303 research outputs found
Association of prognostic cardiovascular biomarkers with non-alcoholic fatty liver disease and effects of high-dose n-3 fatty acids treatment
No full textABSTRACTSCHOOL OF MEDICINEHuman Development & HealthThesis for the degree of Doctor of PhilosophyAssociation of prognostic cardiovascular biomarkers with non-alcoholic fatty liver disease and effects of high-dose n-3 fatty acids treatmentby Lokpal BhatiaNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition affecting up to one-third of the population worldwide, associated with increased cardiovascular (CV) mortality. Little is known about how prognostic CV biomarkers may be altered in association with changes in NAFLD severity over time. Importantly, there is currently no established pharmacological treatment option for NAFLD.The WELCOME* trial was a randomised, double-blind placebo-controlled study testing the effects of 15-18 months of high-dose n-3 fatty acids (FA; Omacor 4g/day) versus placebo in 103 NAFLD subjects to reduce liver fat percentage (measured by magnetic resonance spectroscopy). Prespecified sub-studies also investigated whether prognostic CV biomarkers (carotid intima-media thickness (CIMT) and echocardiographic markers of left ventricular (LV) diastolic function) and insulin sensitivity were related to severity of NAFLD; and also if these biomarkers improved with n-3 FAs in relation to liver fat reduction. We also measured erythrocyte docosahexaenoic acid (DHA) enrichment as a biological measure of treatment compliance.We found that significantly increased DHA enrichment through n-3 FA supplementation over 15-18 months resulted in a significant reduction in liver fat, as well as improving hepatic insulin sensitivity. Conversely, this did not have a beneficial effect on prognostic CV biomarkers with respect to reducing CIMT progression or improving key LV diastolic function indices. However, we also described for the first time, an independent association between percentage liver fat reduction and reduced CIMT progression in the entire cohort over the duration of study. Similarly, we found an independent association between liver fat reduction over 15-18 months and an improvement in markers of LV diastolic function across the entire cohort.In conclusion, n-3 FAs may be a viable therapeutic option for treating liver fat and improving hepatic insulin sensitivity. Reducing liver fat in NAFLD over 15-18 months was independently associated with improvements in prognostic CV biomarkers.*WELCOME study (Wessex evaluation of fatty liver and cardiovascular markers in NAFLD with Omacor therapy; www.clinicaltrials.gov NCT00760513
There is a slight increase in incident diabetes risk with the use of statins, but benefits likely outweigh any adverse effects in those with moderate-to-high cardiovascular risk
No full textStatins are one of the most widely used drug classes, with approximately 50 million prescriptions dispensed in England alone in 2008. Their efficacy and safety in significantly reducing cardiovascular events in moderate-to-high-risk patients has been well documented, both in primary and secondary prevention. 1 Commonly reported side-effects include muscle aches and increases in liver enzymes, but, in general, statins are well tolerated with a low incidence of side-effects. However, the recent collaborative meta-analysis of 13 major placebo-controlled statin trials by Sattar and colleagues reports a 9% increased risk for incident diabetes over 4 years (OR 1.09; 95% CI 1.02-1-17) in patients randomised to statins compared to those assigned to placebo. Heterogeneity between trials was low (I 2=11%), suggesting that this risk appears to be a true class effect, despite known differences in lipophilicity and metabolic clearance pathways between individual statin drugs<br/
Higher body fat percentage is associated with enhanced temperature perception in NAFLD: results from the randomised Wessex Evaluation of fatty Liver and Cardiovascular markers in NAFLD with OMacor thErapy trial (WELCOME) trial
No full textAims/hypothesisThe effect of n-3 fatty acid treatment on temperature perception as a sensory nerve function modality is uncertain. In patients with non-alcoholic fatty liver disease (NAFLD) both with and without type 2 diabetes, we: (1) tested whether 15–18 months’ treatment with 4 g/day of docosahexaenoic plus eicosapentaenoic acid (DHA+EPA) improved hot (HPT) and cold (CPT) temperature perception thresholds and (2) explored factors associated with HPT and CPT, in a randomised, double-blind, placebo-controlled trial.MethodsThe effect of treatment (n=44) on HPT, CPT and temperature perception index (TPI: difference between HPT and CPT) was measured at the big toe in 90 individuals without neuropathy (type 2 diabetes; n=30). Participants were randomised 1:1, using sequential numbering, by personnel independent from the trial team. All participants and all members of the research team were blinded to group assignment. Data were collected in the Southampton National Institute for Health Research Biomedical Research Centre. Treatment effects and the independence of associations were testing by regression modelling.ResultsMean±SD age was 50.9±10.6 years. In men (n=53) and women (n=37), HPTs (°C) were 46.1±5.1 and 43.1±6.4 (p=0.02), CPTs (°C) were 22.7±3.4 and 24.5±3.6 (p=0.07) and TPIs (°C) were 23.4±7.4 and 18.7±9.5 (p=0.008), respectively. In univariate analyses, total body fat percentage (measured by dual-energy x-ray absorptiometry [DXA]) was associated with HPT (r=–0.36 p=0.001), CPT (r=0.35 p=0.001) and TPI (r=0.39 p=0.0001). In multivariable-adjusted regression models, adjusting for age, sex and other potential confounders, only body fat percentage was independently associated with HPT, CPT or TPI (p=0.006, p=0.006 and p=0.002, respectively). DHA+EPA treatment did not modify HPT, CPT or TPI (p=0.93, p=0.44 and p=0.67, respectively). There were no important adverse effects or side effects reported.Conclusions/interpretationHigher body fat percentage is associated with enhanced temperature perception. There was no benefit of treatment with high-dose n-3 fatty acids on the thresholds to detect hot or cold stimuli.Trial registration:ClinicalTrials.gov NCT0076051
Rumblings in the middle: the quest for aazadi in Delhi
No full textTwo major protest movements erupted in the national capital city of Delhi in 2011 and 2012. The India Against Corruption movement that gathered momentum in 2011 and then the anti-rape protests after the gruesome gang-rape of a 23-year-old paramedic student on 16th December 2012. The former was focussed on the demand for the promulgation of the Jan Lokpal Bill in the aftermath of successive corruption scandals in the country, while the latter with its slogan of ‘aazadi’ [freedom], paved way for voicing wider democratic concerns on the safety and dignity of women. Both drew unexpectedly large crowds and also found resonance across other cities of the country
Impact of high dose omega-3 polyunsaturated fatty acid treatment on measures of microvascular function and vibration perception in non-alcoholic fatty liver disease: results from the randomised WELCOME trial
No full textAims/hypothesisThe effect of n-3 fatty acid treatment on vibration perception thresholds (VPTs) and cutaneous microvascular reactivity is not known. We tested whether: (1) a 15–18 month treatment with high dose (4 g/day) docosahexaenoic (DHA) plus eicosapentaenoic (EPA) acid improved VPT and microvascular reactivity in patients with non-alcoholic fatty liver disease; and (2) there are associations between VPT, microvascular reactivity and metabolic variables.MethodsIn the completed single centre, randomised, parallel group, placebo controlled Wessex Evaluation of fatty Liver and Cardiovascular markers in non-alcoholic fatty liver disease with OMacor thErapy (WELCOME) trial, we tested the effect of DHA+EPA on VPT at 125 Hz (big toe) and the cutaneous hyperaemic response (forearm) to arterial occlusion (ratio of maximum to resting blood flux [MF/RF]). Allocation and dispensing was carried out by an independent research pharmacist; all participants and research team members were blinded to group assignment.ResultsIn all, 51 and 49 patients were randomised to placebo and DHA+EPA, respectively (mean age 51.4 years). Of these, 32 had type 2 diabetes. Forty-six (placebo) and 47 (DHA+EPA) patients completed the study; there were no important adverse (or unexpected) effects or side effects. In multivariable-adjusted regression models (intention-to-treat analyses), DHA+EPA treatment was associated with an increase in VPT (? coefficient 1.49 [95% CI 0.04, 2.94], p?=?0.04). For VPT, the adjusted mean differences (95% CIs) in the placebo and DHA+EPA treatment groups were ?0.725 (?1.71, 0.25) and 0.767 (?0.21, 1.75) m/s2, respectively. With DHA+EPA treatment, there was no change in MF/RF (? coefficient 0.07 [95% CI ?0.56, 0.70], p?=?0.84), the adjusted mean differences (95% CIs) in the placebo and DHA+EPA treatment groups were ?0.549 (?1.03, ?0.07) and ?0.295 (?0.77, 0.18) respectively. VPT was independently associated with age (? coefficient 0.019 [95% CI 0.010, 0.029], p?<?0.0001) and MF/RF (? coefficient ?0.074 [95% CI ?0.132, ?0.016], p?=?0.013), but not with diabetes (p?=?0.38).Conclusions/interpretationHigh dose n-3 fatty acid treatment did not improve measures of microvascular function or vibration perception. Ageing and microvascular reactivity are associated with a measure of peripheral nerve function.Trial registration: ClinicalTrials.gov NCT00760513Funding: The study was funded by the National Institute for Health Research UK and Diabetes UK
Treating liver fat and serum triglyceride levels in NAFLD, effects of PNPLA3 and TM6SF2 genotypes: results from the WELCOME trial
No full textBackground & Aims
Genetic variation in both patatin-like phospholipase domain-containing protein-3 (PNPLA3) (I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2) (E167K) influences severity of liver disease, and serum triglyceride concentrations in non-alcoholic fatty liver disease (NAFLD), but whether either genotype influences the responses to treatments is uncertain.
Methods
One hundred three patients with NAFLD were randomised to omega-3 fatty acids (DHA+EPA) or placebo for 15–18 months in a double blind placebo controlled trial. Erythrocyte enrichment with DHA and EPA was measured by gas chromatography. PNPLA3 and TM6SF2 genotypes were measured by PCR technologies. Multivariable linear regression and analysis of covariance were undertaken to test the effect of genotypes on omega-3 fatty acid enrichment, end of study liver fat percentage and serum triglyceride concentrations. All models were adjusted for baseline measurements of each respective outcome.
Results
Fifty-five men and 40 women (Genotypes PNPLA3 I148M, 148I/I = 41, 148I/M = 43, 148M/M = 11; TM6SF2 E167K 167E/E = 78, 167E/K+167K/K = 17 participants) (mean ± SD age, 51 ± 11 years) completed the trial. Adjusting for baseline measurement, measured covariates and confounders, PNPLA3 148M/M variant was independently associated with percentage of DHA enrichment (B coefficient −1.02 (95% CI −1.97, −0.07), p = 0.036) but not percentage of EPA enrichment (B coefficient −0.31 (95% CI −1.38, 0.75), p = 0.56). This genotype was also independently associated with end of study liver fat percentage (B coefficient 9.5 (95% CI 2.53, 16.39), p = 0.008), but not end of study triglyceride concentration (B coefficient −0.11 (95% CI −0.64, 0.42), p = 0.68).
Conclusions
PNPLA3 148M/M variant influences the changes in liver fat and DHA tissue enrichment during the trial but not the change in serum triglyceride concentration
Legislating on Arbitration in Singapore: Linguistic Insights
No full textArbitration, a cost-effective and expeditious alternative to court litigation, takes place within complex and important national and international legal frameworks where legislation, rules, and conventions provide specialized regimes for the conduct of arbitrations. In recent years, Singapore has given evidence of a significant legislative activity in its fervor to make arbitration quicker and more efficient, and therefore has adopted domestic and international regimes that govern private commercial arbitration: the domestic Arbitration Act 2001 (AA) and the International Arbitration Act 2002 (IAA). While these laws differ from each other in matters of arbitral proceedings, they also reflect the best practice in dispute resolution used in the Asia Pacific Region, where Singapore is a regional and financial centre that serves as a gateway between East and West.
The purpose of this paper is to examine the arbitral regime and practice arising from the Singapore Arbitration Act 2001. The paper will look at the piece of legislative drafting from the perspective of language use in order to gain insights into the rhetorical and discursive features realized in the construction of the genre. First, the paper will outline the nature and topic of a two-ranked arbitral regime (AA – IAA) that is of relevance for the arbitration framework in Singapore. Secondly, the paper will analyze quantitatively and qualitatively the linguistic and textual choices realized in the professional/institutional practice and discourse of the genre, while also identifying those features which seem to constrain the accessibility and interpretation of legislative action performed in the genre. To the extent that Singapore inherited the Western-style legal culture of the English common law tradition, this part of the paper will also assess how the Singapore Arbitration Act borrowed semantic resources from the English Arbitration Act 1996 previously investigated by this author (Tessuto 2003), therefore giving rise to manifestations of “interdiscursivity” (Bhatia 2008, 2010a, 2011) from the discursive process and professional practice of English arbitration. Finally, the paper will draw some conclusions from the analysis of the most salient rhetorical and discursive data in the chosen genre, by adding as yet to our understanding of the intercultural and interdiscursive elements of drafting in the Eastern and Western socio-legal contexts
Khoo Kay Kim, professor of Malaysian history : a biobibliometric study
No full textPresents an analysis of the publication productivity, authorship pattern, channels of communication, journal preference and language preference of Professor Dato' Khoo Kay Kim, Professor of Malaysian History in the University of Malaya, Kuala Lumpur. The results of this biobibliometric study indicate that he can be a role model for future Malaysian historians to emulate his various achievements especially in the field of history education
Modeling preference noise and response noise in risky choice: Commentary on Bhatia and Loomes (2017)
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Previous issue date: 2019-04-23Embargo set by: Seth Robbins for item 112194
Lift date: 2021-08-23T20:36:18Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 112194 on 2021-08-24T09:15:10Z."Decision making research often heavily relies on deterministic modeling approaches. However, choice data are stochastic and therefore need to be modeled probabilistically. According to one probabilistic modeling approach, a decision maker has a fixed preference, but makes errors when selecting the utility-maximizing option. In another approach, a decision maker makes no errors, but his preference itself is probabilistic. Bhatia and Loomes (2017) refer to the first approach as ""response noise"" and the second approach as ""preference noise."" To avoid incorrect conclusions of a decision maker's underlying preferences, Bhatia and Loomes (2017) strongly advocate for modeling both types of noise simultaneously. In this commentary, we discuss the methods of Bhatia and Loomes (2017) and revisit a hybrid model, which models response and preference noise simultaneously, to address some limitations of these methods. Furthermore, we illustrate the hybrid model, discuss further refinements to the model, and illustrate model fit using data from hypothetical decision makers."Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-05-01The student, Bryanna Fields, accepted the attached license on 2019-04-22 at 20:15.The student, Bryanna Fields, submitted this Thesis for approval on 2019-04-22 at 20:25.This Thesis was approved for publication on 2019-04-23 at 17:39
Tracing the journey of Thattai Bhatia community through their culinary identity
No full textAbstract The paper acknowledges the remarkable contribution of cookbooks which have always played an instrumental role in researching the history of any community. However, it brings to light the fact that there are several reasons like migration, small size of the community or the nomadic lifestyles when the culinary regime of the community could not be documented. In such cases, the everyday food choices of an ethnic community can lead us to tracing its origin and journey. The paper, thus, argues that in situations where there is paucity of literature documenting the culinary system or foodways, culinary identity of the community can become an effective method to trace the history of the community. The same is proved with the help of a case study of the Thattai Bhatia community. Thattai Bhatia is a small diaspora largely settled in the Persian Gulf, originally migrated from Rajasthan in India and later from Thatta in Sindh, Pakistan. The research reveals the reasons behind their distinct foodways such as abstinence from consuming liquor, meat, garlic and onion in particular, despite their intermingling with different ethnicities due to migration. The paper draws evidences from their regular foodways and traverses backwards to trace their origins, their history and the reasons that have shaped their contemporary food choices. With limited availability of literature, the author had to depend on the information provided during interviews by some of the community members about their food practices. All the findings are substantiated with references from the historical literature available
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