How can the results of a qualitative process evaluation be applied in management, improvement and modification of a preventive community trial? The IHHP Study

BACKGROUND: This study reports the results of the qualitative process evaluation (PE) of the Isfahan Healthy Heart Program (IHHP), an integrated community-based trial for prevention and control of non-communicable diseases in Iran. METHODS: The study explored the overall quality of program implementation. The participants, including designers of IHHP, stakeholders and community members (n = 60) were purposefully recruited from the intervention areas. Data collected from semi-structured interviews and field notes were analyzed using a modified thematic analysis. RESULTS: Four main themes were identified. Our findings highlighted the key role of the resources as both facilitating and hindering factors. IHHP directors faced incompatibilities arising from negative perceptions/attitudes which resulted in decreased adherence to the program. Hence various strategies were used to motivate, strengthen and organize the human workforce implementing the program. CONCLUSION: Recommendations arising from evaluation of the program were used in subsequent stages of implementation. Qualitative research is an important component of community trials which can improve their implementation

Atractivos naturales y culturales para el desarrollo del turismo alternativo en la comunidad de Llullucha - Ocongate

El turismo es una de las actividades económicas que ha tenido un crecimiento importante en los últimos años, convirtiendo a esta industria atractiva para su desarrollo en países con potencial turístico, como el Perú. El turismo Alternativo es una alternativa dentro de la industria del turismo para el desarrollo de las comunidades rurales que mediante una organización adecuada, les permite aprovechar el entorno y específicamente los recursos naturales y culturales con que cuentan. En Latinoamérica y en el Perú se tienen proyectos de turismo Alternativo exitosos que han contribuido a incrementar el ingreso de las comunidades involucradas y disminuir la pobreza permitiendo así la inclusión social. El Perú es un país rico en recursos turísticos, culturales y naturales, lo cual convierte al turismo alternativo en una estrategia para mejorar en la calidad de vida de las comunidades rurales donde se practica. Por su lado, la región Cusco recibe la mayor cantidad de turistas que arriban al Perú, gracias a que cuenta con atractivos como Machu Picchu y la misma ciudad del Cusco que son de interés a nivel mundial, lo cual es una fortaleza destacable para que el turismo alternativo en los segmentos de turismo rural y turismo de naturaleza (turismo de aventura y ecoturismo) constituya en un sector importante de la industria del turismo en la región del Cusco. Después de un análisis del diagnóstico situacional del ámbito de estudio, se desarrolló un listado de varias propuestas, resultado del diagnóstico de la situación turística actual en la comunidad de Llullucha. Dichas propuestas pretenden diversificar la oferta turística actual de la ciudad del Cusco como así atender los principales aspectos deficientes dentro de la comunidad. Finalmente se propone la implementación del desarrollo del turismo alternativo en la comunidad de Uullucha, la instalación de los servicios turísticos y el programa turístico, con la gestión en alianza con los entes públicos, privados y ONG's.Tesi

Tacrolimus phospholipid based nanomicelles as a potential local delivery system for corneal neovascularization therapy

Introduction: Tacrolimus, an immunosuppressive agent, has been shown to be an effective treatment against corneal neovascularization (CNV). However, the poor solubility of this compound restricts its clinical application. The goal of this study was to incorporate tacrolimus into phospholipid-bile salt mixed micelles. Methods and Results: Tacrolimus loaded phospholipid-bile salt mixed micelles were prepared, employing three different methods of direct dispersion, thin film hydration, and remote film loading, and the effects of various formulation parameters (type of dispersion medium, phospholipid to bile salt molar ratio, lipid-to-drug (L/D) molar ratio, time of probe sonication, and type of bile salt) on the physicochemical characteristics of the mixed micelles were assessed. Remote film loading method indicated higher efficacy for drug entrapment in comparison to the other methods. Encapsulation of tacrolimus within the micelles increased remarkably by the use of sodium taurocholate (NaTC) as bile salt, higher phospholipid percentage, and increasing the total lipid level. Atomic force microscopy (AFM) studies confirmed the size and size distribution of the mixed micelles and their spherical morphology. It was observed that release of tacrolimus from the micelles was in a controlled manner, without an initial burst. Conclusions: By adjusting process and formulation factors, phospholipid-bile salt mixed micelles with high entrapment efficiency of (99.5 %) and controlled release behavior were achieved, which possess great potential to be valuable carriers for ocular delivery of tacrolimus for the treatment of CNV.                                                                                                                                       &nbsp

Quantum Mechanics/Molecular Mechanics Study of the Reaction Mechanism of Glyoxalase I

Glyoxalase I (GlxI) is a member of the glyoxalasesystem, which is important in cell detoxification and convertshemithioacetals of methylglyoxal (a cytotoxic byproduct of sugarmetabolism that may react with DNA or proteins and introducenucleic acid strand breaks, elevated mutation frequencies, andstructural or functional changes of the proteins) and glutathioneinto D-lactate. GlxI accepts both the S and R enantiomers ofhemithioacetal, but converts them to only the S-D enantiomer oflactoylglutathione. Interestingly, the enzyme shows this unusualspecificity with a rather symmetric active site (a Zn ioncoordinated to two glutamate residues; Glu-99 and Glu-172),making the investigation of its reaction mechanism challenging.Herein, we have performed a series of combined quantummechanics and molecular mechanics calculations to study the reaction mechanism of GlxI. The substrate can bind to the enzyme in two different modes, depending on the direction of its alcoholic proton (H2; toward Glu-99 or Glu-172). Our results show that the S substrate can react only if H2 is directed toward Glu-99 and the R substrate only if H2 is directed toward Glu-172. In both cases, the reactions lead to the experimentally observed S-D enantiomer of the product. In addition, the results do not show any low- energy paths to the wrong enantiomer of the product from neither the S nor the R substrate. Previous studies have presented several opposing mechanisms for the conversion of R and S enantiomers of the substrate to the correct enantiomer of the product. Our results confirm one of them for the S substrate, but propose a new one for the R substrate

Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.

BACKGROUND: Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. RESULTS: Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. CONCLUSION: Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract

The OpenMolcas Web: A Community-Driven Approach to Advancing Computational Chemistry

The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation

Atractivos naturales y culturales para el desarrollo del turismo alternativo en la comunidad de Llullucha - Ocongate

TesisEl turismo es una de las actividades económicas que ha tenido un crecimiento importante en los últimos años, convirtiendo a esta industria atractiva para su desarrollo en países con potencial turístico, como el Perú. El turismo Alternativo es una alternativa dentro de la industria del turismo para el desarrollo de las comunidades rurales que mediante una organización adecuada, les permite aprovechar el entorno y específicamente los recursos naturales y culturales con que cuentan. En Latinoamérica y en el Perú se tienen proyectos de turismo Alternativo exitosos que han contribuido a incrementar el ingreso de las comunidades involucradas y disminuir la pobreza permitiendo así la inclusión social. El Perú es un país rico en recursos turísticos, culturales y naturales, lo cual convierte al turismo alternativo en una estrategia para mejorar en la calidad de vida de las comunidades rurales donde se practica. Por su lado, la región Cusco recibe la mayor cantidad de turistas que arriban al Perú, gracias a que cuenta con atractivos como Machu Picchu y la misma ciudad del Cusco que son de interés a nivel mundial, lo cual es una fortaleza destacable para que el turismo alternativo en los segmentos de turismo rural y turismo de naturaleza (turismo de aventura y ecoturismo) constituya en un sector importante de la industria del turismo en la región del Cusco. Después de un análisis del diagnóstico situacional del ámbito de estudio, se desarrolló un listado de varias propuestas, resultado del diagnóstico de la situación turística actual en la comunidad de Llullucha. Dichas propuestas pretenden diversificar la oferta turística actual de la ciudad del Cusco como así atender los principales aspectos deficientes dentro de la comunidad. Finalmente se propone la implementación del desarrollo del turismo alternativo en la comunidad de Uullucha, la instalación de los servicios turísticos y el programa turístico, con la gestión en alianza con los entes públicos, privados y ONG's

The Realities of Resilience: An Authentic Leadership Discussion

Presented on August 23, 2019 at 12:30 p.m. in the Coda Building, Room 230.Maryam Alavi is the Stephen P. Zelnak Jr. Dean’s Chair in Business, Professor of IT Management and Dean of the Scheller College of Business at Georgia Tech.Sonia Alvarez-Robinson is the Executive Director for Strategic Consulting and the RESILIENCE Principal Empowerment Office at Georgia Tech.Kim Harrington is the AVP and Chief Human Resources Officer at Georgia Institute of Technology.Steven W. McLaughlin is the dean of the College of Engineering and Southern Company Chair. He serves as the chief academic officer of the college, where he works with the associate deans and chairs for each of the college's eight schools.Runtime: 85:29 minutesIn this rare and candid panel discussion, Georgia Tech leaders share insights on building personal resilience. Through their own stories of adversity, opportunity, tragedy and triumph, the panel will describe ways to use challenges as a catalyst for personal and professional growth