Evaluation of the suitability of the Waterloo Membrane Sampler for sample preconcentration before compound-specific isotope analysis

Compound-specific isotope analysis (CSIA) has been used extensively for fingerprinting applications and for the evaluation of the degradation processes in organic contaminant studies in groundwater. Recently, the potential applications of CSIA in unsaturated and vapour intrusion studies have been explored. A key challenge in these studies is the development of analytical protocols for CSIA that can handle the very low concentrations of organic compounds typically found in the unsaturated zone and indoor samples. The objective of this research was to evaluate the applicability of the Waterloo Membrane Sampler (WMS) for CSIA, with intended applications in the unsaturated zone and in vapour intrusion studies. Tests were performed to evaluate isotope effects associated with sorption and desorption of the analytes under active sampling and passive sampling conditions. A standard gas mixture containing three model analytes, hexane, benzene and trichloroethene, was used in the experiments. Tests were designed to evaluate the isotope effect as a function of the time of exposure (3 to 192 hours), amount of analytes sorbed, and exposure temperature (25°C and 12°C). The results obtained in all studies showed very good reproducibility with standard deviations within the accepted analytical error of ±0.5 ‰. The data also showed that the δ13C values of the analytes collected by passive sampling were more depleted than the values obtained by active sampling. However, the degree of fractionation, ranging from 0.4 to 1.4 ‰, was practically constant and independent of the sampling time, mass adsorbed and temperature in the ranges of variables studied. The lowest concentrations that could be detected were 0.65mg/m3for hexane, 0.88mg/m3benzene and 4.38mg/m3for TCE. The method developed was applied in a field study where the results obtained for benzene and toluene collected in the unsaturated zone showed the expected values compared to carbon isotope data obtained for benzene and toluene at the water table. Results obtained in this study confirmed good data reproducibility. This indicates that CSIA coupled with WMS has the potential to become a valuable tool in unsaturated zone studies and in the environmental forensics field

Hypoxia as a therapy for mitochondrial disease

Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction.National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institute of Mental Health (U.S.) (Grant 1R01-MH110049)National Institute of Neurological Diseases and Stroke (U.S.) (Grant 5R01DK097768-03

Extraction and Characterization of Microplastics from Organic Solid Matrices and their Remediation

Plastics have become an essential commodity due to their superior engineering properties, durability and low cost to be used by a wide range of commercial products. However, the degradation of plastics due to mechanical, chemical, biological, and photolytic stresses has led to the formation of microplastics (MPs). MPs have risen to the top of environmental concerns due to their affinity to pollute the environment, and to pass to the food chain, threatening human health. In this context, attempts have been made to extract and characterize MPs from aqueous and solid matrices. A problem that not only hampers research but also regulatory decisions is the variety of methods used for the extraction and characterization of MPs, especially in organic solid matrices (OSMs) with organic (OM) \u3e 5%, making the comparison of results difficult. This paper aims to address this need, by critically assessing the methodologies and protocols used for extraction of MPs from OSMs, which includes sample collection, dispersion, OM removal, and separation, as well as the qualitative and quantitative characterization of MPs. Further, current impediments in the accurate characterization of MPs are identified along with recommendations for future developments. Finally, recent efforts by various countries to legislate against certain sources of MPs, as well as issues and novel techniques to remediate MPs from the soil, and wastewater have been highlighted

Municipal solid waste management under Covid-19: Challenges and recommendations

Covid-19 is proving to be an unprecedented disaster for human health, social contacts and the economy worldwide. It is evident that SARS-CoV-2 may spread through municipal solid waste (MSW), if collected, bagged, handled, transported or disposed of inappropriately. Under the stress placed by the current pandemic on the sanitary performance across all MSW management (MSWM) chains, this industry needs to re-examine its infrastructure resilience with respect to all processes, from waste identification, classification, collection, separation, storage, transportation, recycling, treatment and disposal. The current paper provides an overview of the severe challenges placed by Covid-19 onto MSW systems, highlighting the essential role of waste management in public health protection during the ongoing pandemic. It also discusses the measures issued by various international organisations and countries for the protection of MSWM employees (MSWEs), identifying gaps, especially for developing countries, where personal protection equipment and clear guidelines to MSWEs may not have been provided, and the general public may not be well informed. In countries with high recycling rates of MSW, the need to protect MSWEs' health has affected the supply stream of the recycling industry. The article concludes with recommendations for the MSW industry operating under public health crisis conditions

Municipal solid waste management under Covid-19: Challenges and recommendations

Covid-19 is proving to be an unprecedented disaster for human health, social contacts and the economy worldwide. It is evident that SARS-CoV-2 may spread through municipal solid waste (MSW), if collected, bagged, handled, transported or disposed of inappropriately. Under the stress placed by the current pandemic on the sanitary performance across all MSW management (MSWM) chains, this industry needs to re-examine its infrastructure resilience with respect to all processes, from waste identification, classification, collection, separation, storage, transportation, recycling, treatment and disposal. The current paper provides an overview of the severe challenges placed by Covid-19 onto MSW systems, highlighting the essential role of waste management in public health protection during the ongoing pandemic. It also discusses the measures issued by various international organisations and countries for the protection of MSWM employees (MSWEs), identifying gaps, especially for developing countries, where personal protection equipment and clear guidelines to MSWEs may not have been provided, and the general public may not be well informed. In countries with high recycling rates of MSW, the need to protect MSWEs' health has affected the supply stream of the recycling industry. The article concludes with recommendations for the MSW industry operating under public health crisis conditions

Sustainable environmental geotechnics practices for a green economy

The revitalisation of the global economy after the Covid-19 era presents environmental geotechnics with the opportunity to reinforce the need for a change in paradigm towards a green, circular economy and to promote aggressively the use and development of sustainable technologies and management practices. This paper aims to assist in this effort by concentrating on several thematic areas where sustainability solutions and future improvements are sought. These include the re-entry of construction and demolition of wastes, excavated materials, industrial wastes and marine sediments into the production cycle and the reuse of existing foundations. Despite the recent trend in advanced countries towards recycling and waste-to-energy thermal treatment, landfills still constitute the most common municipal solid waste management practice, especially in low-and-middle-income countries, and technological solutions to improve their environmental footprint are hereby presented. At the same time, remediation solutions are required to address the multitude of contaminated sites worldwide. Advanced developments that incorporate environmental, economic and social dimensions are expounded by the authors, together with sustainable ground improvement solutions for infrastructure projects conducted in soft and weak soils. The topic of thermo-active geostructures concludes this paper, where, apart from their infrastructure utility, these structures have the potential to contribute to the renewable energy source.Published versionThe second author would like to acknowledge the support of the Office of the Associate Provost for Research and Academic Development at Abu Dhabi University, UAE through grant19300540

Next Generation Network Management Technology

Today's telecommunications networks are becoming increasingly large, complex, mission critical and heterogeneous in several dimensions. For example, the underlying physical transmission facilities of a given network may be ﲭixed media (copper, fiber- optic, radio, and satellite); the sub networks may be acquired from different vendors due to economic, performance, or general availability reasons; the information being transmitted over the network may be ﲭultimedia (video, data, voice, and images) and, finally, varying performance criteria may be imposed e.g. data transfer may require high throughput while the others, whose concern is voice communications, may require low call blocking probability. For these reasons, future telecommunications networks are expected to be highly complex in their services and operations. Due to this growing complexity and the disparity among management systems for individual sub networks, efficient network management systems have become critical to the current and future success of telecommunications companies. This paper addresses a research and development effort which focuses on prototyping configuration management, since that is the central process of network management and all other network management functions must be built upon it. Our prototype incorporates ergonomically designed graphical user interfaces tailored to the network configuration management subsystem and to the proposed advanced object-oriented database structure. The resulting design concept follows open standards such as Open Systems Interconnection (OSI) and incorporates object oriented programming methodology to associate data with functions, permit customization, and provide an open architecture environment. A revised version of this technical report has been published in The 12th Symposium on Space Nuclear Power and Propulsion/Commercialization, pp. 75-82, Albuquerque, NM, January 8-12, 1995.</ul

Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat

BACKGROUND: The angiotensin-converting enzyme (ACE) inhibitors have complicated and poorly characterized pharmacokinetics. There are two binding sites per ACE (high affinity "C", lower affinity "N") that have sub-nanomolar affinities and dissociation rates of hours. Most inhibitors are given orally in a prodrug form that is systemically converted to the active form. This paper describes the first human physiologically based pharmacokinetic (PBPK) model of this drug class. METHODS: The model was applied to the experimental data of van Griensven et. al for the pharmacokinetics of ramiprilat and its prodrug ramipril. It describes the time course of the inhibition of the N and C ACE sites in plasma and the different tissues. The model includes: 1) two independent ACE binding sites; 2) non-equilibrium time dependent binding; 3) liver and kidney ramipril intracellular uptake, conversion to ramiprilat and extrusion from the cell; 4) intestinal ramipril absorption. The experimental in vitro ramiprilat/ACE binding kinetics at 4°C and 300 mM NaCl were assumed for most of the PBPK calculations. The model was incorporated into the freely distributed PBPK program PKQuest. RESULTS: The PBPK model provides an accurate description of the individual variation of the plasma ramipril and ramiprilat and the ramiprilat renal clearance following IV ramiprilat and IV and oral ramipril. Summary of model features: Less than 2% of total body ACE is in plasma; 35% of the oral dose is absorbed; 75% of the ramipril metabolism is hepatic and 25% of this is converted to systemic ramiprilat; 100% of renal ramipril metabolism is converted to systemic ramiprilat. The inhibition was long lasting, with 80% of the C site and 33% of the N site inhibited 24 hours following a 2.5 mg oral ramipril dose. The plasma ACE inhibition determined by the standard assay is significantly less than the true in vivo inhibition because of assay dilution. CONCLUSION: If the in vitro plasma binding kinetics of the ACE inhibitor for the two binding sites are known, a unique PBPK model description of the Griensven et. al. experimental data can be obtained

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries 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 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury. Funding: Bill & Melinda Gates Foundation

Trends in future health financing and coverage: future health spending and universal health coverage in 188 countries, 2016–40

Background: Achieving universal health coverage (UHC) requires health financing systems that provide prepaid pooled resources for key health services without placing undue financial stress on households. Understanding current and future trajectories of health financing is vital for progress towards UHC. We used historical health financing data for 188 countries from 1995 to 2015 to estimate future scenarios of health spending and pooled health spending through to 2040. Methods: We extracted historical data on gross domestic product (GDP) and health spending for 188 countries from 1995 to 2015, and projected annual GDP, development assistance for health, and government, out-of-pocket, and prepaid private health spending from 2015 through to 2040 as a reference scenario. These estimates were generated using an ensemble of models that varied key demographic and socioeconomic determinants. We generated better and worse alternative future scenarios based on the global distribution of historic health spending growth rates. Last, we used stochastic frontier analysis to investigate the association between pooled health resources and UHC index, a measure of a country's UHC service coverage. Finally, we estimated future UHC performance and the number of people covered under the three future scenarios. Findings: In the reference scenario, global health spending was projected to increase from US$10 trillion (95$20 trillion (18 trillion to 22 trillion) in 2040. Per capita health spending was projected to increase fastest in upper-middle-income countries, at 4·2% (3·4–5·1) per year, followed by lower-middle-income countries (4·0%, 3·6–4·5) and low-income countries (2·2%, 1·7–2·8). Despite global growth, per capita health spending was projected to range from only $40 (24–65) to$413 (263–668) in 2040 in low-income countries, and from $140 (90–200) to$1699 (711–3423) in lower-middle-income countries. Globally, the share of health spending covered by pooled resources would range widely, from 19·8% (10·3–38·6) in Nigeria to 97·9% (96·4–98·5) in Seychelles. Historical performance on the UHC index was significantly associated with pooled resources per capita. Across the alternative scenarios, we estimate UHC reaching between 5·1 billion (4·9 billion to 5·3 billion) and 5·6 billion (5·3 billion to 5·8 billion) lives in 2030. Interpretation: We chart future scenarios for health spending and its relationship with UHC. Ensuring that all countries have sustainable pooled health resources is crucial to the achievement of UHC. Funding: The Bill & Melinda Gates Foundation