Search

IntroductionThere is limited guidance on strategies for delivering complex global health programs. We synthesized available evidence on implementation strategies and outcomes utilized in the global polio eradication initiative (GPEI) across low and middle-income country (LMIC) settings.MethodsWe nested our scoping review into a literature review conducted as part of a parent study, STRIPE. This review systematically searched PubMed for articles between 1 January 1988 and 25 April 2018 using polio search terms. Strategies from included studies were organized according to the Expert Recommendations for Implementing Change (ERIC) framework, specified using Proctor's framework, and linked to various outcomes (implementation, services delivery, impact).Results152 unique articles fulfilled our inclusion criteria (from 1,885 articles included in the parent study). Only 43 out of the 152 articles described a suitable quantitative study design for evaluating outcomes. We extracted 66 outcomes from the 43 unique studies. Study publication dates ranged from 1989 to 2018 and represented diverse country settings. The most common implementation strategies were developing mechanisms for feedback, monitoring, and evaluation (n = 69); increasing awareness among the population (n = 58); involving stakeholders, workers, and consumers in the implementation efforts (n = 46); conducting workshops (n = 33); using mass media (n = 31); and building robust record systems to capture outcomes (n = 31). Coverage (n = 13) and morbidity (n = 12) were the most frequently identified outcomes, followed by effectiveness (n = 9) and fidelity (n = 6). Feasibility and sustainability were rarely evaluated.ConclusionsThis review provides a catalogue of implementation strategies and outcomes relevant for advancing global health services delivery in LMICs drawing from the GPEI. Implementation strategies reviewed were poorly described and not adequately linked to outcomes. It calls for additional implementation research to unravel the mechanisms of implementation strategies and their effectiveness, and adaptation of the ERIC framework in LMICs.

Summary: Background: Despite substantial progress in improving maternal and newborn health, India continues to experience high rates of newborn mortality and stillbirths. One reason may be that many births happen in health facilities that lack advanced services—such as Caesarean section, blood transfusion, or newborn intensive care. Stratification based on pregnancy risk factors is used to guide ‘high-risk’ women to advanced facilities. To assess the utility of risk stratification for guiding the choice of facility, we estimated the frequency of adverse newborn outcomes among women classified as ‘low risk’ in India. Methods: We used the 2019–21 Fifth National Family Health Survey (NFHS-5)—India’s Demographic and Health Survey—which includes modules administered to women aged 15–49 years. In addition to pregnancy history and outcomes, the survey collected a range of risk factors, including biomarkers. We used national obstetric risk guidelines to classify women as ‘high risk’ versus ‘low risk’ and assessed the frequency of stillbirths, newborn deaths, and unplanned Caesarean sections for the respondent’s last pregnancy lasting 7 or more months in the past five years. We calculated the proportion of deliveries occurring at non-hospital facilities in all the Indian states. Findings: Using data from nearly 176,699 recent pregnancies, we found that 46.6% of India’s newborn deaths and 56.3% of stillbirths were among women who were ‘low risk’ according to national guidelines. Women classified as ‘low risk’ had a Caesarean section rate of 8.4% (95% CI 8.1–8.7%), marginally lower than the national average of 10.0% (95% CI 9.8–10.3%). In India as a whole, 32.0% (95% CI 31.5–32.5%) of deliveries occurred in facilities that were likely to lack advanced services. There was substantial variation across the country, with less than 5% non-hospital public facility deliveries in Punjab, Kerala, and Delhi compared to more than 40% in Odisha, Madhya Pradesh, and Rajasthan. Newborn mortality tended to be lower in states with highest hospital delivery rates. Interpretation: Individual risk stratification based on factors identified in pregnancy fails to accurately predict which women will have delivery complications and experience stillbirth and newborn death in India. Thus a determination of ‘low risk’ should not be used to guide women to health facilities lacking key life saving services, including Caesarean section, blood transfusion, and advanced newborn resuscitation and care. Funding: Bill and Melinda Gates Foundation and the World Bank. The findings, interpretations and conclusions expressed in the paper are entirely those of the authors, and do not represent the views of the Gates Foundation or of the World Bank, its Executive Directors, or the countries they represent.

Abstract Background With nearly 90% of annual hypertension-related deaths occurring in low- and middle-income countries (LMICs), there is an urgent need to measure the coverage of health services that effectively manage hypertension. However, there is little agreement on how to define effective coverage and the existing hypertension care cascade (hypertension prevalence, percent aware, percent treated, and percent controlled) does not account for the quality of care received by patients. This study reviews definitions of effective coverage and service quality for hypertension management services and proposes an expanded hypertension care cascade to improve measurement of health systems performance. Methods A systematic scoping review of literature published in six electronic databases between January 2000 and October 2020 identified studies that defined effective coverage of hypertension management services or integrated dimensions of service quality into population-based estimates of hypertension management in LMICs. Findings informed an expanded hypertension care cascade from which quality-adjusted service coverage can be calculated to approximate effective coverage. Results The review identified 18 relevant studies, including 6 that defined effective coverage for hypertension management services and 12 that reported a measure of service quality in a population-based study. Based on commonly reported barriers to hypertension management, new steps on the proposed expanded care cascade include (i) population screened, (ii) population linked to quality care, and (iii) population adhering to prescribed treatment. Conclusion There is little consensus on the definition of effective coverage of hypertension management services, and most studies do not describe the quality of hypertension management services provided to populations. Incorporating aspects of service quality to the hypertension care cascade allows for the calculation of quality-adjusted coverage of relevant services, enabling an appropriate measurement of health systems performance through effective coverage.

Abstract Background Improving service delivery is a key strategy for achieving service coverage, one of the two components of universal health coverage (UHC). As one of the largest global public health initiatives, individuals involved with the Global Polio Eradication Initiative (GPEI) have learned many important lessons about service delivery. We identified contributors and challenges to delivering health services at national and subnational levels using experiences from the GPEI. We described strategies used to strengthen service delivery and draw lessons that could be applicable to achieving UHC. Methods Online cross-sectional surveys based on the Consolidated Framework for Implementation Research (CFIR) domains and socioecological model were conducted from 2018–2019. Data were analyzed using an embedded mixed methods approach. Frequencies of the contributors and challenges to service delivery by levels of involvement were estimated. Chi-square tests of independence were used to assess unadjusted associations among categorical outcome variables. Logistic regressions were used to examine the association between respondent characteristics and contributors to successful implementation or implementation challenges. Horizontal analysis of free text responses by CFIR domain was done to contextualize the quantitative results. Results Three thousand nine hundred fifty-five people responded to the online survey which generated 3,659 valid responses. Among these, 887 (24.2%) reported involvement in service delivery at the global, national, or subnational level with more than 90% involved at subnational levels. The main internal contributor of strengthened service delivery was the process of conducting activities (48%); working in frontline role had higher odds of identifying the process of conducting activities as the main internal contributor (AOR: 1.22, p = 0.687). The main external contributor was the social environment (42.5%); having 10–14 years of polio program implementation was significantly associated with identifying the social environment as the main external contributor to strengthened service delivery (AOR: 1.61, p = 0.038). The most frequent implementation challenge was the external environment (56%); working in Eastern Mediterranean region was almost 4 times more likely to identify the external environment as the major challenge in service delivery strengthening (AOR:3.59, p

Background: During and after the SARS-CoV-2 (COVID-19) pandemic, many countries experienced declines in immunization that have not fully recovered to pre-pandemic levels. This study uses routine health facility immunization data to estimate variability between and within countries in post-pandemic immunization service recovery for BCG, DPT1, and DPT3. Methods: After adjusting for data reporting completeness and outliers, interrupted time series regression was used to estimate the expected immunization service volume for each subnational unit, using an interruption point of March 2020. We assessed and compared the percent deviation of observed immunizations from the expected service volume for March 2020 between and within countries. Results: Six countries experienced significant service volume declines for at least one vaccine as of October 2022. The shortfall in BCG service volume was ~6% (95% CI −1.2%, −9.8%) in Guinea and ~19% (95% CI −16%, 22%) in Liberia. Significant cumulative shortfalls in DPT1 service volume are observed in Afghanistan (−4%, 95% CI −1%, −7%), Ghana (−3%, 95% CI −1%, −5%), Haiti (−7%, 95% CI −1%, −12%), and Kenya (−3%, 95% CI −1%, −4%). Afghanistan has the highest percentage of subnational units reporting a shortfall of 5% or higher in DPT1 service volume (85% in 2021 Q1 and 79% in 2020 Q4), followed by Bangladesh (2020 Q1, 83%), Haiti (80% in 2020 Q2), and Ghana (2022 Q2, 75%). All subnational units in Bangladesh experienced a 5% or higher shortfall in DPT3 service volume in the second quarter of 2020. In Haiti, 80% of the subnational units experienced a 5% or higher reduction in DPT3 service volume in the second quarter of 2020 and the third quarter of 2022. Conclusions: At least one region in every country has a significantly lower-than-expected post-pandemic cumulative volume for at least one of the three vaccines. Subnational monitoring of immunization service volumes using disaggregated routine health facility information data should be conducted routinely to target the limited vaccination resources to subnational units with the highest inequities.

Abstract Background Linking facility and household surveys through geographic methods is a popular technique to draw conclusions about the relationship between health services and population health outcomes at local levels. These methods are useful tools for measuring effective coverage and tracking progress towards Universal Health Coverage, but are understudied. This paper compares the appropriateness of several geospatial methods used for linking individuals (within displaced survey cluster locations) to their source of family planning (at undisplaced health facilities) at a national level. Methods In Malawi, geographic methods linked a population health survey, rural clusters from the Woman’s Questionnaire of the 2015 Malawi Demographic and Health Survey (MDHS 2015), to Malawi’s national health facility census to understand the service environment where women receive family planning services. Individuals from MDHS 2015 clusters were linked to health facilities through four geographic methods: (i) closest facility, (ii) buffer (5 km), (iii) administrative boundary, and (iv) a newly described theoretical catchment area method. Results were compared across metrics to assess the number of unlinked clusters (data lost), the number of linkages per cluster (precision of linkage), and the number of women linked to their last source of modern contraceptive (appropriateness of linkage). Results The closest facility and administrative boundary methods linked every cluster to at least one facility, while the 5-km buffer method left 288 clusters (35.3%) unlinked. The theoretical catchment area method linked all but one cluster to at least one facility (99.9% linked). Closest facility, 5-km buffer, administrative boundary, and catchment methods linked clusters to 1.0, 1.4, 21.1, and 3.3 facilities on average, respectively. Overall, the closest facility, 5-km buffer, administrative boundary, and catchment methods appropriately linked 64.8%, 51.9%, 97.5%, and 88.9% of women to their last source of modern contraceptive, respectively. Conclusions Of the methods studied, the theoretical catchment area linking method loses a marginal amount of population data, links clusters to a relatively low number of facilities, and maintains a high level of appropriate linkages. This linking method is demonstrated at scale and can be used to link individuals to qualities of their service environments and better understand the pathways through which interventions impact health.

Abstract Background Afghanistan and Nigeria are two of the three remaining polio endemic countries. While these two countries have unique sociocultural characteristics, they share major polio risk factors. This paper describes the countries’ shared contexts and highlights important lessons on implementing polio eradication activities among hard-to-reach populations relevant for future global health programs. Methods A grey literature review of the Global Polio Eradication Initiative (GPEI) followed by an online survey was conducted in both countries. The survey was targeted to individuals who have been involved continuously in polio eradication activities for 12 months or more since 1988. A sub-set of respondents from the survey was recruited for key-informant interviews (KII). The survey and KIIs were conducted between September 2018–April 2019. A cross-case comparison analysis was conducted to describe shared implementation challenges, strategies, and unintended consequences of polio eradication activities across these contexts. Results Five hundred thirteen and nine hundred twenty-one surveys were completed in Afghanistan and Nigeria respectively; 28 KIIs were conducted in Afghanistan and 29 in Nigeria. Major polio eradication activities in both countries include house-to-house campaigns, cross-border stations, outreach to mobile populations, and surveillance. Common barriers to these activities in both countries include civil unrest and conflict; competing political agendas; and vaccine refusal, fatigue, and mistrust, all of which are all bases for describing hard-to-reach populations. Both countries employed strategies to engage community leadership, political and religious groups through advocacy visits, and recruited community members to participate in program activities to address misconceptions and distrust. Recruitment of female workers has been necessary for accessing women and children in conservative communities. Synergy with other health programs has been valuable; health workers have improved knowledge of the communities they serve which is applicable to other initiatives. Conclusions The power of community engagement at all levels (from leadership to membership) cannot be overstated, particularly in countries facing civil unrest and insecurity. Workforce motivation, community fatigue and mistrust, political priorities, and conflict are intricately interrelated. Community needs should be holistically assessed and addressed;programs must invest in the needs of health workers who engage in these long-term health programs, particularly in unsafe areas, to alleviate demotivation and fatigue.

Abstract Background Previous initiatives have aimed to document the history and legacy of the Smallpox Eradication Program (SEP) and the Global Polio Eradication Initiative (GPEI). In this multi-pronged scoping review, we explored the evolution and learning from SEP and GPEI implementation over time at global and country levels to inform other global health programs. Methods Three related reviews of literature were conducted; we searched for documents on 1) the SEP and 2) GPEI via online database searches and also conducted global and national-level grey literature searches for documents related to the GPEI in seven purposively selected countries under the Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) project. We included documents relevant to GPEI implementation. We conducted full text data analysis and captured data on Expert Recommendations for Implementing Change (ERIC) implementation strategies and principles, tools, outcomes, target audiences, and relevance to global health knowledge areas. Results 200 articles were included in the SEP scoping review, 1885 articles in the GPEI scoping review, and 963 documents in the grey literature review. M&E and engagement strategies were consistently translated from the SEP to GPEI; these evolved into newer approaches under the GPEI. Management strategies including setting up robust record systems also carried forward from SEP to GPEI; however, lessons around the need for operational flexibility in applying these strategies at national and sub-national levels did not. Similarly, strategies and lessons around conducting health systems readiness assessments prior to implementation were not carried forward from SEP to GPEI. Differences in the planning and communication strategies between the two programs included fidelity to implementation blueprints appeared to be higher under SEP, and independent monitoring boards and communication and media strategies were more prominent under GPEI. Conclusions Linear learning did not always occur between SEP and GPEI; several lessons were lost and had to be re-learned. Implementation and adaptation of strategies in global health programs should be well codified, including information on the contextual, time and stakeholders’ issues that elicit adaptations. Such description can improve the systematic translation of knowledge, and gains in efficiency and effectiveness of future global health programs.

Abstract Background Lessons from polio eradication efforts and the Global Polio Eradication Initiative (GPEI) are useful for improving health service delivery and outcomes globally. The Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) is a multi-phase project which aims to map, package and disseminate knowledge from polio eradication initiatives as academic and training programs. This paper discusses initial findings from the knowledge mapping around polio eradication activities across a multi-country context. Methods The knowledge mapping phase (January 2018 – December 2019) encompassed four research activities (scoping review, survey, key informant interviews (KIIs), health system analyses). This paper utilized a sequential mixed method design combining data from the survey and KIIs. The survey included individuals involved in polio eradication between 1988 and 2019, and described the contexts, implementation strategies, intended and unintended outcomes of polio eradication activities across levels. KIIs were conducted among a nested sample in seven countries (Afghanistan, Bangladesh, the Democratic Republic of Congo, Ethiopia, India, Indonesia, Nigeria) and at the global level to further explore these domains. Results The survey generated 3955 unique responses, mainly sub-national actors representing experience in over 74 countries; 194 KIIs were conducted. External factors including social, political, and economic factors were the most frequently cited barriers to eradication, followed by the process of implementing activities, including program execution, planning, monitoring, and stakeholder engagement. Key informants described common strategies for addressing these barriers, e.g. generating political will, engaging communities, capacity-building in planning and measurement, and adapting delivery strategies. The polio program positively affected health systems by investing in system structures and governance, however, long-term effects have been mixed as some countries have struggled to institutionalize program assets. Conclusion Understanding the implementing context is critical for identifying threats and opportunities to global health programs. Common implementation strategies emerged across countries; however, these strategies were only effective where organizational and individual capacity were sufficient, and where strategies were appropriately tailored to the sociopolitical context. To maximize gains, readiness assessments at different levels should predate future global health programs and initiatives should consider system integration earlier to ensure program institutionalization and minimize system distortions.

Abstract Background Complex global initiatives, like the Global Polio Eradication Initiative (GPEI), have prevented millions of paralyses and improved the health status of diverse populations. Despite the logistical challenges these initiatives must overcome at several levels, scant methods exist for systematically identifying and reaching a range of actors involved in their implementation. As a result, efforts to document the lessons learned from such initiatives are often incomplete. This paper describes the development and application of the Synthesis and Translation of Research and Innovations from Polio Eradication (STRIPE) systematic approach for identifying a comprehensive sample of actors involved in the GPEI. Results The survey for collecting lessons learned from the GPEI was conducted at the global level and within seven countries that represented GPEI operational contexts. Standard organizational and operational levels, as well as goals of program activities, were defined across contexts. Each survey iteration followed similar methodologies to theorize a target population or “universe” of all polio-related actors in the study area, enumerate a source population of specific individuals within the target population, and administer the survey to individuals within the source population. Based on the systematic approach used to obtain a comprehensive sample for lessons learned in GPEI, steps for obtaining a comprehensive sample for studying complex initiatives can be summarized as follows: (i) State research goal(s); (ii) Describe the program of interest; (iii) Define a sampling universe to meet these criteria; (iv) Estimate the size of the sampling universe; (v) Enumerate a source population within the universe that can be feasibly reached for sampling; (vi) Sample from the source population; and (vii) Reflect on the process to determine strength of inferences drawn. Conclusions The application of these methods can inform future evaluations of complex public health initiatives, resulting in better adoption of lessons learned, ultimately improving efficacy and efficiency, and resulting in significant health gains. Their use to administer the STRIPE lessons learned survey reflects experiences related to implementation challenges and strategies used to overcome barriers from actors across an extensive range of organizational, programming, and contextual settings.

Effective management of hypertension in low- and middle-income settings is a persistent public health challenge. This study examined supply- and demand-side barriers to receiving quality care and achieving effective hypertension management in rural Bihar, India. A state-representative household survey collected information from adults over 30 years of age on characteristics of the hypertension screening, diagnosis, and management services they received. A linked provider assessment determined the percent of providers who provided quality hypertension care (i.e., had a functioning BP measurement device, measured a patient’s BP, could correctly diagnose hypertension, had at least one first-line antihypertension medication, and could prescribe correctly based on standard guidelines). Patients were linked with their provider to determine the quality-adjusted coverage of hypertension management and logistic regression analysis was conducted to determine characteristics associated with receiving quality care. A total of 14,386 patients and 390 providers were studied. Nearly a quarter (22.5%) of adults had never had their BP measured before and 8.1% of adults reported a previous hypertension diagnosis. Less than one third (31.0%) of all interviewed providers demonstrated ability to provide quality hypertension care, and quality varied between provider types (14.8% of private homeopathic, 25.2% of informal, 40.0% of private modern medicine, and 60.0% of public providers gave quality care). While 95.8% of diagnosed individuals received some treatment, only 10.9% of patients received care from quality local providers. Nearly 45% of individuals with hypertension received care from non-local providers. Individuals from the general caste with comorbidities living in villages with more high-quality providers were most likely to receive quality care from a local provider. Whereas the coverage of services for individuals diagnosed with hypertension is high, the quality of these services is suboptimal for economically and socially vulnerable populations, which limits effective management and control of hypertension in rural Bihar. Efforts should be targeted towards providers to initiate quality treatment upon diagnosis, including correct prescription of antihypertensives.

In this brief autobiographical excursus, Professor Michael Peters not only presents us with the most fundamental aspects of his thinking in philosophy of education, but reveals how, in the midst of some specific concerns, his encounter with Wittgenstein and post-structuralist philosophers ended up shaping the way that he traveled in his intellectual path.

In this brief autobiographical excursus, Professor Michael Peters not only presents us with the most fundamental aspects of his thinking in philosophy of education, but reveals how, in the midst of some specific concerns, his encounter with Wittgenstein and post-structuralist philosophers ended up shaping the way that he traveled in his intellectual path.

This paper investigates the trope of the zombie and the recent upsurge in popular culture surrounding the figure of the zombie described as the “walking dead”. We investigate this trope and figure as a means of analyzing the “pedagogy of the walking dead” with particular attention to the crisis of education in the era of neoliberal capitalism. In particular we examine the professionalization and responsibilization of teachers in the new regulative environment and ask whether there is any room left for the project of critical education.

Purpose —This paper aims at exploring politics of contemporary knowledge cultures and possible directions for responding to the postdigital challenge. Design/Approach/Methods —This paper researches history and present of several prominent strands and readings of the knowledge economy. Following Caruso's work (2016), it examines more closely the differences between the managerial paradigm and the cognitive capitalism paradigm. Recognizing the postdigital nature of contemporary knowledge cultures, it points towards a postdigital merger between the managerial paradigm and the cognitive capitalism paradigm. Findings —The paper identifies individual and social tensions between industrial and post-industrial modes of production and rapidly changing dynamic of social development. It examines the relationships between knowledge cultures and digital technologies. Based on recent insights by the father of the World Wide Web Tim Berners-Lee and his non-determinist views to digital technologies, it identifies knowledge cultures as sites of political struggle against various (material and non-material, technological and non-technological) closures over access to information and knowledge. Finally, it briefly outlines possible directions for responding to the postdigital challenge of knowledge cultures. Originality/Value —The paper provides an original contribution to theory of knowledge cultures and its relationships to the postdigital condition.

Abstract By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.

The second law of thermodynamics and the concept of positive entropy generation are analyzed following classical statistical mechanics methods. Previously, using the generalized Boltzmann–Gibbs entropy and its associated general entropy conservation relation, positive entropy generation expressions were obtained in agreement with phenomenological results and the work of Boltzmann and Gibbs. In this study, using the general approach, we formally and explicitly trace the specific entropy generation expressions to truncations in the full N-body description of the entropy state to a lower s-body description. Using higher-order superposition approximations, it is formally shown that the generalized Boltzmann–Gibbs entropy in the s-order state is always less than the corresponding Boltzmann–Gibbs entropy in the lower (s − 1)-order state. Using the general form of the entropy conservation equation, entropy generation is shown to be a required compensatory effect to ensure that all physical variables and physical processes associated with heat, work, temperature, etc., are independent of the particular entropy definition state.

The Omicron variant and its sub-lineages are the only current circulating SARS-CoV-2 viruses worldwide. In this study, the conformational stability of the isolated Receptor Binding Domain (RBD) of Omicron’s spike protein is examined in detail. The parent Omicron lineage has over ten mutations in the ACE2 binding region of the RBD that are specifically associated with its β hairpin loop domain. It is demonstrated through biophysical molecular computations that the mutations in the β hairpin loop domain significantly increase the intra-protein interaction energies of intra-loop and loop–RBD interactions. The interaction energy increases include the formation of new hydrogen bonds in the β hairpin loop domain that help stabilize this critical ACE2 binding region. Our results also agree with recent experiments on the stability of Omicron’s core β barrel domain, outside of its loop domain, and help demonstrate the overall conformational stability of the Omicron RBD. It is further shown here through dynamic simulations that the unbound state of the Omicron RBD remains closely aligned with the bound state configuration, which was not observed for the wild-type RBD. Overall, these studies demonstrate the significantly increased conformational stability of Omicron over its wild-type configuration and raise a number of questions on whether conformational stability could be a positive selection feature of SARS-CoV-2 viral mutational changes.

In tissues and organs, the extracellular matrix (ECM) helps maintain inter- and intracellular architectures that sustain the structure–function relationships defining physiological homeostasis. Combining fiber scaffolds and cells to form engineered tissues is a means of replicating these relationships. Engineered tissues' fiber scaffolds are designed to mimic the topology and chemical composition of the ECM network. Here, we asked how cells found in the heart compare in their propensity to align their cytoskeleton and self-organize in response to topological cues in fibrous scaffolds. We studied cardiomyocytes, valvular interstitial cells, and vascular endothelial cells as they adapted their inter- and intracellular architectures to the extracellular space. We used focused rotary jet spinning to manufacture aligned fibrous scaffolds to mimic the length scale and three-dimensional (3D) nature of the native ECM in the muscular, valvular, and vascular tissues of the heart. The representative cardiovascular cell types were seeded onto fiber scaffolds and infiltrated the fibrous network. We measured different cell types' propensity for cytoskeletal alignment in response to fiber scaffolds with differing levels of anisotropy. The results indicated that valvular interstitial cells on moderately anisotropic substrates have a higher propensity for cytoskeletal alignment than cardiomyocytes and vascular endothelial cells. However, all cell types displayed similar levels of alignment on more extreme (isotropic and highly anisotropic) fiber scaffold organizations. These data suggest that in the hierarchy of signals that dictate the spatiotemporal organization of a tissue, geometric cues within the ECM and cellular networks may homogenize behaviors across cell populations and demographics.

Introduction The SARS-CoV-2 (COVID-19) pandemic overwhelmed some primary health care (PHC) systems, while others adapted and recovered. In Nigeria, large, within-state variations existed in the ability to maintain PHC service volumes. Identifying characteristics of high-performing local government areas (LGAs) can improve understanding of subnational health systems resilience.Methods Employing a sequential explanatory mixed-methods design, we quantitatively identified ‘positive deviant’ LGAs based on their speed of recovery of outpatient and antenatal care services to prepandemic levels using service volume data from Nigeria’s health management information system and matched them to comparators with similar baseline characteristics and slower recoveries. 70 semistructured interviews were conducted with LGA officials, facility officers and community leaders in sampled LGAs to analyse comparisons based on Kruk’s resilience framework.Results A total of 57 LGAs were identified as positive deviants out of 490 eligible LGAs that experienced a temporary decrease in PHC-level outpatient and antenatal care service volumes. Positive deviants had an average of 8.6% higher outpatient service volume than expected, and comparators had 27.1% lower outpatient volume than expected after the initial disruption to services. Informants in 12 positive deviants described health systems that were more integrated, aware and self-regulating than comparator LGAs. Positive deviants were more likely to employ demand-side adaptations, whereas comparators primarily focused on supply-side adaptations. Barriers included long-standing financing and PHC workforce gaps.Conclusion Sufficient flexible financing, adequate PHC staffing and local leadership enabled health systems to recover service volumes during COVID-19. Resilient PHC requires simultaneous attention to bottom-up and top-down capabilities connected by strong leadership.

Abstract The SARS-CoV-2 prefusion spike protein is characterized by a high degree of flexibility and temporal transformations associated with its multifunctional behavior. In this study, we have examined the dynamics of the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein in detail. Its primary, binding subdomain with human Angiotensin Covering Enzyme II includes a highly conspicuous flap or loop that is part of a beta hairpin loop structural motif. Dynamic details of the RBD obtained through RMSF and Order Parameter calculations are consistent with structural details including the stability of “glue” points or dominant interaction energy residues of the RBD in the Up and Down states with its neighboring N-terminal domain (NTD) protomer. The RBD flap in the Up state protomer periodically obstructs the binding site on an approximate 70 ns time interval and is reminiscent of an HIV-1 protease polypeptide flap that opens and closes to modulate that enzymes activity. No claim is made here regarding the possible modulating role of the flap; however, the flap may be a potential site for therapeutic targeting aimed at keeping it in the closed state, as previously demonstrated in the inhibition of the HIV-1 protease polypeptide. The RBD primary binding subdomain is further shown to have not only similar dynamics but, also, an approximate 30% sequence similarity to the HIV-1 protease polypeptide.

Equilibrium, canonical based expressions of entropy are known to exhibit non-local effects that can complicate statistical mechanical formulations and applications. Here, we demonstrate that proper normalization of the underlying probability density functions can remove non-local effects in entropy. Our analysis is carried out through third order in density function expansions and lead to results consistent with macroscopic thermodynamics, as required. In addition, we provide complete expressions for smaller dimensional systems that may not conform to the thermodynamic limit.

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic has had wide-reaching direct and indirect impacts on population health. In low- and middle-income countries, these impacts can halt progress toward reducing maternal and child mortality. This study estimates changes in health services utilization during the pandemic and the associated consequences for maternal, neonatal, and child mortality.Methods and findingsData on service utilization from January 2018 to June 2021 were extracted from health management information systems of 18 low- and lower-middle-income countries (Afghanistan, Bangladesh, Cameroon, Democratic Republic of the Congo (DRC), Ethiopia, Ghana, Guinea, Haiti, Kenya, Liberia, Madagascar, Malawi, Mali, Nigeria, Senegal, Sierra Leone, Somalia, and Uganda). An interrupted time-series design was used to estimate the percent change in the volumes of outpatient consultations and maternal and child health services delivered during the pandemic compared to projected volumes based on prepandemic trends. The Lives Saved Tool mathematical model was used to project the impact of the service utilization disruptions on child and maternal mortality. In addition, the estimated monthly disruptions were also correlated to the monthly number of COVID-19 deaths officially reported, time since the start of the pandemic, and relative severity of mobility restrictions. Across the 18 countries, we estimate an average decline in OPD volume of 13.1% and average declines of 2.6% to 4.6% for maternal and child services. We projected that decreases in essential health service utilization between March 2020 and June 2021 were associated with 113,962 excess deaths (110,686 children under 5, and 3,276 mothers), representing 3.6% and 1.5% increases in child and maternal mortality, respectively. This excess mortality is associated with the decline in utilization of the essential health services included in the analysis, but the utilization shortfalls vary substantially between countries, health services, and over time. The largest disruptions, associated with 27.5% of the excess deaths, occurred during the second quarter of 2020, regardless of whether countries reported the highest rate of COVID-19-related mortality during the same months. There is a significant relationship between the magnitude of service disruptions and the stringency of mobility restrictions. The study is limited by the extent to which administrative data, which varies in quality across countries, can accurately capture the changes in service coverage in the population.ConclusionsDeclines in healthcare utilization during the COVID-19 pandemic amplified the pandemic's harmful impacts on health outcomes and threaten to reverse gains in reducing maternal and child mortality. As efforts and resource allocation toward prevention and treatment of COVID-19 continue, essential health services must be maintained, particularly in low- and middle-income countries.

Effective management of hypertension in low- and middle-income settings is a persistent public health challenge. This study examined supply- and demand-side barriers to receiving quality care and achieving effective hypertension management in rural Bihar, India. A state-representative household survey collected information from adults over 30 years of age on characteristics of the hypertension screening, diagnosis, and management services they received. A linked provider assessment determined the percent of providers who provided quality hypertension care (i.e., had a functioning BP measurement device, measured a patient's BP, could correctly diagnose hypertension, had at least one first-line antihypertension medication, and could prescribe correctly based on standard guidelines). Patients were linked with their provider to determine the quality-adjusted coverage of hypertension management and logistic regression analysis was conducted to determine characteristics associated with receiving quality care. A total of 14,386 patients and 390 providers were studied. Nearly a quarter (22.5%) of adults had never had their BP measured before and 8.1% of adults reported a previous hypertension diagnosis. Less than one third (31.0%) of all interviewed providers demonstrated ability to provide quality hypertension care, and quality varied between provider types (14.8% of private homeopathic, 25.2% of informal, 40.0% of private modern medicine, and 60.0% of public providers gave quality care). While 95.8% of diagnosed individuals received some treatment, only 10.9% of patients received care from quality local providers. Nearly 45% of individuals with hypertension received care from non-local providers. Individuals from the general caste with comorbidities living in villages with more high-quality providers were most likely to receive quality care from a local provider. Whereas the coverage of services for individuals diagnosed with hypertension is high, the quality of these services is suboptimal for economically and socially vulnerable populations, which limits effective management and control of hypertension in rural Bihar. Efforts should be targeted towards providers to initiate quality treatment upon diagnosis, including correct prescription of antihypertensives.

ABSTRACT Monitoring and strategic response to variants in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent a considerable challenge in the current pandemic and for future viral outbreaks. Mutations/deletions of the virion’s prefusion Spike protein may have significant impact on vaccines and therapeutics that utilize this key structural protein in their mitigation strategies. In this study, we have demonstrated how dominant energetic landscape mappings (“glue points”) based on ab inito all-atom force fields coupled with phylogenetic sequence alignment information can identify key residue mutations and deletions associated with variants. We also found several examples of excellent homology of stabilizing residue glue points across the lineages of betacoronavirus Spike proteins that we have called “sequence homologous glue points.” SARS-CoV-2 demonstrates the least number of stabilizing glue points associated with interchain interactions among Down-state protomers across lineages. Additionally, we computationally studied variants among the trimeric Spike protein of SARS-CoV-2 using all-atom molecular dynamics to ascertain structural and energetic changes among variants. We examined both a theoretically based triple mutant and the UK or B.1.1.7 variant. For the theoretical triple mutant, we demonstrated through alanine substitutions that three key residues could cause the transition of Down-to-Up protomer states, where the transition is characterized by the “arm” length of the receptor-binding domain (RBD) rather than the hinge angle. For the B.1.1.7 variant, we demonstrated the critical importance of mutations D614G and N501Y on the structure and binding, respectively, of the Spike protein. We note that these same two key mutations are also found in the South African B.1.351 variant. IMPORTANCE Viral variants represent a major challenge to monitoring viral outbreaks and formulating strategic health care responses. Variants represent transmitting viruses that have specific mutations and deletions associated with their genome. In the case of SARS-CoV-2 and other related viruses (betacoronaviruses), many of these mutations and deletions are associated with the Spike protein that the virus uses to infect cells. Here, we have analyzed both SARS-CoV-2 variants and related viruses, such as Middle Eastern respiratory syndrome coronavirus (MERS-CoV), in order to understand not only differences, but also key similarities between them. Understanding similarities can be as important as differences in determining key functional features of a class of viruses, such as the betacoronaviruses. We have used both phylogenetic analysis, which traces genetic similarities and differences, along with independent biophysics analysis, which adds function or behavior, in order to determine possible functional differences and hence possible transmission and infection differences among variants and lineages.

Objectives Responding to pandemics is challenging in pluralistic health systems. This study assesses COVID-19 knowledge and case management of informal providers (IPs), trained practitioners of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homeopathy (AYUSH) and Bachelor of Medicine, Bachelor of Surgery (MBBS) medical doctors providing primary care services in rural Bihar, India.Design This was a cross-sectional study of primary care providers conducted via telephone between 1 and 15 July 2020.Setting Primary care providers from 224 villages in 34 districts across Bihar, India.Participants 452 IPs, 57 AYUSH practitioners and 38 doctors (including 23 government doctors) were interviewed from a census of 1138 primary care providers used by community members that could be reached by telephone.Primary outcome measure(s) Providers were interviewed using a structured questionnaire with choice-based answers to gather information on (1) change in patient care seeking, (2) source of COVID-19 information, (3) knowledge on COVID-19 spread, symptoms and methods for prevention and (4) clinical management of COVID-19.Results During the early days of the COVID-19 pandemic, 72% of providers reported a decrease in patient visits. Most IPs and other private primary care providers reported receiving no COVID-19 related engagement with government or civil society agencies. For them, the principal source of COVID-19 information was television and newspapers. IPs had reasonably good knowledge of typical COVID-19 symptoms and prevention, and at levels similar to doctors. However, there was low stated compliance among IPs (16%) and qualified primary care providers (15% of MBBS doctors and 12% of AYUSH practitioners) with all WHO recommended management practices for suspect COVID-19 cases. Nearly half of IPs and other providers intended to treat COVID-19 suspects without referral.Conclusions Poor management practices of COVID-19 suspects by rural primary care providers weakens government pandemic control efforts. Government action of providing information to IPs, as well as engaging them in contact tracing or public health messaging can strengthen pandemic control efforts.

The SARS-CoV-2 virion responsible for the current world-wide pandemic COVID-19 has a characteristic Spike protein (S) on its surface that embellishes both a prefusion state and fusion state. The prefusion Spike protein (S) is a large trimeric protein where each protomer may be in a so-called Up state or Down state, depending on the configuration of its receptor binding domain (RBD) within its distal, prefusion S1 domain. The Up state is believed to allow binding of the virion to ACE-2 receptors on human epithelial cells, whereas the Down state is believed to be relatively inactive or reduced in its binding behavior. We have performed detailed all-atom, dominant energy landscape mappings for noncovalent interactions (charge, partial charge, and van der Waals) of the SARS-CoV-2 Spike protein in its static prefusion state based on two recent and independent experimental structure publications. We included both interchain interactions and intrachain (domain) interactions in our mappings in order to determine any telling differences (different so-called "glue" points) between residues in the Up and Down state protomers. The S2 proximal, fusion domain demonstrated no appreciable energetic differences between Up and Down protomers, including interchain as well as each protomer's intrachain, S1-S2 interactions. However, the S1 domain interactions across neighboring protomers, which include the RBD-NTD cross chain interactions, showed significant energetic differences between Up-Down and Down-Down neighboring protomers. This included, for example, a key RBD residue ARG357 in the Up-Down interaction and a three residue sequence ALA520-PRO521-ALA522, associated with a turn structure in the RBD of the Up state protomer, acting as a stabilizing interaction with the NTD of its neighbor protomer. Additionally, our intra chain dominant energy mappings within each protomer, identified a significant "glue" point or possible "latch" for the Down state protomer between the S1 subdomain, SD1, and the RBD domain of the same protomer that was completely missing in the Up state protomer analysis. Ironically, this dominant energetic interaction in the Down state protomer involved the backbone atoms of the same three residue sequence ALA520-PRO521-ALA522 of the RBD with the amino acid R-group of GLN564 in the SD1 domain. Thus, this same three residue sequence acts as a stabilizer of the RBD in the Up conformation through its interactions with its neighboring NTD chain and a kind of latch in the Down state conformation through its interactions with its own SD1 domain. The dominant interaction energy residues identified here are also conserved across reported variations of SARS-CoV-2, as well as the closely related virions SARS-Cov and the bat corona virus RatG13. We conducted preliminary molecular dynamics simulations across 0.1 μ seconds to see if this latch provided structural stability and indeed found that a single point mutation (Q564G) resulted in the latch releasing transforming the protomer from the Down to the Up state conformation. Full trimeric Spike protein studies of the same mutation across all protomers, however, did not exhibit latch release demonstrating the critical importance of interchain interactions across the S1 domain, including RBD-NTD neighboring chain interactions. Therapies aimed at disrupting these noncovalent interactions could be a viable route for the physico-chemical mitigation of this deadly virion.

In this study, we propose a mesh-free (particle-based) Smoothed Particle Hydrodynamics model for simulating a Rayleigh collapse. Both empty and gas cavities are investigates and the role of heat diffusion is also accounted for. The system behaves very differently according to the ratio between the characteristic time of collapse and the characteristic time of thermal diffusion. This study identifies five different possible behaviours that range from isothermal to adiabatic.

Nonequilibrium statistical mechanics or molecular theory has put the transport equations of mass, momentum and energy on a firm or rigorous theoretical foundation that has played a critical role in their use and applications. Here, it is shown that those methods can be extended to nonequilibrium entropy conservation. As already known, the “closure” of the transport equations leads to the theory underlying the phenomenological laws, including Fick’s Law of Diffusion, Newton’s Law of Viscosity, and Fourier’s Law of Heat. In the case of entropy, closure leads to the relationship of entropy flux to heat as well as the Second Law or the necessity of positive entropy generation. It is further demonstrated how the complete set of transport equations, including entropy, can be simplified under physically restrictive assumptions, such as reversible flows and local equilibrium flows. This analysis, in general, yields a complete, rigorous set of transport equations for use in applications. Finally, it is also shown how this basis set of transport equations can be transformed to a new set of nonequilibrium thermodynamic functions, such as the nonequilibrium Gibbs’ transport equation derived here, which may have additional practical utility.

Hemogen is a vertebrate transcription factor that performs important functions in erythropoiesis and testicular development and may contribute to neoplasia. Here we identify zebrafish Hemogen and show that it is considerably smaller (∼22 kDa) than its human ortholog (∼55 kDa), a striking difference that is explained by an underlying modular structure. We demonstrate that Hemogens are largely composed of 21-25 amino acid repeats, some of which may function as transactivation domains (TADs). Hemogen expression in embryonic and adult zebrafish is detected in hematopoietic, renal, neural and gonadal tissues. Using Tol2- and CRISPR/Cas9-generated transgenic zebrafish, we show that Hemogen expression is controlled by two Gata1-dependent regulatory sequences that act alone and together to control spatial and temporal expression during development. Partial depletion of Hemogen in embryos by morpholino knockdown reduces the number of erythrocytes in circulation. CRISPR/Cas9-generated zebrafish lines containing either a frameshift mutation or an in-frame deletion in a putative, C-terminal TAD display anemia and embryonic tail defects. This work expands our understanding of Hemogen and provides mutant zebrafish lines for future study of the mechanism of this important transcription factor.

In this study, we generalize our previous methods for obtaining entropy generation in gases without the need to carry through a specific expansion method, such as the Chapman–Enskog method. The generalization, which is based on a scaling analysis, allows for the study of entropy generation in gases for any arbitrary state of the gas and consistently across the conservation equations of mass, momentum, energy, and entropy. Thus, it is shown that it is theoretically possible to alter specific expressions and associated physical outcomes for entropy generation by changing the operating process gas state to regions significantly different than the perturbed, local equilibrium or Chapman–Enskog type state. Such flows could include, for example, hypersonic flows or flows that may be generally called hyper-equilibrium state flows. Our formal scaling analysis also provides partial insight into the nature of entropy generation from an informatics perspective, where we specifically demonstrate the association of entropy generation in gases with uncertainty generated by the approximation error associated with density function expansions.

Information on nonbreeding waterbirds using created wetlands in the Central Appalachian region of the United States is limited. We compared waterbird communities of two managed wetlands, created in 2013 and 2001, in West Virginia. We observed 27 species of waterbirds. Species richness and diversity were generally similar between the wetlands, but species composition and use differed. Branta canadensis (Canada Geese), Anas strepera (Gadwall), Bucephala albeola (Buffleheads), Aythya affinis (Lesser Scaup), and Aythya collaris (Ring-Necked Ducks) used the older wetland most frequently. Disparities in species use were the highest in March. The older wetland differed from the younger in supporting species such as diving ducks, possibly due to differences in size, vegetation, water depth, and microtopography. However, the ability to provide habitat for waterbirds during the winter was determined to be comparable between wetlands, despite their age difference.