PCN156 'DE NOVO' Quantification of Genotype-Directed Therapy with Afatinib in Metastatic Lung Cancer

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Factors influencing farmers' forestland-use changes over 15 years (2005–2020) in Thua Thien Hue province, Vietnam

Over the last decades, Vietnam has seen substantial shifts in forest landscape uses and associated livelihoods. We document the livelihood transformations in Nam Dong, a mountainous district of Central Vietnam, where land uses have changed from the utilisation of products from natural forests and shifting cultivation (swidden agriculture) to acacia tree-dominated plantation forestry. Forestry policies (forestland allocation, plantation development agendas), the increase in the economic value of acacia, and household livelihood assets are the primary factors driving these changes. We also found that there are differences in the access to and ownership of forestland with regard to households of different communities and between poor vs wealthy households. Therefore, careful attention needs to be paid to guide future land use policies in the area to foster social and ecological sustainability. HIGHLIGHTS • Major livelihood and forestland-use changes have taken place in central Vietnam over the last two decades. • There has been widespread conversion of forestland (degraded natural forests, swidden land) and cropland to acacia plantations. • Household-scale forestland use changes were primarily driven by forestry policies, the market for woodchips, and land resource access. • There is inequality in access to and ownership of forestland between poor and wealthier households in the mountain district of Vietnam. • Cases of illegal forestland conversions pose challenges to ensuring sustainable forest landscapes

Production Associated to Rare Events in High Energy Hadron-Hadron Collisions

At very high energy the same universal relation between the multiparticle or the transverse energy distribution associated to a rare event $C$, $P_C$ and the corresponding minimum bias distribution P, $P_C(\nu)\equiv \nu/ P(\nu)$, $\nu\equiv n$ or $E_T$ works for nucleus-nucleus collisions as well as for hadron-hadron collisions. This suggests that asymptotically, all hadronic processes are similar.Comment: 9 pages, 4 Postscript figure

MTHFR C677T genotype and small vessel disease

BACKGROUND AND PURPOSE: Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. METHODS: We included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. RESULTS: MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). CONCLUSIONS: MTHFR C677T was associated with magnetic resonance imaging-confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes.Collection of the UK Young Lacunar Stroke DNA Study (DNA Lacunar) was primarily supported by the Wellcome Trust (WT072952) with additional support from the Stroke Association (TSA 2010/01). Genotyping of the DNA Lacunar samples, and Dr Traylor, were supported by a Stroke Association Grant (TSA 2013/01). Genotyping of WTCCC2 ischaemic stroke study was funded by the Wellcome Trust. The Oxford Vascular Study has been funded by Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre. Funding for the genotyping at Massachusetts General Hospital was provided by the Massachusetts General Hospital-Deane Institute for the Integrative Study of Atrial Fibrillation and Stroke and the National Institute of Neurological Disorders and Stroke (U01 NS069208). Dr Rutten-Jacobs was supported by a Stroke Association / British Heart Foundation programme grant (TSA BHF 2010/01). Dr Adib-Samii was supported by a Medical Research Council (United Kingdom) training fellowship. Dr Markus and Dr Bevan are supported by the National Institute for Health Research Cambridge University Hospitals Comprehensive Biomedical Research Centre. Dr Markus is supported by a National Institute for Health Research Senior Investigator award. Dr Thijs is supported by a Clinical Investigator Grant from the scientific research fund, Fonds Wetenschappelijk Onderzoek Flanders. Dr Levi is supported by a National Health and Medical Research Council (NHMRC Australia) Practitioner Fellowship and the Australian Stroke Genetics Collaboration has received Project Grant support from the NHMRC (App 1010287). Dr Rost was supported by a National Institute of Neurological Disorders and Stroke grant (R01 NS082285-01). Professor Rothwell is in receipt of an NIHR Senior Investigator Award and a Wellcome Trust Senior Investigator Award. We also acknowledge the use of the facilities of the Acute Vascular Imaging Centre, Oxford and the Cardiovascular Clinical Research Facility, Oxford. The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication.This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/STROKEAHA.115.01154

Tight-binding parameters for charge transfer along DNA

We systematically examine all the tight-binding parameters pertinent to charge transfer along DNA. The $\pi$ molecular structure of the four DNA bases (adenine, thymine, cytosine, and guanine) is investigated by using the linear combination of atomic orbitals method with a recently introduced parametrization. The HOMO and LUMO wavefunctions and energies of DNA bases are discussed and then used for calculating the corresponding wavefunctions of the two B-DNA base-pairs (adenine-thymine and guanine-cytosine). The obtained HOMO and LUMO energies of the bases are in good agreement with available experimental values. Our results are then used for estimating the complete set of charge transfer parameters between neighboring bases and also between successive base-pairs, considering all possible combinations between them, for both electrons and holes. The calculated microscopic quantities can be used in mesoscopic theoretical models of electron or hole transfer along the DNA double helix, as they provide the necessary parameters for a tight-binding phenomenological description based on the $\pi$ molecular overlap. We find that usually the hopping parameters for holes are higher in magnitude compared to the ones for electrons, which probably indicates that hole transport along DNA is more favorable than electron transport. Our findings are also compared with existing calculations from first principles.Comment: 15 pages, 3 figures, 7 table

Effects of Two Alcohol Reduction Interventions on Depression and Anxiety Symptoms of ART Clients in Vietnam

Little is known about the potential mental health impacts of cognitive behavioral therapy and motivational interviewing interventions that focus on alcohol reduction among people with HIV (PWH). Our study aimed to assess the impact of two evidence-based alcohol reduction interventions on depression and anxiety symptoms of antiretroviral therapy (ART) clients with hazardous alcohol use. We conducted a secondary data analysis of data from a three-arm randomized controlled trial among ART clients in Thai Nguyen, Vietnam that evaluated the impacts of two alcohol reduction interventions in Vietnam. ART clients 18 years old or more with hazardous alcohol use (based on the Alcohol Use Disorders Identification Test-Consumption) were enrolled and randomized into one of three arms: Combined intervention, Brief intervention, and Standard of care (SOC). Symptoms of depression, measured with the Patient Health Questionnaire-9, and anxiety, measured with the Generalized Anxiety Disorder-7 scale, were assessed at baseline and 3, 6, and 12 months post-intervention. Generalized estimating equations were used to evaluate the effects of the interventions on depression and anxiety symptoms. The prevalence of depression and anxiety symptoms at baseline was 25.1% and 16.1%, respectively. Decreases in depression and anxiety symptoms were observed in all three arms from baseline to 12-month follow-up. There were no significant differences in depression and anxiety symptoms among participants receiving either intervention, relative to the SOC. Interventions with a dual focus on alcohol and mental health are needed to achieve more pronounced and sustainable improvements in depression and anxiety symptoms for PWH with hazardous alcohol use

The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial

BACKGROUND: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10(+0)-20(+0) weeks, and BMI ≥25 kg/m(2) were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. RESULTS: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group $11261.19±$14573.97 versus Standard Care Group $11306.70±$14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to$45,000. CONCLUSIONS: Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes. TRIALS REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).Jodie M Dodd, Sharmina Ahmed, Jonathan Karnon, Wendy Umberger, Andrea R Deussen, Thach Tran, Rosalie M Grivell, Caroline A Crowther, Deborah Turnbull, Andrew J McPhee, Gary Wittert, Julie A Owens, Jeffrey S Robinson and For the LIMIT Randomised Trial Grou

Alcohol use as a mediator of the effect of two alcohol reduction interventions on mental health symptoms of ART clients in Vietnam

We aimed to examine the mediating role of alcohol use in the pathway from the interventions to depression and anxiety symptoms using data from a randomized controlled trial among people living with HIV (PWH) with hazardous alcohol use (n = 440) in Thai Nguyen, Vietnam. Participants were randomized into either a combined intervention (CoI), a brief intervention (BI) and a standard of care arm. Both interventions were based on cognitive behavioral therapy and motivational enhancement therapy. Alcohol use was measured as the percentage of days abstinent from alcohol in the last 30 days. Symptoms of depression and anxiety were measured with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scales. Alcohol use was a significant mediator of the effects of two alcohol interventions on depression symptoms, but not anxiety symptoms. There were significant indirect effects via alcohol use of both interventions on depression symptoms at 12 months (CoI: mean difference (MD) = −0.134; 95%CI: −0.251, −0.035); (BI: MD = −0.141; 95%CI: −0.261, −0.038). There were no significant direct or total effects of the interventions on either symptoms at 12 months. Interventions with a dual focus on mental health and alcohol disorders are needed to determine optimal ways to tackle these common comorbidities among PWH

The longitudinal association between depression, anxiety symptoms and HIV outcomes, and the modifying effect of alcohol dependence among ART clients with hazardous alcohol use in Vietnam

Introduction: Mental health disorders may negatively impact HIV outcomes, such as viral suppression (VS) and antiretroviral (ART) adherence among people with HIV (PWH) with hazardous alcohol use. This study evaluates the longitudinal association between depression, anxiety symptoms, VS and complete ART adherence among ART clients with hazardous alcohol use in Vietnam; and examines alcohol dependence as a modifier in this association. Methods: This was a secondary data analysis of a trial for hazardous drinking ART clients in Thai Nguyen, Vietnam. From March 2016 to May 2018, 440 ART clients with an Alcohol Use Disorders Identification Test-Concise (AUDIT-C) score ≥4 for men and ≥3 for women were enrolled. Individuals were randomized to either a combined intervention, a brief intervention or a standard of care. Data on sociodemographics, depression, anxiety symptoms, alcohol use, VS and ART adherence were collected at baseline, three, six, and twelve months. Generalized estimating equation models controlling for intervention exposure were used to estimate time-lagged associations. Risk ratios were estimated using Poisson regression with robust variance estimation. Results: The mean age of participants was 40.2. The majority was male (96.8%), had at least some secondary school education (85.0%) and had a history of injection drug use (80.9%). No overall effect of depression and anxiety symptoms on VS was observed. When stratified by time, increased anxiety symptoms at six months were associated with VS at 12 months (adjusted risk ratio (aRR) = 1.09; 95% CI 1.02 to 1.17). An increase in depression or anxiety symptoms was associated with a decreased probability of complete ART adherence (depression symptoms: aRR = 0.95; 95% CI: 0.91 to 0.99; anxiety symptoms: aRR = 0.93; 85% CI: 0.88 to 0.99). The negative effects of anxiety symptoms on ART adherence were stronger among participants with alcohol dependence, compared to those without. Conclusions: Depression and anxiety symptoms had no overall effect on VS, although they were associated with a lower probability of complete ART adherence. Interventions focusing on mental healthcare for PWH with hazardous alcohol use are needed, and integration of mental healthcare and alcohol reduction should be implemented in HIV primary care settings

Comparing a standard and tailored approach to scaling up an evidence-based intervention for antiretroviral therapy for people who inject drugs in Vietnam: Study protocol for a cluster randomized hybrid type III trial

Background: People who inject drugs (PWID) bear a disproportionate burden of HIV infection and experience poor outcomes. A randomized trial demonstrated the efficacy of an integrated System Navigation and Psychosocial Counseling (SNaP) intervention in improving HIV outcomes, including antiretroviral therapy (ART) and medications for opioid use disorder (MOUD) uptake, viral suppression, and mortality. There is limited evidence about how to effectively scale such intervention. This protocol presents a hybrid type III effectiveness-implementation trial comparing two approaches for scaling-up SNaP. We will evaluate the effectiveness of SNaP implementation approaches as well as cost and the characteristics of HIV testing sites achieving successful or unsuccessful implementation of SNaP in Vietnam. Methods: Design: In this cluster randomized controlled trial, two approaches to scaling-up SNaP for PWID in Vietnam will be compared. HIV testing sites (n = 42) were randomized 1:1 to the standard approach or the tailored approach. Intervention mapping was used to develop implementation strategies for both arms. The standard arm will receive a uniform package of these strategies, while implementation strategies for the tailored arm will be designed to address site-specific needs. Participants: HIV-positive PWID participants (n = 6200) will be recruited for medical record assessment at baseline; of those, 1500 will be enrolled for detailed assessments at baseline, 12, and 24 months. Site directors and staff at each of the 42 HIV testing sites will complete surveys at baseline, 12, and 24 months. Outcomes: Implementation outcomes (fidelity, penetration, acceptability) and effectiveness outcomes (ART, MOUD uptake, viral suppression) will be compared between the arms. To measure incremental costs, we will conduct an empirical costing study of each arm and the actual process of implementation from a societal perspective. Qualitative and quantitative site-level data will be used to explore key characteristics of HIV testing sites that successfully or unsuccessfully implement the intervention for each arm. Discussion: Scaling up evidence-based interventions poses substantial challenges. The proposed trial contributes to the field of implementation science by applying a systematic approach to designing and tailoring implementation strategies, conducting a rigorous comparison of two promising implementation approaches, and assessing their incremental costs. Our study will provide critical guidance to Ministries of Health worldwide regarding the most effective, cost-efficient approach to SNaP implementation. Trial registration: NCT03952520 on Clinialtrials.gov. Registered 16 May 2019