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.

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.

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.

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.

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.

Effect of Dural-Puncture Epidural vs Standard Epidural for Epidural Extension on Onset Time of Surgical Anesthesia in Elective Cesarean Delivery: A Randomized Clinical Trial.

Importance: Dural-puncture epidural (DPE) and standard epidural are common modes of neuraxial labor analgesia. Little is known about conversion of DPE-initiated labor analgesia to surgical anesthesia for cesarean delivery. Objective: To determine whether DPE provides a faster onset and better-quality block compared with the standard epidural technique for cesarean delivery. Design, Setting, and Participants: This double-blind, randomized clinical trial was conducted between April 2019 and October 2022 at a tertiary care university hospital (University of Arkansas for Medical Sciences). Participants included women aged 18 years and older undergoing scheduled cesarean delivery with a singleton pregnancy. Interventions: Participants were randomized to receive DPE or standard epidural in the labor and delivery room. A T10 sensory block was achieved and maintained using a low concentration of bupivacaine with fentanyl through the epidural catheter until the time of surgery. Epidural extension anesthesia was initiated in the operating room. Main Outcomes and Measures: The primary outcome was the time taken from chloroprocaine administration to surgical anesthesia (T6 sensory block). The secondary outcome was the quality of epidural anesthesia, as defined by a composite of the following factors: (1) failure to achieve a T10 bilateral block preoperatively in the delivery room, (2) failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, (3) requirement for intraoperative analgesia, (4) repeat neuraxial procedure, and (5) conversion to general anesthesia. Results: Among 140 women (mean [SD] age, 30.1 [5.2] years), 70 were randomized to the DPE group, and 70 were randomized to the standard epidural group. The DPE group had a faster onset time to surgical anesthesia compared with the standard epidural group (median [IQR], 422 [290-546] seconds vs 655 [437-926] seconds; median [IQR] difference, 233 [104-369] seconds). The composite rates of lower quality anesthesia were 15.7% (11 of 70 women) in the DPE group and 36.3% (24 of 66 women) in the standard epidural group (odds ratio, 0.33; 95% CI, 0.14-0.74; P = .007). Conclusions and Relevance: Anesthesia initiated following a DPE technique resulted in faster onset and improved block quality during epidural extension compared with initiation with a standard epidural technique. Further studies are needed to confirm these findings in the setting of intrapartum cesarean delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03915574.

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.

Anesthesia and Analgesia for the Obese Parturient.

Obesity is a worldwide epidemic and is associated with an increased risk of hypertension, diabetes, and obstructive sleep apnea. Pregnant patients with obesity experience a higher risk of maternal and fetal complications. Anesthesia also poses higher risks for obese parturients and may be more technically challenging due to body habitus. Safe anesthesia practice for these patients must take into consideration the unique challenges associated with the combination of pregnancy and obesity.

Untethered muscle tracking using magnetomicrometry.

Muscle tissue drives nearly all movement in the animal kingdom, providing power, mobility, and dexterity. Technologies for measuring muscle tissue motion, such as sonomicrometry, fluoromicrometry, and ultrasound, have significantly advanced our understanding of biomechanics. Yet, the field lacks the ability to monitor muscle tissue motion for animal behavior outside the lab. Towards addressing this issue, we previously introduced magnetomicrometry, a method that uses magnetic beads to wirelessly monitor muscle tissue length changes, and we validated magnetomicrometry via tightly-controlled in situ testing. In this study we validate the accuracy of magnetomicrometry against fluoromicrometry during untethered running in an in vivo turkey model. We demonstrate real-time muscle tissue length tracking of the freely-moving turkeys executing various motor activities, including ramp ascent and descent, vertical ascent and descent, and free roaming movement. Given the demonstrated capacity of magnetomicrometry to track muscle movement in untethered animals, we feel that this technique will enable new scientific explorations and an improved understanding of muscle function.

Clinical viability of magnetic bead implants in muscle.

Human movement is accomplished through muscle contraction, yet there does not exist a portable system capable of monitoring muscle length changes in real time. To address this limitation, we previously introduced magnetomicrometry, a minimally-invasive tracking technique comprising two implanted magnetic beads in muscle and a magnetic field sensor array positioned on the body's surface adjacent the implanted beads. The implant system comprises a pair of spherical magnetic beads, each with a first coating of nickel-copper-nickel and an outer coating of Parylene C. In parallel work, we demonstrate submillimeter accuracy of magnetic bead tracking for muscle contractions in an untethered freely-roaming avian model. Here, we address the clinical viability of magnetomicrometry. Using a specialized device to insert magnetic beads into muscle in avian and lagomorph models, we collect data to assess gait metrics, bead migration, and bead biocompatibility. For these animal models, we find no gait differences post-versus pre-implantation, and bead migration towards one another within muscle does not occur for initial bead separation distances greater than 3 cm. Further, using extensive biocompatibility testing, the implants are shown to be non-irritant, non-cytotoxic, non-allergenic, and non-irritating. Our cumulative results lend support for the viability of these magnetic bead implants for implantation in human muscle. We thus anticipate their imminent use in human-machine interfaces, such as in control of prostheses and exoskeletons and in closed-loop neuroprosthetics to aid recovery from neurological disorders.

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.

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.

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.

Extramedullary Waldenström Macroglobulinemia Presenting as a Subcutaneous Penile Mass.

Primary penile malignancy is a rare occurrence in the United States, with squamous carcinoma being the most common aetiology. Non-squamous penile cancers are scarcely reported in the literature. We present a unique case of a 65-year-old male with a history of Waldenström macroglobulinemia (WM) previously in remission complaining of a painless subcutaneous bump on the base of the penis. Biopsy with histological and immunohistochemical analysis confirmed the recurrence of WM. This novel case illustrates an unusual presentation of the disease after being successfully managed with chemotherapy and immunotherapy in an asymptomatic individual. There is only another reported case in the literature of a patient with a similar presentation. We highlight the clinical features and presentation of this condition, including a consensus for the approach and management of non-Hodgkin's lymphomas of the penis.

Intermittent Preventive Treatment of Malaria in Pregnancy Coverage Estimates from Population-based Surveys: Reliability of Women's Recall Among Women with ANC Cards.

Large household surveys performed to estimate coverage rates for various health interventions, including intermittent preventive treatment, depend on recall. Many studies question the validity of recalled data. Regarding vaccine coverage rates, it is standard practice to validate responses using medical history cards. To validate the coverage rates of intermittent preventive treatment during pregnancy reported by large household surveys, recalled coverage rates were compared with antenatal care card data in Benin, Ghana, Malawi, and Tanzania. The results indicated that recall was comparable to the coverage rates provided indicated by the antenatal care cards. These findings suggest that intermittent preventive treatment coverage rates reported by large household surveys performed using recalled data are valid.

Estimating the Fraction of Severe Malaria among Malaria-Positive Children: Analysis of Household Surveys in 19 Malaria-Endemic Countries in Africa.

To date, the only robust estimates of severe malaria cases include children who present to the formal healthcare system. It is a challenge to use these data because of varying age ranges of reporting, different diagnosis techniques, surveillance methods, and healthcare utilization. This analysis examined data from 37 Demographic and Health Surveys and Malaria Indicator Surveys across 19 countries in sub-Saharan Africa collected between 2011 and 2018. The outcome of interest is a proxy indicator for severe malaria, defined as a proportion of children aged 6-59 months with at least one self-reported symptom of severe illness including loss of consciousness, rapid breathing, seizures, or severe anemia (hemoglobin < 5 g/dL) among those who were positive for malaria. The study includes a weighted descriptive, country-level analysis and a multilevel mixed-effects logistic regression model to assess the determinants of severe malaria. Among children positive for malaria across all surveys, 4.5% (95% CI: 4.1-4.8) had at least one sign or symptom of severe malaria, which was significantly associated with age, residence, wealth, and year of survey fieldwork at a P-value less than 0.05. This analysis presents a novel and an alternative approach of estimating the fraction of severe malaria cases among malaria-positive children younger than 5 years in malaria-endemic countries. Estimating severe malaria cases through population-based surveys allows countries to estimate severe malaria across time and to compare with other countries. Having a population-level estimate of severe malaria cases helps further our understanding of the burden and epidemiology of severe malaria.

Cellular morphological features are predictive markers of cancer cell state.

Even genetically identical cells have heterogeneous properties because of stochasticity in gene or protein expression. Single cell techniques that assay heterogeneous properties would be valuable for basic science and diseases like cancer, where accurate estimates of tumor properties is critical for accurate diagnosis and grading. Cell morphology is an emergent outcome of many cellular processes, potentially carrying information about cell properties at the single cell level. Here we study whether morphological parameters are sufficient for classification of single cells, using a set of 15 cell lines, representing three processes: (i) the transformation of normal cells using specific genetic mutations; (ii) metastasis in breast cancer and (iii) metastasis in osteosarcomas. Cellular morphology is defined as quantitative measures of the shape of the cell and the structure of the actin. We use a toolbox that calculates quantitative morphological parameters of cell images and apply it to hundreds of images of cells belonging to different cell lines. Using a combination of dimensional reduction and machine learning, we test whether these different processes have specific morphological signatures and whether single cells can be classified based on morphology alone. Using morphological parameters we could accurately classify cells as belonging to the correct class with high accuracy. Morphological signatures could distinguish between cells that were different only because of a different mutation on a parental line. Furthermore, both oncogenesis and metastasis appear to be characterized by stereotypical morphology changes. Thus, cellular morphology is a signature of cell phenotype, or state, at the single cell level.

Quadratus lumborum block for postoperative analgesia after cesarean delivery: A systematic review with meta-analysis and trial-sequential analysis.

STUDY OBJECTIVE: The aim of this study was to investigate the analgesic efficacy of Quadratus lumborum block (QLB) versus controls, transversus abdominis plane (TAP) block and neuraxial morphine, or when added to neuraxial morphine in women undergoing cesarean delivery. DESIGN: Systematic review and meta-analysis with trial sequential analysis. PATIENTS: Parturients undergoing cesarean delivery. INTERVENTION: Quadratus lumborum block for postoperative analgesia. MEASUREMENTS: The primary outcomes were dynamic and static pain scores and cumulative opioid consumption at 24 h. Secondary outcomes were dynamic and static pain scores and opioid consumption at 6 and 12 h. Certainty of evidence was assessed using the GRADE system. Trial sequential analyses (TSA) were performed to determine if the results are supported by sufficient data. MAIN RESULTS: Ten studies involving 761 parturients were included. Compared to controls, no difference in dynamic (MD -6; 95%CI -17 to 5) or static (MD -5; 95%CI -14 to 3) pain scores were noted with QLB at 24 h (moderate certainty), although opioid consumption (MD -10.64 mg morphine equivalents; -16.01 to -5.27) was reduced (high certainty), supported by sufficient data. QLB reduced dynamic pain at 6 h, and static pain and opioid consumption at 6 and 12 h compared to controls. Compared to neuraxial morphine, QLB did not alter opioid consumption or pain scores at 24 h (low certainty), although TSA suggests insufficient data. Due to limited data, meta-analysis and TSA were not performed to compare QLB and TAP blocks. Addition of QLB to neuraxial morphine did not alter dynamic and static pain scores at 24 h (moderate certainty, supported by sufficient data). CONCLUSIONS: QLB improves post-cesarean delivery analgesia in parturients not receiving neuraxial morphine. Addition of QLB to parturients receiving neuraxial morphine has no significant analgesic benefit. Insufficient data are available to draw firm conclusions of QLB compared to TAP blocks or neuraxial morphine.