Online HEPA Filter Replacement

High Efficiency Particulate Arrestance (HEPA) filters serve an important role in safety of nuclear facilities and can be an important tool in safeguards verification of nuclear activities. This paper describes a new design for HEPA filter housing in nuclear facilities to reduce replacement time, improve safety, reduce worker dosage, and facilitate safeguards procedures post replacement. This design must meet the criteria of staying online during filter exchanges, assisting with International Atomic Energy Agency (IAEA) sampling practices, meeting the nuclear air and gas code specifications and relevant subsections, and adhering to the principles of ALARA (as low as reasonably achievable), for maintaining low radiation levels to maximize worker safety. Our new design focuses on improved safety while achieving an online filter exchange. Not only will an online filter exchange reduce facility downtime and save facilities money, it has the potential to offer increased worker safety, and provide easy filter access for IAEA officials who wish to conduct sampling and inspection for safeguards. It would effectively eliminate the need for a facility to shut down for filters to be replaced. In our research, we did not find any current designs on the market that can perform an online HEPA filter exchange. We also conducted research on sealing techniques to support the online system design. We have established a project relationship with Radiation Protection Systems (RPS), Inc.: a contracting company based out of Groton, Connecticut, USA which specializes in mobile HEPA filter and carbon pre-filter housings for nuclear applications. The technical information exchange and partnership with RPS may result in an actual product that could be installed in future nuclear power plants if the design can be proven to work in concept and function. It may also be possible to retrofit existing HEPA installations in some cases. The design includes a double door bag-in, bag-out design and operational procedure to maintain worker safety and allow for zero escape of radioactive volatiles or particulates into the air external to the facility enclosure. A combination of neoprene gasket, silicone gel, and brush sealing techniques are employed in the new design with continuity of airflow during the switch in mind. This innovative design improves safety as well as operational efficiency. The design team is cognizant of safeguards considerations and aimed the design towards facilitating access. In particular, in our new design access to HEPA filter for sampling is much easier which can potentially improve the frequency and quality of sampling during IAEA inspections. Likewise, the lower level of effort (therefore cost) in switching filters will encourage changing filters more frequently. This will lower the risk of filter failures caused by clogged or possibly faulty filters. In fact, the IAEA reported that âAIJInvestigators from other national laboratories have suggested that aging effects could have contributed to over 80 percent of these failures. âAI The prototype design features a HEPA filter train (2 HEPA filters connected by a gel-seal interface) that slide seamlessly through the housing on rollers while the nuclear facility is online, the first (old) filter being dislodged into a sealed bagging unit, and the second (new) filter being clamped into place using a cam shaft clamping mechanism. There are two areas of design innovation here that are particularly exciting. The gel-seal interface that connects the filters will provide an air tight gap between two filters while they are exchanged. The clamping system features a brush seal interface on top and bottom, to maintain airflow and mobility of the filter while facilitating a switch. Because extended radiation exposure may alter the properties of sealants and gaskets we are investigating the use of seals that can be replaced during these quick filter changes. The design prototype is a full-scale model, capable of housing a 12x24x12 inch HEPA filter. Currently, we have completed the design of the new housing unit, created a proof of concept build, as well as conducted the preliminary engineering analysis, cost analysis, and material selection of the final prototype. Manufacturing of the final housing is proceeding and upon completion will be validated with a set of rigorous testing procedures concerning sealing and safety of the system. These tests are standard industry practices and RPS will assist in performing the tests. Namely, ASME test FC-I- 3272, a test in which aerosol particles of 20 m, which are the most penetrating particle sizes (MPPS), are sent through the housing unit and penetration is monitored during an online switch. Further testing will include colored smoke being pumped through the unit to test sealing capabilities and to identify possible particulate buildup. Provided the tests show that the design is successful in maintaining air flow and safety during the filter exchange, methods of improvement for ease of use and the automation of the exchange process, improvements to continuity of knowledge, and radiation monitoring techniques will be investigated for a comprehensive final product design

Regulating Two-Sided Markets: An Empirical Investigation

Two-sided market theory predicts that platforms may subsidize the participation of one type of agent by extracting surplus from another type to internalize indirect network externalities. However, few empirical studies exist to evaluate the impact of government intervention in these markets. We use confidential bank-level data to study the impact of government-encouraged fee reductions for payment card services when merchant acceptance is not complete. We find that consumer and merchant welfare improved when the interchange fees, transfers among banks, were reduced. Furthermore, bank revenues increased because the increase in the number of transactions offset the decrease in the per-transaction revenue

Chapter 1.6: Early warning signals of Earth system tipping points

This chapter focuses on the methods used to predict the movement of parts of the Earth system towards tipping points. It begins by introducing the theory of critical slowing down (CSD), a general phenomenon of slowing recovery from perturbations that happens in many systems being forced slowly towards a tipping point. Then, it describes the various methods that can be used to estimate the occurrence of CSD and the approach of a tipping point, beginning with methods based on changes over time in the system, spatial changes, or changes in network structure, up to more advanced modelling techniques, including AI. These ‘early warning signals’ (EWS) can be used on data from a number of different sources, be these models, field experiments or remotely sensed data from satellites. The chapter considers various case studies that use real-world observations, to show how these methods are being used to predict losses in resilience in these systems. Finally, it explores limitations and potential solutions in the field of EWS, looking ahead to advances in data availability and what this could mean for predicting the movement towards tipping in these systems in the futurePeer ReviewedPostprint (published version

Tipping point detection and early warnings in climate, ecological, and human systems

Tipping points characterize the situation when a system experiences abrupt, rapid, and sometimes irreversible changes in response to only a gradual change in environmental conditions. Given that such events are in most cases undesirable, numerous approaches have been proposed to identify if a system is approaching a tipping point. Such approaches have been termed early warning signals and represent a set of methods for identifying statistical changes in the underlying behaviour of a system across time or space that would be indicative of an approaching tipping point. Although the idea of early warnings for a class of tipping points is not new, in the last 2 decades, the topic has generated an enormous amount of interest, mainly theoretical. At the same time, the unprecedented amount of data originating from remote sensing systems, field measurements, surveys, and simulated data, coupled with innovative models and cutting-edge computing, has made possible the development of a multitude of tools and approaches for detecting tipping points in a variety of scientific fields. However, we miss a complete picture of where, how, and which early warnings have been used so far in real-world case studies. Here we review the literature of the last 20 years to show how the use of these indicators has spread from ecology and climate to many other disciplines. We document what metrics have been used; their success; and the field, system, and tipping points involved. We find that, despite acknowledged limitations and challenges, in the majority of the case studies we reviewed, the performance of most early warnings was positive in detecting tipping points. Overall, the generality of the approaches employed – the fact that most early warnings can in theory be observed in many dynamical systems – explains the continuous multitude and diversification in their application across scientific domains.Chris A. Boulton, Joshua E. Buxton, and David I. Armstrong McKay were supported by the Bezos Earth Fund via the Global Tipping Points Report project. Carlos López Martínez was supported by INTERACT project PID2020-114623RB-C32 funded by MCIN/AEI/10.13039/501100011033.Peer ReviewedPostprint (published version

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention

Hypotension following Patent Ductus Arteriosus Ligation: The Role of Adrenal Hormones

OBJECTIVE: To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. STUDY DESIGN: We performed a multicenter study of infants born at <32 weeks gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured three times: before and after a cosyntropin (1.0 microgram/kg) stimulation test (performed prior to the ligation), and at 10–12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified Inotrope Score (1 x dopamine (μg/kg/min) + 1 x dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their highest Inotrope Score was >15. RESULTS: Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low post-operative cortisol levels were not associated with the overall incidence of hypotension following ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the odds ratio for developing catecholamine-resistant hypotension was OR=36.6, CI=2.8–476, p=0.006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not due to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. CONCLUSION: Infants with low cortisol concentrations following PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0–100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0–100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by 96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4·8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20·9-point to 17·0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17·2-point to 20·4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view—and subsequent provision—of quality health care for all populations.info:eu-repo/semantics/publishedVersio

Ensembl Genomes 2016: more genomes, more complexity

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016

Background: A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97\ub71 (95% UI 95\ub78-98\ub71) in Iceland, followed by 96\ub76 (94\ub79-97\ub79) in Norway and 96\ub71 (94\ub75-97\ub73) in the Netherlands, to values as low as 18\ub76 (13\ub71-24\ub74) in the Central African Republic, 19\ub70 (14\ub73-23\ub77) in Somalia, and 23\ub74 (20\ub72-26\ub78) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91\ub75 (89\ub71-93\ub76) in Beijing to 48\ub70 (43\ub74-53\ub72) in Tibet (a 43\ub75-point difference), while India saw a 30\ub78-point disparity, from 64\ub78 (59\ub76-68\ub78) in Goa to 34\ub70 (30\ub73-38\ub71) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4\ub78-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20\ub79-point to 17\ub70-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17\ub72-point to 20\ub74-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle- SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage hinges upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view-and subsequent provision-of quality health care for all populations