathogenetically relevant peptide antigens in the autoimmune mouse model.

This article is a personal account of experiences of discrimination against an Asian American female educator as she attempted to obtain a county superintendency position. The concept of faultlines is used to address issues of social similarities and differences. Policy implications and practices intended to bring about change are explored.

This case study examines leadership succession by focusing on an elected county superintendent of schools. The Gordon and Rosen theoretical model is extended by (1) identifying factors which trigger succession, (2) examining interim appointments, and (3) identifying succession and organizational elements affected by the nature of elected leadership positions.

In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.

In this report, we demonstrate for autoreactive T cell clones that single amino acid modifications of the antigenic ligand can result in not only abrogated, decreased, or unmodified, but also increased, T cell responsiveness (superagonist ligands). We further studied the effects of combinations of multiple substitutions with different effects in single peptides. Experiments with peptides carrying multiple amino acid exchanges revealed that the final outcome of TCR ligation by a given ligand is the integration of negative, neutral, and positive effects of each single residue. In addition, the introduction of superagonist substitutions together with nonconservative modifications of primary and secondary TCR contacts resulted in stimulatory ligands. These findings indicate that: 1) the specificity of a single TCR is highly degenerate; 2) ligands exist for autoreactive T cells that have higher agonist activity than the autoantigen itself; 3) the rules to search for cross-reactive epitopes in autoimmunity should take into account that amino acids at certain positions within an antigenic peptide may exert superagonist activity and compensate for the negative effects of residues at other positions that would otherwise not be tolerated.

The human Ca(2+)-binding (storage) protein calreticulin, located in the lumen of the endoplasmic reticulum, is proposed to play a role as autoantigen: anticalreticulin autoantibodies occur in the sera of patients with SLE and patients with onchocerciasis (calreticulin shows a high sequence homology to the Onchocerca volvulus antigen RAL-1). Here we present sequencing data of a HLA-DR4Dw4-associated calreticulin peptide fragment, Cal(295-310), purified from a DR4Dw4 self-peptide pool. Cal(295-310) proved to be one of three commonest self-peptides associated with DR4Dw4 molecules that were isolated from the EBV-transformed B-cell line BSM (DR4Dw4, DRw53). We tested the binding of Cal(295-309) and the analogous RAL-1 peptide to HLA-DR molecules: Cal(295-309) exhibited specific binding characteristics for DR4Dw4. Binding assays using self-peptide analogues with replaced amino acids led us to a DR4Dw4-binding motif with anchor residues at relative positions 1 and 6. The sequencing data suggest that calreticulin is a frequently processed intracellular protein. The abundance of calreticulin makes the presentation of different calreticulin peptides associated with HLA-D molecules likely to occur, supporting the immunologic relevance of this molecule.

Antigenic peptides are presented to CD4+ T cells by MHC class II molecules via a highly polymorphic peptide-binding groove. The two HLA-DR alleles isotypically expressed on HLA-DR15Dw2-positive cells, DRB1*1501 (DR2b) and DRB5*0101 (DR2a) molecules, show a number of differences in polymorphic residues of the beta-chain, including the Gly-Val-dimorphism at position beta 86. Therefore, different requirements for interaction of peptides with these alleles must be expected. In this study, naturally processed self-peptides were eluted from purified HLA-DR15Dw2 molecules and related to DRB1*1501 or DRB5*0101 molecules by binding assays. An alignment of self-peptides and foreign peptides allowed the delineation of putative anchor motifs. N- and C-terminally truncated and alanine-substituted derivatives of the DR15Dw2 restricted myelin basic protein epitope MBP(85-105) confirmed their validity. Thus, DRB5*0101 requires a bulky hydrophobic residue (F or Y) at position i as a primary anchor, and Q or an aliphatic residue, such as V, I, or M, at position i + 3; positively charged residues at positions i + 7 and i + 8 are secondary anchors. For DRB1*1501, a nonaromatic, hydrophobic anchor (L, V, or I) at position i is supplemented by a bulky hydrophobic residue (F or Y) at position i + 3 as primary anchor; an additional hydrophobic side chain represented by M, I, V, or F occurs at position i + 6. Therefore, MBP(85-105) seems to contain two MHC interaction sites for DRB1*1501 and DRB5*0101, respectively, that may contribute to its immunodominance. Because HLA-DR15 Dw2 is associated with susceptibility to develop multiple sclerosis, the delineation of ligand motifs of the two DR2 alleles may help to study the interaction between potential autoantigenic peptides and these molecules in the future.

Exogenous antigens are internalized by antigen-processing cells and processed within vesicular compartments to produce antigenic peptides that bind to newly synthetized MHC II molecules. These MHC class II peptide complexes are displayed at the plasma membrane and stimulate specific CD4 + T cells. In the present study, we established a method to isolate intracellular MHC molecules in a preparative scale (2–3 mg HLA-DR1) from endosomal compartments by Percoll density-gradient centrifugation. Peptides associated with HLA-DR1 in these intracellular fractions were released, purified by microbore HPLC, characterized by sequencing, and compared with the amino acid composition of peptides derived from MHC class II molecules obtained by solubilization of the plasma membrane. The binding affinity of these MHC fractions was analyzed by our highly sensitive binding assay using different DR1-restricted IM and Ii peptides. The results indicate that (a) intracellular MHC molecules show higher peptide-binding capacity, (b) peptides that are about 18–25 amino acids long need only a core region of 11 amino acids for binding, (c) specific positions of the peptides are important for DR1 binding, (d) most of the naturally processed peptides show a proline at position 2 or 3 that may represent a stop signal for trimming, and (e) Ii peptides are very abundant in DR1 peptide pools derived from intracellular compartments.

[1] In streams, interaction of current with bed forms and solid objects can produce vertical water flux across the streambed. Instream wood is a major obstacle to flow and alters the bed topography of natural sand bed streams. In the present experimental study in large circulating flumes simulating sand bed streams with low constant slope, we compared systems with and without natural quantities of wood. The introduction of wood resulted in the production of irregular bed forms. As a result, flow resistance tripled, and vertical water flux across the streambed increased by a factor of 1.8 to 2.5. The mixing depth was spatially variable and seemed unrelated to the local bed form. After the addition of wood, surface water mixed deeper into the sediments, and the total sediment pore water volume involved in mixing increased by factors of 1.2 to 1.5. The practice of increasing instream wood should be a valuable tool for hyporheic rehabilitation of degraded sand bed streams.

The spatial pattern and magnitude of mass fluxes at the stream–aquifer interface have important implications for the fate and transport of contaminants in river basins. Integral pumping tests were performed to quantify average concentrations of chlorinated benzenes in an unconfined aquifer partially penetrated by a stream. Four pumping wells were operated simultaneously for a time period of 5 days and sampled for contaminant concentrations. Streambed temperatures were mapped at multiple depths along a 60 m long stream reach to identify the spatial patterns of groundwater discharge and to quantify water fluxes at the stream–aquifer interface. The combined interpretation of the results showed average potential contaminant mass fluxes from the aquifer to the stream of 272 μg m −2 d −1 MCB and 71 μg m −2 d −1 DCB, respectively. This methodology combines a large-scale assessment of aquifer contamination with a high-resolution survey of groundwater discharge zones to estimate contaminant mass fluxes between aquifer and stream.

The MHC class II molecule H2-A(s), expressed in the SJL mouse strain, is the principle restriction element of autoreactive CD4(+) T cells mediating experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. We deduced the H2-A(s) ligand motif from the analysis of naturally processed self peptides and from peptide binding studies. Major anchor residues were identified using various sets of substituted and truncated peptides, derived from natural peptide ligands and known H2-A(s) binders like myelin basic protein 81 - 99. The nine-residue H2-A(s) core binding motif comprises an arrangement of anchors in relative positions P1, P4, P6, P7, and P9. The P1 pocket is relatively unspecific and the P6 pocket favors hydrophobic-aliphatic side chains. The P1 pocket contributes little to peptide binding. Primary anchors were identified in P4, P7, and in particular in P9. The preferred anchor residues are Lys (P4), His/Arg (P7), and Pro (P9), respectively. Ala-polysubstituted peptides containing only one of these dominant anchor residues still retain the capacity to bind to H2-A(s). Thus, the presence of only one suitable anchor side chain in P4, P7, or P9 is sufficient for high-affinity peptide binding, at least in the absence of negatively charged side chains nearby. The identified ligand motif facilitates the analysis of immunogenic peptides interacting with H2-A(s) and will allow a better prediction of pathogenetically relevant peptide antigens in the autoimmune mouse model.

The large, naturally fractured reservoir under investigation is unique with its highly heterogeneous carbonate characteristics. The largest hydrocarbon bearing formations are not only naturally fractured, but also have matrix and vuggy porosity. Special relative permeability, capillary pressure, and compressibility relationships were developed to simulated multi-phase flow in this triple porosity system. Well and interference tests were re-analyzed at several stages in the project to provide input to geology on fracture properties and later to condition the fracture properties coming from the geologic model. The calibrated model acceptably matched the historical pressure and the production of oil, water, and gas for the reservoir complex.