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Background The frequency and clinical presentation of malaria infections show marked heterogeneity in epidemiological studies. However, deeper understanding of this variability is hampered by the difficulty in quantifying all relevant factors. Here, we report the history of malaria infections in twins, who are exposed to the same in utero milieu, share genetic factors, and are similarly exposed to vectors. Methods Data were obtained from a Malian longitudinal birth cohort. Samples from 25 twin pairs were examined for malaria infection and antibody responses. Bayesian models were developed for the number of infections during follow-up. Results In 16 of 25 pairs, both children were infected and often developed symptoms. In 8 of 25 pairs, only 1 twin was infected, but usually only once or twice. Statistical models suggest that this pattern is not inconsistent with twin siblings having the same underlying infection rate. In a pair with discordant hemoglobin genotype, parasite densities were consistently lower in the child with hemoglobin AS, but antibody levels were similar. Conclusions By using a novel design, we describe residual variation in malaria phenotypes in naturally matched children and confirm the important role of environmental factors, as suggested by the between-twin pair heterogeneity in malaria history.

Background Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental disorders later in life. The impact of the gestational timing of MIA exposure on downstream development remains unclear. Methods We characterized neurodevelopmental trajectories of mice exposed to the viral mimetic poly I:C (polyinosinic:polycytidylic acid) either on gestational day 9 (early) or on day 17 (late) using longitudinal structural magnetic resonance imaging from weaning to adulthood. Using multivariate methods, we related neuroimaging and behavioral variables for the time of greatest alteration (adolescence/early adulthood) and identified regions for further investigation using RNA sequencing. Results Early MIA exposure was associated with accelerated brain volume increases in adolescence/early adulthood that normalized in later adulthood in the striatum, hippocampus, and cingulate cortex. Similarly, alterations in anxiety-like, stereotypic, and sensorimotor gating behaviors observed in adolescence normalized in adulthood. MIA exposure in late gestation had less impact on anatomical and behavioral profiles. Multivariate maps associated anxiety-like, social, and sensorimotor gating deficits with volume of the dorsal and ventral hippocampus and anterior cingulate cortex, among others. The most transcriptional changes were observed in the dorsal hippocampus, with genes enriched for fibroblast growth factor regulation, autistic behaviors, inflammatory pathways, and microRNA regulation. Conclusions Leveraging an integrated hypothesis- and data-driven approach linking brain-behavior alterations to the transcriptome, we found that MIA timing differentially affects offspring development. Exposure in late gestation leads to subthreshold deficits, whereas exposure in early gestation perturbs brain development mechanisms implicated in neurodevelopmental disorders.

Generalized estimating equations [Image: see text] are widely used to analyze longitudinal data; however, they are not appropriate for heteroscedastic data, because they only estimate regressor effects on the mean response – and therefore do not account for data heterogeneity. Here, we combine the [Image: see text] with the asymmetric least squares (expectile) regression to derive a new class of estimators, which we call generalized expectile estimating equations [Image: see text] . The [Image: see text] model estimates regressor effects on the expectiles of the response distribution, which provides a detailed view of regressor effects on the entire response distribution. In addition to capturing data heteroscedasticity, the GEEE extends the various working correlation structures to account for within-subject dependence. We derive the asymptotic properties of the [Image: see text] estimators and propose a robust estimator of its covariance matrix for inference (see our R package, github.com/AmBarry/expectgee). Our simulations show that the GEEE estimator is non-biased and efficient, and our real data analysis shows it captures heteroscedasticity.

Diagnosis and minimal residual disease (MRD) monitoring of chronic lymphocytic leukemia (CLL) by flow cytometry currently requires multiple antibody panels. We added CD23 and CD200 to the EuroFlowT...

Background In malaria-endemic areas, pregnant women and especially first-time mothers are more susceptible to Plasmodium falciparum. Malaria diagnosis is often missed during pregnancy, because many women with placental malaria remain asymptomatic or have submicroscopic parasitemia, masking the association between malaria and pregnancy outcomes. Severe maternal anemia and low birthweight deliveries are well-established sequelae, but few studies have confirmed the relationship between malaria infection and severe outcomes like perinatal mortality in high transmission zones. Methods Pregnant women of any gestational age enrolled at antenatal clinic into a longitudinal cohort study in Ouelessebougou, Mali, an area of high seasonal malaria transmission. Follow-up visits included scheduled and unscheduled visits throughout pregnancy. Blood smear microscopy and polymerase chain reaction (PCR) analysis were employed to detect both microscopic and submicroscopic infections, respectively. Intermittent preventative treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) was documented and prompt treatment regardless of symptoms given upon malaria diagnosis. Results Of the 1850 women followed through delivery, 72.6% of women received 2 or more IPTp-SP doses, 67.2% of women experienced at least 1 infection between enrollment up to and including delivery. Malaria infection increased the risks of stillbirth (adjusted hazard ratio [aHR] 3.87, 95% confidence interval [CI]: 1.18–12.71) and preterm delivery (aHR 2.41, 95% CI: 1.35–4.29) in primigravidae, and early neonatal death (death within 7 days) in secundigravidae and multigravidae (aHR 6.30, 95% CI: 1.41–28.15). Conclusions Malaria treatment after diagnosis, alongside IPTp-SP, is insufficient to prevent malaria-related stillbirth, early neonatal death and preterm delivery (PTD). Although IPTp-SP was beneficial in Mali during the study period, new tools are needed to improve pregnancy outcomes. Clinical Trials Registration NCT01168271.

Background Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali. Methods Between 2014 and 2016, 30 977 children aged 3–59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year. Poisson regression with gamma-distributed random effects, accounting for the household randomization and within-individual clustering of illness episodes, was used to compare incidence of prespecified outcomes between SMC+AZ versus SMC+placebo groups in fixed time strata post-treatment. The likelihood ratio test was used to assess evidence for a time-treatment group interaction. Results Relative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration (protective efficacy (PE): 24.2% [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], respectively, in the first 2 weeks postadministration. Protection against nonmalaria fevers with a skin condition persisted up to 28 days: PE: 46.3% [35.1; 55.6%]. Conclusions The benefits of AZ-MDA are broad-ranging but short-lived. To maximize impact, timing of AZ-MDA must address the challenge of targeting asynchronous morbidity and mortality peaks from different causes., Mass administration of azithromycin (AZ-MDA) alongside seasonal malaria chemoprevention in children in Burkina Faso and Mali has broad-ranging but short-lived benefits. To maximize impact, AZ-MDA must address the challenge of targeting asynchronous peaks in morbidity and mortality from different causes.

Maternal mortality remains very high in developing countries. In Guinea, it is 550 maternal deaths in 100.000 living birth. More than half of these deaths occur in the postpartum period. Hence the interests to have a better understanding of the factors that hinder the realization of post-natal care (PNC) arise. It is for this reason that the objective of this study is to identify barriers to the use of post-natal care in Guinea. Methods: A qualitative study was conducted in the prefectures of Kindia and Dubreka, in the Administrative Region of Kindia (Guinea) in April and May 2014. Fourteen focus group discussions of women and girls of the community, as well as fifteen individual in-depth interviews (9 with women and 6 with healthcare providers). Results: Most women do their PNC during their child vaccination or in case of postpartum complications. Financial constraints are the main barrier to using postnatal care identified by participants. In general, distance from the health center associated with lack of transport mean and insufficient staffs are factors related to the health system. In addition, poor reception of clients, women’s experience during childbirth, poor programming for PNC as well as the lack of trust and confidentiality between clients and health care providers are the barriers related to health providers. The participants also mentioned the lack of sensitization and information as well as cultural constraints as barriers to using post-natal care. Conclusion: The removal of these barriers in the use of PNC will significantly reduce maternal and neonatal mortality in Guinea.

Introduction: Maternal mortality remains a major public health problem in the world. Complications during pregnancy and childbirth are the main causes of maternal mortality in low-income countries. It is estimated that 15% of deaths are related to these complications. Studies have shown that women have little or no acquaintance on sign danger and complications during pregnancy and childbirth. Limited literature exists on women’s knowledge and attitudes about pregnancy and childbirth’s complications as well as the barriers for their management, therefore necessity to carry out this study. Objective: To explore women’s knowledge and attitudes in the community about complications during pregnancy and childbirth. Method: A qualitative study was conducted in three prefectures of Guinea. Eighteen focus groups were conducted with women of reproductive age living in urban and rural areas. Results: Complications during pregnancy and childbirth are common among pregnant women in Guinea. Many women have knowledge about various sorts of complications related to pregnancy and childbirth. These complications were mostly vaginal bleeding, abortions and maternal mortality. The use of a health facility in case of complications during pregnancy and childbirth was reported as a major attitude in this study. Accompanying the woman to the health facility was another attitude identified. Lack of financial means, the distance from the health facilities and the lack of means of transport were listed as barriers to the management of complications during pregnancy and childbirth. Conclusion: This study showed that women’s knowledge and attitudes about obstetric complications are insufficient. To that effect, women counselling during prenatal consultations on the risks of complications and especially the identification of sign danger during pregnancy and childbirth is essential to reduce maternal and neonatal mortality in our less equipped countries.

Mass administration of azithromycin has reduced mortality in children in sub-Saharan Africa but its mode of action is not well characterised. A recent trial found that azithromycin given alongside seasonal malaria chemoprevention was not associated with a reduction in mortality or hospital admissions in young children. We investigated the effect of azithromycin on the nutritional status of children enrolled in this study.A total of 19 578 children in Burkina Faso and Mali were randomised to receive either azithromycin or placebo alongside seasonal malaria chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine monthly for three malaria transmission seasons (2014-2016). After each transmission season, anthropometric measurements were collected from approximately 4000 randomly selected children (2000 per country) at a cross-sectional survey and used to derive nutritional status indicators. Binary and continuous outcomes between treatment arms were compared by Poisson and linear regression.Nutritional status among children was poor in both countries with evidence of acute and chronic malnutrition (24.9-33.3% stunted, 15.8-32.0% underweight, 7.2-26.4% wasted). There was a suggestion of improvement in nutritional status in Burkina Faso and deterioration in Mali over the study period. At the end of each malaria transmission season, nutritional status of children did not differ between treatment arms (seasonal malaria chemoprevention plus azithromycin or placebo) in either the intention-to-treat or per-protocol analyses (only children with at least three cycles of SMC in the current intervention year).The addition of azithromycin to seasonal malaria chemoprevention did not result in an improvement of nutritional outcomes in children in Burkina Faso and Mali.L'administration massive d'azithromycine a réduit la mortalité infantile en Afrique subsaharienne mais son mode d'action n'est pas bien caractérisé. Un essai récent a révélé que l'azithromycine administrée parallèlement à la chimioprévention du paludisme saisonnier n'était pas associée à une réduction de la mortalité ou des hospitalisations chez les jeunes enfants. Nous avons étudié l'effet de l'azithromycine sur l'état nutritionnel des enfants inscrits à cette étude. MÉTHODES: 19.578 enfants au Burkina Faso et au Mali ont été randomisés pour recevoir soit de l'azithromycine soit un placebo parallèlement à une chimioprévention du paludisme saisonnier avec du sulfadoxine-pyriméthamine plus de l’amodiaquine par mois pendant trois saisons de transmission du paludisme (2014-2016). Après chaque saison de transmission, des mesures anthropométriques ont été recueillies auprès d'environ 4.000 enfants sélectionnés au hasard (2.000 par pays) lors d'une enquête transversale et utilisées pour dériver des indicateurs de l'état nutritionnel. Les résultats binaires et continus entre les bras de traitement ont été comparés par la régression linéaire et de Poisson. RÉSULTATS: L'état nutritionnel des enfants était médiocre dans les deux pays avec des signes de malnutrition aiguë et chronique (24,9 à 33,3% de retard de croissance, 15,8 à 32,0% d'insuffisance pondérale, 7,2 à 26,4% d'émaciation). Il a été suggéré une amélioration de l'état nutritionnel au Burkina Faso et une détérioration au Mali au cours de la période d'étude. A la fin de chaque saison de transmission du paludisme, l'état nutritionnel des enfants ne différait pas entre les bras de traitement (chimioprévention contre le paludisme saisonnier plus azithromycine ou placebo) dans les analyses en intention de traiter ou selon le protocole (seulement les enfants avec au moins trois cycles de chimioprévention dans l’année d’intervention en cours).L'ajout d'azithromycine à la chimioprévention du paludisme saisonnier n'a pas entraîné d'amélioration des résultats nutritionnels chez les enfants au Burkina Faso et au Mali.

Dans un contexte de villes sénégalaises confrontées à des problèmes d’assainissement, la ville de Rufisque fait face à un problème de santé publique à l’instar d’une insalubrité croissance exposant les populations au syndrome diarrhéique. L’objectif de cette étude est de mesurer la prévalence de la diarrhée chez les enfants de moins de 5 ans. Afin d’établir le lien entre la qualité de l’environnement et la diarrhée infanto-juvénile, un receuil des données sanitaires et une enquête ont été réalisés auprès de 918 ménages sur les conditions socio-environnementales et la morbidité diarrhéique en septembre 2018. Avec l’appui des méthodes statistiques uni-variées et bi-variées, il a été effectué des tests d’association (Khi-2) et de corrélation R de Pearson entre la morbidité diarrhéique et les facteurs de risque potentiels. Les résultats mettent en évidence une variabilité socio-spatiale des maladies diarrhéiques dans l’espace urbain, avec certains quartiers très touchés (Cartor, Gouye Aldiana, Colobane et Escale) et d’autres moins affectés (Hlm, Diokoul, et Rufisque II). Toutefois, cette distribution inégale de la pathologie diarrhéique est infleuncée par un certain nombre de facteurs de risque dont les plus significativement associés à sa survenue sont le mode d’accès à l’eau potable dont le robinet (R = 0,93), le WC branché à une fosse (R = 0,96), l’aire de jeu des enfants dans la cour (R = 0, 99) et dans les espaces péridomestiques (R = 0,81) ainsi que le statut socio-économique (R=0,94). Ces facteurs de risque diarrhéique laisse supposer que les enfants vivant dans des milieux urbains bien assainis sont moins exposés à l’occurrence des maladies diarrhéiques et vice-versa. Mots-clès : environnment, diarrhée, risque, prévalence, ville, Rufisque. English Abstract: Urban environment and health risk: Geographical approach to childhood diarrhoea in the city of Rufisque (Senegal). In a context of Senegalese cities facing sanitation problems, the city of Rufisque faces a public health problem such as growing insalubrity exposing populations to diarrheal syndrome. The objective of this study is to measure the prevalence of diarrhea in children under 5 years old. In order to establish the link between the quality of the environment and infant and juvenile diarrhea, a collection of health data and a survey were carried out among 918 households on socio-environmental conditions and diarrheal morbidity in September 2018. With Supporting univariate and bivariate statistical methods, Pearson association (Chi-square) and R correlation tests were performed between diarrheal morbidity and potential risk factors. The results highlight a socio-spatial variability of diarrheal diseases in urban areas, with some neighborhoods very affected (Cartor, Gouye Aldiana, Colobane and Escale) and others less affected (Hlm, Diokoul, and Rufisque II). However, this uneven distribution of diarrheal pathology is influenced by a number of risk factors, the most significantly associated with its occurrence are the mode of access to drinking water including the tap (R = 0.93), WC connected to a pit (R = 0.96), the children's play area in the yard (R = 0, 99) and in peridomestic spaces (R = 0.81) as well as the socio-economic status ( R = 0.94). These diarrheal risk factors suggest that children living in healthy urban settings are less exposed to the occurrence of diarrheal diseases and vice versa. Keywords: environment, diarrhea, risk, prevalence, city, Rufisque

Background In 2012, seasonal malaria chemoprevention (SMC) was recommended as policy for malaria control by the World Health Organization (WHO) in areas of highly seasonal malaria transmission across the Sahel sub-region in Africa along with monitoring of drug resistance. We assessed the long-term impact of SMC on Plasmodium falciparum resistance to sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) over a 3-year period of SMC implementation in the health district of Ouelessebougou, Mali. Methods In 8 randomly selected sub-districts of Ouelessebougou, Mali, children aged 0–5 years were randomly selected during cross-sectional surveys at baseline (August 2014) and 1, 2 and 3 years post-SMC, at the beginning and end of the malaria transmission season. Blood smears and blood spots on filter paper were obtained and frequencies of mutation in P. falciparum genes related to resistance to SP and AQ (Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt) were assessed by PCR amplification on individual samples and PCR amplification followed by deep sequencing on pooled (by site and year) samples. Results At each survey, approximately 50–100 individual samples were analysed by PCR amplification and a total of 1,164 samples were analysed by deep sequencing with an average read depth of 18,018–36,918 after pooling by site and year. Most molecular markers of resistance did not increase in frequency over the period of study (2014–2016). After 3 years of SMC, the frequencies of Pfdhps 540E, Pfdhps 437G and Pfcrt K76T remained similar compared to baseline (4.0 vs 1.4%, p = 0.41; 74.5 vs 64.6%, p = 0.22; 71.3 vs 67.4%, p = 0.69). Nearly all samples tested carried Pfdhfr 59R, and this proportion remained similar 3 years after SMC implementation (98.8 vs 100%, p = 1). The frequency of Pfmdr1 N86Y increased significantly over time from 5.6% at baseline to 18.6% after 3 years of SMC (p = 0.016). Results of pooled analysis using deep sequencing were consistent with those by individual analysis with standard PCR, but also indicated for the first time the presence of mutations at the Pfdhps A581G allele at a frequency of 11.7% after 2 years of SMC, as well as the Pfdhps I431V allele at frequencies of 1.6–9.3% following 1 and 2 years of SMC, respectively. Conclusion Two and 3 years of SMC implementation were associated with increased frequency of the Pfmdr1 N86Y mutation but not Pfdhps 540E, Pfdhps 437G and Pfcrt K76T. The first-time detection of the Pfdhps haplotype bearing the I431V and A581G mutations in Mali, even at low frequency, warrants further long-term surveillance.

Background Seasonal malaria chemoprevention (SMC) is a novel strategy to reduce malaria infections in children. Infection with Plasmodium falciparum results in immune dysfunction characterized by elevated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOXP3+ T cells. Methods In the current study, the impact of seasonal malaria chemoprevention on malaria-induced immune dysfunction, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow cytometry. Results Children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to children not receiving SMC. Conclusions These results provide important insights into the dynamics of malaria-induced changes in the CD4 T-cell compartment of the immune system and suggest that the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction. Clinical Trials Registration NCT02504918.

Plasmodium falciparum variant antigens named erythrocyte membrane protein 1 (PfEMP1) are important targets for developing a protective immunity to malaria caused by P. falciparum. One of the major challenges in P. falciparum proteomics studies is identifying PfEMP1s at the protein level due to antigenic variation. To identify these PfEMP1s using shotgun proteomics, we developed a pipeline that searches high-resolution mass spectrometry spectra against a custom protein sequence database. A local alignment algorithm, LAX, was developed as a part of the pipeline that matches peptide sequences to the most similar PfEMP1 and calculates a weight value based on peptide's uniqueness used for PfEMP1 protein inference. The pipeline was first validated in the analysis of a laboratory strain with a known PfEMP1, then it was implemented on the analysis of parasite isolates from malaria-infected pregnant women and finally on the analysis of parasite isolates from malaria-infected children where there was an increase of PfEMP1s identified in 27 out of 31 isolates using the expanded database.

This paper aims to how Indonesian Leaders Forum (ILF) as a new talkshow program in Indonesia effort to increasing political interest of citizens. This research uses descriptive qualitative method with a case study of the ILF Program. By using descriptive method, the author can explain the background of the incident, some perspective on the event and analyze in depth. So the ILF can answer the public's concerns about the political situation in Indonesia today conclusion contains the main points of the article.

Adipose tissue is a central regulator of metabolic health and its failure in obesity is a major cause of weight associated comorbidities, such as type 2 diabetes. Many extracellular matrix proteins, represented by matrisome, play a critical role in balancing adipose tissue health and dysfunction. Extracellular matrix components, produced by different cell types of adipose tissue, can modulate adipocyte function, tissue remodeling during expansion, angiogenesis, and inflammation and also form fibrotic lesions in the tissue. In this study, we investigated changes in matrisome of whole adipose tissue and adipocytes in human obesity. We investigated further the networks and biological pathways of the genes related to the changes and their association to development of metabolic dysfunction linked to type 2 diabetes. We used transcriptome data and clinical metabolic parameters from a rare weight-discordant MZ twin cohort. The Heavy-Lean differential matrisome gene expression (Δmatrisome) and differential metabolic parameters reflect changes in adipose tissue upon weight gain and changes in whole body glucose, insulin metabolism, as well as lipid status. We report that obesity Δmatrisome shows high specificity with 130 and 71 of the 1068 matrisome genes showing altered expression in the adipose tissue and adipocytes of heavier co-twin, respectively. The Δmatrisome differs considerably between adipose tissue vs adipocytes which reflects inflammation of hypertrophic adipocytes and the remodeling activity of the rest of the tissue resident cells. The obesity Δmatrisome is discussed extensively in the light of existing evidence and novel significant associations to obesity are reported to matrisome genes; cathepsin A, cathepsin O, FAM20B and N-glycanase1.

Using hand-collected survey and experimental data, we examine the determinants of financial literacy as well as the link between self-reported risk and elicited risk preferences in a least developed African country, Guinea. We measure financial literacy as the sum of three elements: financial knowledge, attitude, and behaviour. Our findings indicate that the lack of a significant relationship between our financial literacy measure and risk preferences is caused by the crowding out effects of financial attitude and knowledge. Individuals who display stronger financial knowledge are more willing to take on risk, but so are those with poor financial attitudes. Among individuals who have extensive financial knowledge, those with lower financial attitude scores or negative attitudes towards future planning and saving are more willing to take risks. These highlight the need to accentuate not only financial knowledge but also strong financial attitude and good financial behaviour to comprehensively and properly manage risks.

Background More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP. Methods In 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4–5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-142 and AMA1 by ELISA. Results The prevalence of antibodies to MSP-142 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62–1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44–6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70–5.76, p 42 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64–1.15) and 0.95 ((0.68–1.15), respectively), anti-CSP (1.30 (1.00–1.56) and 1.17 (0.87–1.47)), and anti-AMA-1 (1.45 (1.24–1.68) and 1.41 (1.17–1.64)). Conclusion In an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-142 and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period.

Background Malaria and malnutrition remain major problems in Sahel countries, especially in young children. The direct effect of malnutrition on malaria remains poorly understood, and may have important implications for malaria control. In this study, nutritional status and the association between malnutrition and subsequent incidence of symptomatic malaria were examined in children in Burkina Faso and Mali who received either azithromycin or placebo, alongside seasonal malaria chemoprevention. Methods Mid-upper arm circumference (MUAC) was measured in all 20,185 children who attended a screening visit prior to the malaria transmission season in 2015. Prior to the 2016 malaria season, weight, height and MUAC were measured among 4149 randomly selected children. Height-for-age, weight-for-age, weight-for-height, and MUAC-for-age were calculated as indicators of nutritional status. Malaria incidence was measured during the following rainy seasons. Multivariable random effects Poisson models were created for each nutritional indicator to study the effect of malnutrition on clinical malaria incidence for each country. Results In both 2015 and 2016, nutritional status prior to the malaria season was poor. The most prevalent form of malnutrition in Burkina Faso was being underweight (30.5%; 95% CI 28.6–32.6), whereas in Mali stunting was most prevalent (27.5%; 95% CI 25.6–29.5). In 2016, clinical malaria incidence was 675 per 1000 person-years (95% CI 613–744) in Burkina Faso, and 1245 per 1000 person-years (95% CI 1152–1347) in Mali. There was some evidence that severe stunting was associated with lower incidence of malaria in Mali (RR 0.81; 95% CI 0.64–1.02; p = 0.08), but this association was not seen in Burkina Faso. Being moderately underweight tended to be associated with higher incidence of clinical malaria in Burkina Faso (RR 1.27; 95% CI 0.98–1.64; p = 0.07), while this was the case in Mali for moderate wasting (RR 1.27; 95% CI 0.98–1.64; p = 0.07). However, these associations were not observed in severely affected children, nor consistent between countries. MUAC-for-age was not associated with malaria risk. Conclusions Both malnutrition and malaria were common in the study areas, high despite high coverage of seasonal malaria chemoprevention and long-lasting insecticidal nets. However, no strong or consistent evidence was found for an association between any of the nutritional indicators and the subsequent incidence of clinical malaria.

Prenatal maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders. How gestational timing of MIA-exposure differentially impacts downstream development remains unclear. Here, we characterize neurodevelopmental trajectories of mice exposed to MIA induced by poly I:C either early (gestational day [GD]9) or late (GD17) in gestation using longitudinal structural magnetic resonance imaging from weaning to adulthood. Early MIA-exposure associated with accelerated brain volume increases in adolescence/early-adulthood that normalized in later adulthood, in regions including the striatum, hippocampus, and cingulate cortex. Similarly, alterations in anxiety, stereotypic, and sensorimotor gating behaviours observed in adolescence normalized in adulthood. In contrast, MIA-exposure in late gestation had less impact on anatomical and behavioural profiles. Using a multivariate technique to relate imaging and behavioural variables for the time of greatest alteration, i.e. adolescence/early adulthood, we demonstrate that variation in anxiety, social, and sensorimotor gating associates significantly with volume of regions including the dorsal and ventral hippocampus, and anterior cingulate cortex. Using RNA sequencing to explore the molecular underpinnings of region-specific alterations in early MIA-exposed mice in adolescence, we observed the most transcriptional changes in the dorsal hippocampus, with regulated genes enriched for fibroblast growth factor regulation, autistic behaviours, inflammatory pathways, and microRNA regulation. This indicates that MIA in early gestation perturbs brain development mechanisms implicated in neurodevelopmental disorders. Our findings demonstrate the inherent strength of an integrated hypothesis- and data-driven approach in linking brain-behavioural alterations to the transcriptome to understand how MIA confers risk for major mental illness.

Background The choice of preprocessing pipeline introduces variability in neuroimaging analyses that affects the reproducibility of scientific findings. Features derived from structural and functional MRI data are sensitive to the algorithmic or parametric differences of preprocessing tasks, such as image normalization, registration, and segmentation to name a few. Therefore it is critical to understand and potentially mitigate the cumulative biases of pipelines in order to distinguish biological effects from methodological variance. Methods Here we use an open structural MRI dataset (ABIDE), supplemented with the Human Connectome Project, to highlight the impact of pipeline selection on cortical thickness measures. Specifically, we investigate the effect of (i) software tool (e.g., ANTS, CIVET, FreeSurfer), (ii) cortical parcellation (Desikan-Killiany-Tourville, Destrieux, Glasser), and (iii) quality control procedure (manual, automatic). We divide our statistical analyses by (i) method type, i.e., task-free (unsupervised) versus task-driven (supervised); and (ii) inference objective, i.e., neurobiological group differences versus individual prediction. Results Results show that software, parcellation, and quality control significantly affect task-driven neurobiological inference. Additionally, software selection strongly affects neurobiological (i.e. group) and individual task-free analyses, and quality control alters the performance for the individual-centric prediction tasks. Conclusions This comparative performance evaluation partially explains the source of inconsistencies in neuroimaging findings. Furthermore, it underscores the need for more rigorous scientific workflows and accessible informatics resources to replicate and compare preprocessing pipelines to address the compounding problem of reproducibility in the age of large-scale, data-driven computational neuroscience.

In this paper, we use U.S. commercial banks' data to investigate whether the effect of unexpected deposit flows on loan production depends on banks' exposure to off-balance sheet funding liquidity risk. We find that lending is sensitive to deposit shocks at small banks but not at large ones. Furthermore, for small banks, the increase in lending explained by unexpected deposit inflows depends on how much they are exposed to funding liquidity risk stemming from their off-balance sheets, as measured by the level of unused commitments. Small banks more exposed to such funding liquidity risk tend to extend fewer new loans. Our results indicate that unexpected deposit inflows from, for instance, the failure of other banks or market disruptions might not as easily be fueled again to borrowers.

Background In sub-Saharan Africa, malaria continues to scourge the population and is the primary cause of morbidity and mortality in young children and pregnant women. As current preventative measures such as intermittent preventive treatment and use of insecticide-treated nets provide incomplete protection, several malaria vaccines are currently under development, including one to specifically prevent pregnancy malaria. Prior to conducting vaccine trials, it is important to obtain background information on poor pregnancy outcomes in the target population to establish a baseline. Methods Pregnant women presenting at community health care centers for antenatal care were recruited to the study. Gestational age was determined by ultrasound examination following recruitment. Antenatal care and pregnancy outcome information were collected during a visit 4–8 weeks post-delivery. Results One thousand eight hundred fifty women completed the study, and analysis included 1814 women after excluding multiple gestations (n = 26) and missing/incomplete data (n = 10). The percentage (95% CI) of adverse pregnancy outcomes is as follows: miscarriage, 0.28% (0.04–0.52); stillbirth, 1.93% (1.30–2.56); early neonatal death, 1.65% (1.03–2.24); late neonatal death, 0.39%, (0.10–0.68); and preterm delivery (PTD), 4.74% (3.76–5.73). The percentages of early and late neonatal deaths and PTD were significantly higher (p Conclusions Low gravidity and young age predict perinatal death and PTD. The information collected here can be used as a baseline for adverse pregnancy outcomes in future vaccine trials in pregnant women.

Background Seasonal malaria chemoprevention is widely implemented in Sahel and sub-Sahel countries in Africa. Few studies have assessed the impact of the SMC on hospital admission and death when it is implemented in the health system. This retrospective study assessed the impact of seasonal malaria chemoprevention (SMC) on hospitalizations and deaths of children under 5 years of age during the second year of implementation of SMC in the health district of Ouelessebougou in Mali. Methods In February 2017, a survey was conducted to assess hospital admissions and deaths in children under 5 years of age in two health sub-districts where SMC was implemented in 2015 and two health sub-districts where SMC was not implemented. The survey reviewed deaths and hospitalizations of children under 5, in the four health sub-districts. The crude and specific incidence rates of hospitalizations and deaths were determined in both groups and expressed per 1000 children per year. A negative binomial regression model and a Cox model were used to estimate the relative risks of hospitalization and death after adjusting for confounders. The R software was used for data analysis. Results A total of 6638 children under 5 years of age were surveyed, 2759 children in the SMC intervention areas and 3879 children in the control areas. All causes mortality rate per 1000 person-years was 8.29 in the control areas compared to 3.63 in the intervention areas; age and gender adjusted mortality rate ratio 0.44 (95% CI 0.22–0.91), p = 0.027. The incidence rate of all causes hospital admissions was 19.60 per 1000 person-years in the intervention group compared to 33.45 per 1000 person-years in the control group, giving an incidence rate ratio (IRR) adjusted for age and gender of 0.61 (95% CI 0.44–0.84), p = 0.003. Conclusion The implementation of SMC was associated with a substantial reduction in hospital admissions and all-cause mortality. Trial registration ClinicalTrials.gov NCT02646410.

Additional file 1 Supplementary Table 1 Multivariate logistic regression analysis of maternal factors associated with pregnancy loss and PTD. AOR: Adjusted odds ratio. Multivariate analysis included variables that were significant in univariate analyses.

Identification of influential observations is crucial in data analysis, particularly with high dimensional datasets, where the number of predictors is higher than the sample size. These rich datasets with extensive detail are increasingly exploited and analyzed in multiple fields of science, e.g., genomics, neuroscience, finance, etc. Unfortunately, classical diagnostic statistical tools are not tailored for identifying influential observations in high dimensional setup. In this paper, we use the concept of expectiles to develop an influence measure in high dimensional regression. The influence measure is based on the asymmetric marginal correlation, and its derived asymptotic distribution is used to define a threshold based on statistical principles. Our comprehensive simulation results display the favorable qualities of this influence measure under various scenarios. The usefulness of the proposed measure is illustrated through the analysis of a neuroimaging dataset. An R package implementing the procedure is publicly available on GitHub (https://github.com/AmBarry/hidetify).

Additional file 2 Supplementary Table 2 Pregnancy outcomes: women diagnosed with malaria (n = 228). 1Pregnancy loss (combined miscarriage, stillbirth and neonatal death)

Background Seasonal malaria chemoprevention (SMC) is now widely deployed in the Sahel, including several countries that are major contributors to the global burden of malaria. Consequently, it is important to understand whether SMC continues to provide a high level of protection and how SMC might be improved. SMC was evaluated using data from a large, household-randomised trial in Houndé, Burkina Faso and Bougouni, Mali. Methods and findings The parent trial evaluated monthly SMC plus either azithromycin (AZ) or placebo, administered as directly observed therapy 4 times per year between August and November (2014–2016). In July 2014, 19,578 children aged 3–59 months were randomised by household to study group. Children who remained within the age range 3–59 months in August each year, plus children born into study households or who moved into the study area, received study drugs in 2015 and 2016. These analyses focus on the approximately 10,000 children (5,000 per country) under observation each year in the SMC plus placebo group. Despite high coverage and high adherence to SMC, the incidence of hospitalisations or deaths due to malaria and uncomplicated clinical malaria remained high in the study areas (overall incidence rates 12.5 [95% confidence interval (CI): 11.2, 14.1] and 871.1 [95% CI: 852.3, 890.6] cases per 1,000 person-years, respectively) and peaked in July each year, before SMC delivery began in August. The incidence rate ratio comparing SMC within the past 28 days with SMC more than 35 days ago—adjusted for age, country, and household clustering—was 0.13 (95% CI: 0.08, 0.20), P < 0.001 for malaria hospitalisations and deaths from malaria and 0.21 (95% CI 0.20, 0.23), P < 0.001 for uncomplicated malaria, indicating protective efficacy of 87.4% (95% CI: 79.6%, 92.2%) and 78.3% (95% CI: 76.8%, 79.6%), respectively. The prevalence of malaria parasitaemia at weekly surveys during the rainy season and at the end of the transmission season was several times higher in children who missed the SMC course preceding the survey contact, and the smallest prevalence ratio observed was 2.98 (95% CI: 1.95, 4.54), P < 0.001. The frequency of molecular markers of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance did not increase markedly over the study period either amongst study children or amongst school-age children resident in the study areas. After 3 years of SMC deployment, the day 28 PCR-unadjusted adequate clinical and parasitological response rate of the SP + AQ regimen in children with asymptomatic malaria was 98.3% (95% CI: 88.6%, 99.8%) in Burkina Faso and 96.1% (95% CI: 91.5%, 98.2%) in Mali. Key limitations of this study are the potential overdiagnosis of uncomplicated malaria by rapid diagnostic tests and the potential for residual confounding from factors related to adherence to the monthly SMC schedule. Conclusion Despite strong evidence that SMC is providing a high level of protection, the burden of malaria remains substantial in the 2 study areas. These results emphasise the need for continuing support of SMC programmes. A fifth monthly SMC course is needed to adequately cover the whole transmission season in the study areas and in settings with similar epidemiology. Trial registration The AZ-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT02211729., Matthew Cairns and colleagues show additional courses of seasonal chemoprevention are needed in Burkina Faso and Mali to control malaria., Author summary Why was this study done? Seasonal malaria chemoprevention (SMC) is recommended for children under 5 years of age in countries of the Sahel and sub-Sahel. Many countries in West and Central Africa now have large-scale SMC programmes. The malaria burden remains high in several countries that have introduced SMC, including Burkina Faso and Mali, which are amongst the most important contributors to the global burden of malaria cases and deaths. It is important to understand whether SMC retains a high level of protection in these areas and how its impact might be improved. What did the researchers do and find? In this study, the level of protection provided by SMC was investigated using data from a large but closely supervised clinical trial in 2 districts in southern Burkina Faso and Mali. SMC was delivered 4 times per year over 3 years, reaching a very high percentage of children. All the daily doses of SMC were supervised by the study team. Specific substudies showed that molecular markers of resistance to the combination of antimalarials used for SMC were rare amongst malaria parasites and that the SMC combination was highly effective in curing infections detected at the end of the rainy season. Malaria incidence was markedly reduced in the period immediately after each SMC course. In the first 4 weeks after SMC, malaria cases were reduced by 78%, and malaria hospitalisations and deaths from malaria were reduced by 87%. Despite the benefits of SMC, the number of malaria cases, hospital admissions for malaria, and deaths from malaria remained very high in the study areas. There was a large peak in July each year, coinciding with the beginning of the rainy season, before SMC delivery began in August. What do these findings mean? SMC is likely to be averting a very large number of malaria cases, hospitalisations, and deaths in the study areas, but malaria has still not been brought under control. At least one additional monthly course of SMC is needed to address the high burden of malaria, including malaria deaths, that currently occurs outside the peak transmission season. This is likely to be the case in other areas of the Sahel that have a longer transmission season than can be covered by a 4-month SMC programme. Additional new tools are needed urgently to further reduce malaria in these districts and areas with similar epidemiology.

European banks have experienced significant changes in the type of entity that owns them (another bank, an individual or a family, a non-financial company, an institutional investor, a government, a foreign entity, a domestic entity…). In this paper, we look at the influence of ownership type changes on performance. Working with a panel of commercial banks from 17 European countries, we find that although banks that experience a change in ownership type do not exhibit lower or higher risk or profitability than other banks, their risk and profitability is significantly affected after the change takes place. The type of the acquirer plays a significant role in explaining the observed changes. When the acquirer is a non-financial company, the state or an institutional investor, the level of risk increases after the change while the level of profitability remains unchanged. Conversely, when the acquirer is a bank, we find that the level of risk-adjusted profitability decreases. Banks acquired by a different type of owner during the global financial crisis do not perform better or worse than they did before.