Rapid, label-free enrichment of lymphocytes in a closed system using a flow-through microfluidic device.

The majority of adoptive cellular therapies are produced from peripheral mononuclear cells obtained via leukapheresis and further enriched for the cells of interest (e.g., T cells). Here, we present a first-of-its-kind closed system, which effectively removes ~85% of monocytes and ~88% of platelets, while recovering ~88% of concentrated T cells in a separate output stream, as the leukapheresis sample flows through a microfluidic device at 5 mL/min. The system is driven by a common peristaltic pump, enabled by a novel pressure wave dampener, and operates in a closed bag-to-bag configuration, without requiring any specialized, dedicated equipment. When compared to standard density gradient centrifugation on paired samples, the new system demonstrated a 1.5-fold increase in T cell recovery and a 2-fold reduction in inter-sample variability for this separation outcome. The T cell-to-monocyte ratio of the leukapheresis sample was increased to 20:1, whereas with density gradient processing it decreased to 2:1. As a result of superior purity and/or gentler processing, T cells enriched by the system showed a 2.7-times higher fold expansion during subsequent culture, and an overall 3.5-times higher cumulative yield. This centrifugation-free and label-free closed system for enriching lymphocytes could significantly simplify and standardize the manufacturing of life-saving cellular therapies.

Environmental sustainability through aggregate demand and knowledge economy interaction-a case of very high-HDI countries.

The magnitude of the economic activities is immense in very high-Human Development Index (HDI) countries, leading to environmental degradation, a crucial problem. This study is aimed at testing aggregate demand's role in the environmental Kuznets curve (EKC) perspective and explores the role of four pillars of the knowledge economy, viz., technology, innovations, education, and institutions, as proposed by World Bank, in maintaining sustainable development of environmental quality in these countries. The analysis covers the period ranging from 1995 to 2022. The departure of normality of the variables provides a solid base for panel quantile regression (PQR). Unlike ordinary least squares (OLS) regression, which estimates the conditional mean of the dependent variable, PQR estimates the conditional quantiles. The estimated results using PQR confirm both U and inverted U-shaped aggregate demand-based EKC. In fact, these knowledge pillars in the model determine the shape of EKC. Results also reveal that two knowledge pillars, i.e., technology and innovations, are responsible for significantly reducing carbon emissions. In comparison, education and institutions are responsible for expanding carbon emissions. As a moderator, all knowledge pillars except institutions are shifting the EKC downward. The key lessons from these findings are that technology and innovation can reduce carbon emissions, while education and institutions may have a mixed impact. The relationship between knowledge pillars and emissions may be moderated by other factors, underscoring the need for further research. Moreover, urbanization, energy intensity, financial development, and trade openness significantly contribute to environmental deterioration.

Sustainable environment quality: moderating role of renewable energy consumption in service sector for selected HDR listed countries.

Considering environmental deterioration, an emerging global problem, this study is aimed at determining the impact of the service sector economic activity on environmental quality from the environmental Kuznets curve (EKC) perspective and finding ways to reduce the carbon impact of service sector within the EKC relationship. This study proposes that renewable energy intensity in the economy plays an important role in reducing carbon print of service sector. This study is based on secondary data from 1995 to 2021 for different development-wise categorized country groups leading to 115 countries, according to the Human Development Report (HDR) on the Human Development Index (HDI). Estimated results using panel feasible generalized least squares (FGLS) have confirmed inverted U-shaped for very high HDI and medium HDI and U-shaped EKC for low HDI countries. This study is instrumental in confirming the moderating role of renewable energy in the service sector EKC. Policymakers can plan a gradual reduction of carbon footprint in the service sector by transitioning toward renewable energy.

Recent advances in microfluidic cell separation to enable centrifugation-free, low extracorporeal volume leukapheresis in pediatric patients.

Leukapheresis is a common extracorporeal procedure for leukodepletion and cellular collection. During the procedure, a patient's blood is passed through an apheresis machine to separate white blood cells (WBCs) from red blood cells (RBCs) and platelets (PLTs), which are then returned to the patient. Although it is well-tolerated by adults and older children, leukapheresis poses a significant risk to neonates and low-weight infants because the extracorporeal volume (ECV) of a typical leukapheresis circuit represents a particularly large fraction of their total blood volume. The reliance of existing apheresis technology on centrifugation for separating blood cells limits the degree to which the circuit ECV could be miniaturized. The rapidly advancing field of microfluidic cell separation holds excellent promise for devices with competitive separation performance and void volumes that are orders of magnitude smaller than their centrifugation-based counterparts. This review discusses recent advancements in the field, focusing on passive separation methods that could potentially be adapted to perform leukapheresis. We first outline the performance requirements that any separation method must meet to replace centrifugation-based methods successfully. We then provide an overview of the passive separation methods that can remove WBCs from whole blood, focusing on the technological advancements made in the last decade. We describe and compare standard performance metrics, including blood dilution requirements, WBC separation efficiency, RBC and PLT loss, and processing throughput, and discuss the potential of each separation method for future use as a high-throughput microfluidic leukapheresis platform. Finally, we outline the primary common challenges that must still be overcome for these novel microfluidic technologies to enable centrifugation-free, low-ECV leukapheresis in the pediatric setting.

Distribution-based effects of disaggregated GDP and environmental quality-a case of quantile on quantile estimates.

There is a strong association between environmental quality and economic activity. Empirical studies term this relationship as environmental Kuznets curve (EKC) using time series or panel data regression analysis, but their estimates are based on several assumptions. This study has explored the distribution oriented robust effect of disaggregated real GDP on environmental quality. These estimates are free of assumptions and provide the actual distribution of effects rather than a single value of the marginal effect. The data is collected for 189 countries between 1990 and 2018, and estimates are generated using panel quantile regression and quantile on quantile regression. The estimation results point towards the U-shaped industry EKC, inverted U-shaped service EKC, and linear agriculture EKC. The robust, practical, and realistic estimates of real economic activity and environment have paved way towards an in-depth analysis to sustain a better environmental quality.

Sustainability assessment using STIRPAT approach to environmental quality: an extended panel data analysis.

The consequence of increasing economic activities is observable in the incidence of environmental deterioration. Many studies have explored the precedents of environment quality. In this regard, the proposed stochastic impacts by regression on population, affluence, and technology (STIRPAT) and environmental Kuznets curve (EKC) analysis are valuable not only for academic analysts, but also for policymakers. This study has focused on 80 selected countries between 1990 and 2017, which confirms the existence of EKC within the STIRPAT framework. The results are estimated with the help of dynamic ordinary least square (DOLS), which controls for the autocorrelation in long periods. According to the estimated results, this study confirms U-shaped EKC based on industrial-, agricultural-, and services-based economic activities. This means that over-reliance on one specific economic activity may harm the environment and create footprint. In this regard, urbanization is responsible for affecting carbon dioxide emissions. Moreover, governance and technology are protecting the environment. This quadratic function had classified the sample countries in terms of the degree of sustainability of their economic activity sectors. This study proposes that countries should work on a balanced composition of economic activity so that the lowest possible environmental deterioration is caused.

Novel capacitive MEMS sensor for monitoring in-stent restenosis.

Cardiovascular is a disorder of the heart and its blood vessels that causes millions of deaths around the world. Implanting stent in patient's artery is a typical procedure of treatment. However, a major problem associated with stents is the buildup of plaque/fatty acids deposits, a condition known as in-stent restenosis. Therefore, one of the preventive solutions is the development of "smart" stents that contain pressure sensors for monitoring stent blockage at early stages. Such sensors need to be associated with high sensitivity for early detection of flow abnormalities within the stent. Here, we propose several capacitive pressure sensor plate designs and analyze their sensitivities. Our results show that a square-shaped plate with straight slots on its edges can drastically improve sensitivity. Several analyses were carried out to optimize dimensions of the proposed design for monitoring in-stent restenosis.