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Graphene is undoubtedly the carbon allotrope that has attracted the attention of a myriad of researchers in the last decades more than any other. The interaction of external or intercalated Li and Li+ with graphene layers has been the subject of particular attention for its importance in the applications of graphene layers in Lithium Batteries (LiBs). It is well known that lithium atoms and Li+ can be found inside and/or outside the double layer of graphene, and the graphene layers are often twisted around its parallel plane to obtain twisted graphene with tuneable properties. Thus, in this research, the interactions between Li and Li+ with bilayer graphene and twisted bilayer graphene were investigated by a first-principles density functional theory method, considering the lithium atom and the cation at different symmetry positions and with two different adsorption configurations. Binding energies and equilibrium interlayer distances of filled graphene layers were obtained from the computed potential energy profiles. This work shows that the twisting can regulate the interaction of bilayer graphene with Li and Li+. The binding energies of Li+ systematically increase from bilayer graphene to twisted graphene regardless of twisted angles, while for lithium atoms, the binding energies decrease or remain substantially unchanged depending on the twist angles. This suggests a higher adsorption capacity of twisted graphene towards Li+, which is important for designing twisted graphene-based material for LiB anode coating. Furthermore, when the Li or Li+ is intercalated between two graphene layers, the equilibrium interlayer distances in the twisted layers increase compared to the unrotated bilayer, and the relaxation is more significant for Li+ with respect to Li. This suggests that the twisted graphene can better accommodate the cation in agreement with the above result. The outcomes of this research pave the way for the study of the selective properties of twisted graphene.

Background Azithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone. Methods The Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme. Discussion The trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa. Trial registration ClinicalTrials.gov NCT04235816. Registered on 22 January 2020. Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020.

Background Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. Methods A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10–23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence—assessed with rapid diagnostic tests—were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. Results A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38–55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81–31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30–84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30–83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20–62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. Conclusion In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.

BackgroundIn sub-Saharan Africa (SSA), millions of pregnant women are exposed to malaria infection. The cornerstone of the WHO strategy to prevent malaria in pregnancy in moderate to high-transmission areas is the administration of intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine at each scheduled antenatal care (ANC) visit. However, overall coverage remains low. ‘Transforming IPT for Optimal Pregnancy’ (TIPTOP) project aims at delivering IPTp at the community level (C-IPTp) to complement ANC provision with the goal of increasing IPTp coverage and improving maternal and infant’s health. This protocol describes the approach to measure the effect of this strategy through household surveys (HHS) in four SSA countries: Democratic Republic of Congo (DRC), Madagascar, Mozambique and Nigeria.Methods and analysisA quasi-experimental evaluation has been designed. Delivery of C-IPTp will start first in one area per country, and later it will be extended to two more areas per country. HHS will be carried out before C-IPTp implementation in all study sites, at midterm in initial implementation areas, and after the implementation in all project areas. A multistage cluster sampling method will be followed for the selection of participants. Women of reproductive age who had a pregnancy that ended in the 6 or 12 months prior to the interview, depending on the survey, will be invited to participate by responding to a questionnaire. The main indicators will be coverage of three or more doses of IPTp and attendance to at least four ANC visits. A difference-in-difference analysis will be performed to evaluate the effectiveness of C-IPTp.Ethics and disseminationThe project has been reviewed by the ethics committees of WHO, Hospital Clinic of Barcelona and all project country boards. Project results will be disseminated to in-country stakeholders and at regional and international meetings. TIPTOP project aims to develop and disseminate global recommendations for C-IPTp delivery.Trial registration numberNCT03600844; Pre-results.

Background Malaria in pregnancy is a major public health problem in sub-Saharan Africa (SSA), which imposes a significant economic burden. We provide evidence on the costs of malaria care in pregnancy to households and the health system in four high-burden countries in SSA.  Methods Household and health system economic costs associated with malaria control in pregnancy were estimated in selected areas of the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA). An exit survey was administered to 2,031 pregnant women when leaving the antenatal care (ANC) clinic from October 2020 to June 2021. Women reported the direct and indirect costs associated to malaria prevention and treatment in pregnancy. To estimate health system costs, we interviewed health workers from 133 randomly selected health facilities. Costs were estimated using an ingredients-based approach. Results Average household costs of malaria prevention per pregnancy were USD6.33 in DRC, USD10.06 in MDG, USD15.03 in MOZ and USD13.33 in NGA. Household costs of treating an episode of uncomplicated/complicated malaria were USD22.78/USD46 in DRC, USD16.65/USD35.65 in MDG, USD30.54/USD61.25 in MOZ and USD18.92/USD44.71 in NGA, respectively. Average health system costs of malaria prevention per pregnancy were USD10.74 in DRC, USD16.95 in MDG, USD11.17 in MOZ and USD15.64 in NGA. Health system costs associated with treating an episode of uncomplicated/complicated malaria were USD4.69/USD101.41 in DRC, USD3.61/USD63.33 in MDG, USD4.68/USD83.70 in MOZ and USD4.09/USD92.64 in NGA. These estimates resulted in societal costs of malaria prevention and treatment per pregnancy of USD31.72 in DRC, USD29.77 in MDG, USD31.98 in MOZ and USD46.16 in NGA. Conclusions Malaria in pregnancy imposes a high economic burden on households and the health system. Findings emphasize the importance of investing in effective strategies that improve access to malaria control and reduce the burden of the infection in pregnancy.

Objectives The primary objectives of the study are: 1. To assess the effect of hydroxychloroquine (HCQ) in reducing SARS-CoV-2 viral shedding by PCR in infected pregnant women with mild symptoms. 2. To assess the efficacy of HCQ to prevent SARS-CoV-2 infection in pregnant women in contact with an infected or suspected case. 3. To evaluate the effect of HCQ in preventing the development of the COVID-19 disease in asymptomatic SARS-CoV-2-infected pregnant women. The secondary objectives are: 1. To determine the effect of HCQ on the clinical course and duration of the COVID-19 disease in SARS-CoV-2-infected pregnant women. 2. To determine the impact of HCQ on the risk of hospitalization and mortality of SARS-CoV-2-infected pregnant women. 3. To assess the safety and tolerability of HCQ in pregnant women. 4. To describe the clinical presentation of SARS-CoV-2 infection during pregnancy. 5. To describe the effects of maternal SARS-CoV-2 infection on pregnancy and perinatal outcomes by treatment group. 6. To determine the risk of vertical transmission (intra-utero and intra-partum) of SARS-CoV-2. Trial design Randomized double-blind placebo-controlled two-arm multicentre clinical trial to evaluate the safety and efficacy of HCQ to prevent and/or minimize SARS-CoV-2 infection during pregnancy. Participants will be randomized to receive a 14-day oral treatment course of HCQ or placebo, ratio 1:1. Participants Study population: pregnant women undergoing routine prenatal follow up or attending emergency units at the participating hospitals who report either symptoms/signs suggestive of COVID-19 disease or close contact with a suspected or confirmed COVID-19 case. Inclusion criteria Women will be invited to participate in the trial and sign an informed consent if they meet the following inclusion criteria. • Presenting with fever (≥37.5°C) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, dysgeusia, headache) OR being contact* of a SARS-CoV-2 confirmed or suspected case in the past 14 days • More than 12 weeks of gestation (dated by ultrasonography) • Agreement to deliver in the study hospitals Exclusion criteria • Known hypersensitivity to HCQ or other 4-amonoquinoline compounds • History of retinopathy of any aetiology • Concomitant use of digoxin, cyclosporine, cimetidine • Known liver disease • Clinical history of cardiac pathology including known long QT syndrome • Unable to cooperate with the requirements of the study • Participating in other intervention studies • Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours) The study participants will be stratified by clinical presentation and SARS-CoV-2 PCR results. Assignment of participants to study groups will be as follows: • SARS-CoV-2-PCR confirmed, infected pregnant women: a. symptomatic (n=100) b. asymptomatic (n=100) • SARS-CoV-2 PCR negative pregnant women in contact* with a SARS-CoV-2-infected confirmed or suspected case (n=514). *The ECDC definition of close contact will be followed. The trial will be conducted in five hospitals in Spain: Hospital Clínic of Barcelona, Hospital Sant Joan de Déu and Hospital de la Santa Creu i Sant Pau, in Barcelona, and HM Puerta del Sur and Hospital Universitario de Torrejón, in Madrid. Intervention and comparator Participants will be randomized to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days) or placebo (2 tablets for three days, followed by one tablet for 11 days). Main outcomes The primary outcome is the number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start (one week after treatment is completed). Randomisation Allocation of participants to study arms will be done centrally by the trial’s Sponsor (the Barcelona Institute for Global Health, ISGlobal) by block randomization. This method will ensure balanced allocation to both arms. The electronic CRF will automatically assign a study number to each participant, depending on her study group and recruitment site. Each number will be related to a treatment number, which assigns them to one of the study arms. Blinding (masking) Participants, caregivers, investigators and those assessing the outcomes will be blinded to group assignment. Study tablets (HCQ and placebo) will be identically packaged in small opaque bottles. Numbers to be randomised (sample size) This study requires 200 SARS-CoV-2 infected and 514 contact pregnant women, randomised 1:1 with 100 and 227 respectively in each study arm. Trial Status Protocol version 1.0, from May 8 th , 2020. Recruitment is ongoing (first patient recruited the 19 th May 2020 and recruitment end anticipated by December 2020). Trial registration EudraCT number: 2020-001587-29, registered 2 April 2020. Clinicaltrials.gov identifier: NCT04410562 , retrospectively registered 1 June 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

This work introduces a novel approach to stability and stabilization of nonlinear systems with delayed multivariable inputs; it provides exponential estimates as well as a guaranteed cost of the system solutions. The result is based on an exact convex representation of the nonlinear system which allows a Lyapunov–Krasovskii functional to be applied in order to obtain sufficient conditions in the form of linear matrix inequalities. These are efficiently solved via convex optimization techniques. A real-time implementation of the developed approach on the twin rotor MIMO system is included.

Malaria in pregnancy is a major driver of maternal and infant mortality in sub-Saharan Africa. The WHO recommends the administration of intermittent preventive treatment with sulfadoxine pyrimethamine (IPTp-SP) at antenatal care (ANC) visits. Despite being a highly cost-effective strategy, IPTp-SP coverage and uptake remains low. A pilot project was conducted to assess the cost-effectiveness (CE) of community-based delivery of IPTp (C-IPTp) in addition to ANC delivery to increase IPTp uptake in the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA). Costs and CE estimates of C-IPTp were calculated according to two scenarios: (1) costs in 'programmatic mode' (ie, costs if C-IPTp was to be implemented by national health systems) and (2) costs from the pilot project. The effectiveness of C-IPTp was obtained through estimates of the averted disability-adjusted life-years (DALYs) associated with maternal clinical malaria and anaemia, low birth weight and neonatal mortality. Net incremental costs of C-IPTp ranged between US$6138-US$47 177 (DRC), US$5552-US$31 552 (MDG), US$10 202-US$53 221 (MOZ) and US$667-US$28 645 (NGA) per 1000 pregnant women, under scenarios (1) and (2), respectively. Incremental cost-effectiveness ratios (ICERs) ranged between US$15-US$119 in DRC, US$9-US$53 in MDG, US$104-US$543 in MOZ and US$2-US$66 in NGA per DALY averted, under scenarios (1) and (2), respectively. ICERs fall below the WHO recommended CE threshold based on the gross domestic product per capita. Findings suggest that C-IPTp is a highly cost-effective intervention. Results can inform policy decisions on adopting and optimising effective interventions for preventing malaria in pregnancy.

Background Malaria in pregnancy is a major public health problem in sub-Saharan Africa (SSA), which imposes a significant economic burden. We provide evidence on the costs of malaria care in pregnancy to households and the health system in four high-burden countries in SSA.  Methods Household and health system economic costs associated with malaria control in pregnancy were estimated in selected areas of the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA). An exit survey was administered to 2,031 pregnant women when leaving the antenatal care (ANC) clinic from October 2020 to June 2021. Women reported the direct and indirect costs associated to malaria prevention and treatment in pregnancy. To estimate health system costs, we interviewed health workers from 133 randomly selected health facilities. Costs were estimated using an ingredients-based approach. Results Average household costs of malaria prevention per pregnancy were USD6.33 in DRC, USD10.06 in MDG, USD15.03 in MOZ and USD13.33 in NGA. Household costs of treating an episode of uncomplicated/complicated malaria were USD22.78/USD46 in DRC, USD16.65/USD35.65 in MDG, USD30.54/USD61.25 in MOZ and USD18.92/USD44.71 in NGA, respectively. Average health system costs of malaria prevention per pregnancy were USD10.74 in DRC, USD16.95 in MDG, USD11.17 in MOZ and USD15.64 in NGA. Health system costs associated with treating an episode of uncomplicated/complicated malaria were USD4.69/USD101.41 in DRC, USD3.61/USD63.33 in MDG, USD4.68/USD83.70 in MOZ and USD4.09/USD92.64 in NGA. These estimates resulted in societal costs of malaria prevention and treatment per pregnancy of USD31.72 in DRC, USD29.77 in MDG, USD31.98 in MOZ and USD46.16 in NGA. Conclusions Malaria in pregnancy imposes a high economic burden on households and the health system. Findings emphasize the importance of investing in effective strategies that improve access to malaria control and reduce the burden of the infection in pregnancy.

BackgroundIntermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of sulfadoxine-pyrimethamine alongside routine immunizations. IPTi has been renamed as Perennial Malaria Chemoprevention (PMC), accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy was assessed in children in selected areas of Sierra Leone. MethodsA cross-sectional, community-based, multi-stage cluster survey was conducted in 2021 in three districts in Northern and northwestern provinces of Sierra Leone among 10- 23 months old children. IPTi coverage was calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with iPTi coverage including malaria RDT were assessed.ResultsA total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38 – 55.75). Adjusted for all other studied covariates, older children (OR per month increase 1.07, 95% CI 1.02–1.11, P-value 0.0056), those who slept under a mosquito net the previous night (OR 1.76, 95% CI 1.22–2.53, P-value 0.0029) and those whose caretaker was paid-employed (OR 2.74, 95%CI 1.11, 6.74, P-value 0.0290) were more likely to have received the complete three IPTi doses. Children whose caretakers were males (OR 0.50, 95% CI 0.28–0.91, P-value 0.0251), residing in Port Loko district (OR 0.40, 95% CI 0.19–0.87, P-value 0.0212) and those with a positive RDT result (OR 0.57, 95% CI 0.39–0.82, P-value 0.0035), were less likely to have received complete three doses of IPTi. ConclusionIn this survey, IPTi coverage was around 50%. A positive health behaviour possibly explains the association with use of mosquito nets. This implies that positive health behaviour messaging is key in improving coverage of IPTi, a key malaria prevention strategy.