Investigation of the absorptive potential of polymeric nanoparticles across the lungs and their development for efficient systemic delivery following pulmonary administration

The lungs are an attractive route for drug delivery due to their high epithelial surface area available for absorption, a thin epithelium and extensive vasculature to name a few. Accordingly, a vast number of small molecule drugs, peptides, and proteins have been used to investigate their translocation across the lungs with many of the tested candidates showing excellent pharmacokinetics following pulmonary administration. Findings from all these studies over the years have strongly established the lungs as a route for drug delivery of small molecules and proteins. Nanoparticles on the other hand have gained increasing interest in drug delivery due to the wide variety of advantages they possess that allow for temporal, spatial and targeted delivery of therapeutics that can be fine tuned for various applications. Further, the pulmonary administration of polymeric nanoparticle based drug delivery systems is of great interest for both systemic and localized therapies. However, little is understood about the relationship between nanoparticle size and its effect on pulmonary absorption from a drug delivery perspective. Therefore the aim of this study was to investigate the effect of nanoparticle size on their biodistribution from lungs after pulmonary administration with a special emphasis on their lymph node distribution. Interesting observations were made wherein polystyrene nanoparticles demonstrated significant translocation out of the lungs into extrapulmonary organs. Nanoparticles predominantly deposited in the regional lymph nodes surrounding the lungs as compared to that in other tissues. Furthermore, lymph node deposition of nanoparticles occurred in a time dependent and size dependent manner. The smallest size nanoparticles (50 nm) demonstrated the highest lymph node deposition among all sizes tested and increased with time. Results from this study suggest that nanoparticles may potentially be employed in the treatment of lymph related diseases following pulmonary administration

Optimum design of flexural strength and stiffness for reinforced concrete beams using machine learning

In this paper, an optimization approach was presented for the flexural strength and stiffness design of reinforced concrete beams. Surrogate modeling based on machine learning was applied to predict the responses of the structural system in three-point flexure tests. Three design input variables, the area of steel bars in the compression zone, the area of steel bars in the tension zone, and the area of steel bars in the shear zone, were adopted for the dataset and arranged by the Box-Behnken design method. The dataset was composed of thirteen specimens of reinforced concrete beams. The specimens were tested under three-points flexure loading at the age of 28 days and both the failure load and the maximum deflection values were recorded. Compression and tension tests were conducted to obtain the concrete data for the analysis and numerical modeling. Afterward, finite element modeling was performed for all the specimens using the ATENA program to verify the experimental tests. Subsequently, the surrogate models for the flexural strength and the stiffness were constructed. Finally, optimization was conducted supporting on the factorial method for the predicted responses. The adopted approach proved to be an excellent tool to optimize the design of reinforced concrete beams for flexure and stiffness. In addition, experimental and numerical results were in very good agreement in terms of both the failure type and the cracking pattern. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A computational fluid dynamics study of combustion and emission performance in an annular combustor of a jet engine

This paper is a Computational Fluid Dynamics (CFD) study of the performance of a jet engine annular combustor that was subjected to various loading conditions. The aim is to comprehend the effect of various genuine working conditions on ignition and emission performance. The numerical models utilized for fuel ignition is the feasible k-ω model for turbulent stream, species transport (aviation fuel and air) with eddy-dissipation reaction modelling and pollution model for nitrogen oxides (NOX) emission. The results obtained confirm the findings described in the literature

Experimental and numerical study of stenotic flows

Atherosclerosis has been leading cause of deaths in several countries. Recent technical advances have allowed the investigation of stenotic flows and in understanding the implications with increased severity. Such studies shall provide detailed understanding of flow across stenosis and its progression. In the present study, a large artery representing segment of aorta is considered as test specimen. Experimental study is carried out by generating the pulsatile flow through pulsatile duplicator. Flow across normal and various severities of stenosis such as 25%, 50% and 75% are studied. Numerical simulation using CFD is also carried out in similar normal and stenosed models. A novel concept of using pulse duplicator to generate pulsatile waves and investigate the different stenosed models has been adopted. Results obtained experimentally and numerically are compared and agree well with that of clinical observations. This study demonstrates significant variation of haemodynamic in post-stenotic region with increased stenosis. Increased pulse pressure, phase lag is observed with increased severity. It is also observed that stenosis greater than 75% is significant as flow complexity is induced with considerable disturbance even in early and latter part of pulse cycle. Such study shall be useful in understanding the flow changes in stenosis and enhance clinical observation

Fluid-structure interaction study of stenotic flow in subject specific carotid bifurcation: a case study

Advances in numerical simulation have allowed the investigation of complex interaction of blood flow through elastic arteries which can be useful in demonstrating the disease progression and haemodynamics of cardiovascular diseases such as atherosclerosis. In the present study, patient is diagnosed with an occluded right Internal Carotid Artery (ICA) with partial stenosis at root of right External Carotid Artery (ECA) and partial stenosis at the root of left ICA. 3D patient specific carotid bifurcation is generated based on CT scan data using MIMICS-14.0 and numerical analysis is performed using FSI in ANSYS-14.5. The blood flow is assumed to be incompressible, homogenous and Newtonian, while artery wall is assumed to behave linearly elastic. The two-way sequentially coupled transient FSI analysis is performed using FSI solver for three pulse cycles and haemodynamic parameters such as flow pattern, Wall Shear Stress (WSS), pressure contours and arterial wall deformation are studied at the bifurcation and critical zones. The variation in flow behavior is investigated throughout the pulse and simulation results obtained reveals that there is a considerable increase in the flow behavior in partially stenosed carotid unlike occluded carotid. The investigation also demonstrates disturbed flow pattern especially at the bifurcation and stenosed zone elevating the haemodynamic variation during peak systole and later part of pulse cycle. The obtained results agree well with the clinical observation and demonstrate the potential of patient specific numerical studies in prognosis of disease progression and plaque rupture

Artificial intelligence-driven approach to identify and recommend the winner in a tied event in sports surveillance

The proliferation of fractal artificial intelligence (AI)-based decision-making has propelled advances in intelligent computing techniques. Fractal AI-driven decision-making approaches are used to solve a variety of real-world complex problems, especially in uncertain sports surveillance situations. To this end, we present a framework for deciding the winner in a tied sporting event. As a case study, a tied cricket match was investigated, and the issue was addressed with a systematic state-of-the-art approach by considering the team strength in terms of the player score, team score at different intervals, and total team scores (TTSs). The TTSs of teams were compared to recommend the winner. We believe that the proposed idea will help to identify the winner in a tied match, supporting intelligent surveillance systems. In addition, this approach can potentially address many existing issues and future challenges regarding critical decision-making processes in sports. Furthermore, we posit that this work will open new avenues for researchers in fractal AI

Neonatal, infant, and under-5 mortality and morbidity burden in the Eastern Mediterranean region: findings from the Global Burden of Disease 2015 study

Objectives Although substantial reductions in under-5 mortality have been observed during the past 35 years, progress in the Eastern Mediterranean Region (EMR) has been uneven. This paper provides an overview of child mortality and morbidity in the EMR based on the Global Burden of Disease (GBD) study. Methods We used GBD 2015 study results to explore under-5 mortality and morbidity in EMR countries. Results In 2015, 755,844 (95% uncertainty interval (UI) 712,064–801,565) children under 5 died in the EMR. In the early neonatal category, deaths in the EMR decreased by 22.4%, compared to 42.4% globally. The rate of years of life lost per 100,000 population under 5 decreased 54.38% from 177,537 (173,812–181,463) in 1990 to 80,985 (76,308–85,876) in 2015; the rate of years lived with disability decreased by 0.57% in the EMR compared to 9.97% globally. Conclusions Our findings call for accelerated action to decrease child morbidity and mortality in the EMR. Governments and organizations should coordinate efforts to address this burden. Political commitment is needed to ensure that child health receives the resources needed to end preventable deaths

Maternal mortality and morbidity burden in the Eastern Mediterranean region : findings from the Global Burden of Disease 2015 study

Assessing the burden of maternal mortality is important for tracking progress and identifying public health gaps. This paper provides an overview of the burden of maternal mortality in the Eastern Mediterranean Region (EMR) by underlying cause and age from 1990 to 2015. We used the results of the Global Burden of Disease 2015 study to explore maternal mortality in the EMR countries. The maternal mortality ratio in the EMR decreased 16.3% from 283 (241-328) maternal deaths per 100,000 live births in 1990 to 237 (188-293) in 2015. Maternal mortality ratio was strongly correlated with socio-demographic status, where the lowest-income countries contributed the most to the burden of maternal mortality in the region. Progress in reducing maternal mortality in the EMR has accelerated in the past 15 years, but the burden remains high. Coordinated and rigorous efforts are needed to make sure that adequate and timely services and interventions are available for women at each stage of reproductive life

Trends in HIV/AIDS morbidity and mortality in Eastern 3 Mediterranean countries, 1990–2015: findings from the Global 4 Burden of Disease 2015 study

Objectives We used the results of the Global Burden of Disease 2015 study to estimate trends of HIV/AIDS burden in Eastern Mediterranean Region (EMR) countries between 1990 and 2015. Methods Tailored estimation methods were used to produce final estimates of mortality. Years of life lost (YLLs) were calculated by multiplying the mortality rate by population by age-specific life expectancy. Years lived with disability (YLDs) were computed as the prevalence of a sequela multiplied by its disability weight. Results In 2015, the rate of HIV/AIDS deaths in the EMR was 1.8 (1.4–2.5) per 100,000 population, a 43% increase from 1990 (0.3; 0.2–0.8). Consequently, the rate of YLLs due to HIV/AIDS increased from 15.3 (7.6–36.2) per 100,000 in 1990 to 81.9 (65.3–114.4) in 2015. The rate of YLDs increased from 1.3 (0.6–3.1) in 1990 to 4.4 (2.7–6.6) in 2015. Conclusions HIV/AIDS morbidity and mortality increased in the EMR since 1990. To reverse this trend and achieve epidemic control, EMR countries should strengthen HIV surveillance,and scale up HIV antiretroviral therapy and comprehensive prevention services

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe