IN VIVO AND IN VITRO EVALUATION OF PHARMACOLOGICAL ACTIVITIES OF Hedychium coccineum RHIZOMES EXTRACT

The study reports the in vivo antidiarrheal and in vitro anthelmintic, cytotoxic, and thrombolytic activity of methanol extract of Hedychium coccineum rhizomes (MEHC). The antidiarrheal activity was determined using Castor oil-induced diarrhea and Gastrointestinal motility test in mice at the doses of 200 and 400 mg/kg body weight, whereas an aquarium worm, Tubifex tubifex, was used to determine the anthelmintic activity. The cytotoxic and thrombolytic activity of MEHC was performed by Brine shrimp lethality bioassay and clot lysis method respectively. In antidiarrheal, castor oil-induced diarrhea and gastrointestinal motility exhibited a significant reduction in diarrhea and defecation and an extremely significant inhibition in intestinal motility and peristalsis index by 200 and 400 mg/kg of MEHC. The MEHC (5, 10, and 20 mg/mL) showed a significant dose-dependent manner paralysis time and times to death in multiple comparisons to the different levamisole concentrations (0.5, 0.8, and 1 mg/mL) at in vitro anthelmintic activity. The brine shrimp lethality bioassay exhibited a weak LC50 (681.95 µg/mL; R² = 0.951) while in thrombolytic a significant percentage of clot lysis (32.70%, P < 0.05) demonstrated. The findings demonstrate that H. coccineum rhizomes could be potential sources for biological activity

本学看護学部における3年次OSCEの実施と今後の課題

本報告は、2013年4月に開設した当看護学部において、2015年8月に3年生に対して初めて行ったOSCE (客観的臨床能力試験)の準備から実施までの総括である。一連の記録やマニュアル等から経過を振り返り、今後の改善点を検討した結果、学生の基礎技術の習熟に資する自主練習環境の整備、模擬患者の効果的な導入、評価者役や模擬患者役として実習病院や近隣機関の関係者が教育に参加できるような協力関係の構築が課題として示された

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations. METHODS: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Stanaway JD, Afshin A, Gakidou E, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1923-1994.Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd

Laminar-turbulenter Strömungsumschlag in Rohrströmungen durch Puffs und Slugs

A classical problem in fluid mechanics, laminar to turbulent transition in pipe flow, was investigated and the results of new findings are summarized in this thesis. The investigation of transitions in pipe flows was started by Reynolds (1883) and continued subsequently, hence it has a long history. Nevertheless, there are still many unknown issues that need clarification, which are presented as an introduction containing a brief literature survey. For the actual experimental investigations, an experimental test rig, built by Durst & Ünsal (2006), was applied after some modifications. The test rig, containing a mass flow controller, a flow conditioner, a brass pipe, devices to trigger transition and also measuring equipment, is described in detail. Through some preliminary research works, a natural transition and also a transition triggered by ring obstacles were studied. The investigation showed clearly the dependence on the height of the ring obstacles and also on Reynolds number that a flow was triggered to a transitional flow. The Reynolds number was defined as Re = u_bulk D/nu;, where u_bulk is the bulk velocity, D is the pipe diameter and nu; is the kinematic viscosity of the fluid. As is well known, two distinct types of flow structure exist during a laminar to turbulent transition, namely puffs and slugs, first introduced by Wygnanski & Champagne (1973). The test rig was then applied to investigate the development of puffs and slugs which were triggered in a repeatable way in a pipe at different Reynolds numbers. Also considered is a transformation from puffs to slugs through puff splittings, occurring while they propagate in a pipe or occurring by an increase in Reynolds number. There are other interesting issues observed in low Reynolds number pipe flows, such as the dissipation of puffs. The time between when puffs were created and dissipated is named ‘full-lifetime’ in this thesis work. The full-lifetime of puffs is measured directly with a pressure transducer and the results are presented and discussed. Through the investigation of lifetime, the possible evolutions of flow structures occurring in laminar to turbulent transitions observed in low Reynolds number pipe flows could be well explained. Finally, for further understanding of transitional phenomena in pipe flows, Reynolds stress anisotropy invariant of the slug structure was carefully measured by using hot wire anemometry. The results indicated that the Reynolds stress anisotropy model is able to predict the transition. Conclusions and final remarks are presented, summarizing all the investigations carried out.In der vorliegenden Dissertationsarbeit wird ein klassisches Problem der Strömungsmechanik nämlich die laminar-turbulente Transition in der Rohrströmung untersucht und die gefundenen neuen Erkenntnisse werden zusammengefasst. Untersuchungen zur Transition im Rohr haben eine lange Geschichte, die zurück geht bis Reynolds (1883) und seither laufend fortgeschrieben wurde. Dennoch gibt es immer noch eine ganze Reihe offener Fragen, die auf eine Klärung warten. In der Einleitung werden diese Fragen auf der Basis einer kurzen Literaturübersicht herausgearbeitet. Für die anschließend durchgeführten Experimente wurde ein Versuchsaufbau verwendet, der von Durst & Ünsal (2006) erstellt und mit einigen Modifikationen an die geänderte Aufgabenstellung angepasst wurde. Der Versuchstand, der aus einem Massenstromkontroller, einem Strömungskonditionierer, einem Messrohr, einer Einrichtung zur Auslösung der Strömungstransition und den Messgeräten bestand, wird im Detail beschrieben. In einer einleitenden Studie wurde die natürliche Transition sowie die Transition, die durch ringförmige Hindernisse ausgelöst wird, betrachtet. Es zeigte sich eine deutliche Abhängigkeit der Transitionsauslösung von der Höhe des ringförmigen Hindernisses sowie von der Reynoldszahl, wobei die Reynoldszahl definiert ist als Re = ubulkD/nu;, mit ubulk der Durchflussgeschwindigkeit, D dem Rohrdurchmesser und nu; der kinematischen Viskosität des Fluids. Wie bekannt ist, können zwei unterschiedliche Arten von Strömungsstrukturen bei der laminar-turbulenten Transition in Rohren beobachtet werden, nämlich Puffs und Slugs, wie sie erstmals von Wygnanski & Champagne (1973) eingeführt wurden. In der vorliegenden Arbeit wurde die Entwicklung von kontrolliert erzeugten Puffs und Slugs während ihres Transports entlang der Rohrlänge bei unterschiedlichen Reynoldszahlen untersucht. Dabei konnte auch die Umwandlung von Puffs zu Slugs über ein Puff-splitting oder aber das Abklingen der Puffs bei niedrigen Reynoldszahlen beobachtet werden. Der Zeitraum zwischen der Erzeugung der Puffs und ihrem Verschwinden wurde als ‘full-lifetime’ definiert und konnte mit einem Drucksensor direkt gemessen werden. Auf der Basis dieser Lebenszeitmessungen konnten die möglichen Entwicklungen der Strömungsstrukturen, die bei der laminar-turbulenten Transition von Rohrströmungen niedriger Reynoldszahl auftreten, diskutiert und weitgehend geklärt werden. Für das weitergehende Verständnis der Übergangsphänomene in Rohrströmungen wurde die Anisotropie der Reynoldsspannungen in der Slugsstruktur mit Hilfe der Hitzdraht-Anemometrie vermessen. Die Ergebnisse zeigen, dass das Reynoldsspannungsanisotropiemodell in der Lage ist, den Übergang gut vorherzusagen

The origin of turbulence in wall-bounded flows

The motion of liquids and gases can be either laminar, flowing slowly in orderly parallel and continuous layers of fluid that cannot mix, or turbulent in which motion exhibits disorder in time and space with the ability to promote mixing. Breakdown of ordered to disordered motion can follow different scenarios so that no universal mechanism can be identified even in similar flow configurations [1]. Only under very special circumstances can the mechanism associated with the appearance of turbulence be studied within the deterministic theory of hydrodynamic stability [2] or employing direct numerical simulations [3] which themselves cannot provide the necessary understanding [4]. Here we show that the representative mechanism responsible for the origin of turbulence in wallbounded flows is associated with large variations of anisotropy in the disturbances [5]. During the breakdown process, anisotropy decays from a maximum towards its minimum value, inducing the explosive production of the dissipation which logically leads to the appearance of small-scale three-dimensional motions. By projecting the sequence of events leading to turbulence in the space which emphasizes the anisotropic nature in the disturbances [6], we explain why, demonstrate how and present what can be achieved if the process is treated analytically using statistical techniques [7]. It is shown that the statistical approach provides not only predictions of the breakdown phenomena which are in fair agreement with available data but also requirements which ensure persistence of the laminar regime up to very high Reynolds numbers

Laminar-to-turbulent transition of pipe flows through puffs and slugs

Laminar-to-turbulent transition of pipe flows occurs, for sufficiently high Reynolds numbers, in the form of slugs. These are initiated by disturbances in the entrance region of a pipe flow, and grow in length in the axial direction as they move downstream. Sequences of slugs merge at some distance from the pipe inlet to finally form the state of fully developed turbulent pipe flow. This formation process is generally known, but the randomness in time of naturally occurring slug formation does not permit detailed study of slug flows. For this reason, a special test facility was developed and built for detailed investigation of deterministically generated slugs in pipe flows. It is also employed to generate the puff flows at lower Reynolds numbers. The results reveal a high degree of reproducibility with which the triggering device is able to produce puffs. With increasing Reynolds number, 'puff splitting' is observed and the split puffs develop into slugs. Thereafter, the laminar-to-turbulent transition occurs in the same way as found for slug flows. The ring-type obstacle height, h, required to trigger fully developed laminar flows to form first slugs or puffs is determined to show its dependence on the Reynolds number, Re=DU/ν (where D is the pipe diameter, U is the mean velocity in the axial direction and ν is the kinematic viscosity of the fluid). When correctly normalized, h+ turns out to be independent of Reτ (where h+=hUτ/ν, Reτ=DUτ/ν and Uτ=√τw/ρ τw is the wall shear stress and ρ is the density of the fluid)