Разработка бизнес-модели стартапа системы совместного использования велосипедов

В работе приведены теоретические основы построения бизнес-моделей и оценки их эффективности. Исследована сфера систем совместного использования велосипедов, выявлены проблемы и перспективы. На основе проведенной работы была проведена разработка и тестирование бизнес-модели стартап-проекта системы совместного использования велосипедов. В результате была описана концепция данного проекта, практическая значимость которой заключается в запуске проекта системы совместного использования велосипедов в формате стартапа. Методы исследования включают в себя: конкурентный анализ, анализ научной и бизнес литературы, изучение актуальной практики, сравнение, а также customer development, инвестиционный анализ.The theoretical foundations of building business models and assessing their effectiveness are presented in the dissertation. The bicycle sharing systems has been investigated, problems and prospects have been identified. Based on the work carried out, the development and testing of a business model of a startup project for a bicycle sharing system was carried out. As a result, the concept of this project was described, the practical significance of which lies in the launch of a project for a bicycle sharing system in a startup format. Research methods include: competitive analysis, analysis of scientific and business literature, study of current practice, comparison, as well as customer development, investment analysis

Розробка структури та електричної частини трекерної фотоелектричної станції потужністю 2,12 МВт

Спроектована електрична частина, вибір захистного обладнання для трекерної сонячної станції. Проаналізовано технічний процес надання зеленого тарифу промисловим сонячним станціям підчас проведення аукціону. Проведено розрахунки струмів короткого замикання на різних ступенях, Спираючись на одержані розрахунки було вибране захистне та комутаційне обладнання. Враховуючи втрати напруги в мережах до 1000В було обрано силовий кабель оптимального перерізу. Розраховано капітальні та експлуатаційні витрати повя’зані з розробкою електричної частини сонячної станці 2.12МВ

Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice.

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson\u27s disease. The expression of the shRNA was tightly regulated and, when induced, silenced the Pink1 gene product by more than 95% in mouse brain. However, these mice did not develop dopaminergic neurodegeneration, suggesting that silencing of the Pink1 gene expression from embryo in mice is insufficient to cause similar biochemical or morphological changes that are observed in Parkinson\u27s disease. The results demonstrate that silencing of the PINK1 gene does not induce a reliable mouse model for Parkinson\u27s disease, but that technically the inducible U6 promoter is useful for conditional RNAi in vivo

Effects of safinamide on pain in patients with fluctuating Parkinson's disease

Background: Non-motor symptoms (NMS) are integral to Parkinson's Disease (PD) and management remains a challenge. Safinamide is a novel molecule in relation to addressing NMS due to its multifocal mechanism of action with both dopaminergic and non-dopaminergic properties. Objective: To investigate the efficacy of safinamide on NMS and its burden in PD patients with motor fluctuations after 6 months of treatment. Methods: This observational, multicenter, open-label, pilot study assessed a wide range of NMS using the following rating scales, NMSS (non-motor symptom scale), KPPS (King's PD pain scale), HADS (hospital anxiety and depression scale), PDQ-8 (Parkinson's disease quality of life questionnaire), and PDSS-2 (Parkinson's disease sleep scale), EuroQol-5D 3 level version (EQ-5D-3L), CGI-I (clinical global impression of improvement), and PGI-C (patient global impression of change). Motor examination using UPDRS part III (Unified Parkinson's disease rating scale, motor examination), UPDRS IV (complications of therapy) and Hoehn and Yahr staging were also obtained. Results: 27 patients were included in the analysis and were evaluated at baseline and ≥ 6 months after safinamide treatment. 26 patients had a daily maintenance dose of 100 mg and 1 patient a daily dose of 50 mg. Significant improvements in UPDRS IV, KPPS item 5 (region-specific "off" dystonia), KPPS domain 3 (items 4-6, fluctuation related pain) and KPPS total score were observed after treatment with safinamide, while maintaining stable dopaminergic medication. No statistically significant differences were found in NMSS, HADS, PDSS-2, EQ-5D-3L, and PDQ-8 after treatment. Conclusions: Our results suggest that safinamide may have a beneficial effect on pain, a key unmet need in fluctuating PD patients.The study was funded by Zambon SpA with an unconditional research grant. In addition, the study was funded by MultiPark, the strategic research area for neuroscience at Lund University; the Swedish Parkinson Foundation; the Swedish Parkinson Academy and the Faculty of Medicine at Lund University.I was not given any grant numbers or any other details. The funds were used to finance the study personell and the logistic needs of the study.S

Long-term planning and its role as a tool of fiscal security of the economy

Актуальность исследования определяется тем, что обеспечение бюджетно-финансовой безопасности в России связано с проведением исполнительными органами государственной власти бюджетно-финансового планирования, основанного на принципах законности, плановости и открытости, прописанных в Бюджетном кодексе РФ. Все это рождает острую необходимость принятия базового документа (Долгосрочной бюджетной стратегии). Цель работы: провести анализ бюджетно-финансового планирования в его историческом, межстрановом и правовом аспектах, дать характеристику современного состояния бюджетно-финансового планирования в России. Методы исследования: моделирование, обобщение зарубежного опыта использования долгосрочного планирования, сопоставление и контент-анализ, который позволил выявить принципы долгосрочного планирования в бюджетной сфере, а также острую необходимость принятия Долгосрочной бюджетной стратегии на современном этапе в России. Результаты. Проведенное исследование отражает генезис бюджетного планирования в России в 1917-2017 гг. Анализ применения такого планирования в развитых странах (США, Германия, Великобритания, Франция и др.) определил основные принципы, которые могут быть заложены в основу Долгосрочной бюджетной стратегии в России на федеральном и региональном уровнях. Как основной базовый документ бюджетно-финансового планирования текущего периода утвержденная Долгосрочная бюджетная стратегия позволит предопределить результаты долгосрочного развития и обеспечить достаточный уровень экономической безопасности бюджетно- финансовой сферы.The relevance of this research is determined by the fact that ensuring fiscal security in Russia is connected with the Executive bodies of state power, budget and financial planning based on the principles of legality, planning and openness spelled out in the Budget code of the Russian Federation. All this creates an urgent need of adoption of the core document (Long-term budget strategy). The aim of the work is to analyze the budget and financial planning in its historical, interstate and legal aspects, State of fiscal planning in Russia. Research methods: modeling, generalization of foreign experience in using long-term planning. Comparison and content analysis, which allowed revealing the principles of long-term planning in the budgetary sphere and urgent need to adopt a Long-term budget strategy at the present stage in Russia. Results. The study reflects the Genesis of budget planning in Russia in 1917-2017. Analysis of application of such planning in developed countries (USA, Germany, UK, France, etc.) helped identify basic principles that can be the base of Long-term budget strategy in Russia at Federal and regional levels. The approved Long-term budget strategy, as the base document for budget and financial planning of the current period, will enable to predetermine the outcome of long-term development and to ensure a sufficient level of economic security fiscal sphere

GBA-associated PD: chances and obstacles for targeted treatment strategies.

Given the clear role of GBA in the pathogenesis of Parkinson's disease (PD) and its impact on phenotypical characteristics, this review provides an overview of the current knowledge of GBA-associated PD with a special focus on clinical trajectories and the underlying pathological mechanisms. Importantly, differences and characteristics based on mutation severity are recognized, and current as well as potential future treatment options are discussed. These findings will inform future strategies for patient stratification and cohort enrichment as well as suitable outcome measures when designing clinical trials

Versorgungssituation von Parkinson-Patienten in Sachsen: Eine sekundärdatenbasierte Analyse der Inanspruchnahme im Beobachtungszeitraum 2011 bis 2019

Als Bundesland mit dem höchsten Altersdurchschnitt in Deutschland und besonderen Strukturmerkmalen ländlich geprägter Gebiete sind die Folgen des demographischen Wandels bereits heute in Sachsen spürbar. Um die medizinische Versorgung von Parkinson-Patienten zu verbessern, bedarf es einer Status-quo-Analyse der aktuellen Versorgungspraxis. Ziel der Arbeit (Fragestellung) Inwieweit unterscheidet sich die Inanspruchnahme der medizinischen Leistungserbringung von Parkinson-Patienten im Vergleich von städtisch und ländlich geprägten Gebieten sowie im Vergleich von Parkinson-Patienten mit und ohne Neurologenkontakt im Beobachtungszeitraum von 2011 bis 2019? Material und Methoden Die Kohortenstudie basiert auf umfangreichen Routinedaten der Krankenkasse AOK PLUS der Jahre 2010 bis 2019 für Sachsen. Untersucht wurde eine Kohorte von insgesamt 15.744 Parkinson-Patienten (n = 67.448 Patientenjahre) und eine gematchte Vergleichskohorte (n = 674.480 Patientenjahre; Kriterien: Geburtsjahr, Geschlecht, Versicherungsjahr, Wohnsitz Stadt/Land) ohne ICD-10-Kodierung einer Bewegungsstörung. Ergebnisse Insgesamt war eine kontinuierliche Zunahme der Anzahl der Erkrankten in der dynamischen Kohorte von 2011 (n = 6829) bis 2019 (n = 8254) zu beobachten. Stadt-Land-Unterschiede zeigten sich insbesondere in der geringeren (Mit‑)Behandlung durch niedergelassene Neurologen in ländlich geprägten Gebieten. Parkinson-Patienten hatten ein 3,5- bzw. 4‑fach erhöhtes Risiko zu versterben im Vergleich zu Versicherten der Vergleichskohorte. Veränderungen der medikamentösen Parkinson-Therapie (Zunahme COMT- und MAO-Inhibitoren) sowie der Heilmittelerbringung (Zunahme Ergotherapie und Logopädie) über die Beobachtungszeit zeigten sich primär bei Parkinson-Patienten mit Neurologenkontakt. Diskussion In der Studie konnten eine erhöhte Morbidität und Mortalität bei Parkinson-Patienten identifiziert werden, die sich als Ziel für innovative Versorgungskonzepte eignen. Die zunehmende Zahl an Patienten und die beschriebenen Unterschiede dokumentieren hierfür den Bedarf. Gleichzeitig zeigen die Veränderungen in der Verordnungspraxis, dass innovative Therapien von niedergelassenen Neurologen eingesetzt werden.Background The consequences of demographic change are already noticeable in Saxony, the federal state with the highest average age in Germany and predominantly rural areas. In order to improve medical care for patients with Parkinson’s disease (PwP), a status quo analysis of current care practice is required. Objective To what extent does the utilization of medical services by PwP differ a) between urban and rural areas in Saxony and b) between PwP with and without neurologist contact in the observation period from 2011 to 2019? Material and methods The cohort study was based on extensive routine data for Saxony from the health insurance company AOK PLUS from 2010 to 2019. A cohort of 15,744 PwP (n = 67,448 patient-years) was compared to a matched cohort (n = 674,480 patient-years; criteria: year of birth, gender, year of insurance, place of residence: urban/rural) without an ICD-10 coding of a movement disorder. Results Overall, there was a steady increase in the number of PwP in the dynamic cohort from 2011 (n = 6829) to 2019 (n = 8254). Urban-rural differences included a smaller proportion of patients being seen by a neurologist in rural areas. The PwP had a 3.5 to 4‑fold higher risk of dying compared to those in the comparison cohort. Changes in drug therapy for Parkinson’s disease (i.e., increases in COMT and MAO inhibitors) and in remedy delivery (i.e., increases in occupational therapy and speech therapy) over the observation period were primarily seen in PwP who were seen by a neurologist. Discussion The study identified increased morbidity and mortality in PwP who are suitable targets for innovative care concepts. The increasing number of patients and the described differences document the need for this. At the same time, changes in prescription practice show that innovative forms of treatment are being used by neurologists in outpatient care