Vegetation structure drives mosquito community composition in UK's largest managed lowland wetland.

PURPOSE: The rising burden of mosquito-borne diseases in Europe extends beyond urban areas, encompassing rural and semi-urban regions near managed and natural wetlands evidenced by recent outbreaks of Usutu and West Nile viruses. While wetland management policies focus on biodiversity and ecosystem services, few studies explore the impact on mosquito vectors. METHODS: Our research addresses this gap, examining juvenile mosquito and aquatic predator communities in 67 ditch sites within a South England coastal marsh subjected to different wetland management tiers. Using joint distribution models, we analyse how mosquito communities respond to abiotic and biotic factors influenced by wetland management. RESULTS: Of the 12 mosquito species identified, Culiseta annulata (Usutu virus vector) and Culex pipiens (Usutu and West Nile virus vector) constitute 47% of 6825 larval mosquitoes. Abundant predators include Coleoptera (water beetles) adults, Corixidae (water boatmen) and Zygoptera (Damselfy) larvae. Models reveal that tier 3 management sites (higher winter water levels, lower agricultural intensity) associated with shade and less floating vegetation are preferred by specific mosquito species. All mosquito species except Anopheles maculipennis s.l., are negatively impacted by potential predators. Culiseta annulata shows positive associations with shaded and turbid water, contrary to preferences of Corixidae predators. CONCLUSIONS: Tier 3 areas managed for biodiversity, characterised by higher seasonal water levels and reduced livestock grazing intensity, provide favourable habitats for key mosquito species that are known vectors of arboviruses, such as Usutu and West Nile. Our findings emphasise the impact of biodiversity-focused wetland management, altering mosquito breeding site vegetation to enhance vector suitability. Further exploration of these trade-offs is crucial for comprehending the broader implications of wetland management.

Cooking with liquefied petroleum gas or biomass and fetal growth outcomes: a multi-country randomised controlled trial.

BACKGROUND: Household air pollution might lead to fetal growth restriction during pregnancy. We aimed to investigate whether a liquefied petroleum gas (LPG) intervention to reduce personal exposures to household air pollution during pregnancy would alter fetal growth. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial was an open-label randomised controlled trial conducted in ten resource-limited settings across Guatemala, India, Peru, and Rwanda. Pregnant women aged 18-34 years (9-19 weeks of gestation) were randomly assigned in a 1:1 ratio to receive an LPG stove, continuous fuel delivery, and behavioural messaging or to continue usual cooking with biomass for 18 months. We conducted ultrasound assessments at baseline, 24-28 weeks of gestation (the first pregnancy visit), and 32-36 weeks of gestation (the second pregnancy visit), to measure fetal size; we monitored 24 h personal exposures to household air pollutants during these visits; and we weighed children at birth. We conducted intention-to-treat analyses to estimate differences in fetal size between the intervention and control group, and exposure-response analyses to identify associations between household air pollutants and fetal size. This trial is registered with ClinicalTrials.gov (NCT02944682). FINDINGS: Between May 7, 2018, and Feb 29, 2020, we randomly assigned 3200 pregnant women (1593 to the intervention group and 1607 to the control group). The mean gestational age was 14·5 (SD 3·0) weeks and mean maternal age was 25·6 (4·5) years. We obtained ultrasound assessments in 3147 (98·3%) women at baseline, 3052 (95·4%) women at the first pregnancy visit, and 2962 (92·6%) at the second pregnancy visit, through to Aug 25, 2020. Intervention adherence was high (the median proportion of days with biomass stove use was 0·0%, IQR 0·0-1·6) and pregnant women in the intervention group had lower mean exposures to particulate matter with a diameter less than 2·5 µm (PM2·5; 35·0 [SD 37·2] µg/m3vs 103·3 [97·9] µg/m3) than did women in the control group. We did not find differences in averaged post-randomisation Z scores for head circumference (0·30 vs 0·39; p=0·04), abdominal circumference (0·38 vs 0·39; p=0·99), femur length (0·44 vs 0·45; p=0·73), and estimated fetal weight or birthweight (-0·13 vs -0·12; p=0·70) between the intervention and control groups. Personal exposures to household air pollutants were not associated with fetal size. INTERPRETATION: Although an LPG cooking intervention successfully reduced personal exposure to air pollution during pregnancy, it did not affect fetal size. Our findings do not support the use of unvented liquefied petroleum gas stoves as a strategy to increase fetal growth in settings were biomass fuels are used predominantly for cooking. FUNDING: US National Institutes of Health and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Kinyarwanda, Spanish and Tamil translations of the abstract see Supplementary Materials section.

Speciation within the Anopheles gambiae complex: high-throughput whole genome sequencing reveals evidence of a putative new cryptic taxon in 'far-west' Africa.

The two main Afrotropical malaria vectors - Anopheles coluzzii and An. gambiae - are genetically distinct and reproductively isolated across West Africa. However, populations at the western extreme of their range are assigned as "intermediate" between the two species by whole genome sequence (WGS) data, and as hybrid forms by conventional molecular diagnostics. By exploiting WGS data from 1,190 specimens collected across west Africa via the Anopheles gambiae 1000 Genomes network, we identify a novel putative taxon in the far-west (provisionally named Bissau molecular form), which did not arise by admixture but rather originated at the same time as the split between An. coluzzii and An. gambiae. Intriguingly, these populations lack insecticide resistance mechanisms commonly observed in the two main species. These findings lead to a change of perspective on malaria vector species in the far-west region with potential for epidemiological implications, and a new challenge for genetic-based mosquito control approaches.

Predictors of Prolonged Hospital Stay After Segmentectomy.

OBJECTIVE: Segmentectomy is becoming the standard of care for small, peripheral non-small cell lung cancer. To improve perioperative management in this population, this study aims to identify factors influencing hospital length of stay after segmentectomy. METHODS: Patients who underwent segmentectomy for any indication between 01/2018-05/2023 were identified using a prospectively maintained institutional database. Multivariable logistic regression models were used to estimate associations between clinical features and prolonged (≥ 3days) hospital stay. A nomogram was designed to understand better, and possibly calculate the individual risk of prolonged hospital stays. RESULTS: In total, 533 cases were included; 337 (63%) were females. Median age was 66 years (IQR: 63-75). The median size of resected lesions was 1.6cm (IQR 1.3-2.1). Median hospital stay was 3 days (IQR: 2-4). Major adverse events occurred in 31 (5.8%) cases. The 30-day readmission rate was 5.8% (n=31). There was no 30-day mortality; 90-day mortality was <1%. Patients older than 75 years (OR=2.01, 95%CI: 1.15-3.57, P=0.02), those with FEV1 < 88% predicted (OR = 1.99, 95%CI: 1.38-2.89, P<0.001), or positive smoking history (OR=1.72, 95%CI: 1.15-2.60, P=0.01) were more likely to have prolonged hospital stays after segmentectomy. A nomogram accounting for age, sex, FEV1, body mass index, smoking history, and comorbidities was created to predict the probability of prolonged hospital stay with an AUC of 0.66. CONCLUSIONS: Older patients, those with reduced pulmonary function, current, and past smokers have elevated risk for prolonged hospital stays after segmentectomy. Validation of our nomogram could improve perioperative risk stratification in segmentectomy patients.

Complete anatomic segmentectomy shows improved oncologic outcomes compared to incomplete anatomic segmentectomy.

OBJECTIVES: To compare oncologic outcomes after segmentectomy with division of segmental bronchus, artery and vein (complete anatomic segmentectomy) versus segmentectomy with division of <3 segmental structures (incomplete anatomic segmentectomy). METHODS: We conducted a single-centre, retrospective analysis of patients undergoing segmentectomy from March 2005 to May 2020. Operative reports were audited to classify procedures as complete or incomplete anatomic segmentectomy. Patients who underwent neoadjuvant therapy or pulmonary resection beyond indicated segments were excluded. Survival was estimated with Kaplan-Meier models and compared using log-rank tests. Cox proportional hazards models were used to estimate hazard ratios (HRs) for death. Cumulative incidence functions for loco-regional recurrence were compared with Gray's test, with death considered a competing event. Cox and Fine-Gray models were used to estimate cause-specific and subdistribution HRs, respectively, for loco-regional recurrence. RESULTS: Of 390 cases, 266 (68.2%) were complete and 124 were incomplete anatomic segmentectomy. Demographics, pulmonary function, tumour size, stage and perioperative outcomes did not significantly differ between groups. Surgical margins were negative in all but 1 case. Complete anatomic segmentectomy was associated with improved lymph node dissection (5 vs 2 median nodes sampled; P < 0.001). Multivariable analysis revealed reduced incidence of loco-regional recurrence (cause-specific HR = 0.42; 95% confidence interval 0.22-0.80; subdistribution HR = 0.43; 95% confidence interval 0.23-0.81), and non-significant improvement in overall survival (HR = 0.66; 95% confidence interval: 0.43-1.00) after complete versus incomplete anatomic segmentectomy. CONCLUSIONS: This single-centre experience suggests complete anatomic segmentectomy provides superior loco-regional control and may improve survival relative to incomplete anatomic segmentectomy. We recommend surgeons perform complete anatomic segmentectomy and lymph node dissection whenever possible.

Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation.

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.

Sustained and Localized Drug Depot Release Using Radiation-Activated Scintillating Nanoparticles.

Clinical treatment of cancer commonly incorporates X-ray radiation therapy (XRT), and developing spatially precise radiation-activatable drug delivery strategies may improve XRT efficacy while limiting off-target toxicities associated with systemically administered drugs. Nevertheless, achieving this has been challenging thus far because strategies typically rely on radical species with short lifespans, and the inherent nature of hypoxic and acidic tumor microenvironments may encourage spatially heterogeneous effects. It is hypothesized that the challenge could be bypassed by using scintillating nanoparticles that emit light upon X-ray absorption, locally forming therapeutic drug depots in tumor tissues. Thus a nanoparticle platform (Scintillating nanoparticle Drug Depot; SciDD) that enables the local release of cytotoxic payloads only after activation by XRT is developed, thereby limiting off-target toxicity. As a proof-of-principle, SciDD is used to deliver a microtubule-destabilizing payload MMAE (monomethyl auristatin E). With as little as a 2 Gy local irradiation to tumors, MMAE payloads are released effectively to kill tumor cells. XRT-mediated drug release is demonstrated in multiple mouse cancer models and showed efficacy over XRT alone (p < 0.0001). This work shows that SciDD can act as a local drug depot with spatiotemporally controlled release of cancer therapeutics.

Genome sequence of bacteriophage Djungelskog isolated from an Arthrobacter globiformis culture.

Actinobacteriophage Djungelskog was isolated from a sample of degraded organic material in Poughkeepsie, NY, using Arthrobacter globiformis B-2979. Its genome is 54,512 bp and encodes 86 putative protein-coding genes. Djungelskog has a siphovirus morphology and is assigned to cluster AW based on gene content similarity to actinobacteriophages.

Effects of a liquefied petroleum gas stove intervention on stillbirth, congenital anomalies and neonatal mortality: A multi-country household air pollution intervention network trial.

Household air pollution (HAP) from cooking with solid fuels used during pregnancy has been associated with adverse pregnancy outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial that assessed the impact of a liquefied petroleum gas (LPG) stove and fuel intervention on health in Guatemala, India, Peru, and Rwanda. Here we investigated the effects of the LPG stove and fuel intervention on stillbirth, congenital anomalies and neonatal mortality and characterized exposure-response relationships between personal exposures to fine particulate matter (PM2.5), black carbon (BC) and carbon monoxide (CO) and these outcomes. Pregnant women (18 to <35 years of age; gestation confirmed by ultrasound at 9 to <20 weeks) were randomly assigned to intervention or control arms. We monitored these fetal and neonatal outcomes and personal exposure to PM2.5, BC and CO three times during pregnancy, we conducted intention-to-treat (ITT) and exposure-response (E-R) analyses to determine if the HAPIN intervention and corresponding HAP exposure was associated with the risk of fetal/neonatal outcomes. A total of 3200 women (mean age 25.4 ± 4.4 years, mean gestational age at randomization 15.4 ± 3.1 weeks) were included in this analysis. Relative risks for stillbirth, congenital anomaly and neonatal mortality were 0.99 (0.60, 1.66), 0.92 (95 % CI 0.52, 1.61), and 0.99 (0.54, 1.85), respectively, among women in the intervention arm compared to controls in an ITT analysis. Higher mean personal exposures to PM2.5, CO and BC during pregnancy were associated with a higher, but statistically non-significant, incidence of adverse outcomes. The LPG stove and fuel intervention did not reduce the risk of these outcomes nor did we find evidence supporting an association between personal exposures to HAP and stillbirth, congenital anomalies and neonatal mortality.

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Effects of Cooking with Liquefied Petroleum Gas or Biomass on Stunting in Infants.

BACKGROUND: Household air pollution is associated with stunted growth in infants. Whether the replacement of biomass fuel (e.g., wood, dung, or agricultural crop waste) with liquefied petroleum gas (LPG) for cooking can reduce the risk of stunting is unknown. METHODS: We conducted a randomized trial involving 3200 pregnant women 18 to 34 years of age in four low- and middle-income countries. Women at 9 to less than 20 weeks' gestation were randomly assigned to use a free LPG cookstove with continuous free fuel delivery for 18 months (intervention group) or to continue using a biomass cookstove (control group). The length of each infant was measured at 12 months of age, and personal exposures to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm) were monitored starting at pregnancy and continuing until the infants were 1 year of age. The primary outcome for which data are presented in the current report - stunting (defined as a length-for-age z score that was more than two standard deviations below the median of a growth standard) at 12 months of age - was one of four primary outcomes of the trial. Intention-to-treat analyses were performed to estimate the relative risk of stunting. RESULTS: Adherence to the intervention was high, and the intervention resulted in lower prenatal and postnatal 24-hour personal exposures to fine particulate matter than the control (mean prenatal exposure, 35.0 µg per cubic meter vs. 103.3 µg per cubic meter; mean postnatal exposure, 37.9 µg per cubic meter vs. 109.2 µg per cubic meter). Among 3061 live births, 1171 (76.2%) of the 1536 infants born to women in the intervention group and 1186 (77.8%) of the 1525 infants born to women in the control group had a valid length measurement at 12 months of age. Stunting occurred in 321 of the 1171 infants included in the analysis (27.4%) of the infants born to women in the intervention group and in 299 of the 1186 infants included in the analysis (25.2%) of those born to women in the control group (relative risk, 1.10; 98.75% confidence interval, 0.94 to 1.29; P = 0.12). CONCLUSIONS: An intervention strategy starting in pregnancy and aimed at mitigating household air pollution by replacing biomass fuel with LPG for cooking did not reduce the risk of stunting in infants. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Effects of Zinc Supplementation on Metabolomic Profiles in Tanzanian Infants: A Randomized Trial.

BACKGROUND: Provision of zinc supplementation to young children has been associated with reduced infectious morbidity and better growth outcomes. However, the metabolic pathways underlying these outcomes are unclear, and metabolomic data from humans undergoing zinc supplementation, particularly infants, are generally lacking. OBJECTIVES: This study aimed to examine the effect of zinc supplementation on metabolic profiles in Tanzanian infants aged 6 wk and 6 mo. METHODS: Blood samples were collected at age 6 wk and 6 mo from 50 Tanzanian infants who were enrolled in a randomized placebo-controlled trial of zinc supplementation (5 mg oral daily). Metabolomic analysis using an ultrahigh-performance liquid chromatography/tandem mass spectroscopy platform was performed to identify potential metabolomic profiles and biomarkers associated with zinc supplementation. Principal component analysis (PCA) was used to summarize metabolomic data from all samples. Two-way repeated measures analysis of variance with compound symmetry covariance structures were used to compare metabolome levels over time between infants in the 2 treatment arms. RESULTS: In PCA, the samples tended to be more separated by child age (6 wk compared with 6 mo) than by zinc supplementation status. We found that zinc supplementation affected a variety of metabolites associated with amino acid, lipid, nucleotide, and xenobiotic metabolism, including indoleacetate in the tryptophan metabolism pathway; 3-methoxytrosine and 4-hydrxoyphenylphruvate in the tyrosine pathway; eicosanedioate, 2-aminooctanoate, and N-acetyl-2-aminooctanoate in the fatty acid pathway; and N6-succinyladenosine in the purine metabolism pathway. Compared to the relatively small number of metabolites associated with zinc supplements, many infant metabolites changed significantly from age 6 wk to 6 mo. CONCLUSIONS: Zinc supplementation, despite having overall clinical benefits, appears to induce limited metabolomic changes in blood metabolites in young infants. Future larger studies may be warranted to further examine metabolic pathways associated with zinc supplementation. The parent trial was registered at clinicaltrials.gov as NCT00421668.

Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo.

BACKGROUND: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H2 O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. PURPOSE: Validate theory describing blood behavior of R1 and R2 * in an animal model. STUDY TYPE: Prospective, animal. ANIMAL MODEL: Seven swine (54-65 kg). FIELD STRENGTH/SEQUENCE: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences. ASSESSMENT: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R1 and R2 * effects (whole-blood model) and simpler models incorporating linear R1 , with and without R2 * effects. Predicted SIs were compared to measured aortic SI. STATISTICAL TESTS: Linear correlation (coefficient of determination, R2 ) and mean errors were compared across the SI prediction models. RESULTS: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R1 and high blood R2 * (regression slopes 0.91-1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2 * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). DATA CONCLUSION: Incorporating sub-linear R1 and high first-pass R2 * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Human YRNA 4 (HY4) plasma levels are a prognostic indicator of SARS-CoV-2 infection clinical severity.

SARS-CoV-2 infection can result in a range of outcomes from asymptomatic/mild disease to severe COVID-19/fatality. In this study, we investigated the differential expression of small noncoding RNAs (sncRNAs) between patient cohorts defined by disease severity. We collected plasma samples, stratified these based on clinical outcomes, and sequenced their circulating sncRNAs. Excitingly, we found YRNA HY4 displays significant differential expression (p=0.025) between patients experiencing mild and severe disease. In agreement with recent reports identifying plasma YRNAs as indicators of influenza infection severity, our results strongly suggest that circulating HY4 levels represent a powerful prognostic indicator of likely SARS-CoV-2 patient infection outcome.

Contributions of CO2, O2, and H2O to the Oxidative Stability of Solid Amine Direct Air Capture Sorbents at Intermediate Temperature.

Aminopolymer-based sorbents are preferred materials for extraction of CO2 from ambient air [direct air capture (DAC) of CO2] owing to their high CO2 adsorption capacity and selectivity at ultra-dilute conditions. While those adsorptive properties are important, the stability of a sorbent is a key element in developing high-performing, cost-effective, and long-lasting sorbents that can be deployed at scale. Along with process upsets, environmental components such as CO2, O2, and H2O may contribute to long-term sorbent instability. As such, unraveling the complex effects of such atmospheric components on the sorbent lifetime as they appear in the environment is a critical step to understanding sorbent deactivation mechanisms and designing more effective sorbents and processes. Here, a poly(ethylenimine) (PEI)/Al2O3 sorbent is assessed over continuous and cyclic dry and humid conditions to determine the effect of the copresence of CO2 and O2 on stability at an intermediate temperature of 70 °C. Thermogravimetric and elemental analyses in combination with in situ horizontal attenuated total reflection infrared (HATR-IR) spectroscopy are performed to measure the extent of deactivation, elemental content, and molecular level changes in the sorbent due to deactivation. The thermal/thermogravimetric analysis results reveal that incorporating CO2 with O2 accelerates sorbent deactivation using these sorbents in dry and humid conditions compared to that using CO2-free air in similar conditions. The in situ HATR-IR spectroscopy results of PEI/Al2O3 sorbent deactivation under a CO2-air environment show the formation of primary amine species in higher quantity (compared to that in conditions without O2 or CO2), which arises due to the C-N bond cleavage at secondary amines due to oxidative degradation. We hypothesize that the formation of bound CO2 species such as carbamic acids catalyzes C-N cleavage reactions in the oxidative degradation pathway by shuttling protons, resulting in a low activation energy barrier for degradation, as probed by metadynamics simulations. In the cyclic experiment after 30 cycles, results show a gradual loss in stability (dry: 29%, humid: 52%) under CO2-containing air (0.04% CO2/21% O2 balance N2). However, the loss in capacity during cyclic studies is significantly less than that during continuous deactivation, as expected.

Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets.

Progesterone prevents development of endometrial cancers through its receptor (PR) although the molecular mechanisms have yet to be fully characterized. In this study, we performed a global analysis of gene regulation by progesterone using human endometrial cancer cells that expressed PR endogenously or exogenously. We found progesterone strongly inhibits multiple components of the platelet derived growth factor receptor (PDGFR), Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathway through PR. The PDGFR/JAK/STAT pathway signals to control numerous downstream targets including AP-1 transcription factors Fos and Jun. Treatment with inhibitors of the PDGFR/JAK/STAT pathway significantly blocked proliferation in multiple novel patient-derived organoid models of endometrial cancer, and activation of this pathway was found to be a poor prognostic signal for the survival of patients with endometrial cancer from The Cancer Genome Atlas. Our study identifies this pathway as central to the growth-limiting effects of progesterone in endometrial cancer and suggests that inhibitors of PDGFR/JAK/STAT should be considered for future therapeutic interventions.

Fidelity and adherence to a liquefied petroleum gas stove and fuel intervention: The multi-country Household Air Pollution Intervention Network (HAPIN) trial.

BACKGROUND: Reducing household air pollution (HAP) to levels associated with health benefits requires nearly exclusive use of clean cooking fuels and abandonment of traditional biomass fuels. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3,195 pregnant women in Guatemala, India, Peru, and Rwanda to receive a liquefied petroleum gas (LPG) stove intervention (n = 1,590), with controls expected to continue cooking with biomass fuels (n = 1,605). We assessed fidelity to intervention implementation and participant adherence to the intervention starting in pregnancy through the infant's first birthday using fuel delivery and repair records, surveys, observations, and temperature-logging stove use monitors (SUMs). RESULTS: Fidelity and adherence to the HAPIN intervention were high. Median time required to refill LPG cylinders was 1 day (interquartile range 0-2). Although 26% (n = 410) of intervention participants reported running out of LPG at some point, the number of times was low (median: 1 day [Q1, Q3: 1, 2]) and mostly limited to the first four months of the COVID-19 pandemic. Most repairs were completed on the same day as problems were reported. Traditional stove use was observed in only 3% of observation visits, and 89% of these observations were followed up with behavioral reinforcement. According to SUMs data, intervention households used their traditional stove a median of 0.4% of all monitored days, and 81% used the traditional stove < 1 day per month. Traditional stove use was slightly higher post-COVID-19 (detected on a median [Q1, Q3] of 0.0% [0.0%, 3.4%] of days) than pre-COVID-19 (0.0% [0.0%, 1.6%] of days). There was no significant difference in intervention adherence pre- and post-birth. CONCLUSION: Free stoves and an unlimited supply of LPG fuel delivered to participating homes combined with timely repairs, behavioral messaging, and comprehensive stove use monitoring contributed to high intervention fidelity and near-exclusive LPG use within the HAPIN trial.

Distribution and Transport of CO2 in Hyperbranched Poly(ethylenimine)-Loaded MCM-41: A Molecular Dynamics Simulation Approach.

Fossil fuel use is accelerating climate change, driving the need for efficient CO2 capture technologies. Solid adsorption-based direct air capture (DAC) of CO2 has emerged as a promising mode for CO2 removal from the atmosphere due to its potential for scalability. Sorbents based on porous supports incorporating oligomeric amines in their pore spaces are widely studied. In this study, we investigate the intermolecular interactions and adsorption of CO2 and H2O molecules in hyperbranched poly(ethylenimine) (HB-PEI) functionalized MCM-41 systems to understand the distribution and transport of CO2 and H2O molecules. Density Functional Theory (DFT) is employed to compute the binding energies of CO2 and H2O molecules with HB-PEI and MCM-41 and to develop force field parameters for molecular dynamics (MD) simulations. The MD simulations are performed to examine the distribution and transport of CO2 and H2O molecules as a function of the HB-PEI content. The study finds that an HB-PEI content of approximately 34 wt % is thermodynamically favorable, with an upper limit of HB-PEI loading between 45 and 50 wt %. The distribution of CO2 and H2O molecules is primarily determined by their adsorptive binding energies, for which H2O molecules dominate the occupation of binding sites due to their strong affinity with silanol groups on MCM-41 and amine groups of HB-PEI. The HB-PEI content has a considerable impact on the diffusion of CO2 and H2O molecules. Furthermore, a larger number of water molecules (higher relative humidity) reduces the correlation of CO2 with the MCM-41 pore surface while enhancing the correlation of CO2 with the amine groups of the HB-PEI. Overall, the presence of H2O molecules increases the CO2 correlation with the amine groups and also the CO2 transport within HB-PEI-loaded MCM-41, meaning that the presence of H2O enhances the CO2 capture in the HB-PEI-loaded MCM-41. These findings are consistent with experimental observations of the impact of increasing humidity on CO2 capture while providing new, molecular-level explanations for the macroscopic experimental findings.

Effects of a LPG stove and fuel intervention on adverse maternal outcomes: A multi-country randomized controlled trial conducted by the Household Air Pollution Intervention Network (HAPIN).

Household air pollution from solid cooking fuel use during gestation has been associated with adverse pregnancy and birth outcomes. The Household Air Pollution Intervention Network (HAPIN) trial was a randomized controlled trial of free liquefied petroleum gas (LPG) stoves and fuel in Guatemala, Peru, India, and Rwanda. A primary outcome of the main trial was to report the effects of the intervention on infant birth weight. Here we evaluate the effects of a LPG stove and fuel intervention during pregnancy on spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality compared to women who continued to use solid cooking fuels. Pregnant women (18-34 years of age; gestation confirmed by ultrasound at 9-19 weeks) were randomly assigned to an intervention (n = 1593) or control (n = 1607) arm. Intention-to-treat analyses compared outcomes between the two arms using log-binomial models. Among the 3195 pregnant women in the study, there were 10 spontaneous abortions (7 intervention, 3 control), 93 hypertensive disorders of pregnancy (47 intervention, 46 control), 11 post postpartum hemorrhage (5 intervention, 6 control) and 4 maternal deaths (3 intervention, 1 control). Compared to the control arm, the relative risk of spontaneous abortion among women randomized to the intervention was 2.32 (95% confidence interval (CI): 0.60, 8.96), hypertensive disorders of pregnancy 1.02 (95% CI: 0.68, 1.52), postpartum hemorrhage 0.83 (95% CI: 0.25, 2.71) and 2.98 (95% CI: 0.31, 28.66) for maternal mortality. In this study, we found that adverse maternal outcomes did not differ based on randomized stove type across four country research sites.

Fidelity and adherence to a liquefied petroleum gas stove and fuel intervention: the multi-country Household Air Pollution Intervention Network (HAPIN) trial.

Background: Reducing household air pollution (HAP) to levels associated with health benefits requires nearly exclusive use of clean cooking fuels and abandonment of traditional biomass fuels. Methods: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3,195 pregnant women in Guatemala, India, Peru, and Rwanda to receive a liquefied petroleum gas (LPG) stove intervention (n=1,590), with controls expected to continue cooking with biomass fuels (n=1,605). We assessed fidelity to intervention implementation and participant adherence to the intervention starting in pregnancy through the infant's first birthday using fuel delivery and repair records, surveys, observations, and temperature-logging stove use monitors (SUMs). Results: Fidelity and adherence to the HAPIN intervention were high. Median time required to refill LPG cylinders was 1 day (interquartile range 0-2). Although 26% (n=410) of intervention participants reported running out of LPG at some point, the number of times was low (median: 1 day [Q1, Q3: 1, 2]) and mostly limited to the first four months of the COVID-19 pandemic. Most repairs were completed on the same day as problems were reported. Traditional stove use was observed in only 3% of observation visits, and 89% of these observations were followed up with behavioral reinforcement. According to SUMs data, intervention households used their traditional stove a median of 0.4% of all monitored days, and 81% used the traditional stove <1 day per month. Traditional stove use was slightly higher post-COVID-19 (detected on a median [Q1, Q3] of 0.0% [0.0%, 3.4%] of days) than pre-COVID-19 (0.0% [0.0%, 1.6%] of days). There was no significant difference in intervention adherence pre- and post-birth. Conclusion: Free stoves and an unlimited supply of LPG fuel delivered to participating homes combined with timely repairs, behavioral messaging, and comprehensive stove use monitoring contributed to high intervention fidelity and near-exclusive LPG use within the HAPIN trial.