Chemoproteomics Identifies State-Dependent and Proteoform-Selective Caspase-2 Inhibitors.

Caspases are a highly conserved family of cysteine-aspartyl proteases known for their essential roles in regulating apoptosis, inflammation, cell differentiation, and proliferation. Complementary to genetic approaches, small-molecule probes have emerged as useful tools for modulating caspase activity. However, due to the high sequence and structure homology of all 12 human caspases, achieving selectivity remains a central challenge for caspase-directed small-molecule inhibitor development efforts. Here, using mass spectrometry-based chemoproteomics, we first identify a highly reactive noncatalytic cysteine that is unique to caspase-2. By combining both gel-based activity-based protein profiling (ABPP) and a tobacco etch virus (TEV) protease activation assay, we then identify covalent lead compounds that react preferentially with this cysteine and afford a complete blockade of caspase-2 activity. Inhibitory activity is restricted to the zymogen or precursor form of monomeric caspase-2. Focused analogue synthesis combined with chemoproteomic target engagement analysis in cellular lysates and in cells yielded both pan-caspase-reactive molecules and caspase-2 selective lead compounds together with a structurally matched inactive control. Application of this focused set of tool compounds to stratify the functions of the zymogen and partially processed (p32) forms of caspase-2 provide evidence to support that caspase-2-mediated response to DNA damage is largely driven by the partially processed p32 form of the enzyme. More broadly, our study highlights future opportunities for the development of proteoform-selective caspase inhibitors that target nonconserved and noncatalytic cysteine residues.

Heritability of complex traits in sub-populations experiencing bottlenecks and growth.

Populations that have experienced a bottleneck are regularly used in Genome Wide Association Studies (GWAS) to investigate variants associated with complex traits. It is generally understood that these isolated sub-populations may experience high frequency of otherwise rare variants with large effect size, and therefore provide a unique opportunity to study said trait. However, the demographic history of the population under investigation affects all SNPs that determine the complex trait genome-wide, changing its heritability and genetic architecture. We use a simulation based approach to identify the impact of the demographic processes of drift, expansion, and migration on the heritability of complex trait. We show that demography has considerable impact on complex traits. We then investigate the power to resolve heritability of complex traits in GWAS studies subjected to demographic effects. We find that demography is an important component for interpreting inference of complex traits and has a nuanced impact on the power of GWAS. We conclude that demographic histories need to be explicitly modelled to properly quantify the history of selection on a complex trait.

Reported reasons for non-use of insecticide-treated nets in large national household surveys, 2009-2021.

BACKGROUND: Insecticide-treated nets (ITN) are the cornerstone of modern malaria vector control, with nearly 3 billion ITNs delivered to households in endemic areas since 2000. ITN access, i.e. availability within the household, based on the number of ITNs and number of household members, is a pre-requisite for ITN use. Factors determining ITN use are frequently examined in published literature, but to date, large household survey data on reasons given for non-use of nets have not been explored. METHODS: A total of 156 DHS, MIS, and MICS surveys conducted between 2003 and 2021 were reviewed for questions on reasons why nets were not used the previous night, identifying twenty-seven surveys. The percent of nets that were reported used the previous night was calculated for the 156 surveys, and frequencies and proportions of reasons for non-use were calculated within the twenty-seven surveys. Results were stratified by household supply of ITNs in three categories (not enough", "enough", and "more than enough") and by residence (urban/rural). RESULTS: The proportion of nets used the previous night averaged over 70% between 2003 and 2021, with no discernible change over this period. Reported reasons for why a net goes unused fell largely into three categories-nets that are extra/being saved for future use; the perception that there is little risk of malaria (particularly in dry season); and "other" responses. Net attributes such as colour, size, shape, and texture, and concerns related to chemicals were the least frequent reasons given. Reasons for non-use of nets varied by household net supply, and in some surveys by residence. In Senegal's continuous DHS, the proportion of nets used peaked during high transmission season, and the proportion of nets that went unused due to "no/few mosquitoes" peaked during the dry season. CONCLUSIONS: Unused nets were primarily those being saved for later use, or were not used due to perceived low risk of malaria. Classifying reasons for non-use into broader categories facilitates the design of appropriate social and behaviour change interventions to address the major underlying reasons for non-use, where this is feasible.

Wettability-tuned silica particles for emulsion-templated microcapsules.

Pickering emulsions play a significant role in generating advanced materials and have widespread application in personal care products, consumer goods, crude oil refining, energy management, etc. Herein, we report a class of wettability tuned silica-based Pickering emulsifiers which stabilize a diverse range of fluid-fluid interfaces: oil/water, ionic liquid/oil, and oil/oil, and their use to prepare microcapsules via interfacial polymerization. To alter particle wettability, colloidal suspensions of SiO2 particles (22 nm) were modified via silanization with reagents of varied hydrophilicity/hydrophobicity, giving particles that could be dispersed in solvents that became the continuous phase of the emulsions. To test the viability of this system as templates for the fabrication of composite materials, the different particle-stabilized emulsions were coupled with interfacial polymerization, leading to microcapsules with polyurea/silica shells. These results demonstrate that a single particle feedstock can be coupled with fundamental chemical transformation to access a versatile toolkit for the stabilization of diverse fluid interfaces and serve as a template for the preparation of hybrid architectures.

Microgrewiapine C: Asymmetric Synthesis, Spectroscopic Data, and Configuration Assignment.

The first asymmetric synthesis of microgrewiapine C, a piperidine alkaloid isolated from Microcos paniculata, is reported. This synthesis prompted correction of the 1H and 13C NMR data for the natural sample of the alkaloid, which was achieved by reanalysis of the original spectra. The corrected data for the natural product were found to be identical to those of the synthetic sample prepared herein, thus confirming the structural and relative configurational assignment of microgrewiapine C. Although comparison of specific rotation values indicates that the (1R,2S,3S,6S) absolute configuration should be assigned to the alkaloid, consideration of potential common biosynthetic origins of microgrewiapine C and congeners suggests that further phytochemical investigations are warranted.

Synthesis and Configuration of O-Acetyl Microgrewiapine A: Phantomization of O-Acetyl 6-epi-Microgrewiapine A.

The formation of O-acetyl microgrewiapine A is investigated. NMR data for the authentic sample derived from the natural product are corrected. Wholly synthetic samples, produced from reductive N-methylation of synthetic microcosamine A (to give synthetic microgrewiapine A) followed by O-acetylation, exhibit NMR data that are identical to those of the authentic sample. The previous report that this two-step transformation proceeds with epimerization at C-6 is thus shown to be in error: the purported sample of O-acetyl 6-epi-microgrewiapine A is structurally misassigned and is, in fact, O-acetyl microgrewiapine A. A plausible rationale for the structural misassignment is advanced.

ED 90 of Intrathecal Chloroprocaine With Fentanyl for Prophylactic Cervical Cerclage: A Sequential Allocation Biased-Coin Design.

BACKGROUND: Chloroprocaine is a short-acting local anesthetic that has been used for spinal anesthesia in outpatient surgery. There is limited experience with spinal chloroprocaine for prophylactic cervical cerclage placement. We sought to determine the effective dose of intrathecal chloroprocaine for 90% of patients (ED90) undergoing prophylactic cervical cerclage placement. We hypothesized that the ED90 of intrathecal chloroprocaine when combined with 10-ug fentanyl would be between 33 and 54 mg. METHODS: In this prospective 2-center double-blinded study, we enrolled women undergoing prophylactic cervical cerclage placement under combined spinal-epidural anesthesia. A predetermined dose of intrathecal 3% chloroprocaine with fentanyl 10 ug was administered. The initial dose was 45-mg intrathecal chloroprocaine. Subsequent dose adjustments were determined based on the response of the previous subject using an up-down sequential allocation with a biased-coin design. A dose was considered effective if at least a T12 block was achieved, and there was no requirement for epidural activation or intraoperative analgesic supplementation during the procedure. The primary outcome was the ED90 of intrathecal chloroprocaine with fentanyl 10 ug. Secondary outcomes included duration of surgery, anesthetic side effects, time to resolution of motor and sensory block, time to achieve recovery room discharge criteria, and patient satisfaction with anesthetic care. Isotonic regression was used to estimate the ED90. RESULTS: Forty-seven patients were enrolled into the study. Two patients were excluded (1 protocol violation and 1 failed block). In total, 45 patients completed the study. The estimated ED90 (95% confidence interval) for intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg (45.0-50.1 mg). The median (interquartile range [IQR]) duration of surgery was 15 (10-24) minutes. Resolution of the motor (Bromage 0) and sensory block took a median time of 60 (45-90) minutes and 90 (75-105) minutes, respectively. The median time to achieve recovery room discharge criteria was 150 (139-186) minutes. Satisfaction with anesthetic management was high in all patients. There were no reports of postdural puncture headache or transient neurological symptoms postoperatively. CONCLUSIONS: The ED90 of intrathecal chloroprocaine combined with fentanyl 10 ug was 49.5 mg. Intrathecal chloroprocaine was associated with rapid block recovery and high patient satisfaction, which makes it well suited for outpatient obstetric procedures.

Uterine exteriorization versus in situ repair in Cesarean delivery: a systematic review and meta-analysis.

PURPOSE: We conducted an updated systematic review and meta-analysis on maternal outcomes associated with uterine exteriorization compared with in situ repair in women undergoing Cesarean delivery. METHODS: We searched for randomized controlled trials comparing uterine exteriorization with in situ repair during Cesarean delivery. Primary outcomes were intraoperative nausea and vomiting (IONV) and perioperative decrease in hemoglobin concentration. Secondary outcomes were postoperative nausea and vomiting (PONV), estimated blood loss, fever, endometritis, wound infection, intraoperative and postoperative pain, postoperative analgesic use, duration of surgery and hospital stay, and time to return of bowel function. RESULTS: Twenty studies with 20,909 parturients were included. Exteriorization was associated with higher risk of IONV (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.66 to 2.63; I2 = 0%), with no difference in perioperative hemoglobin concentration decrease (mean difference, - 0.06 g·dL-1; 95% CI, - 0.20 to 0.08; I2 = 97%) compared with in situ repair. There were no significant differences in estimated blood loss, transfusion requirement, PONV, duration of surgery, duration of hospital stay, time to return of bowel function, fever, endometritis, or wound infection. Postoperative pain (incidence of pain graded > 5/10) at six hours (OR, 1.64; 95% CI, 1.31 to 2.03; I2 = 0%) was higher with exteriorization, but there was no difference in need for rescue analgesia (OR, 2.48; 95% CI, 0.89 to 6.90; I2 = 94%) or pain scores at 24 hr compared with in situ repair. CONCLUSIONS: In this updated systematic review and meta-analysis, uterine exteriorization was associated with an increased risk of IONV but no significant change in perioperative hemoglobin decrease compared with in situ repair. STUDY REGISTRATION: PROSPERO (CRD42020190074); registered 5 July 2020.

RéSUMé: OBJECTIF: Nous avons réalisé une mise à jour d'une revue systématique et une méta-analyse portant sur les issues maternelles associées à l'extériorisation de l'utérus par rapport à une réparation in situ chez les femmes accouchant par césarienne. MéTHODE: Nous avons recherché des études randomisées contrôlées comparant l'extériorisation de l'utérus à la réparation in situ pendant un accouchement par césarienne. Les critères d'évaluation principaux étaient les nausées et vomissements peropératoires (NVPerO) et la réduction périopératoire de l'hémoglobine. Les critères d'évaluation secondaires étaient les nausées et vomissements postopératoires (NVPO), la perte de sang estimée, la fièvre, l'endométrite, l'infection de la plaie, la douleur per- et postopératoire, l'utilisation d'analgésiques postopératoires, la durée de la chirurgie et du séjour à l'hôpital, et le délai jusqu'au retour du transit. RéSULTATS: Vingt études portant sur 20 909 parturientes ont été incluses. L'extériorisation était associée à un risque plus élevé de NVPerO (rapport de cotes [RC], 2,09; intervalle de confiance à 95 % [IC], 1,66 à 2,63; I2 = 0 %), sans différence dans la réduction de l'hémoglobine périopératoire (différence moyenne, − 0,06 g·dL-1; IC 95 %, − 0,20 à 0,08; I2 = 97 %) par rapport à une réparation in situ. Il n'y avait pas de différences significatives dans la perte de sang estimée, les besoins transfusionnels, les NVPO, la durée de la chirurgie, la durée du séjour à l'hôpital, le délai jusqu'au retour du transit, la fièvre, l'endométrite ou l'infection de la plaie. La douleur postopératoire (incidence de la douleur graduée > 5/10) à six heures (RC, 1,64; IC 95 %, 1,31 à 2,03; I2 = 0 %) était plus élevée avec une extériorisation, mais il n'y avait aucune différence dans les besoins d'analgésie de secours (RC, 2,48; IC 95 %, 0,89 à 6,90; I2 = 94 %) ou les scores de douleur à 24 heures par rapport à une réparation in situ. CONCLUSION: Dans cette revue systématique et méta-analyse mises à jour, l'extériorisation utérine était associée à un risque accru de NVPerO, mais à aucun changement significatif dans la réduction de l'hémoglobine périopératoire par rapport à la réparation in situ. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020190074); enregistrée le 5 juillet 2020.

Examination of malaria service utilization and service provision: an analysis of DHS and SPA data from Malawi, Senegal, and Tanzania.

BACKGROUND: Ensuring universal access to malaria diagnosis and treatment is a key component of Pillar 1 of the World Health Organization Global Technical Strategy for Malaria 2016-2030. To achieve this goal it is essential to know the types of facilities where the population seeks care as well as the malaria service readiness of these facilities in endemic countries. METHODS: To investigate the utilization and provision of malaria services, data on the sources of advice or treatment in children under 5 years with fever from the household-based Demographic and Health Surveys (DHS) and on the components of malaria service readiness from the facility-based Service Provision Assessment (SPA) surveys were examined in Malawi, Senegal and Tanzania. Facilities categorized as malaria-service ready were those with: (1) personnel trained in either malaria rapid diagnostic testing (RDT), microscopy or case management/treatment of malaria in children; (2) national guidelines for the diagnosis and treatment of malaria; (3) diagnostic capacity (available RDT tests or microscopy equipment as well as staff trained in its use); and, (4) unexpired artemisinin-based combination therapy (ACT) available on the day of the survey. RESULTS: In all three countries primary-level facilities (health centre/health post/health clinic) were the type of facility most used for care of febrile children. However, only 69% of these facilities in Senegal, 32% in Malawi and 19% in Tanzania were classified as malaria-service ready. Of the four components of malaria-service readiness in the facilities most frequented by febrile children, diagnostic capacity was the weakest area in all three countries, followed by trained personnel. All three countries performed well in the availability of ACT. CONCLUSIONS: This analysis highlights the need to improve the malaria-service readiness of facilities in all three countries. More effort should be focused on facilities that are commonly used for care of fever, especially in the areas of malaria diagnostic capacity and provider training. It is essential for policymakers to consider the malaria-service readiness of primary healthcare facilities when allocating resources. This is particularly important in limited-resource settings to ensure that the facilities most visited for care are properly equipped to provide diagnosis and treatment for malaria.

Measuring malaria diagnosis and treatment coverage in population-based surveys: a recall validation study in Mali among caregivers of febrile children under 5 years.

BACKGROUND: Nationally-representative household surveys are the standard approach to monitor access to and treatment with artemisinin-based combination therapy (ACT) among children under 5 years (U5), however these indicators are dependent on caregivers' recall of the treatment received. METHODS: A prospective case-control study was performed in Mali to validate caregivers' recall of treatment received by U5s when seeking care for fever from rural and urban public health facilities, community health workers and urban private facilities. Clinician-recorded consultation details were the gold standard. Consenting caregivers were followed-up for interview at home within 2 weeks using standard questions from Demographic and Health Surveys and Malaria Indicator Surveys. RESULTS: Among 1602 caregivers, sensitivity of recalling that the child received a finger/heel prick was 91.5%, with specificity 85.7%. Caregivers' recall of a positive malaria test result had sensitivity 96.2% with specificity 59.7%. Irrespective of diagnostic test result, the sensitivity and specificity of caregivers' recalling a malaria diagnosis made by the health worker were 74.3% and 74.9%, respectively. Caregivers' recall of ACT being given had sensitivity of 43.2% and specificity 90.2%, while recall that any anti-malarial was given had sensitivity 59.0% and specificity 82.7%. Correcting caregivers' response of treatment received using a combination of a visual aid with photographs of common drugs for fever, prescription documents and retained packaging changed ACT recall sensitivity and specificity to 91.5% and 71.1%, respectively. CONCLUSIONS: These findings indicate that caregivers' responses during household surveys are valid when assessing if a child received a finger/heel prick during a consultation in the previous 2 weeks, and if the malaria test result was positive. Recall of ACT treatment received by U5s was poor when based on interview response only, but was substantially improved when incorporating visual aids, prescriptions and drug packaging review.

Consultative meeting that examined alignment and discrepancies between health facility and household survey data in Malawi.

Malawi is midway through its current Malaria Strategic Plan 2017-2022, which aims to reduce malaria incidence and deaths by at least 50% by 2022. Malariometric data are available with health surveillance data housed in District Health Information Software 2 (DHIS2) and household survey data from two recent Malaria Indicator Surveys (MIS) and a Demographic and Health Survey (DHS). Strengths and weaknesses of the data were discussed during a consultative meeting in Lilongwe, Malawi in July 2019. The first 3 days included in-depth exploration and analysis of surveillance and survey data by 13 participants from the National Malaria Control Programme, district health offices, and partner organizations. Key indicators derived from both DHIS2 and MIS/DHS sources were analysed with three case studies, and presented to stakeholders on the fourth day of the meeting. Applications of the findings to programmatic decision-making and strategic plan evaluation were critiqued and discussed.

A stakeholder workshop about modelled maps of key malaria indicator survey indicators in Madagascar.

The Demographic and Health Surveys (DHS) Program has supported three household Malaria Indicator Surveys (MIS) in Madagascar. The results of 13 key malaria indicators from these surveys have been mapped as continuous surfaces using model-based geostatistical methods. The opportunities and limitations of these mapped outputs were discussed during a workshop in Antananarivo, Madagascar in July 2018, attended by 15 representatives from various implementation, policy and research stakeholder institutions in Madagascar. Participants evaluated the findings from the maps, using these to develop figures and narratives to support their work in the control of malaria in Madagascar.

Assessing whether universal coverage with insecticide-treated nets has been achieved: is the right indicator being used?

BACKGROUND/METHODS: Insecticide-treated nets (ITNs) are the primary tool for malaria vector control in sub-Saharan Africa, and have been responsible for an estimated two-thirds of the reduction in the global burden of malaria in recent years. While the ultimate goal is high levels of ITN use to confer protection against infected mosquitoes, it is widely accepted that ITN use must be understood in the context of ITN availability. However, despite nearly a decade of universal coverage campaigns, no country has achieved a measured level of 80% of households owning 1 ITN for 2 people in a national survey. Eighty-six public datasets from 33 countries in sub-Saharan Africa (2005-2017) were used to explore the causes of failure to achieve universal coverage at the household level, understand the relationships between the various ITN indicators, and further define their respective programmatic utility. RESULTS: The proportion of households owning 1 ITN for 2 people did not exceed 60% at the national level in any survey, except in Uganda's 2014 Malaria Indicator Survey (MIS). At 80% population ITN access, the expected proportion of households with 1 ITN for 2 people is only 60% (p = 0.003 R2 = 0.92), because individuals in households with some but not enough ITNs are captured as having access, but the household does not qualify as having 1 ITN for 2 people. Among households with 7-9 people, mean population ITN access was 41.0% (95% CI 36.5-45.6), whereas only 6.2% (95% CI 4.0-8.3) of these same households owned at least 1 ITN for 2 people. On average, 60% of the individual protection measured by the population access indicator is obscured when focus is put on the household "universal coverage" indicator. The practice of limiting households to a maximum number of ITNs in mass campaigns severely restricts the ability of large households to obtain enough ITNs for their entire family. CONCLUSIONS: The two household-level indicators-one representing minimal coverage, the other only 'universal' coverage-provide an incomplete and potentially misleading picture of personal protection and the success of an ITN distribution programme. Under current ITN distribution strategies, the global malaria community cannot expect countries to reach 80% of households owning 1 ITN for 2 people at a national level. When programmes assess the success of ITN distribution activities, population access to ITNs should be considered as the better indicator of "universal coverage," because it is based on people as the unit of analysis.

Equity trends in ownership of insecticide-treated nets in 19 sub-Saharan African countries.

OBJECTIVE: To examine the change in equity of insecticide-treated net (ITN) ownership among 19 malaria-endemic countries in sub-Saharan Africa before and after the launch of the Cover The Bed Net Gap initiative. METHODS: To assess change in equity in ownership of at least one ITN by households from different wealth quintiles, we used data from Demographic and Health Surveys and Malaria Indicator Surveys. We assigned surveys conducted before the launch (2003-2008) as baseline surveys and surveys conducted between 2009-2014 as endpoint surveys. We did country-level and pooled multicountry analyses. Pooled analyses based on malaria transmission risk, were done by dividing geographical zones into either low- and intermediate-risk or high-risk. To assess changes in equity, we calculated the Lorenz concentration curve and concentration index (C-index). FINDINGS: Out of the 19 countries we assessed, 13 countries showed improved equity between baseline and endpoint surveys and two countries showed no changes. Four countries displayed worsened equity, two favouring the poorer households and two favouring the richer. The multicountry pooled analysis showed an improvement in equity (baseline survey C-index: 0.11; 95% confidence interval, CI: 0.10 to 0.11; and endpoint survey C-index: 0.00; 95% CI: -0.01 to 0.00). Similar trends were seen in both low- and intermediate-risk and high-risk zones. CONCLUSION: The mass ITN distribution campaigns to increase coverage, linked to the launch of the Cover The Bed Net Gap initiative, have led to improvement in coverage of ITN ownership across sub-Saharan Africa with significant reduction in inequity among wealth quintiles.

Interventions to improve adherence to cardiovascular disease guidelines: a systematic review.

BACKGROUND: Successful management of cardiovascular disease (CVD) is impaired by poor adherence to clinical practice guidelines. The objective of our review was to synthesize evidence about the effectiveness of interventions that target healthcare providers to improve adherence to CVD guidelines and patient outcomes. METHODS: We searched PubMed, EMBASE, Cochrane Library, PsycINFO, Web of Science and CINAHL databases from inception to June 2014, using search terms related to adherence and clinical practice guidelines. Studies were limited to randomized controlled trials testing an intervention to improve adherence to guidelines that measured both a patient and adherence outcome. Descriptive summary tables were created from data extractions. Meta-analyses were conducted on clinically homogeneous comparisons, and sensitivity analyses and subgroup analyses were carried out where possible. GRADE summary of findings tables were created for each comparison and outcome. RESULTS AND DISCUSSION: We included 38 RCTs in our review. Interventions included guideline dissemination, education, audit and feedback, and academic detailing. Meta-analyses were conducted for several outcomes by intervention type. Many comparisons favoured the intervention, though only the adherence outcome for the education intervention showed statistically significant improvement compared to usual care (standardized mean difference = 0.58 [95 % confidence interval 0.35 to 0.8]). CONCLUSIONS: Many interventions show promise to improve practitioner adherence to CVD guidelines. The quality of evidence and number of trials limited our ability to draw conclusions.

Ionic Liquid-Glycol Mixtures for Direct Air Capture of CO2: Decreased Viscosity and Mitigation of Evaporation Via Encapsulation.

Herein we address the efficiency of the CO2 sorption of ionic liquids (IL) with hydrogen bond donors (e.g., glycols) added as viscosity modifiers and the impact of encapsulating them to limit sorbent evaporation under conditions for the direct air capture of CO2. Ethylene glycol, propylene glycol, 1,3-propanediol, and diethylene glycol were added to three different ILs: 1-ethyl-3-methylimidazolium 2-cyanopyrrolide ([EMIM][2-CNpyr]), 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM][BF4]), and 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]). Incorporation of the glycols decreased viscosity by an average of 51% compared to bulk IL. After encapsulation of the liquid mixtures using a soft template approach, thermogravimetric analysis revealed average reductions in volatility of 36 and 40% compared to the unencapsulated liquid mixtures, based on 1 h isothermal experiments at 25 and 55 °C, respectively. The encapsulated mixtures of [EMIM][2-CNpyr]/1,3-propanediol and [EMIM][2-CNpyr]/diethylene glycol exhibited the lowest volatility (0.0019 and 0.0002 mmol/h at 25 °C, respectively) and were further evaluated as CO2 absorption/desorption materials. Based on the capacity determined from breakthrough measurements, [EMIM][2-CNpyr]/1,3-propanediol had a lower transport limited absorption rate for CO2 sorption compared to [EMIM][2-CNpyr]/diethylene glycol with 0.08 and 0.03 mol CO2/kg sorbent, respectively; however, [EMIM][2-CNpyr]/diethylene glycol capsules exhibited higher absorptions capacity at ∼500 ppm of CO2 (0.66 compared to 0.47 mol of CO2/kg sorbent for [EMIM][2-CNpyr]/1,3-propanediol). These results show that glycols can be used to not only reduce IL viscosity while increasing physisorption sites for CO2 sorption, but also that encapsulation can be utilized to mitigate evaporation of volatile viscosity modifiers.

Non-pyrogenicity and biocompatibility of parylene-coated magnetic bead implants.

Clinical grade magnetic bead implants have important applications in interfacing with the human body, providing contactless mechanical attachment or wireless communication through human tissue. We recently developed a new strategy, magnetomicrometry, that uses magnetic bead implants as passive communication devices to wirelessly sense muscle tissue lengths. We manufactured clinical-grade magnetic bead implants and verified their biocompatibility via intramuscular implantation, cytotoxicity, sensitization, and intracutaneous irritation testing. In this work, we test the pyrogenicity of the magnetic bead implants via a lagomorph model, and we test the biocompatibility of the magnetic bead implants via a full chemical characterization and toxicological risk assessment. Further, we test the cleaning, sterilization, and dry time of the devices that are used to deploy these magnetic bead implants. We find that the magnetic bead implants are non-pyrogenic and biocompatible, with the insertion device determined to be safe to clean, sterilize, and dry in a healthcare setting. These results provide confidence for the safe use of these magnetic bead implants in humans.

Travel history and malaria infection risk in a low-transmission setting in Ethiopia: a case control study.

BACKGROUND: Malaria remains the leading communicable disease in Ethiopia, with around one million clinical cases of malaria reported annually. The country currently has plans for elimination for specific geographic areas of the country. Human movement may lead to the maintenance of reservoirs of infection, complicating attempts to eliminate malaria. METHODS: An unmatched case-control study was conducted with 560 adult patients at a Health Centre in central Ethiopia. Patients who received a malaria test were interviewed regarding their recent travel histories. Bivariate and multivariate analyses were conducted to determine if reported travel outside of the home village within the last month was related to malaria infection status. RESULTS: After adjusting for several known confounding factors, travel away from the home village in the last 30 days was a statistically significant risk factor for infection with Plasmodium falciparum (AOR 1.76; p=0.03) but not for infection with Plasmodium vivax (AOR 1.17; p=0.62). Male sex was strongly associated with any malaria infection (AOR 2.00; p=0.001). CONCLUSIONS: Given the importance of identifying reservoir infections, consideration of human movement patterns should factor into decisions regarding elimination and disease prevention, especially when targeted areas are limited to regions within a country.

Exploring the urban gradient in population health: insights from satellite-derived urbanicity classes across multiple countries and years in sub-Saharan Africa.

The demographic, ecological and socioeconomic changes associated with urbanisation are linked to changes in disease incidence, health service provision and mortality. These effects are heterogeneous between and within urban areas, yet without a clear definition of what constitutes an 'urban' area, their measurement and comparison are constrained. The definitions used vary between countries and over time hindering analyses of the relationship between urbanisation and health outcomes, evaluation of policy actions and results in uncertainties in estimated differences. While a binary urban-rural designation fails to capture the complexities of the urban-rural continuum, satellite data augmented with models of population density and built-up areas offer an opportunity to develop an objective, comparable and continuous measure which captures urbanisation gradient at high spatial resolution. We examine the urban gradient within the context of population health. We compare the categorisation of urban and rural areas (defined by national statistical offices) used in household surveys in sub-Saharan Africa (SSA) to an urban-rural gradient derived from augmented satellite data within a geospatial framework. Using nine Demographic and Health Surveys (DHS) conducted between 2005 and 2019 in six SSA countries, we then assess the extent of misalignment between urbanicity based on DHS categorisation compared with a satellite-derived measure, while discussing the implications on the coverage of key maternal health indicators. The proposed indicator provides a useful supplement to country-specific urbanicity definitions and reveals new health dynamics along the rural-urban gradient. Satellite-derived urbanicity measures will need frequent updates to align with years when household surveys are conducted.