Accurate prediction of clinical stroke scales and improved biomarkers of motor impairment from robotic measurements

Objective: One of the greatest challenges in clinical trial design is dealing with the subjectivity and variability introduced by human raters when measuring clinical end-points. We hypothesized that robotic measures that capture the kinematics of human movements collected longitudinally in patients after stroke would bear a significant relationship to the ordinal clinical scales and potentially lead to the development of more sensitive motor biomarkers that could improve the efficiency and cost of clinical trials. Materials and methods: We used clinical scales and a robotic assay to measure arm movement in 208 patients 7, 14, 21, 30 and 90 days after acute ischemic stroke at two separate clinical sites. The robots are low impedance and low friction interactive devices that precisely measure speed, position and force, so that even a hemiparetic patient can generate a complete measurement profile. These profiles were used to develop predictive models of the clinical assessments employing a combination of artificial ant colonies and neural network ensembles. Results: The resulting models replicated commonly used clinical scales to a cross-validated R2 of 0.73, 0.75, 0.63 and 0.60 for the Fugl-Meyer, Motor Power, NIH stroke and modified Rankin scales, respectively. Moreover, when suitably scaled and combined, the robotic measures demonstrated a significant increase in effect size from day 7 to 90 over historical data (1.47 versus 0.67). Discussion and conclusion: These results suggest that it is possible to derive surrogate biomarkers that can significantly reduce the sample size required to power future stroke clinical trials

Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors

Background/Aims: The response to the liver damage caused by portacaval shunt (PCS) is characterized by low-grade hyperplasia and atrophy. To clarify mechanisms of this dissociation, we correlated the expression of 'hepatotrophic factors' and the antihepatotrophic and proapoptotic peptide, transforming growth factor (TGF)-β, with the pathologic changes caused by PCS in rats. Methods: PCS was created by side-to-side anastomosis between the portal vein and inferior vena cava, with ligation of the hilar portal vein. Hepatic growth mediators were measured to 2 months. Results: The decrease in the liver/body weight ratio during the first 7 days which stabilized by day 15, corresponded to parenchymal cell apoptosis and increases in hepatic TGF-β concentration that peaked at 1.4 × baseline at 15 days before returning to control levels by day 30. Variable increases in the concentrations of growth promoters (hepatocyte growth factor, TGF-α and augmenter of liver regeneration) also occurred during the period of hepatocellular apoptosis. Conclusions: The development of hepatic atrophy was associated with changes in TGF-β concentration, and occurred despite increased expression of multiple putative growth promoters. The findings suggest that apoptosis set in motion by TGF-β constrains the amount of hepatocyte proliferation independently from control of liver volume. © 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy : Insights From Wave Intensity Analysis and Magnetic Resonance

Background: Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives: Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods: Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results: Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions: Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment

Expression of human beta-defensins 1 and 2 in kidneys with chronic bacterial infection

BACKGROUND: Constitutive expression and localization of antimicrobial human β-defensin-1 (HBD-1) in human kidneys as a potential mechanism of antimicrobial defense has been previously reported. Inducible expression of human β-defensin-2 (HBD-2) has been described in various epithelial organs but not for the urogenital tract. METHODS: We investigated the gene- and protein expression of HBD-1 and HBD-2 by reverse transcriptase-polymerase chain reaction, and immunohistochemistry in 15 normal human kidney samples and 15 renal tissues with chronic bacterial infection. Additionally, cell culture experiments were performed to study HBD gene expression by real-time RT-PCR in response to inflammatory cytokines TNFα and IL-1β as well as lipopolysaccharide from Gram-negative bacteria. RESULTS: Constitutive HBD-1 gene- and protein expression was detected in normal renal tissue and kidneys with chronic infection. As a novel finding, inducible HBD-2 gene- and protein expression was demonstrated in tubulus epithelia with chronic infection but not in normal renal tissue. In pyelonephritic kidneys HBD-1 and HBD-2 expression showed a similar pattern of localizaton in distal tubules, loops of Henle and in collecting ducts of the kidney. Furthermore, real-time RT-PCR of kidney derived cell lines stimulated with inflammatory agents TNF-α, IL-1β and LPS revealed a strong increase in relative HBD-2 transcription level and also a slight increase in relative HBD-1 transcription level. CONCLUSIONS: Upregulated HBD-2 expression in renal tubulus epithelium indicates a role of a wider range of human defensins for antimicrobial host defense in the urogenital tract than previously recognized

A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs

<p>Abstract</p> <p>Background</p> <p>The association of elevated serum levels of secretory phospholipase A₂(sPLA₂) in patients with cardiovascular disease and their presence in atherosclerotic lesions suggest the participation of sPLA₂enzymes in this disease. The presence of more advanced atherosclerotic lesions in mice that overexpress sPLA₂enzymes suggest their involvement in the atherosclerotic process. Therefore, the sPLA₂family of enzymes could provide reasonable targets for the prevention and treatment of atherosclerosis. Thus, A-002 (varespladib), an inhibitor of sPLA₂enzymes, is proposed to modulate the development of atherosclerosis.</p> <p>Methods</p> <p>Twenty-four guinea pigs were fed a high saturated fat, high cholesterol diet (0.25%) for twelve weeks. Animals were treated daily with A-002 (n = 12) or vehicle (10% aqueous acacia; n = 12) by oral gavage. After twelve weeks, animals were sacrificed and plasma, heart and aorta were collected. Plasma lipids were measured by enzymatic methods, lipoprotein particles size by nuclear magnetic resonance, aortic cytokines by a colorimetric method, and aortic sinus by histological analyses.</p> <p>Results</p> <p>Plasma total cholesterol, HDL cholesterol and triglycerides were not different among groups. However, the levels of inflammatory cytokines interleukin (IL)-10, IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were significantly reduced in the treatment group. This group also had a significant 27% reduction in cholesterol accumulation in aorta compared with placebo group. Morphological analysis of aortic sinus revealed that the group treated with A-002 reduced atherosclerotic lesions by 24%.</p> <p>Conclusion</p> <p>The use of A-002 may have a beneficial effect in preventing diet-induced atherosclerosis in guinea pigs.</p

Международный музыкальный конкурс в формировании имиджа страны проведения (на примере Евровидения 2017)

Аннотация выпускной квалификационной работы Орлов Никита Сергеевич «МЕЖДУНАРОДНЫЙ МУЗЫКАЛЬНЫЙ КОНКУРС В ФОРМИРОВАНИИ ИМИДЖА СТРАНЫ ПРОВЕДЕНИЯ (НА ПРИМЕРЕ ЕВРОВИДЕНИЯ-2017)» Н. рук. - Быкова Елена Владимировна, доктор филологических наук, доцент Кафедра связей с общественностью Очная форма обучения Актуальность: международный музыкальный конкурс Евровидение как самое масштабное регулярное высокотехнологичное телевизионное и медиа-событие, которое . Е ежегодно акцентирует внимание аудитории на национально-культурных особенностях страны-организатора конкурса, формирует значительные туристические потоки и тем самым способствует формированию имиджа территории. Более того, победа страны-участницы конкурса Евровидения зачастую отражает идеолого-политический вектор Европы и по сути дела выполняет функцию политического PR страны-победителя и страны-хозяйки мероприятия. Следовательно анализ используемых на мероприятии коммуникативных технологий является актуальным и востребованным для событийного и устроительного PR Объект исследования: коммуникационные активности международного музыкального конкурса (на примере Евровидения в Киеве в 2017 г.). Предмет исследования: функция статусного PR-мероприятия в формировании имиджа страны. Цель исследования: доказать, что международный музыкальный конкурс Евровидение способствует формированию имиджа страны проведения. Задачи исследования: разработать терминологический аппарат исследования на основе научной литературы по имиджмейкингу, брендингу и ивент-менеджменту; определить актуальные коммуникационные технологии, применяемые в рамках специальных событий для формирования имиджа страны; описать роль Европейского Вещательного Союза как организатора Евровидения в формировании имиджа страны проведения конкурса; оценить эффективность реализованных коммуникативных технологий формирования имиджа страны в рамках Евровидения; дать рекомендации по формированию имиджа страны с помощью Евровидения. Теоретическая база: научные труды Е. Быковой, Д. Гавры, А. Панкрухина, Б. Дженеса, Е. Кавериной, У. Хальцбаура, Дж. Голдблатта а также труды Д. Пассмана о музыкальном бизнесе, П. Джордана о продвижении имиджа стран с помощью Евровидения и др. Эмпирическая база: PR-документы, размещенные на сайте Евровидения и Европейского Вещательного Союза; более полутора миллиона статей об Украине в европейских СМИ, размещенные в базе проекта мониторинга международного имиджа Украины «Oko»; данные базы материалов СМИ и социальных медиа Factiva; данные Google.Analytics. Практическая значимость: исследование доказывает, что международный музыкальный конкурс Евровидение формирует имидж страны проведения независимо от успешности использования конкретных технологий формирования имиджа страны. Тезисы исследования были апробированы на международном научном форуме «Медиа в современном мире. 57-е Петербургские чтения», опубликованы в сборнике материалов статей форума и имеют статус научной статьи, размещенной в базе РИНЦ. Структура работы: Работа состоит из введения, 3 глав: «функция специального события в формировании имиджа страны», «Евровидение как специальное событие Европейского Вещательного Союза» и «коммуникационный потенциал Евровидения как площадки для формирования имиджа страны», заключения, списка использованной литературы из 67 позиций и 12 приложений. Общий объем 76 страниц.Abstract of graduating qualification thesis Mikita Arlou INTERNATIONAL MUSIC CONTEST IN HOST COUNTRY IMAGE FORMATION (ON THE EXAMPLE OF EUROVISION 2017) Supervisor associate professor Elena Bykova, doctor of philology Department of PR in business full-time study Relevance: the international music contest Eurovision as the most wide scale regular high tech TV and Media event which annually emphasizes audience attention on national cultural features of the host country, forms tourist flows which have huge influence on territorial image formation. Besides the win of a participating in the Eurovision country often shows the ideological and political European vector and in fact serves as political PR of the winning or host country. Consequently the analysis of applied communication technologies is relevant and in-demand for event PR. Research object: communication activities of international music contest (on the example of Eurovision in Kyiv in 2017). Research subject: function of status PR event in country image formation. The aim of research: to prove that international music contest Eurovision contributes host country image formation. The tasks of research: to develop research terminology based on scientific literature on image making, branding and event management; to define actual communication technologies applied in special PR events on country image formation; to describe European Broadcasting Union role in host country image formation; to appreciate effectiveness of applied communication technologies on host country image formation in Eurovision; to give recommendations for host country image formation with the help of Eurovision. Theoretical base: scientific works written by E. Bykova, D. Gavra, A. Pankrukhin, B. Jenes, E. Kaverina, U. Halcbaur, J. Goldblatt and D. Passman´s works on music business and P. Jordan on county image building with the help of Eurovision, etc. The empirical base: PR documents from official Eurovision and European Broadcasting Union websites; more than 1.5 million articles on Ukraine in European media stored in the base of international Ukrainian image monitoring project Oko; content of the mass media and social media base Factiva; Google.Analytics data. Practical significance: the research proves that international music contest Eurovision is relevant for the host country image formation independently of the success level of applied country image formation communication technologies. Approbation: General positions of current thesis were aprobated on international scientific forum Media in modern world and were published at the collection of articles of the forum and have the status of a scientific article posted in the RINC database. Thesis structure: Research consists of introduction, 3 chapters: Special event function in country image formation, Eurovision as EBU special event and communication potential of Eurovision as a platform for image formation; conclusion, literature list from 67 positions and 12 attachments. The total volume is 76 pages

The effect of climate change on avian offspring production: A global meta-analysis

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to repro- ductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young