To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
In The Pune Maternal Nutrition Study, vitamin B12 deficiency was seen in 65% of pregnant women, folate deficiency was rare. Maternal total homocysteine concentrations were inversely associated with offspring birthweight, and low vitamin B12 and high folate concentrations predicted higher offspring adiposity and insulin resistance. These findings guided a nested pre-conceptional randomised controlled trial ‘Pune Rural Intervention in Young Adolescents’. The interventions included: (1) vitamin B12+multi-micronutrients as per the United Nations International Multiple Micronutrient Antenatal Preparation, and proteins (B12+MMN), (2) vitamin B12 (B12 alone), and (3) placebo. Intervention improved maternal pre-conceptional and in-pregnancy micronutrient nutrition. Gene expression analysis in cord blood mononuclear cells in 88 pregnancies revealed 75 differentially expressed genes between the B12+MMN and placebo groups. The enriched biological processes included G2/M phase transition, chromosome segregation, and nuclear division. Enriched pathways included, mitotic spindle checkpoint and DNA damage response while enriched human phenotypes were sloping forehead and decreased head circumference. Fructose-bisphosphatase 2 (FBP2) and Cell Division Cycle Associated 2 (CDCA2) genes were under-expressed in the B12 alone group. The latter, involved in chromosome segregation was under-expressed in both intervention groups. Based on the role of B-complex vitamins in the synthesis of nucleotides and S-adenosyl methionine, and the roles of vitamins A and D on gene expression, we propose that the multi-micronutrient intervention epigenetically affected cell cycle dynamics. Neonates in the B12+MMN group had the highest ponderal index. Follow-up studies will reveal if the intervention and the altered biological processes influence offspring diabesity.
Politiko-Troullia has generated the largest radiocarbon (14C) dataset from a Prehistoric Bronze Age settlement on Cyprus. We present Bayesian modeling of 25 calibrated AMS ages, which contributes to an emerging multi-site 14C chronology for Cyprus covering most of the Prehistoric Bronze Age. Our analysis places the six stratified phases of occupation at Troullia between about 2050 and 1850 cal BCE, in contrast to a longer estimated occupation inferred from pottery analysis. We provide a rare 14C determination for the transition from Prehistoric Bronze Age 1 to 2 just after 2000 cal BCE, associated with a major architectural dislocation at Politiko-Troullia in response to local landscape erosion, possibly due to increased regional precipitation. We present a regional 14C model for Prehistoric Bronze Age Cyprus combining the chronology for Politiko-Troullia with modeled 14C ages from Sotira Kaminoudhia and Marki Alonia, which is bolstered by individual ages from five other settlements on Cyprus. Through the Prehistoric Bronze Age, agrarian villages on Cyprus developed the foundations for the emergence of urbanized settlement and society during the ensuing Protohistoric Bronze Age. Politiko-Troullia, in conjunction with other key settlements on Cyprus, provides a significant independent contribution to increasingly robust Bronze Age 14C chronologies in the Eastern Mediterranean.
In the wake of the demise of the WTO's Appellate Body, there has been a growing trend of states resorting to the dispute settlement mechanisms under their regional trade agreements (RTAs) to resolve international trade disputes. While the vast majority of these mechanisms have never been used, many contain defective procedural provisions that are likely to slow down or completely derail the dispute settlement process should those provisions be invoked. This is particularly true of mechanisms that effectively permit a respondent to block or delay the composition of a panel to hear a dispute. This article examines the issues of ‘panel blocking’ and panel composition delay tactics in RTA dispute settlement with reference to both past and present practice, and provides a textual analysis of a cross-section of existing RTAs to identify procedural defects and prescribe solutions for ensuring timely panel composition in future disputes.
To identify peri-conceptional diet patterns among women in Bangalore and examine their associations with risk of gestational diabetes mellitus (GDM).
BAngalore Nutrition Gestational diabetes LifEstyle Study, started in June 2016, was a prospective observational study, in which women were recruited at 5–16 weeks’ gestation. Peri-conceptional diet was recalled at recruitment, using a validated 224-item FFQ. GDM was assessed by a 75-g oral glucose tolerance test at 24–28 weeks’ gestation, applying WHO 2013 criteria. Diet patterns were identified using principal component analysis, and diet pattern–GDM associations were examined using multivariate logistic regression, adjusting for ‘a priori’ confounders.
Antenatal clinics of two hospitals, Bangalore, South India.
Seven hundred and eighty-five pregnant women of varied socio-economic status.
GDM prevalence was 22 %. Three diet patterns were identified: (a) high-diversity, urban (HDU) characterised by diverse, home-cooked and processed foods was associated with older, more affluent, better-educated and urban women; (b) rice-fried snacks-chicken-sweets (RFCS), characterised by low diet diversity, was associated with younger, less-educated, and lower-income, rural and joint families; and (c) healthy, traditional vegetarian (HTV), characterised by home-cooked vegetarian and non-processed foods, was associated with less-educated, more affluent, and rural and joint families. The HDU pattern was associated with a lower GDM risk (adjusted odds ratio (aOR): 0·80/sd, 95 % CI (0·64, 0·99), P = 0·04) after adjusting for confounders. BMI was strongly related to GDM risk and possibly mediated diet–GDM associations.
The findings support global recommendations to encourage women to attain a healthy pre-pregnancy BMI and increase diet diversity. Both healthy and unhealthy foods in the patterns indicate low awareness about healthy foods and a need for public education.
With type 2 diabetes presenting at younger ages, there is a growing need to identify biomarkers of future glucose intolerance. A high (20%) prevalence of glucose intolerance at 18 years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. We investigated the potential of circulating microRNAs in risk stratification for future pre-diabetes in these women. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N = 10) and glucose intolerant (N = 8) women (ADA criteria) at 6, 12 and 17 years of their age using discovery analysis (OpenArray™ platform). Machine-learning workflows involving Lasso with bootstrapping/leave-one-out cross-validation identified microRNAs associated with glucose intolerance at 18 years of age. Several microRNAs, including miR-212-3p, miR-30e-3p and miR-638, stratified glucose-intolerant women from NGT at childhood. Our results suggest that circulating microRNAs, longitudinally assessed over 17 years of life, are dynamic biomarkers associated with and predictive of pre-diabetes at 18 years of age. Validation of these findings in males and remaining participants from the PMNS birth cohort will provide a unique opportunity to study novel epigenetic mechanisms in the life-course progression of glucose intolerance and enhance current clinical risk prediction of pre-diabetes and progression to type 2 diabetes.
OBJECTIVES/GOALS: Our goal is to develop a cost-effective approach for precision medicine treatment by providing computational predictions for new uses of currently available FDA approved, and experimental drugs for NSCLC. METHODS/STUDY POPULATION: Cell Lines: A549 (ATCC- CCL-185) Human epithelial Lung Carcinoma cells, H1792 (ATCC-CRL-5895) Human Lung Carcinoma cells. In Vitro Cytotoxicity Assay: A VybrantÂ® MTT Cell Proliferation Assay was used. Colony Formation Assay: NCI-H1792, A549 cells were seeded at a density of 500 cells/ dish, then treated with ARS-1620, Osimertinib. The Computational Analysis of Novel Drug Opportunities (CANDO): Â Herein, we employed the bioanalytic docking (BANDOCK) protocol within CANDO to calculate the compound-protein interaction scores for a library of 13,218 compounds from DrugBank against a library of 5,317 protein structures from the Protein Data Bank, resulting in a proteomic interaction signature for each compound, and identified Osimertinib as the most likely EGFR/ErbB inhibitor to synergize with ARS-1620. RESULTS/ANTICIPATED RESULTS: ARS-1620 and Osimertinib in combination displays potent anti-tumor activity as evident by a decrease in cell viability with cytotoxicity assays, as well as reduced number of colonies in the colony formation assay for both A549 and H1792 cells. By using CANDO, and cross-referencing the obtained rankings with known experimental information, we have obtained drug predictions within the context of precision medicine. Our preliminary data indicates that EGFR inhibitor Osimertinib may be most structurally similar to KRAS G12C inhibitors overall, compared to other ErbB/ EGFR inhibitors. Validations with human cancer cell lines A549 and H1792 have confirmed that Osimertinib in combination with KRAS G12C inhibitor ARS-1620 may exhibit a synergistic effect in decreasing cellular proliferation and colony formation. DISCUSSION/SIGNIFICANCE: This suggests that this innovative drug combination therapy may help improve treatment outcomes for KRAS G12C(H1792) and KRASG12S(A549) mutant cancers. Cell migration and cell invasion studies in response to treatment with Osimertinib and ARS-1620 are currently ongoing.
We present the first Bayesian 14C modeling based on AMS ages from stratified sediments representing continuous occupation across the Early Bronze III/IV interface in the Southern Levant. This new high-precision modeling incorporates 12 calibrated AMS ages from Khirbat Iskandar Area C using OxCal 4.4.4 and the IntCal 20 calibration curve to specify the EB III/IV transition at or slightly before 2500 cal BCE. Our results contribute to the continuing emergence of a high chronology for the Levantine Early Bronze Age, which shifts the end of EB III 200–300 years earlier than the traditional time frame and increases the length of EB IV to about 500 years. Data from Khirbat Iskandar also help direct greater attention to the importance of sedentary communities through EB IV, in contrast to the traditional emphasis on non-sedentary pastoral encampments and cemeteries. Modeling of AMS data from Khirbat Iskandar bolsters the ongoing revision of Early Bronze Age Levantine chronology and its growing interpretive independence from Egyptian history and contributes particularly to re-examination of the EB III/IV nexus in the Southern Levant.
Gestational diabetes mellitus (GDM) is a global public health problem, and in India, it affects about 20% of pregnancies. India, despite being a tropical country with abundant sunshine has a high prevalence (80%) of vitamin D deficiency (VDD) among reproductive-aged women. Global and Indian evidence links VDD with a higher risk of hyperglycaemia in pregnancy and GDM. VDD has also been implicated in gestational hypertension, preterm birth and poorer offspring health. Global scientific consensus acknowledges the need for maternal vitamin D screening and supplementation, but knowledge gaps exist about optimal blood levels (50–100 nmol/l), and the required vitamin D dosage (400–4000 IU). Diet can provide <10% of the vitamin D requirements, food fortification can deliver limited amounts, and hence optimal antenatal supplementation is key. Prenatal calcium supplements containing 400 IU of vitamin D may be sufficient for calcium absorption and bone health, but may not provide immunomodulatory benefits, including GDM prevention. Increasing evidence calls for higher maternal vitamin D requirements (2000–4000 IU) for skeletal, metabolic and immune health benefits. Current screening and supplementation for maternal VDD in India is low. We need to invest in future studies to determine optimal maternal vitamin D requirements and formulate policies for vitamin D supplementation to prevent GDM. Improving the maternal vitamin D status is an important nutritional priority for policymakers to reduce the large economic burden of non-communicable diseases (10% of India's gross domestic product), and eventually achieve the 2030 UN sustainable development goals.
To examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming.
Longitudinal follow-up of a birth cohort.
CSI Holdsworth Memorial Hospital (HMH), Mysore South India.
721 men and women (55–80 years) whose size at birth was recorded at HMH. Approximately 20 years earlier, a subset (n = 522) of them had assessments for cardiometabolic disorders in mid-life.
Standardized measurement of cognitive function, depression, sociodemographic, and lifestyle factors; blood tests and assessments for cardiometabolic disorders
Participants who were heavier at birth had higher composite cognitive scores (0.12 SD per SD birth weight [95% CI 0.05, 0.19] p = 0.001) in late life. Other lifecourse factors independently positively related to cognition were maternal educational level and participants’ own educational level, adult leg length, body mass index, and socioeconomic position, and negatively were diabetes in mid-life and current depression and stroke. The association of birth weight with cognition was independent cardiometabolic risk factors and was attenuated after adjustment for all lifecourse factors (0.08 SD per SD birth weight [95% CI −0.01, 0.18] p = 0.07).
The findings are consistent with positive effects of early life environmental factors (better fetal growth, education, and childhood socioeconomic status) on brain development resulting in greater long-term cognitive function. The results do not support a pathway linking poorer fetal development with reduced late life cognitive function through cardiometabolic programming.
Experience gained from responding to major outbreaks may have influenced the early coronavirus disease-2019 (COVID-19) pandemic response in several countries across Africa. We retrospectively assessed whether Guinea, Liberia and Sierra Leone, the three West African countries at the epicentre of the 2014–2016 Ebola virus disease outbreak, leveraged the lessons learned in responding to COVID-19 following the World Health Organization's (WHO) declaration of a public health emergency of international concern (PHEIC). We found relatively lower incidence rates across the three countries compared to many parts of the globe. Time to case reporting and laboratory confirmation also varied, with Guinea and Liberia reporting significant delays compared to Sierra Leone. Most of the selected readiness measures were instituted before confirmation of the first case and response measures were initiated rapidly after the outbreak confirmation. We conclude that the rapid readiness and response measures instituted by the three countries can be attributed to their lessons learned from the devastating Ebola outbreak, although persistent health systems weaknesses and the unique nature of COVID-19 continue to challenge control efforts.
To carry out a qualitative evidence synthesis to explore what influences the diet and physical activity of adolescents living in five countries that constitute the Transforming Adolescent Lives through Nutrition (TALENT) consortium (Cote D’Ivoire, Ethiopia, India, South Africa and The Gambia).
A search of electronic databases was conducted for qualitative articles published between 2000 and 2019.
Studies that explore influences on the diets and physical activity habits of adolescents aged 10–19 years.
Of the twelve included studies, none were identified from The Gambia or Cote D’Ivoire. The existing qualitative literature focussed on three major areas in relation to adolescents’ diet and physical activity: (1) the influence of body image and self-esteem; (2) social and environmental influences and (3) poverty. The limited existing literature focusses heavily on girls’ experiences particularly in relation to body image and dysfunctional eating practices.
In-depth research exploring adolescents’ perceptions of diet and physical activity is needed to better understand how both boys and girls, at different stages of adolescence, perceive health, diet and physical activity. More research with young people is required especially in countries where little exists to cover a wider range of issues that play a role in diet and physical activity.
In the introduction to his landmark 2005 critical edition of Nicholas Love's Mirror of the Blessed Life of Jesus Christ, Michael Sargent noted that ‘we simply have not yet done enough exploration of fifteenth-century vernacular theological literature’. Indeed, while the study of religious writing in English became a popular area of study in the late twentieth century, the vast majority of scholarship on such works focused largely on its position in relation to the intellectual and theological debate between fifteenth-century ecclesiastical authorities and Oxford theologian John Wycliff and his followers. This conflict has provided the contextual background for the study of the composition and circulation of much of the theological literature produced in the late fourteenth and early fifteenth centuries. However, as is now becoming increasingly apparent, even if this conflict was as influential on the composition of religious writing during this period as scholars often posit, the circulation and copying of such texts by individual fifteenth-century readers suggest that the textual cultures of the era were in fact much more complex and flexible.
While a macro analysis of trends in English religious writing at the turn of the fifteenth century often focuses on the inherent tensions between such cultural landmarks as the 1401 Oxford Translation Debate and Archbishop Thomas Arundel's infamous 1409 ‘Constitutions’, famously explored in Nicholas Watson's hugely influential 1995 Speculum article, ‘Censorship and Cultural Change in Late-Medieval England’ – as well as their great textual champions, the Wycliffite Bible and Nicholas Love's Mirror of the Blessed Life of Jesus Christ – a micro analysis of the circulation of individual texts copied in the period seems to suggest a pattern of praxis which Stephen Kelly and Ryan Perry have dubbed ‘devotional cosmopolitanism’: a practice in which supposedly ‘orthodox’ and ‘heterodox’ texts sit side by side with one another in theological and devotional miscellanies.
The methodological framework which shed light on such patterns in Kelly and Perry's work, and which informed much of the findings of this author's previous writing on Nicholas Love's Mirror, was developed as part of the Arts and Humanities Research Council-funded Geographies of Orthodoxy research project hosted by Queen's University Belfast and the University of St Andrews, which sought to build on works such as Sargent's critical edition of Love's Mirror.
The COVID-19 pandemic is giving way to increases in military engagements in health-related activities at the domestic level. This article situates these engagements amid issues of continuity, change, and resistance in contemporary redefinitions of military health roles. It positions the COVID-19 pandemic as a pivotal moment in global health military practice. I identify three emerging trends within national military responses to COVID-19: (1) Minimal technical military support; (2) Blended civil-military responses; and (3) Military-led responses. The dynamics that underpin each type of military involvement follow context-specific military political legacies. These levels of involvement also relate to national public health approaches and the degree of capacity within health care systems. Each identified trend points towards specific trajectories for the future co-constitution of global and local civil-military engagements.
Expansion of cultivated lands and field management impacts greenhouse gas (GHG) emissions from agriculture soils. Soils naturally cycle GHGs and can be sources or sinks depending on physical and chemical properties affected by cultivation and management status. We looked at how cultivation history influences GHG emissions from subtropical soils. We measured CO2, N2O, and CH4 fluxes, and soil properties from newly converted and continuously cultivated lands during the summer rainy season in calcareous soils from south Florida. Newly converted soils had more soil organic matter (OM), more moisture, higher porosity, and lower bulk density, leading to more GHG emissions compared to historically cultivated soils. Although more nutrients make newly converted lands more desirable for cultivation, conversion of new areas for agriculture was shown to release more GHGs than cultivated lands. Our data suggest that GHG emissions from agricultural soils may decrease over time with continued cultivation.
We present two new Bayesian 14C models using IntCal20 that incorporate 17 new calibrated AMS ages for Early Bronze IV Tell Abu en-Ni‘aj and Middle Bronze Age Tell el-Hayyat, located in the northern Jordan Valley, Jordan. These freshly augmented suites of carbonized seed dates now include 25 AMS dates from Tell Abu en-Ni‘aj and 31 AMS dates from Tell el-Hayyat. The modeled founding date for Tell Abu en-Ni‘aj strengthens an emerging high chronology for Early Bronze IV starting by 2500 cal BC, while the end of its habitation by 2200 cal BC may exemplify a regional pattern of increasingly pervasive abandonment among late Early Bronze IV settlements in the Southern Levant. In turn, our modeled date for the Early Bronze IV/Middle Bronze Age transition at Tell el-Hayyat around 1900 cal BC pushes this interface about a century later than surmised traditionally, and its abandonment in Middle Bronze III marks an unexpectedly early end date before 1600 cal BC. These inferences, which coordinate Bayesian AMS models and typological ceramic sequences for Tell Abu en-Ni‘aj and Tell el-Hayyat, contribute to an ongoing revision of Early and Middle Bronze Age Levantine chronologies and uncoupling of their attendant interpretive links between the Southern Levant and Egypt.
Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups.
Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries.
Focus groups with adolescents and caregivers carried out by trained researchers.
Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to ‘belong’ in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time.
Interventions to improve adolescents’ diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.