A scalable health system model to achieve high coverage and quality of Kangaroo mother care in Uttar Pradesh, India.

AIM: To design a health system model for scaling-up Kangaroo mother care (KMC) and assess its impact on the population-level coverage and quality of KMC in Uttar Pradesh, India. METHODS: We co-developed the model with mothers and health system stakeholders using human-centred design over multiple cycles of implementation, learning and data-driven refinement. Infants with birthweight <2000 g in the study district were prospectively followed to assess the 'effective coverage' of KMC. Effective coverage referred to the proportion of eligible infants receiving ≥8 h of daily skin-to-skin contact and exclusive breastfeeding. RESULTS: High delivery load facilities were equipped with a KMC Lounge to ensure comfort, respectful care of mothers and high-quality KMC over prolonged periods. Systems to ensure weighing at birth, referral of infants with birthweight <2000 g to KMC facilities, initiation of KMC for all stable low birthweight infants, improving quality of care within KMC facilities and supporting families to continue KMC at home post discharge, were integrated into existing services. KMC was initiated in 93.3% of eligible infants with effective coverage of 52.7% and 64.8% at discharge and 7 days post discharge, respectively. CONCLUSION: The model addressed critical barriers to KMC implementation and adoption, contributing to its scale-up across the state.

Effect of sunflower seed oil emollient therapy on newborn infant survival in Uttar Pradesh, India: A community-based, cluster randomized, open-label controlled trial.

BACKGROUND: Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in newborn infants. We hypothesized that SSO therapy may reduce NMR in such settings. METHODS AND FINDINGS: This was a population-based, cluster randomized, controlled trial in 276 clusters in rural Uttar Pradesh, India. All newborn infants identified through population-based surveillance in the study clusters within 7 days of delivery were enrolled from November 2014 to October 2016. Exclusive, 3 times daily, gentle applications of 10 ml of SSO to newborn infants by families throughout the neonatal period were recommended in intervention clusters (n = 138 clusters); infants in comparison clusters (n = 138 clusters) received usual care, such as massage practice typically with mustard oil. Primary analysis was by intention-to-treat with NMR and post-24-hour NMR as the primary outcomes. Secondary analysis included per-protocol analysis and subgroup analyses for NMR. Regression analysis was adjusted for caste, first-visit weight, delivery attendant, gravidity, maternal age, maternal education, sex of the infant, and multiple births. We enrolled 13,478 (52.2% male, mean weight: 2,575.0 grams ± standard deviation [SD] 521.0) and 13,109 (52.0% male, mean weight: 2,607.0 grams ± SD 509.0) newborn infants in the intervention and comparison clusters, respectively. We found no overall difference in NMR in the intervention versus the comparison clusters [adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.84 to 1.11, p = 0.61]. Acceptance of SSO in the intervention arm was high at 89.3%, but adherence to exclusive applications of SSO was 30.4%. Per-protocol analysis showed a significant 58% (95% CI 42% to 69%, p < 0.01) reduction in mortality among infants in the intervention group who were treated exclusively with SSO as intended versus infants in the comparison group who received exclusive applications of mustard oil. A significant 52% (95% CI 12% to 74%, p = 0.02) reduction in NMR was observed in the subgroup of infants weighing ≤1,500 g (n = 589); there were no statistically significant differences in other prespecified subgroup comparisons by low birth weight (LBW), birthplace, and wealth. No severe adverse events (SAEs) were attributable to the intervention. The study was limited by inability to mask allocation to study workers or participants and by measurement of emollient use based on caregiver responses and not actual observation. CONCLUSIONS: In this trial, we observed that promotion of SSO therapy universally for all newborn infants was not effective in reducing NMR. However, this result may not necessarily establish equivalence between SSO and mustard oil massage in light of our secondary findings. Mortality reduction in the subgroup of infants ≤1,500 g was consistent with previous hospital-based efficacy studies, potentially extending the applicability of emollient therapy in very low-birth-weight (VLBW) infants along the facility-community continuum. Further research is recommended to develop and evaluate therapeutic regimens and continuum of care delivery strategies for emollient therapy for newborn infants at highest risk of compromised skin barrier function. TRIAL REGISTRATION: ISRCTN Registry ISRCTN38965585 and Clinical Trials Registry-India (CTRI/2014/12/005282) with WHO UTN # U1111-1158-4665.

Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.

BACKGROUND: Maternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa. METHODS AND FINDINGS: This is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes. CONCLUSIONS: Our findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths. TRIAL REGISTRATION: The study is not a clinical trial.

Unravelling the nature of citric acid:L-arginine:water mixtures: the bifunctional role of water.

The use of water as a component of deep eutectic systems (DES) has raised some questions regarding its influence on the nature of the mixture. Does it form a DES or an aqueous solution and what is the role of water? In this work, the nature of citric acid:l-arginine:water mixtures was explored through phase equilibria studies and spectroscopic analysis. In a first step, PC-SAFT was validated as a predictive tool to model the water influence on the solid liquid equilibria (SLE) of the DES reline using the individual-component approach. Hence, activity coefficients in the ternary systems citric acid:l-arginine:water and respective binary combinations were studied and compared using ePC-SAFT. It was observed that the water-free mixtures citric acid:l-arginine showed positive deviation from Raoult's law, while upon addition of water strong negative deviation from Raoult's law was found, yielding melting depressions around 100 K. Besides these strong interactions, pH was found to become acidic (pH = 3.5) upon water addition, which yields the formation of charged species ([H2Cit]- and [l-arg]+). Thus, the increased interactions between the molecules upon water addition might be caused by several mechanisms such as hydrogen bonding or ionic forces, both being induced by water. For further investigation, the liquid mixtures citric acid:l-arginine:water were studied by FTIR and NMR spectroscopy. FTIR spectra disproved a possible solubility enhancement caused by salt formation between citric acid and l-arginine, while NMR spectra supported the formation of a hydrogen bonding network different from the binary systems citric acid:water and l-arginine:water. Either being a DES or other type of non-ideal solution, the liquefaction of the studied systems is certainly caused by a water-mediator effect based on the formation of charged species and cross interactions between the mixture constituents.

Tungstate Control of Microbial Sulfidogenesis and Souring of the Engineered Environment.

Sulfide accumulation in oil reservoir fluids (souring) from the activity of sulfate-reducing microorganisms (SRM) is of grave concern because of the associated health and facility failure risks. Here, we present an assessment of tungstate as a selective and potent inhibitor of SRM. Dose-response inhibitor experiments were conducted with a number of SRM isolates and enrichments at 30-80 °C and an increase in the effectiveness of tungstate treatment at higher temperatures was observed. To explore mixed inhibitor treatment modes, we tested synergy or antagonism between several inhibitors with tungstate, and found synergism between WO42- and NO2-, while additive effects were observed with ClO4- and NO3-. We also evaluated SRM inhibition by tungstate in advective upflow oil-sand-packed columns. Although 2 mM tungstate was initially sufficient to inhibit sulfidogenesis, subsequent temporal CaWO4 precipitation resulted in loss of the bioavailable inhibitor from solution and a concurrent increase in effluent sulfide. Mixing 4 mM sodium carbonate with the 2 mM tungstate was enough to promote tungstate solubility to reach inhibitory concentrations, without precipitation, and completely inhibit SRM activity. Overall, we demonstrate the effectiveness of tungstate as a potent SRM inhibitor, particularly at higher temperatures, and propose a novel carbonate-tungstate formulation for application to soured oil reservoirs.

Early adversity in rural India impacts the brain networks underlying visual working memory.

There is a growing need to understand the global impact of poverty on early brain and behavioural development, particularly with regard to key cognitive processes that emerge in early development. Although the impact of adversity on brain development can trap children in an intergenerational cycle of poverty, the massive potential for brain plasticity is also a source of hope: reliable, accessible, culturally agnostic methods to assess early brain development in low resource settings might be used to measure the impact of early adversity, identify infants for timely intervention and guide the development and monitor the effectiveness of early interventions. Visual working memory (VWM) is an early marker of cognitive capacity that has been assessed reliably in early infancy and is predictive of later academic achievement in Western countries. Here, we localized the functional brain networks that underlie VWM in early development in rural India using a portable neuroimaging system, and we assessed the impact of adversity on these brain networks. We recorded functional brain activity as young children aged 4-48 months performed a VWM task. Brain imaging results revealed localized activation in the frontal cortex, replicating findings from a Midwestern US sample. Critically, children from families with low maternal education and income showed weaker brain activity and poorer distractor suppression in canonical working memory areas in the left frontal cortex. Implications of this work are far-reaching: it is now cost-effective to localize functional brain networks in early development in low-resource settings, paving the way for novel intervention and assessment methods.

Practice Variation in the Diagnosis of Aneurysmal Subarachnoid Hemorrhage: A Survey of US and Canadian Emergency Medicine Physicians.

BACKGROUND AND AIMS: Spontaneous subarachnoid hemorrhage (SAH) from a brain aneurysm, if untreated in the acute phase, leads to loss of functional independence in about 30% of patients and death in 27-44%. To evaluate for SAH, the American College of Emergency Physicians (ACEP) Clinical Policy recommends obtaining a non-contrast brain computed tomography (CT) scan followed by a lumbar puncture (LP) if the CT is negative. On the other hand, current evidence from prospectively collected data suggests that CT alone may be sufficient to rule out SAH in patients who present within 6 h of symptom onset while anecdotal evidence suggests that CT angiogram (CTA) may be used to detect aneurysms, which are the probable cause of SAH. Since many different options are available to emergency physicians, we examined their practice pattern variation by observing their diagnostic approaches and their adherence to the ACEP Clinical Policy. METHODS: We developed, validated, and distributed a survey to emergency physicians at three practice sites: (1) Stanford Healthcare, California, (2) Intermountain Healthcare (five emergency departments), Utah, and (3) Ottawa General Hospital, Toronto. The survey questions examined physician knowledge on CT and LP's test performance and used case-based scenarios to assess diagnostic approaches, variation in practice, and adherence to guidelines. Results were presented as proportions with 95% CIs. RESULTS: Of the 216 physicians surveyed, we received 168 responses (77.8%). The responses by site were: (1) (n = 38, 23.2%), (2) (n = 70, 42.7%), (3) (n = 56, 34.1%). To the CT and LP test performance question, most physicians indicated that CT alone detects > 90% of SAH in those with a confirmed SAH [n = 150 (89.3%, 95% CI 83.6-93.5]. To the case-based questions, most physicians indicated that they would perform a CTA along with a CT [n = 110 (65.5%, 95% CI 57.8-72.6)], some indicated a LP along with a CT [n = 57, 33.9% 95% CI 26.8-41.6)], and a few indicated both a CTA and a LP [n = 16, 9.5%, 95% CI 5.5-15.0]. We also observed practice site variation in the proportion of physicians who indicated that they would use CTA: (1) (n = 25, 65.8%), (2) (n = 54, 77.1%), and (3) (n = 28, 50.0%) (p = 0.006). CONCLUSIONS: Survey responses indicate that physicians use some or all of the imaging tests, with or without LP to diagnose SAH. We observed variation in the use of CTA by site and academic setting and divergence from ACEP Clinical Policy.

Improving performance of the Tariff Method for assigning causes of death to verbal autopsies.

BACKGROUND: Reliable data on the distribution of causes of death (COD) in a population are fundamental to good public health practice. In the absence of comprehensive medical certification of deaths, the only feasible way to collect essential mortality data is verbal autopsy (VA). The Tariff Method was developed by the Population Health Metrics Research Consortium (PHMRC) to ascertain COD from VA information. Given its potential for improving information about COD, there is interest in refining the method. We describe the further development of the Tariff Method. METHODS: This study uses data from the PHMRC and the National Health and Medical Research Council (NHMRC) of Australia studies. Gold standard clinical diagnostic criteria for hospital deaths were specified for a target cause list. VAs were collected from families using the PHMRC verbal autopsy instrument including health care experience (HCE). The original Tariff Method (Tariff 1.0) was trained using the validated PHMRC database for which VAs had been collected for deaths with hospital records fulfilling the gold standard criteria (validated VAs). In this study, the performance of Tariff 1.0 was tested using VAs from household surveys (community VAs) collected for the PHMRC and NHMRC studies. We then corrected the model to account for the previous observed biases of the model, and Tariff 2.0 was developed. The performance of Tariff 2.0 was measured at individual and population levels using the validated PHMRC database. RESULTS: For median chance-corrected concordance (CCC) and mean cause-specific mortality fraction (CSMF) accuracy, and for each of three modules with and without HCE, Tariff 2.0 performs significantly better than the Tariff 1.0, especially in children and neonates. Improvement in CSMF accuracy with HCE was 2.5%, 7.4%, and 14.9% for adults, children, and neonates, respectively, and for median CCC with HCE it was 6.0%, 13.5%, and 21.2%, respectively. Similar levels of improvement are seen in analyses without HCE. CONCLUSIONS: Tariff 2.0 addresses the main shortcomings of the application of the Tariff Method to analyze data from VAs in community settings. It provides an estimation of COD from VAs with better performance at the individual and population level than the previous version of this method, and it is publicly available for use.

A shortened verbal autopsy instrument for use in routine mortality surveillance systems.

BACKGROUND: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed. In this paper we describe a shortened version of the VAI developed for the Population Health Metrics Research Consortium (PHMRC) Gold Standard Verbal Autopsy Validation Study using a systematic approach. METHODS: We used data from the PHMRC validation study. Using the Tariff 2.0 method, we first established a rank order of individual questions in the PHMRC VAI according to their importance in predicting causes of death. Second, we reduced the size of the instrument by dropping questions in reverse order of their importance. We assessed the predictive performance of the instrument as questions were removed at the individual level by calculating chance-corrected concordance and at the population level with cause-specific mortality fraction (CSMF) accuracy. Finally, the optimum size of the shortened instrument was determined using a first derivative analysis of the decline in performance as the size of the VA instrument decreased for adults, children, and neonates. RESULTS: The full PHMRC VAI had 183, 127, and 149 questions for adult, child, and neonatal deaths, respectively. The shortened instrument developed had 109, 69, and 67 questions, respectively, representing a decrease in the total number of questions of 40-55%. The shortened instrument, with text, showed non-significant declines in CSMF accuracy from the full instrument with text of 0.4%, 0.0%, and 0.6% for the adult, child, and neonatal modules, respectively. CONCLUSIONS: We developed a shortened VAI using a systematic approach, and assessed its performance when administered using hand-held electronic tablets and analyzed using Tariff 2.0. The length of a VA questionnaire was shortened by almost 50% without a significant drop in performance. The shortened VAI developed reduces the burden of time and resources required for data collection and analysis of cause of death data in civil registration systems.

Male youth with eating disorders: clinical and medical characteristics of a sample of inpatients.

A retrospective chart review was conducted to elucidate the clinical and medical characteristics of male youth admitted to a tertiary inpatient treatment center for eating disorders. A total of 23 male youth were identified who had received treatment between January 2003 and February 2014, and for whom charts were available. The majority of the sample (n = 19; 82.6%) received a diagnosis of anorexia nervosa, and the data suggest that these male youth were significantly medically compromised. The patterns in this data will be discussed in the context of previous published research on male youth with eating disorders.

Using verbal autopsy to measure causes of death: the comparative performance of existing methods.

BACKGROUND: Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability. METHODS: We investigated the validity of five automated VA methods for assigning cause of death: InterVA-4, Random Forest (RF), Simplified Symptom Pattern (SSP), Tariff method (Tariff), and King-Lu (KL), in addition to physician review of VA forms (PCVA), based on 12,535 cases from diverse populations for which the true cause of death had been reliably established. For adults, children, neonates and stillbirths, performance was assessed separately for individuals using sensitivity, specificity, Kappa, and chance-corrected concordance (CCC) and for populations using cause specific mortality fraction (CSMF) accuracy, with and without additional diagnostic information from prior contact with health services. A total of 500 train-test splits were used to ensure that results are robust to variation in the underlying cause of death distribution. RESULTS: Three automated diagnostic methods, Tariff, SSP, and RF, but not InterVA-4, performed better than physician review in all age groups, study sites, and for the majority of causes of death studied. For adults, CSMF accuracy ranged from 0.764 to 0.770, compared with 0.680 for PCVA and 0.625 for InterVA; CCC varied from 49.2% to 54.1%, compared with 42.2% for PCVA, and 23.8% for InterVA. For children, CSMF accuracy was 0.783 for Tariff, 0.678 for PCVA, and 0.520 for InterVA; CCC was 52.5% for Tariff, 44.5% for PCVA, and 30.3% for InterVA. For neonates, CSMF accuracy was 0.817 for Tariff, 0.719 for PCVA, and 0.629 for InterVA; CCC varied from 47.3% to 50.3% for the three automated methods, 29.3% for PCVA, and 19.4% for InterVA. The method with the highest sensitivity for a specific cause varied by cause. CONCLUSIONS: Physician review of verbal autopsy questionnaires is less accurate than automated methods in determining both individual and population causes of death. Overall, Tariff performs as well or better than other methods and should be widely applied in routine mortality surveillance systems with poor cause of death certification practices.

Leveraging technological advances to assess dyadic visual cognition during infancy in high- and low-resource settings.

Caregiver-infant interactions shape infants' early visual experience; however, there is limited work from low-and middle-income countries (LMIC) in characterizing the visual cognitive dynamics of these interactions. Here, we present an innovative dyadic visual cognition pipeline using machine learning methods which captures, processes, and analyses the visual dynamics of caregiver-infant interactions across cultures. We undertake two studies to examine its application in both low (rural India) and high (urban UK) resource settings. Study 1 develops and validates the pipeline to process caregiver-infant interaction data captured using head-mounted cameras and eye-trackers. We use face detection and object recognition networks and validate these tools using 12 caregiver-infant dyads (4 dyads from a 6-month-old UK cohort, 4 dyads from a 6-month-old India cohort, and 4 dyads from a 9-month-old India cohort). Results show robust and accurate face and toy detection, as well as a high percent agreement between processed and manually coded dyadic interactions. Study 2 applied the pipeline to a larger data set (25 6-month-olds from the UK, 31 6-month-olds from India, and 37 9-month-olds from India) with the aim of comparing the visual dynamics of caregiver-infant interaction across the two cultural settings. Results show remarkable correspondence between key measures of visual exploration across cultures, including longer mean look durations during infant-led joint attention episodes. In addition, we found several differences across cultures. Most notably, infants in the UK had a higher proportion of infant-led joint attention episodes consistent with a child-centered view of parenting common in western middle-class families. In summary, the pipeline we report provides an objective assessment tool to quantify the visual dynamics of caregiver-infant interaction across high- and low-resource settings.

Shifts in Serum Bile Acid Profiles Associated With Barrett's Esophagus and Stages of Progression to Esophageal Adenocarcinoma.

INTRODUCTION: Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression. METHODS: Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression. RESULTS: A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11-3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04-3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes. DISCUSSION: Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.

Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy.

INTRODUCTION: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease. METHODS: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups. RESULTS: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations. DISCUSSION: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

Prospective multi-centre sentinel surveillance for Haemophilus influenzae type b & other bacterial meningitis in Indian children.

BACKGROUND & OBJECTIVES: Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance. METHODS: Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per µl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens. RESULTS: A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively). INTERPRETATION & CONCLUSIONS: Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.

Maternal-child consumption of ultra-processed foods and sugar-sweetened beverages in informal settlements in Mumbai, India.

BACKGROUND: The global nutrition transition is associated with increased consumption of ultra-processed snack foods and sugar-sweetened beverages (UPF/SSB), contributing to the double burden of child obesity and undernutrition. METHODS: This cross-sectional study describes the prevalence of maternal and child UPF/SSB consumption and the factors associated with frequent consumption in a convenience sample of 749 children ages 6 months through 6 years and their mothers participating in a community-based child oral health program in five informal settlement communities in Mumbai, India. Mothers were interviewed regarding maternal and child oral health and nutrition characteristics, including consumption of beverages and foods associated with tooth decay-milk, soda, tea with sugar, sweets, and chips/biscuits-using standardized questionnaires. Spearman correlations were used to assess for associations between various social factors and the frequency of maternal and child consumption of the five food categories. Chi-square tests were used to assess differences in child consumption patterns by age groups. RESULTS: Though reported soda consumption was low among both mothers and children, nearly 60% of children consumed sweets and chips/biscuits daily, four to five times the rate of mothers. Factors associated with children's frequent consumption of UPF/SSB included lower maternal education level, frequent maternal consumption of UPF/SSB, greater number of household members, greater amount of money given to the child, and closer proximity to a store. CONCLUSION: Our findings demonstrate social factors that may promote UPF/SSB consumption. The nutritional dangers of sugary drinks and non-nutritious snacks for mothers and young children should be addressed across maternal-child health, education, and social service programs. Early childhood nutrition interventions should involve the entire family and community and emphasize the need to limit children's consumption of unhealthy foods and beverages from an early age.

Poor air quality is associated with impaired visual cognition in the first two years of life: A longitudinal investigation.

Background: Poor air quality has been linked to cognitive deficits in children, but this relationship has not been examined in the first year of life when brain growth is at its peak. Methods: We measured in-home air quality focusing on particulate matter with diameter of <2.5 µm (PM2.5) and infants' cognition longitudinally in a sample of families from rural India. Results: Air quality was poorer in homes that used solid cooking materials. Infants from homes with poorer air quality showed lower visual working memory scores at 6 and 9 months of age and slower visual processing speed from 6 to 21 months when controlling for family socio-economic status. Conclusions: Thus, poor air quality is associated with impaired visual cognition in the first two years of life, consistent with animal studies of early brain development. We demonstrate for the first time an association between air quality and cognition in the first year of life using direct measures of in-home air quality and looking-based measures of cognition. Because indoor air quality was linked to cooking materials in the home, our findings suggest that efforts to reduce cooking emissions should be a key target for intervention. Funding: Bill & Melinda Gates Foundation grant OPP1164153.

Stunting in infancy is associated with atypical activation of working memory and attention networks.

Stunting is associated with poor long-term cognitive, academic and economic outcomes, yet the mechanisms through which stunting impacts cognition in early development remain unknown. In a first-ever neuroimaging study conducted on infants from rural India, we demonstrate that stunting impacts a critical, early-developing cognitive system-visual working memory. Stunted infants showed poor visual working memory performance and were easily distractible. Poor performance was associated with reduced engagement of the left anterior intraparietal sulcus, a region involved in visual working memory maintenance and greater suppression in the right temporoparietal junction, a region involved in attentional shifting. When assessed one year later, stunted infants had lower problem-solving scores, while infants of normal height with greater left anterior intraparietal sulcus activation showed higher problem-solving scores. Finally, short-for-age infants with poor physical growth indices but good visual working memory performance showed more positive outcomes suggesting that intervention efforts should focus on improving working memory and reducing distractibility in infancy.

Association of leisure-time physical activity and sedentary behavior with carotid atherosclerosis morphology: The ARIC carotid-MRI study.

Objective: We evaluated the prospective association of midlife leisure-time physical activity (LTPA) and sedentary behavior (SB), and their temporal patterns, with MRI-measured carotid atherosclerotic morphology. Methods: Participants enrolled in the Carotid MRI substudy (2004-2006) of the Atherosclerosis Risk in Communities (ARIC) Study and with self-reported assessments of LTPA and SB at visits 1 (1987-1989) and 3 (1993-1995) were included in this study. LTPA was ascertained using the ARIC/Baecke physical activity questionnaire and categorized according to the American Heart Association's metric of poor, intermediate, or ideal physical activity. SB, measured as TV viewing frequency, was categorized as high, medium, and low. We used multivariable adjusted linear and logistic regression models to examine the associations between midlife (visit 3 only) and persistent (visit 1 to 3) LTPA and TV viewing with carotid artery plaque burden and components. Results: Among the 1,582 (mean age: 59 years, 43% male, 18% Black) participants, 45.7%, 21.7%, and 32.6% reported ideal, intermediate, or poor LTPA, respectively. High TV viewing was reported in 33.8% of participants, with 46.4% and 19.8% reporting medium or low TV viewing, respectively. Compared to poor LTPA, ideal LTPA in midlife was not associated with total wall volume (ß=0.01, 95% CI: -0.01, 0.03), maximum carotid wall thickness (ß=0.06, 95% CI: -0.08, 0.21), normalized wall index (ß=-0.01, 95% CI: -0.03, 0.01), or maximum stenosis (ß=-0.11, 95% CI: -1.98, 1.76). Low or middle, compared to high, TV viewing was also not associated with carotid artery measures of plaque burden. Compared to poor LTPA or high TV viewing, ideal LTPA (odds ratio (OR): 0.82, 95% CI: 0.55, 1.23) and low TV viewing (OR=0.90, 95% CI: 0.56, 1.44) was not associated with odds of lipid core presence, respectively. Conclusion: Overall, this study does not provide strong evidence for an association between LTPA and SB with carotid plaque measures.

Impact of community-based behaviour-change management on perceived neonatal morbidity: a cluster-randomized controlled trial in Shivgarh, Uttar Pradesh, India.

In the context of high neonatal mortality rate (NMR) in developing country settings, a promising strategy for enhancing newborn health is promotion of preventive newborn care practices. We measured the effect of a behaviour-change intervention on perceived neonatal illnesses in rural Uttar Pradesh, India. The study was nested in a cluster-randomized controlled trial of the impact of a package of essential newborn care on NMR. We prospectively enrolled 802 mothers and administered a questionnaire on perceived neonatal morbidities. Regression analysis showed that newborns in the intervention clusters had significantly lower risk of perceived diarrhoea [adjusted relative risk (aRR) 0.67, 95% confidence interval (CI) 0.49-0.90] and skin-related complications [aRR 0.67, 95% CI 0.45-1.00] compared to newborns in the comparison area. Assuming incidence of perceived illnesses is a proxy for actual morbidity rates, we conclude that promotion of preventive care practices through behaviour-change interventions was effective in reducing neonatal morbidities.