Clinical investigation of pharmaceutical and lifestyle interventions in persons with chronic kidney disease

Chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is aserious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is characterized by a range of complex deleterious physiological and metabolic function alterations including disruptions in lipid, amino acid, and carbohydrate metabolism; skeletal muscle dysfunction, insulin resistance, and heightened inflammation/oxidative stress. In addition, concurrent comorbidities such as diabetes, hypertension, and dyslipidemia further exacerbate cardiometabolic risk and worsen patient outcomes. Emerging evidence suggest that dysfunctional mitochondria have a pivotal role in both the development of CKD and its associated comorbidities highlighting it as a promising target for therapeutic intervention. The goal of my work was to comprehensively explore the diverse pathophysiologies linked to CKD, its nutritional implications, and treatment modalities; and the potential to modify health and outcome by pharmacological and non-pharmacological means. By elucidating the interplay between CKD and metabolic derangements, as well as the impact of mitochondrial dysfunction, we aimed to pave the way for novel therapeutic approaches that address management of CKD and improve patient prognosis. In this dissertation, we have focused on patient-oriented research using metabolic imaging and multi-omics approaches to better understand the pathophysiology of CKD and linking alterations in metabolism with muscle function and physical performance. In doing so, we performed a 2 comprehensive investigation of metabolic, physiological, and cardiometabolic disturbances in CKD. Chapter 1 provides a comprehensive overview of CKD and CKD-related comorbidities as well as metabolic and physiological complications. Chapter 2 investigates the impact of nicotinamide riboside (NR) and coenzyme Q10 (CoQ10) that target mitochondrial metabolism for their potential effects on systemic markers of mitochondrial metabolism and physical endurance in a sedentary CKD cohort. Chapter 3 and 4 investigate metabolic derangements in non-diabetic moderate-severe CKD. Chapter 3 focuses on identifying altered metabolic pathways contributing to disruptions to insulin response in response to oral glucose tolerance testing in CKD. In chapter 4 we build on the findings from chapter 3 by investigating postprandial incretin hormone levels and their determinants using a standardized OGTT comparing non-diabetic patients with CKD and controls. We separately investigate the association of postprandial circulating incretin hormones with insulin, c-peptide, and glucagon levels during an OGTT by CKD status. Chapter 5 provides a summary of the work performed, concluding remarks, and plans for future studies

Transit Network Design using GIS and Metaheuristics in Sanandaj, IRAN

The public transit system in Sanandaj has been under review and modification for the last several years. The goal is to reduce the traffic congestion and the share of private car usage in the city and increase the very low share of the public transit. The bus routes in Sanandaj are not connected. There is no connected transit network with the ability to transfer between the routes in locations outside of the downtown terminal. The routes mostly connect the downtown core directly to the peripheries without providing travel options for passengers between peripheries. Although there has been some improvement in the transit system, but lack of service in many populated districts of Sanandaj and town nearby makes the transit system unpopular and unreliable. This research is an attempt to provide solutions for the transit network design (TND) problem in Sanandaj using the capabilities of GIS and artificial intelligence methods. GIS offers several tools that enables the decision-makers to investigate the spatial correlations between different features. One of the contributions of this research is developing a transit network design with utilizing a spectrum of GIS software modeling functionalities. The visual ability of GIS is used to generate TNDs. Many studies focus on artificial intelligence as the main method to generate the TNDs, but the focus of this research is to combine GIS and artificial intelligence capabilities in order to generate a multi-objective GIS-based procedure to construct different bus network designs and explore and evaluate them to find the suitable transit network alternative. The GIS-based procedure results will be assessed and compared with the results of metaheuristic approaches. Metaheuristic methods are partial search procedures that may provide sufficiently good solutions to an optimization problem characterized by incomplete information or limited computation capacity (Talbi, 2009). Yang, Cui, Xiao, Gandomi, and Karamanoglu (2013) classified metaheuristic methods into two groups: single-agent procedures (e.g., simulated annealing algorithm involves one agent navigating in the environment), and multiple agents (e.g., population-based genetic algorithm, and swarm intelligence methods). This study focuses on swarm intelligence methods, such as ant colony optimization and honeybee algorithm. These methods provide a multi-objective assessment of the TND scenarios generated by GIS applications. The outcome of this study will help us to find the optimal solutions for the TND in Sanandaj

A Novel Model for Driver Lane Change Prediction in Cooperative Adaptive Cruise Control Systems

Accurate lane change prediction can reduce potential accidents and contribute to higher road safety. Adaptive cruise control (ACC), lane departure avoidance (LDA), and lane keeping assistance (LKA) are some conventional modules in advanced driver assistance systems (ADAS). Thanks to vehicle-to-vehicle communication (V2V), vehicles can share traffic information with surrounding vehicles, enabling cooperative adaptive cruise control (CACC). While ACC relies on the vehicle's sensors to obtain the position and velocity of the leading vehicle, CACC also has access to the acceleration of multiple vehicles through V2V communication. This paper compares the type of information (position, velocity, acceleration) and the number of surrounding vehicles for driver lane change prediction. We trained an LSTM (Long Short-Term Memory) on the HighD dataset to predict lane change intention. Results indicate a significant improvement in accuracy with an increase in the number of surrounding vehicles and the information received from them. Specifically, the proposed model can predict the ego vehicle lane change with 59.15% and 92.43% accuracy in ACC and CACC scenarios, respectively

Increase of hepatic nitric oxide levels in a nutritional model of fatty liver in broiler breeder hens

Fatty liver hemorrhagic syndrome (FLHS) is a metabolic condition of laying hens characterized by the accumulation of excess fat in the liver and liver hemorrhage. It suggested that oxidative damage to the cellular and organelle membranes of the liver increases the susceptibility of the liver to hemorrhage. However, a local chemical component that may affect the incidence of hemorrhage in liver, by affecting the blood pressure of liver, is nitric oxide. To clarify the effects of high (20 and 40% more than normal) and low (20% less than normal) food intake on plasma and liver oxidative products, malondialdehyde (MDA) and protein carbonyl (PC), and also nitric oxide (NO) in over fed broiler breeder hens, 198 hens (30 weeks old) were fed for 30 days (two 14-day period). Feed intake, body weight (BW), egg production (EP), plasma NO, MDA and CP were measured at the end of each 14-day periods. Food intake did not reduce during 4 weeks of experiment in hens fed with 20 and 40% above their estimated requirement. Increased food intake resulted in increased body weight gain significantly (P < 0.05). Egg production significantly declined in hens provided with C+40% diet (P < 0.05). Liver MDA, NO and PC concentrations were increased in C+40% hens in second period of experiment (P < 0.05). Liver hemorrhage score of hens fed C+40% diet significantly was higher in the second period of the experiment. It was concluded that an increase in liver hemorrhage in over fed broiler breeder can be associated with the oxidative stress components (MDA, PC) and liver NO concentration.Keywords: Fatty liver, nitric oxide, malondialdehyde, protein carbonyl, broiler breederAfrican Journal of Biotechnology Vol. 9(35), pp. 5775-5778, 30 August, 201

Ocean remote sensing techniques and applications: a review (Part II)

As discussed in the first part of this review paper, Remote Sensing (RS) systems are great tools to study various oceanographic parameters. Part I of this study described different passive and active RS systems and six applications of RS in ocean studies, including Ocean Surface Wind (OSW), Ocean Surface Current (OSC), Ocean Wave Height (OWH), Sea Level (SL), Ocean Tide (OT), and Ship Detection (SD). In Part II, the remaining nine important applications of RS systems for ocean environments, including Iceberg, Sea Ice (SI), Sea Surface temperature (SST), Ocean Surface Salinity (OSS), Ocean Color (OC), Ocean Chlorophyll (OCh), Ocean Oil Spill (OOS), Underwater Ocean, and Fishery are comprehensively reviewed and discussed. For each application, the applicable RS systems, their advantages and disadvantages, various RS and Machine Learning (ML) techniques, and several case studies are discussed.Peer ReviewedPostprint (published version

Dynamic temporary blood facility location-allocation during and post-disaster periods

The key objective of this study is to develop a tool (hybridization or integration of different techniques) for locating the temporary blood banks during and post-disaster conditions that could serve the hospitals with minimum response time. We have used temporary blood centers, which must be located in such a way that it is able to serve the demand of hospitals in nearby region within a shorter duration. We are locating the temporary blood centres for which we are minimizing the maximum distance with hospitals. We have used Tabu search heuristic method to calculate the optimal number of temporary blood centres considering cost components. In addition, we employ Bayesian belief network to prioritize the factors for locating the temporary blood facilities. Workability of our model and methodology is illustrated using a case study including blood centres and hospitals surrounding Jamshedpur city. Our results shows that at-least 6 temporary blood facilities are required to satisfy the demand of blood during and post-disaster periods in Jamshedpur. The results also show that that past disaster conditions, response time and convenience for access are the most important factors for locating the temporary blood facilities during and post-disaster periods

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe