MesoHOPS: Size-invariant scaling calculations of multi-excitation open quantum systems.

The photoexcitation dynamics of molecular materials on the 10-100 nm length scale depend on complex interactions between electronic and vibrational degrees of freedom, rendering exact calculations difficult or intractable. The adaptive Hierarchy of Pure States (adHOPS) is a formally exact method that leverages the locality imposed by interactions between thermal environments and electronic excitations to achieve size-invariant scaling calculations for single-excitation processes in systems described by a Frenkel-Holstein Hamiltonian. Here, we extend adHOPS to account for arbitrary couplings between thermal environments and vertical excitation energies, enabling formally exact, size-invariant calculations that involve multiple excitations or states with shared thermal environments. In addition, we introduce a low-temperature correction and an effective integration of the noise to reduce the computational expense of including ultrafast vibrational relaxation in Hierarchy of Pure States (HOPS) simulations. We present these advances in the latest version of the open-source MesoHOPS library and use MesoHOPS to characterize charge separation at a one-dimensional organic heterojunction when both the electron and hole are mobile.

Simulating optical linear absorption for mesoscale molecular aggregates: An adaptive hierarchy of pure states approach.

In this paper, we present dyadic adaptive HOPS (DadHOPS), a new method for calculating linear absorption spectra for large molecular aggregates. This method combines the adaptive HOPS (adHOPS) framework, which uses locality to improve computational scaling, with the dyadic HOPS method previously developed to calculate linear and nonlinear spectroscopic signals. To construct a local representation of dyadic HOPS, we introduce an initial state decomposition that reconstructs the linear absorption spectra from a sum over locally excited initial conditions. We demonstrate the sum over initial conditions can be efficiently Monte Carlo sampled and that the corresponding calculations achieve size-invariant [i.e., O(1)] scaling for sufficiently large aggregates while trivially incorporating static disorder in the Hamiltonian. We present calculations on the photosystem I core complex to explore the behavior of the initial state decomposition in complex molecular aggregates as well as proof-of-concept DadHOPS calculations on an artificial molecular aggregate inspired by perylene bis-imide to demonstrate the size-invariance of the method.

Exact Results for the Tavis-Cummings and Hückel Hamiltonians with Diagonal Disorder.

We present an exact method to calculate the electronic states of one electron Hamiltonians with diagonal disorder. We show that in cases where the disorder has a Cauchy distribution, the disorder averaged one particle Green's function can be calculated directly, using a deterministic, complex (non-Hermitian) Hamiltonian. For this we use the supersymmetric method which has already been used in problems of solid state physics. Using the method we find exact solution for the case of N molecules with site disorder, confined to a microcavity, for any value of N. Our analysis shows that the width of the polaritonic states as a function of N depends on the nature of disorder, and hence it can be used to probe the way molecular energy levels are distributed. We also show how one can find exact results for Hückel type Hamiltonians with on-site Cauchy disorder and demonstrate its use.

Effects of disorder on polaritonic and dark states in a cavity using the disordered Tavis-Cummings model.

We consider molecules confined to a microcavity of dimensions such that an excitation of the molecule is nearly resonant with a cavity mode. The molecular excitation energies are assumed to be Gaussianly distributed with mean ϵa and variance σ. We find an asymptotically exact solution for large number density N. Conditions for the existence of the polaritonic states and expressions for their energies are obtained. Polaritonic states are found to be quite stable against disorder. Our results are verified by comparison with simulations. When ϵa is equal to energy of the cavity state ϵc, the Rabi splitting is found to increase by 2σ2N|V|, where V is the coupling of a molecular excitation to the cavity state. An analytic expression is found for the disorder-induced width of the polaritonic peak. Results for various densities of states and the absorption spectrum are presented. The dark states turn "gray" in the presence of disorder with their contribution to the absorption increasing with σ. Lifetimes of the cavity and molecular states are found to be important, and for sufficiently large Rabi splitting, the width of the polaritonic peaks is dominated by them. We also give analytical results for the case where the molecular levels follow a uniform distribution. We conclude that the study of the width of the polaritonic peaks as a function of the Rabi splitting can give information on the distribution of molecular energy levels. Finally, the effects of (a) orientational disorder and (b) spatial variation on the cavity field are presented.

Solution to the Kramers barrier crossing problem caused by two noises: Thermal noise and Poisson white noise.

We consider the escape of a particle trapped in a metastable potential well and acted upon by two noises. One of the noises is thermal and the other is Poisson white noise, which is non-Gaussian. Using path integral techniques, we find an analytic solution to this generalization of the classic Kramers barrier crossing problem. Using the "barrier climbing" path, we calculate the activation exponent. We also derive an approximate expression for the prefactor. The calculated results are compared with the simulations, and a good agreement between the two is found. Our results show that, unlike in the case of thermal noise, the rate depends not just on the barrier height but also on the shape of the whole barrier. A comparison between the simulations and the theory also shows that a better approximation for the prefactor is needed for agreement for all values of the parameters.

Zinc Supplementation for Promoting Growth in Children Under 5 years of age in Low- and Middle-income Countries: A Systematic Review.

OBJECTIVE: To study the effect of zinc supplementation in children under 5 years of age rom low- and middle-income countries (LMICs) on anthropometry and prevalence of malnutrition. Design: Systematic review of randomized controlled trials and cluster randomized trials. SETTING: Low- and middle-income countries. PARTICIPANTS: 63 trials with zinc supplementation, incorporating data on 27372 children. Trials conducted exclusively in specifically diseased participants and in children with severe acute malnutrition were excluded. Intervention: Zinc supplementation, provided either as medicinal supplementation or through food fortification. OUTCOME MEASURES: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference, head circumference; (ii) Prevalence of malnutrition. RESULTS: There was no evidence of effect on height-for-age Z score at the end of supplementation period (25 trials; 9165 participants; MD= 0.00 Z; 95% CI -0.07, 0.07; P=0.98; moderate quality evidence) with significant heterogeneity (I² = 57%; P<0.001) related to dose and duration of zinc between trials. There was little or no effect on change in height-for-age Z score (13 trials; 8852 participants; MD= 0.11 Z; 95% CI -0.00, 0.21; P=0.05), but the heterogeneity was considerable (I²=94%; P<0.001). There was no evidence of effect on length (6303 participants; MD= 1.18 cm; 95% CI -0.63, 2.99 cm, P=0.20; moderate quality evidence; considerable heterogeneity, I²=99%) but a little positive effect on change in length (19 trials; 10783 participants; MD= 0.43 cm; 95% CI 0.16, 0.70, P=0.002; moderate quality evidence; considerable heterogeneity, I²=93%). There was no evidence of effect on weight-for-age Z score or change in weight-for-age Z score but a little positive effect on weight (19 trials; 8851 study participants; MD= 0.23 kg; 95% CI 0.03, 0.42; P=0.02; considerable heterogeneity, I²=91%) and change in weight (kg) (23 trials; 10143 study participants; MD= 0.11 kg; 95% CI 0.05, 0.17, P<0.001, substantial heterogeneity, I²=80%). There was no evidence of effect on weight-for-height Z score, and mid upper arm circumference at the end of supplementation period, but there was a little positive effect on change in MUAC from baseline (8 trials; 1724 participants; MD = 0.09 cm; 95% CI 0.01, 0.16; P=0.03; no heterogeneity, I²=0%). Head circumference in zinc supplemented group was marginally higher compared to control (2966 study participants; MD= 0.39 cm; 95% CI 0.03, 0.75; P=0.03; substantial heterogeneity, I²=67%). There was no evidence of benefit in stunting (10 trials; 11838 study participants; RR= 1.0; 95% CI 0.95, 1.06; P=0.89; Moderate Quality Evidence; no significant heterogeneity, I²=11%), wasting (7 trials; 8988 study participants; RR= 0.94; 95% CI 0.82, 1.06; P=0.31; Moderate Quality Evidence; no significant heterogeneity, I²=13%) or underweight (7 trials; 8677 study participants; RR= 1.08; 95% CI 0.96, 1.21; P=0.19; Moderate Quality Evidence; substantial heterogeneity, I²=73%). CONCLUSION: Available evidence suggests that zinc supplementation probably leads to little or no improvement in anthropometric indices and malnutrition (stunting, underweight and wasting) in children under five years of age in LMICs. Advocating zinc supplementation as a public health measure to improve growth, therefore appears unjustified in these settings with scarce resources.

Impact of Water, Sanitation and Hygiene Interventions on Growth, Non-diarrheal Morbidity and Mortality in Children Residing in Low- and Middle-income Countries: A Systematic Review.

OBJECTIVE: To evaluate the impact of water, sanitation and hygiene (WASH) interventions in children (age <18 y) on growth, non-diarrheal morbidity and mortality in children. DESIGN: Systematic review of randomized controlled trials, non-randomized controlled trials and controlled before-after studies. SETTING: Low- and middle-income countries. PARTICIPANTS: 41 trials with WASH intervention, incorporating data on 113055 children. INTERVENTION: Hygiene promotion and education (15 trials), water intervention (10 trials), sanitation improvement (7 trials), all three components of WASH (4 trials), combined water and sanitation (1 trial), and sanitation and hygiene (1 trial). OUTCOME MEASURES: (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference; (ii) Prevalence of malnutrition; (iii) Non-diarrheal morbidity; and (iv) mortality. RESULTS: There may be little or no effect of hygiene intervention on most anthropometric parameters (low- to very-low quality evidence). Hygiene intervention reduced the risk of developing Acute respiratory infections by 24% (RR 0.76; 95% CI 0.59, 0.98; moderate quality evidence), cough by 10% (RR 0.90; 95% CI 0.83, 0.97; moderate quality evidence), laboratory-confirmed influenza by 50% (RR 0.5; 95% CI 0.41, 0.62; very low quality evidence), fever by 13% (RR 0.87; 95% CI 0.74, 1.02; moderate quality evidence), and conjunctivitis by 51% (RR 0.49; 95% CI 0.45, 0.55; low quality evidence). There was low quality evidence to suggest no impact of hygiene intervention on mortality (RR 0.65; 95% CI 0.25, 1.7). Improvement in water supply and quality was associated with slightly higher weight-for-age Z-score (MD 0.03; 95% CI 0, 0.06; low quality evidence), but no significant impact on other anthropometric parameters or infectious morbidity (low to very low quality evidence). There was very low quality evidence to suggest reduction in mortality (RR 0.45; 95% CI 0.25, 0.81). Improvement in sanitation had a variable effect on the anthropometry and infectious morbidity. Combined water, sanitation and hygiene intervention improved height-for-age Z scores (MD 0.22; 95% CI 0.12, 0.32) and decreased the risk of stunting by 13% (RR 0.87; 95% CI 0.81, 0.94) (very low quality of evidence). There was no evidence of significant effect of combined WASH interventions on non-diarrheal morbidity (fever, respiratory infections, intestinal helminth infection and school absenteeism) (low- to very-low quality of evidence). Any WASH intervention (considered together) resulted in lower risk of underweight (RR 0.81; 95% CI 0.69, 0.96), stunting (RR 0.77; 95% CI 0.68, 0.86) and wasting (RR 0.12, 0.85) (low- to very-low quality of evidence). CONCLUSIONS: Available evidence suggests that there may be little or no effect of WASH interventions on the anthropometric indices in children from low- and middle-income countries. There is low- to very-low quality of evidence to suggest decrease in prevalence of wasting, stunting and underweight. WASH interventions (especially hygiene intervention) were associated with lower risk of non-diarrheal morbidity (very low to moderate quality evidence). There was very low quality evidence to suggest some decrease to no change in mortality. These potential health benefits lend support to the ongoing efforts for provision of safe and adequate water supply, sanitation and hygiene.

Lipid based nutrient supplements (LNS) for treatment of children (6 months to 59 months) with moderate acute malnutrition (MAM): A systematic review.

BACKGROUND: Moderate acute malnutrition is a major public health problem affecting children from low- and middle-income countries. Lipid nutrient supplements have been proposed as a nutritional intervention for its treatment. OBJECTIVES: To evaluate the effectiveness and safety of LNS for the treatment of MAM in infants and children 6 to 59 months of age. STUDY DESIGN: Systematic review of randomized-controlled trials and controlled before-after studies. RESULTS: Data from nine trials showed that use of LNS, in comparison to specially formulated foods, improved the recovery rate (RR 1.08; 95% CI 1.02-1.14, 8 RCTs, 8934 participants, low quality evidence); decreased the chances of no recovery (RR 0.70; 95% CI 0.58-0.85, 7 RCTs, 8364 participants, low quality evidence) and the risk of deterioration into severe acute malnutrition (RR 0.87; 95% CI 0.73-1.03, 6 RCTs, 6788 participants, low quality evidence). There was little impact on mortality (RR 0.94, 95% CI 0.54-1.52, 8 RCTs, 8364 participants, very-low- quality evidence) or default rate (RR 1.32; 95% CI 0.73-2.4, 7 studies, 7570 participants, low quality evidence). There was improvement in weight gain, weight-for-height z-scores, height-for-age z-scores and mid-upper arm circumference. Subset analyses suggested higher recovery rates with greater amount of calories provided and with ready-to-use therapeutic foods, in comparison to ready-to-use supplementary foods. One study comparing LNS with nutritional counselling (very low quality evidence) showed higher chance of recovery, lower risk of deteriorating into severe acute malnutrition and lower default rate, with no impact on mortality, and no recovery. CONCLUSIONS: Evidence restricted to the African regions suggests that LNS may be slightly more effective than specially formulated fortified foods or nutritional counselling in recovery from MAM, lowering the risk of deterioration into SAM, and improving weight gain with little impact on mortality or default rate.

Integrated management of childhood illness (IMCI) strategy for children under five.

BACKGROUND: More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the integrated management of childhood illness (IMCI) strategy to reduce mortality and morbidity and to improve quality of care by improving the delivery of a variety of curative and preventive medical and behavioral interventions at health facilities, at home, and in the community. OBJECTIVES: To evaluate the effects of programs that implement the IMCI strategy in terms of death, nutritional status, quality of care, coverage with IMCI deliverables, and satisfaction of beneficiaries. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; MEDLINE; EMBASE, Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EbscoHost; the Latin American Caribbean Health Sciences Literature (LILACS), Virtual Health Library (VHL); the WHO Library & Information Networks for Knowledge Database (WHOLIS); the Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Science; Population Information Online (POPLINE); the WHO International Clinical Trials Registry Platform (WHO ICTRP); and the Global Health, Ovid and Health Management, ProQuest database. We performed searches until 30 June 2015 and supplemented these by searching revised bibliographies and by contacting experts to identify ongoing and unpublished studies. SELECTION CRITERIA: We sought to include randomised controlled trials (RCTs) and controlled before-after (CBA) studies with at least two intervention and two control sites evaluating the generic IMCI strategy or its adaptation in children younger than age five, and including at minimum efforts to improve health care worker skills for case management. We excluded studies in which IMCI was accompanied by other interventions including conditional cash transfers, food supplementation, and employment. The comparison group received usual health services without provision of IMCI. DATA COLLECTION AND ANALYSIS: Two review authors independently screened searches, selected trials, and extracted, analysed and tabulated data. We used inverse variance for cluster trials and an intracluster co-efficient of 0.01 when adjustment had not been made in the primary study. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach to assess the certainty of evidence. MAIN RESULTS: Two cluster-randomised trials (India and Bangladesh) and two controlled before-after studies (Tanzania and India) met our inclusion criteria. Strategies included training of health care staff, management strengthening of health care systems (all four studies), and home visiting (two studies). The two studies from India included care packages targeting the neonatal period.One trial in Bangladesh estimated that child mortality may be 13% lower with IMCI, but the confidence interval (CI) included no effect (risk ratio (RR) 0.87, 95% CI 0.68 to 1.10; 5090 participants; low-certainty evidence). One CBA study in Tanzania gave almost identical estimates (RR 0.87, 95% CI 0.72 to 1.05; 1932 participants).One trial in India examined infant and neonatal mortality by implementing the integrated management of neonatal and childhood illness (IMNCI) strategy including post-natal home visits. Neonatal and infant mortality may be lower in the IMNCI group compared with the control group (infant mortality hazard ratio (HR) 0.85, 95% CI 0.77 to 0.94; neonatal mortality HR 0.91, 95% CI 0.80 to 1.03; one trial, 60,480 participants; low-certainty evidence).We estimated the effect of IMCI on any mortality measured by combining infant and child mortality in the one IMCI and the one IMNCI trial. Mortality may be reduced by IMCI (RR 0.85, 95% CI 0.78 to 0.93; two trials, 65,570 participants; low-certainty evidence).Two trials (India, Bangladesh) evaluated nutritional status and noted that there may be little or no effect on stunting (RR 0.94, 95% CI 0.84 to 1.06; 5242 participants, two trials; low-certainty evidence) and there is probably little or no effect on wasting (RR 1.04, 95% CI 0.87 to 1.25; two trials, 4288 participants; moderate-certainty evidence).The Tanzania CBA study showed similar results.Investigators measured quality of care by observing prescribing for common illnesses at health facilities (727 observations, two studies; very low-certainty evidence) and by observing prescribing by lay health care workers (1051 observations, three studies; very low-certainty evidence). We could not confirm a consistent effect on prescribing at health facilities or by lay health care workers, as certainty of the evidence was very low.For coverage of IMCI deliverables, we examined vaccine and vitamin A coverage, appropriate care seeking, and exclusive breast feeding. Two trials (India, Bangladesh) estimated vaccine coverage for measles and reported that there is probably little or no effect on measles vaccine coverage (RR 0.92, 95% CI 0.80 to 1.05; two trials, 4895 participants; moderate-certainty evidence), with similar effects seen in the Tanzania CBA study. Two studies measured the third dose of diphtheria, pertussis, and tetanus vaccine; and two measured vitamin A coverage, all providing little or no evidence of increased coverage with IMCI.Four studies (2 from India, and 1 each from Tanzania and Bangladesh) reported appropriate care seeking and derived information from careful questioning of mothers about recent illness. Some studies on effects of IMCI may report better care seeking behavior, but others do not report this.All four studies recorded maternal responses on exclusive breast feeding. They provided mixed results and very low-certainty evidence. Therefore, we do not know whether IMCI impacts exclusive breast feeding.No studies reported on the satisfaction of mothers and service users. AUTHORS' CONCLUSIONS: The mix of interventions examined in research studies evaluating the IMCI strategy varies, and some studies include specific inputs to improve neonatal health. Most studies were conducted in South Asia. Implementing the integrated management of childhood illness strategy may reduce child mortality, and packages that include interventions for the neonatal period may reduce infant mortality. IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage. Maternal care seeking behavior may be more appropriate with IMCI, but study results have been mixed, providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding.

Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population.

BACKGROUND: Zinc deficiency is a global nutritional problem, particularly in children and women residing in settings where diets are cereal based and monotonous. It has several negative health consequences. Fortification of staple foods with zinc may be an effective strategy for preventing zinc deficiency and improving zinc-related health outcomes. OBJECTIVES: To evaluate the beneficial and adverse effects of fortification of staple foods with zinc on health-related outcomes and biomarkers of zinc status in the general population. SEARCH METHODS: We searched the following databases in April 2015: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3 of 12, 2015, the Cochrane Library), MEDLINE & MEDLINE In Process (OVID) (1950 to 8 April 2015), EMBASE (OVID) (1974 to 8 April 2015), CINAHL (1982 to April 2015), Web of Science (1900 to 9 April 2015), BIOSIS (1969 to 9 April 2015), POPLINE (1970 to April 2015), AGRICOLA, OpenGrey, BiblioMap, and Trials Register of Promoting Health Interventions (TRoPHI), besides regional databases (April 2015) and theses. We also searched clinical trial registries (17 March 2015) and contacted relevant organisations (May 2014) in order to identify ongoing and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials, randomised either at the level of the individual or cluster. We also included non-randomised trials at the level of the individual if there was a concurrent comparison group. We included non-randomised cluster trials and controlled before-after studies only if there were at least two intervention sites and two control sites. Interventions included fortification (central/industrial) of staple foods (cereal flours, edible fats, sugar, condiments, seasonings, milk and beverages) with zinc for a minimum period of two weeks. Participants were members of the general population who were over two years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies, and assessed the risk of bias of the included studies. MAIN RESULTS: We included eight trials (709 participants); seven were from middle-income countries of Asia, Africa, Europe, and Latin America where zinc deficiency is likely to be a public health problem. Four trials compared the effect of zinc-fortified staple foods with unfortified foods (comparison 1), and four compared zinc-fortified staple foods in combination with other nutrients/factors with the same foods containing other nutrients or factors without zinc (comparison 2). The interventions lasted between one and nine months. We categorised most trials as having unclear or high risk of bias for randomisation, but low risk of bias for blinding and attrition. None of the studies in comparison 1 reported data on zinc deficiency.Foods fortified with zinc increased the serum or plasma zinc levels in comparison to foods without added zinc (mean difference (MD) 2.12 µmol/L, 95% confidence interval (CI) 1.25 to 3.00 µmol/L; 3 studies; 158 participants; low-quality evidence). Participants consuming foods fortified with zinc versus participants consuming the same food without zinc had similar risk of underweight (average risk ratio 3.10, 95% CI 0.52 to 18.38; 2 studies; 397 participants; low-quality evidence) and stunting (risk ratio (RR) 0.88, 95% CI 0.36 to 2.13; 2 studies; 397 participants; low-quality evidence). A single trial of addition of zinc to iron in wheat flour did not find a reduction in proportion of zinc deficiency (RR 0.17, 95% CI 0.01 to 3.94; very low-quality evidence). We did not find a difference in serum or plasma zinc levels in participants consuming foods fortified with zinc plus other micronutrients when compared with participants consuming the same foods with micronutrients but no added zinc (MD 0.03 µmol/L, 95% CI -0.67 to 0.72 µmol/L; 4 studies; 250 participants; low-quality evidence). No trial in comparison 2 provided information about underweight or stunting.There was no reported adverse effect of fortification of foods with zinc on indicators of iron or copper status. AUTHORS' CONCLUSIONS: Fortification of foods with zinc may improve the serum zinc status of populations if zinc is the only micronutrient used for fortification. If zinc is added to food in combination with other micronutrients, it may make little or no difference to the serum zinc status. Effects of fortification of foods with zinc on other outcomes including zinc deficiency, children's growth, cognition, work capacity of adults, or on haematological indicators are unknown. Given the small number of trials and participants in each trial, further investigation of these outcomes is required.

Association between anthropometry, cardiometabolic risk factors, & early life factors & adult measures of endothelial function: Results from the New Delhi Birth Cohort.

BACKGROUND & OBJECTIVES: Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease. METHODS: Absolute changes in brachial artery diameter following cuff inflation and sublingual nitroglycerin (400 µg) were recorded to evaluate endothelium-dependent and -independent measures of endothelial function in 600 participants (362 men; 238 women) from the New Delhi Birth Cohort (2006-2009). Data on anthropometry, cardiometabolic risk factors, medical history, socio-economic position, and lifestyle habits were collected. Height and weight were recorded at birth, two and 11 yr of age. Age- and sex-adjusted linear regression models were developed to evaluate these associations. RESULTS: The mean age of participants was 36±1 yr. Twenty two per cent men and 29 per cent women were obese (BMI th > 30 kg/m [2] ). Mean systolic blood pressure (SBP) was 131±14 and 119±13 mmHg, and diabetes prevalence was 12 and 8 per cent for men and women, respectively. Brachial artery diameter was higher for men compared with women both before (3.48±0.37 and 2.95±0.35 cm) and after hyperaemia (3.87±0.37 vs. 3.37±0.35 cm). A similar difference was seen before and after nitroglycerin. Markers of increased adiposity, smoking, SBP, and metabolic syndrome, but not early life anthropometry, were inversely associated with endothelial function after adjustment for age and sex. INTERPRETATION & CONCLUSIONS: The analysis of the current prospective data from a young urban Indian cohort showed that cardiometabolic risk factors, but not early life anthropometry, were associated with worse endothelial function.

Radicular cyst with severe destruction of the buccal cortical plate secondary to endodontic failure.

This case report highlights a massive radicular cyst with respect to the lower left premolars, that developed secondary to endodontic failure and resulted in buccal cortical bone destruction. It also discusses the investigation and the surgical approach which were carried out with regard to the cyst. Following surgical closure, the teeth were endodontically retreated. It also highlights the fact that mandibular true occlusal radiographs could be misleading with regard to the extent of bone destruction, which can otherwise be confirmed on CT scans.

Effect of attractive interactions on the water-like anomalies of a core-softened model potential.

It is now well established that water-like anomalies can be reproduced by a spherically symmetric potential with two length scales, popularly known as core-softened potential. In the present study we aim to investigate the effect of attractive interactions among the particles in a model fluid interacting with core-softened potential on the existence and location of various water-like anomalies in the temperature-pressure plane. We employ extensive molecular dynamic simulations to study anomalous nature of various order parameters and properties under isothermal compression. Order map analyses have also been done for all the potentials. We observe that all the systems with varying depth of attractive wells show structural, dynamic, and thermodynamic anomalies. As many of the previous studies involving model water and a class of core softened potentials have concluded that the structural anomaly region encloses the diffusion anomaly region, which in turn, encloses the density anomaly region, the same pattern has also been observed in the present study for the systems with less depth of attractive well. For the systems with deeper attractive well, we observe that the diffusion anomaly region shifts toward higher densities and is not always enclosed by the structural anomaly region. Also, density anomaly region is not completely enclosed by diffusion anomaly region in this case.

Promoting appropriate management of diarrhea: a systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India.

BACKGROUND: Scaling up of evidence-based management and prevention of childhood diarrhea is a public health priority in India, and necessitates robust literature review, for advocacy and action. OBJECTIVE: To identify, synthesize and summarize current evidence to guide scaling up of management of diarrhea among under-five children in India, and identify existing knowledge gaps. METHODS: A set of questions pertaining to the management (prevention, treatment, and control) of childhood diarrhea was identified through a consultative process. A modified systematic review process developed a priori was used to identify, synthesize and summarize, research evidence and operational information, pertaining to the problem in India. Areas with limited or no evidence were identified as knowledge gaps. RESULTS: Childhood diarrhea is a significant public health problem in India; the point (two weeks) prevalence is 9 to 20%. Diarrhea accounts for 14% of the total deaths in under-five children in India. Infants aged 6 to 24 months are at the highest risk of diarrhea. There is a lack of robust nation-wide data on etiology; rotavirus and diarrheogenic E.coli are the most common organisms identified. The current National Guidelines are sufficient for case-management of childhood diarrhea. Exclusive breastfeeding, handwashing and point of use water treatment are effective strategies for prevention of all-cause diarrhea; rotavirus vaccines are efficacious to prevent rotavirus specific diarrhea. ORS and zinc are the mainstay of management during an episode of childhood diarrhea but have low coverage in India due to policy and programmatic barriers, whereas indiscriminate use of antibiotics and other drugs is common. Zinc therapy given during diarrhea can be upscaled through existing infrastructure is introducing the training component and information, education and communication activities. CONCLUSION: This systematic review summarizes current evidence on childhood diarrhea and provides evidence to inform child health programs in India.

Effect of iron-fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials.

BACKGROUND: The utility of iron fortification of food to improve iron deficiency, anemia, and biological outcomes is not proven unequivocally. OBJECTIVES: The objectives were to evaluate 1) the effect of iron fortification on hemoglobin and serum ferritin and the prevalence of iron deficiency and anemia, 2) the possible predictors of a positive hemoglobin response, 3) the effect of iron fortification on zinc and iron status, and 4) the effect of iron-fortified foods on mental and motor development, anthropometric measures, and infections. DESIGN: Randomized and pseudorandomized controlled trials that included food fortification or biofortification with iron were included. RESULTS: Data from 60 trials showed that iron fortification of foods resulted in a significant increase in hemoglobin (0.42 g/dL; 95% CI: 0.28, 0.56; P < 0.001) and serum ferritin (1.36 µg/L; 95% CI: 1.23, 1.52; P < 0.001), a reduced risk of anemia (RR: 0.59; 95% CI: 0.48, 0.71; P < 0.001) and iron deficiency (RR: 0.48; 95% CI: 0.38, 0.62; P < 0.001), improvement in other indicators of iron nutriture, and no effect on serum zinc concentrations, infections, physical growth, and mental and motor development. Significant heterogeneity was observed for most of the evaluated outcomes. Sensitivity analyses and meta-regression for hemoglobin suggested a higher response with lower trial quality (suboptimal allocation concealment and blinding), use of condiments, and sodium iron edetate and a lower response when adults were included. CONCLUSION: Consumption of iron-fortified foods results in an improvement in hemoglobin, serum ferritin, and iron nutriture and a reduced risk of remaining anemic and iron deficient.

Community based newborn care: a systematic review and metaanalysis of evidence: UNICEF-PHFI series on newborn and child health, India.

BACKGROUND: The neonatal mortality rate (NMR) in India has remained virtually unchanged in the last 5 years. To achieve the Millennium Development Goal (MDG) 4 on child mortality (two thirds reduction from 1990 to 2015), it is essential to reduce NMR. A systematic review of the evidence on community-based intervention packages to reduce NMR is essential for advocacy and action to reach MDG-4. OBJECTIVE: To assess the effect of community based neonatal care by community health workers (CHWs) on NMR in resource-limited settings. DESIGN: Systematic review and meta-analysis of controlled trials. DATA SOURCES: Electronic databases and hand search of reviews, and abstracts and proceedings of conferences. RESULTS: A total of 13 controlled trials involving about 192000 births were included in this systematic review. Community based neonatal care by CHWs was associated with reduced neonatal mortality in resource-limited settings [RR=0.73 (0.65 to 0.83); P<0.0001]. The identified studies were a heterogeneous mix with respect to the extent and quality of community based neonatal care provided and the characteristics of the CHWs delivering the intervention. There was no consistent effect of training duration of the health workers, type of intervention (home visitation versus community participatory action and learning), number of home visits done by CHWs, and provision of only preventive versus both preventive and therapeutic care. Limited data suggests that the ideal time for the first postnatal visit is the first two days of life. The interventions are highly effective when baseline NMR is above 50/1000 live births [RR=0.64(0.54 to 0.77)]. The interventions show a significant decrease in efficacy as the NMR drops below 50/1000 live births [RR=0.85 (0.73 to 0.99)], however is still substantial. NMR gains from home visitation approach are going to materialize only in the presence of high program coverage of 50% or more. CONCLUSION: A significant decrease in NMR is possible by providing community based neonatal care in areas with high NMR by community health workers with a modest training duration and ensuring high program coverage with home visitation on the first two days of life.

UNICEF-PHFI Series on newborn and child health, India: methodology for systematic reviews on child health priorities for advocacy and action.

India is committed to reducing childhood mortality and morbidity. This requires evidence-based policy and practice in the realm of public health. This in turn necessitates advocacy and action (among all stakeholders), focused on locally relevant issues. A collaboration to work towards this goal was forged between the Public Health Foundation of India (PHFI), United Nations International Childrens Emergency Fund (UNICEF), India; and a team of independent researchers. As a first step, a systematic review of literature on four priority areas of newborn care (community based interventions) and child health (acute respiratory infection, diarrheal disease, anemia), was undertaken to address important issues including epidemiology, interventions for management, and operational issues of planning, implementing, and measuring actions at a programmatic level. This paper describes the development of the methodology for undertaking these systematic reviews including the process for framing of research questions, building a research team, and executing the systematic review (literature search strategy, data extraction, analysis, and reporting). The challenges associated with ensuring robust methodology, are also described.

Acute respiratory infection and pneumonia in India: a systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India.

BACKGROUND: Scaling up of evidence based management of childhood acute respiratory infection/pneumonia, is a public health priority in India, and necessitates robust literature review, for advocacy and action. OBJECTIVE: To identify, synthesize and summarize current evidence to guide scaling up of management of childhood acute respiratory infection/pneumonia in India, and identify existing knowledge gaps. METHODS: A set of ten questions pertaining to the management (prevention, treatment, and control) of childhood ARI/pneumonia was identified through a consultative process. A modified systematic review process developed a priori was used to identify, synthesize and summarize, research evidence and operational information, pertaining to the problem in India. Areas with limited or no evidence were identified as knowledge gaps. RESULTS: Childhood ARI/pneumonia is a significant public health problem in India, although robust epidemiological data is not available on its incidence. Mortality due to pneumonia accounts for approximately one-fourth of the total deaths in under five children, in India. Pneumonia affects children irrespective of socioeconomic status; with higher risk among young infants, malnourished children, non-exclusively breastfed children and those with exposure to solid fuel use. There is lack of robust nation-wide data on etiology; bacteria (including Pneumococcus, H. influenzae, S. aureus and Gram negative bacilli), viruses (especially RSV) and Mycoplasma, are the common organisms identified. In-vitro resistance to cotrimoxazole is high. Wheezing is commonly associated with ARI/pneumonia in children, but difficult to appreciate without auscultation. The current WHO guidelines as modified by IndiaCLEN Task force on Penumonia (2010), are sufficient for case-management of childhood pneumonia. Other important interventions to prevent mortality are oxygen therapy for those with severe or very severe pneumonia and measles vaccination for all infants. There is insufficient evidence for protective or curative effect of vitamin A; zinc supplementation could be beneficial to prevent pneumonia, although it has no therapeutic benefit. There is insufficient evidence on potential effectiveness and cost-effectiveness of Hib and Pneumococcal vaccines on reduction of ARI specific mortality. Case-finding and community-based management are effective management strategies, but have low coverage in India due to policy and programmatic barriers. There is a significant gap in the utilization of existing services, provider practices as well as family practices in seeking care. CONCLUSION: The systematic review summarizes current evidence on childhood ARI and pneumonia management and provides evidence to inform child health programs in India.

Efficacy and safety of therapeutic nutrition products for home based therapeutic nutrition for severe acute malnutrition a systematic review.

CONTEXT: Severe acute malnutrition (SAM) in children is a significant public health problem in India with associated increased morbidity and mortality. The current WHO recommendations on management of SAM are based on facility based treatment. Given the large number of children with SAM in India and the involved costs to the care-provider as well as the care-seeker, incorporation of alternative strategies like home based management of uncomplicated SAM is important. The present review assesses (a) the efficacy and safety of home based management of SAM using therapeutic nutrition products or ready to use therapeutic foods (RUTF); and (b) efficacy of these products in comparison with F-100 and home-based diet. EVIDENCE ACQUISITION: Electronic database (Pubmed and Cochrane Controlled Trials Register) were scanned using keywords severe malnutrition, therapy, diet, ready to use foods and RUTF. Bibliographics of identified articles, reviews and books were scanned. The information was extracted from the identified papers and graded according to the CEBM guidelines. RESULTS: Eighteen published papers (2 systematic reviews, 7 controlled trials, 7 observational trials and 2 consensus statements) were identified. Systematic reviews and RCTs showed RUTF to be at least as efficacious as F-100 in increasing weight (WMD=3.0 g/kg/day; 95% CI -1.70, 7.70) and more effective in comparison to home based dietary therapies. Locally made RUTFs were as effective as imported RUTFs (WMD=0.07 g/kg/d; 95% CI=-0.15, 0.29). Data from observational studies showed the energy intake with RUTF to be comparable to F-100. The pooled recovery rate, mortality and default in treatment with RUTF was 88.3%, 0.7% and 3.6%, respectively with a mean weight gain of 3.2 g/kg/day. The two consensus statements supported the use of RUTF for home based management of uncomplicated SAM. CONCLUSIONS: The use of therapeutic nutrition products like RUTF for home based management of uncomplicated SAM appears to be safe and efficacious. However, most of the evidence on this promising strategy has emerged from observational studies conducted in emergency settings in Africa. There is need to generate more robust evidence, design similar products locally and establish their efficacy and cost-effectiveness in a non-emergency setting, particularly in the Indian context.