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Background: Cities are an important driving force to implement the Sustainable Development Goals (SDGs) and the New Urban Agenda. The SDGs provide an operational framework to consider urbanization globally, while providing local mechanisms for action and careful attention to closing the gaps in the distribution of health gains. While health and well-being are explicitly addressed in SDG 3, health is also present as a pre condition of SDG 11, that aims at inclusive, safe, resilient and sustainable cities. Health in All Policies (HiAP) is an approach to public policy across sectors that systematically takes into account the health implications of decisions, seeks synergies, and avoids harmful health impacts in order to improve population health and health equity. HiAP is key for local decision-making processes in the context of urban policies to promote public health interventions aimed at achieving SDG targets. HiAPs relies heavily on the use of scientific evidence and evaluation tools, such as health impact assessments (HIAs). HIAs may include city-level quantitative burden of disease, health economic assessments, and citizen and other stakeholders' involvement to inform the integration of health recommendations in urban policies. The Barcelona Institute for Global Health (ISGlobal)'s Urban Planning, Environment and Health Initiative provides an example of a successful model of translating scientific evidence into policy and practice with regards to sustainable and healthy urban development. The experiences collected through ISGlobal's participation implementing HIAs in several cities worldwide as a way to promote HiAP are the basis for this analysis. Aim: The aim of this article is threefold: to understand the links between social determinants of health, environmental exposures, behaviour, health outcomes and urban policies within the SDGs, following a HiAP rationale; to review and analyze the key elements of a HiAP approach as an accelerator of the SDGs in the context of urban and transport planning; and to describe lessons learnt from practical implementation of HIAs in cities across Europe, Africa and Latin-America. Methods: We create a comprehensive, urban health related SDGs conceptual framework, by linking already described urban health dimensions to existing SDGs, targets and indicators. We discuss, taking into account the necessary conditions and steps to conduct HiAP, the main barriers and opportunities within the SDGs framework. We conclude by reviewing HIAs in a number of cities worldwide (based on the experiences collected by co-authors of this publication), including city-level quantitative burden of disease and health economic assessments, as practical tools to inform the integration of health recommendations in urban policies.Results: A conceptual framework linking SDGs and urban and transportplanning, environmental exposures, behaviour and health outcomes, following a HiAP rationale, is designed. We found at least 38 SDG targets relevant to urban health, corresponding to 15 SDGs, while 4 important aspects contained in our proposed framework were not present in the SDGs (physical activity, noise, quality of life or social capital). Thus, a more comprehensive HiAP vision within the SDGs could be beneficial. Our analysis confirmed that the SDGs framework provides an opportunity to formulate and implement policies with a HiAP approach. Three important aspects are highlighted: 1) the importance of the intersectoral work and health equity as a cross-cutting issue in sustainable development endeavors; 2) policy coherence, health governance, and stakeholders' participation as key issues; and 3) the need for high quality data. HIAs are a practical tool to implement HiAP. Opportunities and barriers related to the political, legal and health governance context, the capacity to inform policies in other sectors, the involvement of different stakeholders, and the availability of quality data are discussed based on our experience. Quantitative assessments can provide powerful data such as: estimates of annual preventable morbidity and disability-adjusted life-years (DALYs) under compliance with international exposure recommendations for physical activity, exposure to air pollution, noise, heat, and access to green spaces; the associated economic impacts in health care costs per year; and the number of preventable premature deaths when improvements in urban and transport planning are implemented. This information has been used to support the design of policies that promote cycling, walking, public, zero and lowemitting modes of transport, and the provision of urban greening or healthy public open spaces in Barcelona (e.g. Urban Mobility, Green Infrastructure and Biodiversity Plans, or the Superblocks's model), the Bus Rapid Transit and Open Streets initiatives in several Latin American cities or targeted SDGs assessments in Morocco. Conclusions: By applying tools such as HIA, HiAP can be implemented to inform and improve transport and urban planning to achieve the 2030 SDG Agenda. Such a framework could be potentially used in cities worldwide, including those of less developed regions or countries. Data availability, taking into account equity issues, strenghtening the communication between experts, decision makers and citizens, and the involvement of all major stakeholders are crucial elements for the HiAP approach to translate knowledge into SDG implementation.

In "Iconography after Identity," a text published as a part of the book Shades of Black: Assembling Black Arts in 1980s Britain, art historian Kobena Mercer puts forward a challenge.1 He calls for artists, curators, and critics to begin the long, overdue process of constructing an art history that maps the dialogues and developments of black British art onto broader stories of British and twentieth-century art as a whole. He urges the reader to confront the critical tendencies that have sidelined comprehensive analysis of black British art, and move beyond narratives that approach the creative production of black artists instrumentally, as a lens through which, at best, to examine (and, at worst, explain) the social and political implications of race and ethnicity in twentieth century Britain. Echoing Mercer's assessment, recent publications by scholars such as Leon Wainwright and, from an American perspective, Darby English have highlighted the ways in which this problematic halfstory has been written both by racism's "inventive way of isolating black realities from the spaces whose purity it would conserve by doing so" and also – notably – even by some countermeasures against this systemic racism. Returning to British shores, to these two factors we might also add the dominance of voices from the fields of sociology and cultural theory, not least in important foundational works by Stuart Hall and Paul Gilroy, in the establishment of early scholarship around "black art" and black British artists. Arguing for a loosely reconfigured version of Erwin Panofsky's iconographic model, Mercer offers one possibility for object-based engagement. More recently, English, Wainwright and others have looked to frameworks of materiality and phenomenology (respectively), to de-center narratives of racial and ethnic identity in art historical assessments of works by black and diaspora artists. But, of course, these critiques are not new, nor is the stilted discourse that they observe. They join the voices of Rasheed Araeen, Sonia Boyce, Lubaina Himid, Eddie Chambers, Keith Piper, Veronica Ryan, Rotimi Fani-Kayode, Marlene Smith, and others, a chorus gathering force since the late 1970s, when the constellation of artists, activists, and critics of what has come to be known, in some circles, as the Black Arts Movement burst on the British art scene. Working in relation to questions of "blackness" in Britain and the possibilities and implications of a black British art through visual practice and in art-adjacent practices as artist-curators, artist-critics, artist-researchers and artist-archivists, though somewhat imprecise and contested, the Black Arts Movement laid the foundations for the radical art history that lies at the root of Mercer's challenge: an art history that accounts for the work of black British artists within the context of wider national and international aesthetic, cultural and historical formations, rather than footnotes haphazardly inserted into mainstream narratives of art in the twentieth century, if they (black British artists) are included at all. This article springs from the interstices of a pair of projects—one that is wrapping up, and the other starting out—which continue the work of excavating this art history, building on a rapidly growing literature around the Black Arts Movement in Britain by tracing its roots from the early 1960s. Following the contours of the first two of what Stuart Hall has called "waves" of black arts activity in postwar Britain, this article takes as a starting point a critical examination of the notion of "black art" in a British context in order to unravel attendant questions around the formation and framing of what has come to be generally known as a Black Arts Movement. This mode of engagement with the creative products of black British artists must address, as Mercer notes, "the necessity of interpreting the work as a document of the human imagination that exists as an object of aesthetic attention in its own right." This is not to say, however, that we should, or even can, disavow the politics of identity or politics more broadly. Indeed, much of the work created during the broad period from the early 1960s is overtly concerned with the radical possibilities made available by the construction and interrogation of identities that are variously and simultaneously defined by race, gender, class, and sexuality. To disentangle aesthetics and politics entirely in these cases would be futile and tell a different, but still problematic, half-story. Rather, building on and supplementing the work that has been done in this field by earlier historians and critics working within identity-based frameworks, this article, and the projects from which it arises, aim to create a more comprehensive understanding of artworks that at times deal explicitly, though not exclusively, with identity, together with wider questions of politics, aesthetics, and the construction of art's histories.

哈薩克的領土遼闊而人口稀少,僅有549萬5千人,與鄰國接壤的領界非常長,形成了易攻難守的戰略困境。地理上夾在中國與俄國兩大強鄰之間,戰略要衝的位置造成維護國家主權獨立極不容易。哈薩克是冷戰結束後最後一個擺脫蘇聯的附庸國身分,1991年12月16日才獲得獨立地位,執政當局必須維持戰略平衡與經濟轉型發展,博奕在各方強權之間,其戰略思考值得研究。無論是俄羅斯的歐亞經濟聯盟還是中國的一帶一路,對哈薩克而言既是豐富的資源也是嚴峻的挑戰。努爾蘇丹(Nursultan,哈薩克首都新名,原為Astana)利用冷戰結束初期美俄關係和緩的蜜月期,迅速引進美國的勢力進入哈薩克,同時又與日本建立戰略合作夥伴關係,進行能源技術開發,經常能夠在東西兩陣營之間左右逢源。因此,不受意識形態限制的多方外交,是哈薩克的最佳戰略選擇,幫助哈薩克從天然資源出口經濟轉型為多元創新的經濟模式。本研究從核心問題出發,釐清哈薩克的多方外交仍然深受國際體系因素影響,在國際秩序穩定的階段,努爾蘇丹可以左右逢源,但是當國際秩序受到挑戰時,努爾蘇丹的多方外交將被迫扈從對其最有影響力的俄羅斯。本文將利用新古典現實主義作為研究理論架構,兼顧國內外政治與經濟的因素,分析哈薩克在中、俄、美各強權之間的平衡,最終還是有其限制。 ; Kazakh's territory is vast and sparsely populated, with only 5.49 million people. The border with neighboring countries is very long, forming a strategic dilemma that is easy to attack but hard to defend. Geographically sandwiched between China and Russia's, it is extremely difficult for maintaining a sovereign dependent country. Kazakh was the last vassal state to get rid of the Soviet Union after the end of the Cold War and won independence on December 16, 1991. It is also difficult that ruling party keep maintaining its strategic balance and economic transformation and development. Thus, it has great value to study Kazakhstan's strategic thinking. Whether it is Russia's Eurasian Economic Union or China's Belt and Road Initiative, it is both a rich resource and a serious challenge for Kazakhstan. Kazakh took advantage of the end of the Cold War, which is the honeymoon period in US-Russia relations. This leads the American interest groups into Kazakhstan. At the same time, it has established a strategic partnership with Japan to develop energy technologies. It allows Nursultan to be able to achieve success one way or another. Multi-Vector Foreign Policy is not subject to ideology but best strategic choice, helping Kazakh to transform from a natural resource export economy to a multi-innovative economic model. Starting from the core issues, this paper clarifies that Kazakhstan's Multi-Vector Foreign Policy is deeply influenced by international system and structural factors. In the stable stage of the international order, Nursultan can get the benefit from both sides. However, when the international order is shifted, Nursultan will be forced to bandwagon Russia. This paper will use neoclassical realism as the theoretical framework of research, taking into account the political and economic factors at home and abroad, and analyzing the balance between Kazakh's powers in China, Russia and the United States, and ultimately has its limitations.

國際關係理論流派之一的「制度主義」提倡國際制度的改良,新制度主義繼之主張國際成員並非僅限主權國家,其他新興的國際組織(政府間的和非政府間的)、跨國公司、其他非國家成員、及個人,都是組成國際社會不可分割的成員,一應受到重視和關注。特別是透過國際組織的改良或重建,解決主權國家共同關切卻力有未逮的議題。這種趨勢有助於世界共議「全球治理」。全球治理乃為解決國際爭端、促進國際合作、解決共同挑戰的新途徑。習近平主政後,在2013年推動一帶一路倡議,以因應中國大陸發展需要,特別是運用中國的過剩產能、豐沛資金,為國家發展和國家安全找尋新的出路,而以多數中東、東歐、中亞、東盟、甚至部分非洲與拉美地區國家為合作夥伴。這是新類型經濟合作模式,外溢效果宏大,距全球治理的概念和規模不遠。西方國家學者的全球治理端賴非政府國際組織,但無論主導或扈從一帶一路倡議行為者,大都是主權國家。北京多方闡釋中國大陸對一帶一路倡議的努力,並稱將致力防範其負面影響,甚至保證該倡議是各方合作平台,「並非中國的地緣政治工具」。隨著一帶一路倡議的擴大與深化,正要驗證中國大陸透過一帶一路倡議將形成何種面貌的全球治理,以及根據這個趨勢,將出現何種新型的國際關係。 ; Institutionalism, as one of the major branches of international relations theories, calls for the renovation of the international institutions. Following this idea, the Neoinstitutionalism argues that the indivisible actors like nation states, newly developed international organizations (both governmental and nongovernmental), multinational corporations, and individuals should be counted and concerned. It is especially crucial to solve those thorny issues that may not be dealt with by sovereign states via the renovation or establishment of international organizations. This trend attributes to the consensus resulting in the operation of "global governance" as the new channels of solving the international disputes, accelerating cooperation, and encountering challenges. Xi Jinping, the PRC's president since 2013, proclaimed his "Belt and Road" initiative that year for the purpose of adapting China's national development, particularly based on China's excessive productivity and abundant currency reserves, and invites the partnership of major Middle East, East European, Central Asian, ASEAN, African and Latin American countries for better chances of cooperation and development. This kind of economic cooperation originated from economic need, but infers massive spillover effect, and brings about new elements of global governance. Instead of inviting international nongovernmental organizations as the backbones of global governance, the Belt and Road initiative has been primarily nation-state operated. Beijing tries to sell its Belt and Road initiative while emphasizing its efforts in detracting the side effects caused, arguing that the Belt and Road initiative will "never be China's tool for geopolitics." Nonetheless, China's Belt and Road initiative, after its being introduced and enhanced, will be carefully scrutinized globally whether it is conducive to global governance and whether new-style of international relations be established.

Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40–69) and 5-year overall survival was 65% (95% CI 52–81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Funding German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

Purpose of Article. The goal of the work is to analyze the structure of salon paired dances of ballroom group on the frontier of the XIX-XX centuries. While considering mentioned dances, the author put the target not only to open the specific of dance group culture of the pointed time but conceptually tried to form the material in such way that it would have methodical value. Methodology of the research is based on the combination of historical-stylistic and analytically- synthetic approach with the method of content analysis. Scientific Novelty. In the article on the owned level, the «ballroom» group of salon paired dances on the frontier of XIX-XX centuries is considered, among the famous representatives are Pas de Quatre, Mignon, Pas de Grace, La Caprice, The Tom Tit. Their structure is analyzed with the description of necessary tact and figures, which has the important theoretical and methodical meaning. Besides the author emphasizes on their weighty role they play in understanding the specific of historical-social dance, and also in an affirmation of the modern dance culture basics including Ukraine. Conclusions. Performed analysis of the salon ballroom dances structure of the pointed period testified that like that period society had the necessity in the renewal of plastic culture, in new dances and about the crisis of noble manners and tastes which was conditioned by the democratization not only of social traditions but also of structural and technical measures of choreographic art. On the example of salon paired dances is possible to note like the dance culture foundations of the future century were laid and which opened the great space for the further evaluation of other groups of salon paired dances among which «folk», «ancient,» and «american» salon dances are deserved a special attention. ; Цель работы — проанализировать структуры салонных парных танцев бальной группы на рубеже ХІХ-ХХ веков. Рассматривая структуры указанных танцев, автор ставит перед собой цель не просто раскрыть специфику танцевальной культуры указанного времени, но и концептуально оформить материал таким образом, чтоб он имел методическую ценность. Методология исследования базируется на сочетании историкостилистического и аналитико-синтетического подходов с методом контент-анализа. Научная новизна. В статье на должном теоретическом уровне рассматривается «балльная» группа салонных парных танцев на рубеже ХІХ — XX веков, среди наиболее известных репрезентантов которой является Падекатр (Pas de Quatre), Миньон (Mignon), Падеграс (Pas de Grace), Каприз (La Caprice ) и Том-тит (The Tom Tit). Анализируется их структура с описанием необходимых тактов и фигур, что имеет большое теоретическое и методическое значение. Делается упор на важную роль, которую они играют в понимании специфики историко-бытового танца, а также в утверждении основ современной танцевальной культуры, в том числе и в Украине. Выводы. Проведенный анализ структуры салонных бальных танцев указанного времени свидетельствует о том, как тогдашнее общество почувствовало потребность в обновлении пластической культуры, в новых танцах и о кризисе благородных манер и вкусов, который был обусловлен демократизацией не только социальных устоев, но и структурных и технических основ хореографического искусства. На примере салонных парных танцев можно заметить, как закладывались основы танцевальной культуры будущего века, это открывает большой простор для дальнейших исследований других групп салонных парных танцев, среди которых отдельного внимания заслуживают «народные», «старинные» и «американские» салонные танцы. ; Мета роботи - проаналізувати структури салонних парних танців бальної групи на рубежі ХІХ-ХХ століть. Розглядаючи структури зазначених танців, автор ставить перед собою ціль не просто розкрити специфіку танцювальної культури зазначеного часу, але й концептуально оформити матеріал таким чином, щоб він мав методичну цінність. Методологія дослідження базується на поєднанні історико-стилістичного і аналітико- синтетичного підходів з методом контент-аналізу. Наукова новизна. У статті на належному теоретичному рівні розглядається «бальна» група салонних парних танців на рубежі XIX - XX століть, серед найбільш відомих репрезентантів якої є Падекатр (Pas de Quatre), Міньйон (Mignon), Падеграс (Pas de Grace), Каприз (La Caprice) і Том-тіт (The Тот Tit). Аналізується їх структура з описом необхідних тактів і фігур, що має вагоме теоретичне та методичне значення. Робиться наголос на важливій ролі, яку вони відіграють у розумінні специфіки історико-побутового танцю, а також у ствердженні засад сучасної танцювальної культури, у тому числі й в Україні. Висновки. Проведений аналіз структури салонних бальних танців означеного часу свідчить про те, як тодішнє суспільство відчуло потребу в оновленні пластичної культури, в нових танцях і про кризу шляхетних манер і смаків, яка була зумовлена демократизацією не лише соціальних устоїв, але й структурних і технічних засад хореографічного мистецтва. На прикладі салонних парних танців можна помітити, як закладалися підвалини танцювальної культури майбутнього століття, що відкриває великий простір для подальших досліджень інших груп салонних парних танців, серед яких на окрему увагу заслуговують «народні», «старовинні» та «американські» салонні танці.

The article is dedicated to the study of certain elements of the system of criminalprocedural legislation of Ukraine. The scientific position that the Constitution of Ukraineis the source of criminal procedural law is supported, since it contains a large numberof regulations, which are important for the regulation of criminal procedural activities.Analyzing the conceptual regulations of the constitutional reform in relation tojustice of the year 2016, it is concluded, that such changes are aimed at improving theconstitutional basis of justice for the practical implementation of the supremacy of lawand insuring the right to a fair trial. The conceptual provisions of judicial reform in thepart of criminal justice include, in particular, judicial procedures (ensuring theindependence of the judiciary by forming the bodies responsible for the judiciary;increasing the requirements and professional standards of the judiciary, limiting theimmunity of judges to functional; optimizing the system of judicial system by improvingthe provisions on jurisdiction courts and out-of-court settlement of disputes, etc.); thoserelating to the principles of justice (in particular, the principle for ensuring the right toappeal the case and to judgement cassation appeal has received a new normativecontent) and the status of participants in criminal proceedings (concerning theinstitutional capacity of the prosecutor's office and the advocacy).Considerable attention is paid to the issue of ensuring the unity of judicial practice.Based on the study of the views of scientists on the role and place of the judicial precedentin the Anglo-American and Romano-Germanic legal systems at various historical stagesof the development of legal thought, it is stated that the unity of judicial practice shouldbe ensured by the Supreme Court. Due to the creation of a new Supreme Court and thefunctioning of new collegial bodies there, the emphasis is placed on the importance offurther studies of the procedure for the mandatory introduction of decisions by theSupreme Court in similar cases of criminal justice in our country. ; Статья посвящена исследованию отдельных элементов системы уголовно-го процессуального законодательства Украины. Поддерживается научная позицияо том, что Конституция Украины является источником уголовного процессуаль-ного права, поскольку содержит большое количество нормативных положений,имеющих значение для регулирования уголовной процессуальной деятельности.Анализируя концептуальные положения Конституционной реформы право-судия 2016 г., сделан вывод о том, что такие изменения направлены на совершен-ствование конституционных основ правосудия для реализации принципа верхо-венства права и обеспечения права на справедливый суд. К концептуальнымположениям судебной реформы в части уголовного судопроизводства относятся,в частности, судоустройственные (обеспечение независимости судебной властипутем формирования органов, ответственных за судейский корпус, повышениетребований и профессиональных стандартов к судейскому корпусу, ограниченияиммунитета судей до функционального; оптимизация системы судоустройствапутем усовершенствования положений о юрисдикции судов и внесудебного урегу-лирования споров и т. д.); касающиеся принципов судопроизводства (в частности,новое нормативное содержание приобрело право на апелляционный пересмотрдела и кассационное обжалование судебного решения) и статуса участниковуголовного судопроизводства (институциональная состоятельность прокурату-ры и адвокатуры).Значительное внимание в статье уделено вопросу обеспечения единствасудебной практики. На основании исследования взглядов ученых о роли и местесудебного прецедента в англо-американской и романо-германской правовых си-стемах на разных исторических этапах развития правовой мысли, отмечается,что единство судебной практики должно обеспечиваться Верховным Судом.Учитывая создание нового Верховного Суда и функционирования в нем новыхколлегиальных органов, сделан акцент на важности дальнейших исследованийпроцедуры приобретения обязательного характера в нашем государстве решенийВерховного Суда по аналогичным делам уголовного судопроизводства. ; Стаття присвячена дослідженню окремих елементів системи кримінальногопроцесуального законодавства України. Підтримується наукова позиція про те,що Конституція України є джерелом кримінального процесуального права,оскільки містить велику кількість нормативних положень, які мають значеннядля регулювання кримінальної процесуальної діяльності.Аналізуючи концептуальні положення конституційної реформи щодо право-суддя 2016 р., зроблено висновок, що такі зміни спрямовано на удосконаленняконституційних основ правосуддя для практичної реалізації принципу верховенстваправа і забезпечення права на справедливий суд. До концептуальних положеньсудової реформи у частині кримінального судочинства належать, зокрема,судоустрійні (забезпечення незалежності судової влади шляхом формуванняорганів, відповідальних за суддівський корпус; підвищення вимог та професійнихстандартів суддівського корпусу; обмеження імунітету суддів до функціонального;оптимізація системи судоустрою шляхом удосконалення положень щодоюрисдикції судів та позасудового врегулювання спорів тощо); ті, що стосуютьсязасад судочинства (зокрема, нового нормативного змісту набула засада забез-печення права на апеляційний перегляд справи та касаційне оскарження судовогорішення) та статусу учасників кримінального провадження (стосуютьсяінституційної спроможності прокуратури та адвокатури).Значну увагу у статті приділено питанню забезпечення єдності судовоїпрактики. На підставі дослідження поглядів вчених щодо ролі та місця судовогопрецеденту в англо-американській та романо-германській правових системах нарізних історичних етапах розвитку правової думки, зазначається, що єдністьсудової практики має забезпечуватися Верховним Судом. З огляду на створеннянового Верховного Суду та функціонування у ньому нових колегіальних органів,зроблено акцент на важливості подальших досліджень процедури запроваджен-ня обов'язкового характеру в нашій державі рішень Верховного Суду в аналогічнихсправах кримінального судочинства.

Суммируются различные аспекты научной дискуссии, вращающейся вокруг понятия современной теории модернизации и ее сложных вопросов. Отмечено, что один из наиболее важных моментов дискуссии определяется новой взаимосвязью между столь различными концепциями, как модернизация, демократизация и глобализация. Данные концепции с конца ХХ в. обычно обсуждаются в их взаимосвязи, нередко сохраняя гетерогенный смысл. Указано, что в общественном дискурсе понятия «модернизация» и «глобализация» приобрели эмоциональный оттенок: одни связывают их с международным гражданским обществом, ведущим к новой эре мира и демократизации; другие видят в них угрозу американской экономической и политической гегемонии с таким ее культурным следствием, как гомогенизированный мир. Тем не менее действительно существуют некоторые отчетливые характеристики, определяющие общие тенденции процесса модернизации. Констатируется, что главной тенденцией является изменяющееся значение современности, или возникновение «альтернативных современностей», и все большее значение приобретает феномен альтернативных глобализаций, т. е. культурных движений, имеющих глобальное измерение, возникающих за пределами западного мира и оказывающих на него влияние. Другая тенденция связана с кризисом легитимности традиции национального государства, вынуждающим пересмотреть проблему роли демократии в современном мире. Показано, что мнение С. М. Липсета о соотношении демократии с экономическим развитием породило широкий спектр исследований и затронуло разнообразные аспекты политической науки. Выявлены два ясно выраженных довода в пользу такой взаимосвязи: демократии могут возникать по мере того, как страны развиваются экономически (С. П. Хантингтон, Р. Инглхарт), или устанавливаться независимо от уровня экономического развития (более способны к выживанию демократии в развитых странах). Замечено, что базовое утверждение теории модернизации в любой из ее версий заключается в том, что существует единый общий процесс, завершающей стадией которого является демократизация. Модернизация состоит в постепенной дифференциации и специализации социальных структур и завершается отделением политических структур от всех остальных, что и делает демократию возможной. Указано, что в настоящее время превалирует точка зрения, в соответствии с которой возникновение демократии не является побочным продуктом экономического развития (Г. О'Доннелл). Сторонники этого подхода не верят, что судьба демократического правления детерминирована исключительно имеющимися в наличии уровнями экономического развития. Они утверждают, что, несмотря на все сдерживающие моменты, демократизация – это прежде всего следствие человеческих действий, а не экономических условий или же наследия исторического прошлого (Э. Гидденс, Р. М. Унгер). ; The purpose of this article is to summarize the diverse aspects of scientific discussion revolving around the notion itself and complicated questions of the theory of modernization. One of the main point of discussion is the new relationship between once so dissimilar conceptions like modernization, democratization and globalization. These conceptions have been brought together in the end of the XX century and since that time usually discussed interconnected, often maintaining a heterogeneous sense. The terms «modernization» and «globalization» have come to be emotionally charged in public discourse. For some, they imply the promise of an international civil society, conducive to a new era of peace and democratization. For others, they imply the threat of an American economic and political hegemony, with its cultural consequence being a homogenized world. Nevertheless, some distinct characteristics defining the general tendencies of the modernization process really exist. The main tendency is the changing meaning of modernity, or the emergence of «alternative modernities». There is also the increasingly significant phenomenon of alternative globalizations that is, cultural movements with a global outreach originating outside the Western world and indeed impacting on the latter. The second trend is related to a crisis in the legitimacy of the nation-state tradition forcing to review the problem of the role of democracy in the modern world. S. M. Lipset's observation that democracy is related to economic development, first advanced in 1959, has generated the largest body of research on any topic in political science. Yet there are two distinct reasons this relation may hold: either democracies may be more likely to emerge as countries develop economically (S. P. Huntington, R. Inglehart), or they may be established independently of economic development but may be more likely to survive in developed countries. The basic assumption of the theory of modernization, in any of its versions, is that there is one general process of which democratization is but the final stage. Modernization consists of a gradual differentiation and specialization of social structures that culminates in a separation of political structures from other structures and makes democracy possible. But now a prevailing view, according to which the emergence of democracy is not a by-product of economic development (G. O'Donnell). The protagonists of this approach do not believe that the fate of democratic rule would be determined exclusively by current levels of economic development. They maintained that, albeit within constraints, democratization was an outcome of actions, not just of economic conditions as like as historical past (A. Giddens, R. M. Unger).

La diversidad genética de las poblaciones humanas del centro de Argentina es resultado de un proceso de movimientos migratorios y mestizaje, consecuencia de cinco siglos de contacto entre los nativos americanos y los migrantes principalmente de Europa, Medio Oriente y África. Estos eventos histórico-demográficos no fueron homogéneos, sino que difirieron según condiciones ambientales, económicas y políticas de cada subregión. En este trabajo estudiamos la estructura genética del Valle de Traslasierra a partir del análisis de 8 inserciones Alu (PV92, FXIIIB, APO, TPA25, ACE, A25, B65 y D1). El objetivo es contribuir al conocimiento de su historia evolutiva reciente, principalmente en lo referente a patrones migratorios y a la posible existencia de consanguinidad, empleando metodologías propias de la Antropología Genética. La muestra investigada incluyó a 97 individuos de varias localidades, mayormente rurales, y fue subdividida en tres submuestras, de acuerdo con la orientación norte-sur del valle. Los resultados revelaron la ausencia de diferenciación entre submuestras y un déficit significativo de heterocigotas en 7 de los 8 marcadores utilizados. Los índices de endogamia local (FIS) y total (FIT), que miden el aumento de homocigosis debido a apareamientos consanguíneos, muestran valores positivos y estadísticamente significativos, tanto en la población total como en cada una de las subpoblaciones. Estos resultados confirman la existencia de consanguinidad estimada previamente de forma indirecta a partir de isonimia, distancias maritales y otros estimadores biodemográficos. Finalmente, si bien cinco de las inserciones Alu estudiadas presentaron diferencias altamente significativas entre grupos continentales, la estimación de ancestría genética no refleja la contribución de las poblaciones parentales al acervo genético de la población según lo esperado a partir de evidencias obtenidas de marcadores uniparentales y autosomales o de la historia migratoria reciente. ; The genetic diversity of human populations in central Argentina is the result of a process of migratory movements and admixture, after five centuries of contact between Native Americans and migrants, mainly from Europe, the Middle East, and Africa. These historical and demographic events were not homogeneous; rather, they showed differences related to the environmental, economic, and political conditions of each sub-region. In this work we studied the genetic structure of Traslasierra Valley from the analysis of 8 Alu insertions (PV92, FXIIIB, APO, TPA25, ACE, A25, B65, and D1). Our objective is to contribute to the knowledge of its recent evolutionary history, mainly in relation to migratory patterns and the possible existence of consanguinity, using methodologies of anthropological genetics research. The sample examined included 97 individuals from several localities, mostly rural, and was divided into three subsamples, according to the north-south orientation of the valley. The results revealed the lack of differentiation between subsamples and a significant deficit of heterozygotes in 7 of the 8 markers used Local (FIS) and total (FIT) inbreeding coefficients, which measure the increase of homozygosis due to consanguineous mating, show positive and statistically significant values, both in the total population and in each of the subpopulations. The results confirm the existence of inbreeding, previously estimated indirectly by isonymy, marital distance, and other biodemographic estimators. Although five of the Alu insertions showed highly significant differences between continental groups, the estimation of genetic ancestry does not reflect the contribution of parental populations to the population's gene pool, as expected from evidence obtained from uniparental and autosomal markers, or from recent migration history. ; A diversidade genética das populações humanas na Argentina central é o resultado de um processo de movimentos migratórios e miscigenação, resultado de cinco séculos de contato entre nativos americanos e migrantes, principalmente da Europa, Oriente Médio e África. Esses eventos histórico-demográficos não foram homogêneos, mas diferiram de acordo com as condições ambientais, econômicas e políticas de cada sub-região. Neste trabalho, estudamos a estrutura genética do Valle de Traslasierra a partir da análise de 8 inserções Alu (PV92, F13B, APO, TPA25, ACE, A25, B65 e D1). O objetivo é contribuir para o conhecimento de sua história evolutiva recente, principalmente em relação aos padrões migratórios e a possível existência de consanguinidade, utilizando metodologias da Antropologia Genética. A amostra investigada incluiu 97 indivíduos de várias localidades, na sua maioria rurais, e subdividiu-se em três subamostras, de acordo com a orientação norte-sul do vale. Os resultados revelaram a ausência de diferenciação entre subamostras e um déficit significativo de heterozigotos em 7 dos 8 marcadores usados. Os índices de endogamia local (FIS) e total (FIT), que medem o aumento da homozigose devido a acasalamentos consanguíneos, mostram valores positivos e estatisticamente significativos, tanto na população total como em cada uma das subpopulações. Estes resultados, obtidos a partir de polimorfismos genéticos, confirmam a existência de consanguinidade previamente estimada indiretamente a partir de isonimia, distâncias conjugais e outros estimadores biodemográficos.

BACKGROUND: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

BACKGROUND Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. METHODS In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB), SHH (MB), group 3 (MB), and group 4 (MB). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. FINDINGS We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MB subgroup). Patients with germline APC mutations developed MB and accounted for most (five [71%] of seven) cases of MB that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MB. Germline TP53 mutations presented only in childhood patients in the MB subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MB, MB, and MB molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. INTERPRETATION Genetic counselling and testing should be used as a standard-of-care procedure in patients with MB and MB because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. FUNDING German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

Engineering enterprises are the basis of the country's industrial production. The importance of their stable development for the country's economy is determined by the fact that for several centuries the sector remains the only supplier of capital resources to enterprises of other industries. Machine-building enterprises provide any production with machinery and equipment, and the population with consumer goods. The products of engineering enterprises are used in all spheres of human life. The history of the development of engineering enterprises continues for almost a millennium. Significant changes in the organizational structure and production of new types of products of machine-building enterprises have combined hundreds of sub-sectors specializing in the production of various types of products: from household products to complex units. The main premise underlying the analysis of the current state of machine-building enterprises in terms of their attractiveness indicates that the level of profitability depends not only on internal impact, but also on the impact of external factors. The analysis of the dynamics of changes in the number of domestic engineering enterprises in 2010–2017 indicates that the number of domestic engineering enterprises over the period under review tended to decrease, this is due to economic, social and political problems that were formed under the influence of internal and external factors outflow of investors and a decrease in the level of innovative development. The difficult situation of machine-building enterprises is not saved by the successful implementation of new technologies and borrowing the experience of foreign countries. The pace of innovation development is insufficient for competition with European, Asian and American engineering enterprises. The main factor restraining the innovative activity of domestic engineering enterprises is the lack of own financial resources and the low level of support from the state. ; Предприятия машиностроительной отрасли являются основой промышленного производства страны. Важность их стабильного развития для экономики страны определяется, тем фактом, что в течение нескольких веков сектор остается единственным поставщиком капитальных ресурсов на предприятия других отраслей. Машиностроительные предприятия обеспечивают любое производство машинами и оборудованием, а население - предметами потребления. Продукция машиностроительных предприятий используется во всех сферах существования человеческой жизни. История развития предприятий машиностроения продолжается почти тысячелетие. Существенные изменения в организационной структуре и производстве новых видов продукции машиностроительных предприятий объединили в себе сотни подотраслей, специализирующихся на выпуске различных видов продукции: от бытовой продукции до сложных агрегатов. Основная предпосылка, лежащая в основе анализа текущего состояния машиностроительных предприятий с точки зрения их привлекательности свидетельствует о том, что уровень доходности зависит не только от внутреннего воздействия, но и от воздействия внешних факторов. Проведенный анализ динамики изменения количества отечественных машиностроительных предприятий за 2010–2017 гг., свидетельствует о том, что количество отечественных машиностроительных предприятий за рассматриваемый период имела тенденцию к снижению, это связано с экономическими, социальными и политическими проблемами, которые формировались под влиянием внутренних и внешних факторов, оттока инвесторов и снижение уровня инновационного развития. Трудную ситуацию машиностроительных предприятий не спасают успешные внедрения новых технологий и заимствования опыта зарубежных стран. Темпы инновационного развития недостаточны для конкурентной борьбы с европейскими, азиатскими и американскими машиностроительными предприятиями. Основным фактором, сдерживающим инновационную активность отечественных машиностроительных предприятий, является отсутствие собственных финансовых средств и низкий уровень поддержки со стороны государства. ; Підприємства машинобудівної галузі є основою промислового виробництва країни. Важливість їх стабільного розвитку для економіки країни визначається, тим фактом, що протягом кількох століть сектор залишається єдиним постачальником капітальних ресурсів на підприємства інших галузей. Машинобудівні підприємства забезпечують будь-яке виробництво машинами та обладнанням, а населення – предметами споживання. Продукція машинобудівних підприємств використовується у всіх сферах існування людського життя. Історія розвитку підприємств машинобудування триває майже тисячоліття. Суттєві зміни у організаційній структурі та виробництві нових видів продукції машинобудівних підприємств об'єднали в собі сотні підгалузей, що спеціалізуються на випуску різних видів продукції: від побутової продукції до найскладніших агрегатів. Основна передумова, яка лежить в основі аналізу поточного стану машинобудівних підприємств з точки зору їх привабливості - це висновок про те, що рівень прибутковості залежить не тільки від внутрішнього впливу, а й від впливу зовнішніх факторів. Проведений аналіз динаміки зміни кількості вітчизняних машинобудівних підприємств за 2010–2017рр. свідчить про те, що кількість вітчизняних машинобудівних підприємств за розглянутий період мала тенденцію до зниження, це пов'язано з економічними, соціальними та політичними проблемами, які формувались під впливом внутрішніх та зовнішніх факторів, відтоку інвесторів та зниження рівня інноваційного розвитку. Скрутну ситуацію машинобудівних підприємств не рятують успішні впровадження нових технологій і запозичення досвіду зарубіжних країн. Темпи інноваційного розвитку недостатні для конкурентної боротьби з європейськими, азіатськими та американськими машинобудівними підприємствами. Основним фактором, що стримують інноваційну активність вітчизняних машинобудівних підприємств, є відсутність власних фінансових коштів та низький рівень підтримки з боку держави.

The project had as an objective an approximation to the concept of environmental liability, on the part of both the private legal persons and the State. This concept influences the legal description of environmental damage and of its compensation. The aforementioned analysis received a differentiated dimension in this project, via the comparison between the Argentine legislation and that of the MERCOSUR members, and the French and European ones. The objectives of the project were achieved. Comparative studies were carried out in parallel on the environmental liability regimes of France, the European Union, Argentina and the MERCOSUR members, through inductive and deductive methods, jurisprudential cases and survey techniques among the sectors involved. The relevance obtained by the project during its execution, both in France and in Argentina, merited the collaboration of other specialists in the subject, among them Prof. François Trebulle, Dean of the School of Law of the Sorbonne. The result of the project was a work written in collaboration with colleagues of Environmental Law from Université Paris I Pantheón-Sorbonne. It is worth emphasizing that it was the first initiative of this kind that was carried out at Universidad del Salvador, fulfilling the objective of the internationalization of the research. Responsibility in environmental matters presents major challenges: from the principle of common but differentiated responsibility, at international level, to the amount of compensation awarded to society for the collective values affected. The work included recommendations for an effective and efficient application of environmental principles to the subject. As a final conclusion to the analysis of the situation on the topic of environmental liability at regional and international level, we arrived at the following idea, as expressed in the joint work: "From the point of view of Environmental International Law, we should think about the environmental principles in the light of the current regional scene and of the incorporation of some Latin-American countries to the Organization for Economic Cooperation and Development (OECD). Another topic of major relevancy is the financial mechanisms. We are facing a new reconsideration of the increasingly scanty resources from the Global Environment Fund (GEF), which proposes the use of our own financial resources and also the incorporation of a budget line for the resolution of the environmental problems in our countries and in the world." ; El proyecto tuvo como objetivo una aproximación al concepto de responsabilidad ambiental, no solo por parte de las personas jurídicas privadas, sino también por el Estado. Dicho concepto influye en la descripción jurídica de daño ambiental y de su recomposición. El mencionado análisis, en este proyecto, cobró una dimensión diferenciada, a través de la comparación de la legislación argentina, y la de los países del MERCOSUR, con la francesa y europea. Los objetivos del proyecto fueron alcanzados. Se realizaron los estudios comparativos en forma paralela sobre los regímenes de responsabilidad ambiental de Francia, la Unión Europea, Argentina y los países del MERCOSUR a través del método deductivo inductivo, casos jurisprudenciales y técnicas de encuestas entre los sectores involucrados. La relevancia que cobró el proyecto durante su ejecución, tanto en Francia como en Argentina, ameritó la colaboración de otros especialistas del tema, entre ellos el Decano de la Facultad de Derecho de la Sorbonne, Prof. François Trebulle. El resultado fue la redacción de una obra en conjunto con los colegas de Derecho del Medioambiente de la Université. Paris I Pantheón-Sorbonne. Es dable destacar que se trató de la primera iniciativa de este tipo que se llevó adelante en la Universidad del Salvador, con el consecuente cumplimiento del objetivo de internacionalización de la investigación. La responsabilidad en materia ambiental presenta grandes desafíos, partiendo del principio de responsabilidad común pero diferenciada a nivel internacional hasta el monto de la indemnización a la sociedad por los valores colectivos afectados. En la obra se incluyeron recomendaciones para una eficaz y eficiente aplicación de los principios ambientales al tema. Como conclusión final al análisis de la situación acerca de la responsabilidad ambiental a nivel regional e internacional, se arribó a la siguiente noción, plasmada en la obra conjunta: "Desde la visión del Derecho Internacional del Ambiente, debemos reflexionar sobre los principios ambientales a la luz del actual escenario regional y del ingreso de algunos países latinoamericanos a la Organización de Cooperación y Desarrollo. Otro tema no menor y de gran relevancia son los mecanismos financieros. Estamos frente a un nuevo replanteamiento de los recursos provenientes del Fondo Global para el Medio Ambiente (GEF) cada vez más escasos y que plantea el uso de nuestros propios recursos financieros y en incorporar una línea presupuestaria para la resolución de los problemas ambientales en nuestros países y en el mundo".

BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40-69) and 5-year overall survival was 65% (95% CI 52-81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes.InterpretationGenetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics.FundingGerman Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.

Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MB SHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MB SHH subgroup). Patients with germline APC mutations developed MB WNT and accounted for most (five [71%] of seven) cases of MB WNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MB SHH . Germline TP53 mutations presented only in childhood patients in the MB SHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MB SHH , MB Group3 , and MB Group4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 40–69) and 5-year overall survival was 65% (95% CI 52–81); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation: Genetic counselling and testing should be used as a standard-of-care procedure in patients with MB WNT and MB SHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Funding: German Cancer Aid; German Federal Ministry of Education and Research; German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung); European Research Council; National Institutes of Health; Canadian Institutes for Health Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer Research; Sontag Foundation; Musicians Against Childhood Cancer; BC Cancer Foundation; Swedish Council for Health, Working Life and Welfare; Swedish Research Council; Swedish Cancer Society; the Swedish Radiation Protection Authority; Danish Strategic Research Council; Swiss Federal Office of Public Health; Swiss Research Foundation on Mobile Communication; Masaryk University; Ministry of Health of the Czech Republic; Research Council of Norway; Genome Canada; Genome BC; Terry Fox Research Institute; Ontario Institute for Cancer Research; Pediatric Oncology Group of Ontario; The Family of Kathleen Lorette and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents Association; Cure Search Foundation; Pediatric Brain Tumor Foundation; Brainchild; and the Government of Ontario.