120 research outputs found

    The Nation and its citizens: Tales of Bondage and Belonging

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    The Nation and Its Citizens: Tales of Bondage and Belonging is about nationalism as a uniquely modern political doctrine, shaped by the lived experience of citizens. Nationalism has changed in its appeal through history, as have its manifestations. Getting to know these may be part of the challenge of negotiating the ongoing turmoil, both internal and external to the nation. In addressing these issues, this book offers several propositions on how the construct of ‘identity’ is crafted, with all its power to influence modern politics. It then explores how well India’s practice of republican democracy has lived up to the competing dynamics of identity and equality. As India celebrates 75 years of Independence, author Sukumar Muralidharan takes the readers on a journey into how the sense of fellow-feeling and mutual dependence of the nation are consolidated, and under what circumstances these could fray. The Nation and Its Citizens offers many fresh perspectives in understanding India’s unique political trajectory

    Novel biomarkers associated with gestational diabetes mellitus and metabolic outcomes of pregnancy.

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    Gestational diabetes mellitus (GDM), defined as glucose intolerance first identified during pregnancy, is an escalating problem worldwide which affects 5-20% of all pregnant women. It is associated with long-term consequences such as obesity, metabolic syndrome and type 2 diabetes in both the mother and affected offspring, the latter mediated in part by birthweight (“diabetes begets diabetes”). However, selective screening strategies based on established risk factors for GDM, accurately identify only around 60% of cases suggesting that there are other mechanisms involved. The aim of my thesis was to investigate the role of 2 novel biomarkers, vitamin B12 (B12) and glucagon-like peptide (GLP-1) in the development of GDM and related metabolic outcomes. A systematic review and meta-analysis showed that B12 insufficiency in pregnancy was in the order of 20-30% across the world and was associated with marginally higher, but significant, odds of low birthweight babies but these findings may be isolated to high-risk countries. In a local UK population, B12 insufficiency was independently associated with obesity, 2.6-fold higher risk of GDM and fetal macrosomia. A nationwide survey of women of child-bearing age confirmed that 12% were B12 insufficient with associated hyperhomocysteinaemia, despite apparently adequate dietary intakes of B12. This warrants urgent review of the recommended nutrient intake guidelines to optimise B12 status prior to conception. In the second part of my thesis, it was shown that overall GLP-1 response during a diagnostic glucose tolerance test is reduced in GDM women compared to controls, with a decrease in the early phase particularly predictive of post-prandial glucose levels. This potentially provides a novel mechanism to explain the delayed first phase insulin response which has been noted in GDM and T2D. Finally, to better understand how GLP-1 may exert a protective effect on the vascular complications of hyperglycaemia, a basic science project was carried out which demonstrated that liraglutide, a GLP-1 receptor agonist, enhanced the AMPK and phospho-AKT signaling pathways thereby contributing to the reduction of oxidative cell damage. In summary, this thesis supports the hypothesis there are multiple mechanisms which give rise to GDM (e.g. predominant insulin resistance or insulin secretion or combination of factors) and biomarkers such as B12 and GLP-1 can be clinically useful in identification of high-risk women. If proven in larger prospective studies, with measurements of the biomarkers from early pregnancy, these markers may be used to risk-stratify these women with the ultimate goal of reducing the transgenerational perpetuation of diabetes

    Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study)

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    Aims/hypothesis: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide in all ethnic groups. Low vitamin B12 and low/high folate levels may contribute to GDM risk, but there is conflicting evidence. Our aim is to assess the relationships of early pregnancy vitamin B12 and folate levels with the risk of GDM status at 26–28 weeks of gestation. Methods: This was a prospective, multi-centre, multi-ethnic cohort study (n = 4746) in the UK. Participants who were eligible to be selectively screened as per the National Institute for Health and Care Excellence (NICE) criteria were included in the study. Results: GDM prevalence was 12.5% by NICE and 14.7% by International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Folate deficiency (1.3%) was rare but B12 insufficiency (42.3% at < 220 pmol/l) and folate excess (36.5%) were common in early pregnancy. Early pregnancy median B12 levels were lower, and folate levels higher, in women who were diagnosed with GDM at 26–28 weeks. B12 was negatively associated with fasting plasma glucose (1 SD: −0.06 mmol/l; 95% CI −0.04, −0.08; p <  0.0001) and 2 h plasma glucose levels (−0.07 mmol/l; 95% CI −0.02, −0.12; p = 0.004). Higher B12 was associated with 14.4% lower RR of IADPSG-GDM (0.856; 95% CI 0.786, 0.933; p = 0.0004) after adjusting for key confounders (age, parity, smoking status, ethnicity, family history, household income and folate status). Approximately half of this association was mediated through BMI. Folate was positively associated with 2 h plasma glucose levels (0.08 mmol/l; 95% CI 0.04, 0.13; p = 0.0005) but its relationship with fasting plasma glucose was U-shaped (quadratic β: 0.011; p = 0.05). Higher folate was associated with 11% higher RR of IADPSG-GDM (adjusted RR 1.11; 95% CI 1.036, 1.182; p = 0.002) (age, parity, smoking status, ethnicity, family history, household income and B12 status). Although no interactions were observed for B12 and folate (as continuous variables) with glucose levels and GDM risk, a low B12–high folate combination was associated with higher blood glucose level and risk of IADPSG-GDM (adjusted RR 1.742; 95% CI 1.226, 2.437; p = 0.003). Conclusions/interpretation: B12 insufficiency and folate excess were common in early pregnancy. Low B12 and high folate levels in early pregnancy were associated with small but statistically significant changes in maternal blood glucose level and higher RR of GDM. Our findings warrant additional studies on the role of unmetabolised folic acid in glucose metabolism and investigating the effect of optimising early pregnancy or pre-conception B12 and folate levels on subsequent hyperglycaemia

    Pharmacogenomic and mechanistic studies on dietary factors in chemoprevention of cancer

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    Pharmacogenomic profiling of cancer has recently seen much activity with the accessibility of the newest generation of high-throughput platforms and technologies. A myriad of mechanistic studies have been devoted to identifying dietary factors that can help prevent cancer, with evidence gleaned from epidemiologic studies revealing an inverse correlation between the intake of cruciferous vegetables and the risk of certain types of cancer. To develop a comprehensive understanding of cancer pathogenesis, and potential for chemopreventive intervention with dietary factors, an integrated approach that encompasses both pharmacogenomic and mechanistic aspects is desirable. Our transcriptomic profiling of butylated hydroxyanisole-induced Nuclear Factor-E2-related factor 2 (Nrf2)-dependent genes in Nrf2-deficient mice identified several germane molecular targets for prevention. Toxicogenomic analyses of endoplasmic reticulum stress inducer tunicamycin in Nrf2-deficient mice elucidated Nrf2-regulated unfolded protein response effects. Mechanistic studies on a combination of sulforaphane and (-) epigallocatechin-3-gallate in HT-29 AP-1 (Activator Protein-1) cells revealed a synergy in colon cancer chemoprevention. Pharmacogenomic studies of this combination in PC-3 AP-1 cells provided a discursive framework for understanding putative crosstalk between Nrf2 and AP-1 in prostate cancer chemoprevention. Regulatory potential for concerted modulation of Nrf2 and Nuclear Factor-κB (Nfκb1) in inflammation and carcinogenesis was delineated by bioinformatic analyses. Metabolomic approaches identified potential prognostic biomarkers in human prostate cancer. Differential biological networks in prostate cancer were elicited in androgen-dependent 22Rv1 cells, androgen- and estrogen-dependent LNCaP cells and androgen-independent DU 145 and PC-3 cells. Taken together, our identification of Nrf2-regulated molecular targets by expression profiling using dietary factors, synergistic effects in combinatorial use of dietary factors in colon cancer, regulatory studies on crosstalk between Nrf2 and AP-1 in prostate cancer, bioinformatic analyses of concerted modulation of Nrf2 and Nfkb1 in inflammation and carcinogenesis, metabolomic identification of biomarkers, and delineation of target hubs in differential prostate cancer biological networks, greatly enhance our understanding of the transcriptional circuitry in cancer and important master regulatory nodes including Nrf2 that might potentially be exploited for chemopreventive intervention with dietary factors.Ph.D.Includes bibliographical references (p. 311-331)

    The Influence of the Increasing Penetration of Photovoltaic Generation on Integrated Transmission-Distribution Power Systems

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    Power system simulations should be adapted to be applicable to the trends that are currently evoked by the energy transition. This transition is pushing our power system from a traditional hierarchical system to a modern interactive system. In order to keep the supply and transport of energy safe and reliant, we need to change the way we perform power system simulations. This requires a comprehensive framework in which both transmission and distribution systems are simultaneously analyzed. This chapter describes how transmission and distribution networks are modeled together as an integrated network and used to do steady-state operation analysis in order to assess the interaction of these two networks. Furthermore, we investigate the influence of the increasing amount of imbalance at distribution level on the transmission network that is evoked by the increase of highly variable resources and loads at distribution level. This influence is not taken into account in traditional power system simulations as power networks are analyzed on its own. We show that the hybrid network representation is a powerful tool to analyze modern power systems and that the effects of increased PV penetration under normal operating conditions are limitedGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Numerical Analysi

    Disparity in endoscopic localisation of early distal colorectal cancers: a retrospective cohort analysis from a single institution

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    BACKGROUND: Accurate staging of distal colorectal cancers is paramount in guiding neoadjuvant therapy, peri-operative, and ostomy planning. Early colonic lesions can be difficult to visualise on computed tomography (CT) scans, with tumour location solely deduced via endoscopy with the potential for introducing error. We aimed to address the paucity in literature in this area and assessed the accuracy of radiological and endoscopic localisation of distal colorectal cancers. METHODS: Retrospective analysis of an electronic database of patients at a large District General Hospital (DGH) diagnosed with distal colorectal cancer between January 2014 to January 2023 was performed. Patient demographics, investigations, endoscopic, and operative findings were analysed. Outcomes were assessed to determine disparities between pre-operative endoscopy and final tumour location. RESULTS: A total of 212 patients were endoscopically diagnosed with distal sigmoid tumour. Of these, 207 (97.6%) had a CT scan performed with 25.1% (52/207) lesions not being identified on this imaging modality with the remainder (74.9%; 155/207) being reported as visible. 38.2% (79/207) of tumours were in the sigmoid colon, 17.4% (36/207) rectosigmoid, and 19.3% (40/207) in the rectum. Pre-operative magnetic resonance imaging (MRI) was performed in 42.5% (90/212) of cases showing 84 tumours: 6.0% (5/84) sigmoid colon, 9.5% (8/84) rectosigmoid and 83.3% (70/84) rectal cancers (upper: 34, mid-rectum: 26, low: 10), with one anal cancer. 42.3% (22/52) of patients with non-visible lesions on CT had MRI scans: 68.2% (15/22) had rectal cancer (upper: 10, mid-rectum: 4, low: 1). Of the 30 where MRI was not performed, 46.7% (14) had sigmoid cancer, 16.7% (5) rectosigmoid, and 33.3% (10) rectal intraoperatively. Overall, 30.7% (65/212) of patients reported as having a distal sigmoid lesion endoscopically in fact had rectal cancer intra-operatively (rectosigmoid lesions excluded). CONCLUSION: Endoscopic localisation of distal colorectal tumours can be unreliable for accurate staging and operative planning. A pre-operative MRI scan should be considered in such instances, and particularly for non-visible lesions on CT scan. This may improve peri-operative planning, staging accuracy and patient outcomes.Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.Not hel

    Regulation of bone quality and calcium absorption in obesity and during caloric restriction in women

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    Weight loss (WL) is associated with loss of bone loss due to several factors such as decrease in intake of calcium, true fractional calcium absorption (TFCA), serum insulin like growth factor -1 (IGF-1) , reduced weight bearing . The aim in this dissertation was to understand whether a higher intake of dietary protein and vitamin D can attenuate bone loss during caloric restriction (CR), and addresses bone quality and altered hormonal milieu in obesity. In the first trial, our goal was to examine how bone responds to CR during a 1 year randomized trial using 2 levels of protein intake with controlled calcium intake of 1.2 g/d in both groups. Forty seven women were randomized to either a normal (18%) or higher (24%) protein intake for 1 year. Our results showed greater loss of BMD at certain sites and lower IGF-1 in the NP compared to HP diet (p <0.05). The second trial hypothesized that a higher compared to normal vitamin D supplementation will attenuate the decrease in TFCA associated with CR. Eighty four women were supplemented with either 2500 IU/d or 400 IU/d of vitamin D3 for 6 weeks during WL or weight maintenance (WM). TFCA increased with 2500 IU/d D supplementation in the WM-D group by 3.7% (p <0.05) however did not attenuate the decrease in TFCA associated with CR, with the greatest increase in 25 hydroxy vitamin D (25OHD) in the WL-D group. These findings suggest that vitamin D supplementation does not attenuate the decrease in TFCA associated with CR. The cross sectional study in this dissertation aimed at evaluating bone quality in obesity using peripheral quantitative computed tomography (pQCT). Our results in 211 women showed that obesity is associated with higher trabecular bone and lower cortical BMD. A separate case control clinical study in 111 women shows that high serum PTH in obesity is also associated with higher monocyte chemoattractant protein (MCP-1). This unique effect of parathyroid hormone (PTH) on MCP-1 is independent of the level of adiposity. Together these studies evaluate nutrient supplementation in attenuating bone loss during CR and help better understand bone quality and higher serum PTH in obesity.Ph. D.Includes bibliographical referencesIncludes vitaby Deeptha Sukuma

    Study of Mass Transfer Phenomena During Frying of Potato Slice

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    This Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page

    Frying Studies of Potato Strips using Dry Coating Materials

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    This Dissertation / Report is the outcome of investigation carried out by the creator(s) / author(s) at the department/division of Central Food Technological Research Institute (CFTRI), Mysore mentioned below in this page
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