Occupational Heat Stress in the Floriculture Industry of Ethiopia: Health Risks and Productivity Losses

Background: The Ethiopian flower industry is growing fast with successful diversification of export products under greenhouse structures. Higher temperatures in the greenhouses pose a serious threat to the health of workers and add to the risk of occupational heat stress. Excessive heat in workplace settings also reduces work capacity and labour productivity. This study aims to investigate the level of heat exposure, and workers’ and managers’ perceptions and behavioural responses towards extreme heat exposure in a warming climate. Methods: We used the Wet Bulb Globe Temperature (WBGT) measured in representative greenhouses to capture the heat exposure during hotter and cooler seasons following ISO 7243 (generally risk of heat stress occurs when WBGT exceeds 26°C). A comparative cross-sectional study design with a stratified sampling method was used to assess occupational heat stress and workers’ perceptions of the impact of heat on their health and productivity in six different floriculture greenhouses in Ethiopia representing three different agro-ecologies and products. A questionnaire survey was conducted (30 managers/supervisors and 305 workers;76.1% female) to capture perceptions on heat exposures, symptoms of potential health impacts, productivity losses and coping mechanisms. Results: Heat exposure varied across different agroecologies, product types and greenhouse materials with a median WBGT Index of 25.5°C and a range from 18.1°C to 31.5°C. The impact of heat stress also varied across different employment sectors and geographical regions. Overall, workers in cut-flower greenhouses are exposed to higher than recommended WBGT Index (26°C) for 3 - 6 working hours daily. 65% of the managers reported that heat stress has a significant impact on the workers’ labour productivity, but do not have guidance about working in hot conditions. Workers reported more heat-related health issues and reduced productivity, especially in the mid-altitude greenhouses. About 50% of the workers reported that heat exposure decreased work productivity during hot hours. Sweating, exhaustion, heat-rashes, dehydration, crumps, nausea and headache were self-reported health issues. Labour productivity losses ranged from no loss to 19.5% in the mid- and low-altitudes. Conclusions and Recommendations: Excessive workplace heat in the greenhouses is both an occupational health hazard and detrimental to productivity in the floriculture industry. However, the level of understanding and actions on the ground regarding occupational heat stress are low. The code of conduct in place now does not consider the occupational heat stress issues. Multiple actions (engineering, management, training and policy-related recommendations) have to be implemented by Ethiopian Horticultural Producers and Exporters Association (EHPEA) and farm owners to mitigate heat stress and loss of productivity. Designing and implementing these heat prevention strategies and incorporating them into the code of conduct is in the interests of both employers and employees.

Asian-American elders’ health and physician use: An examination of social determinants and lifespan influences

While the Asian American population is growing rapidly, relatively little research has focused on intergroup health comparisons. The application of the life course perspective sheds new light on the inter-section of the ageing process and social determinants of health. This study compares physician use and health equity among Asian ethnic groups and non-Hispanic Whites. Data on Asian American and non-Hispanic White immigrants over 65 were extracted from the California Health Interview Survey. Weighted logistic regression models were tested applying the Commission on Social Determinants of Health model. Intergroup differences in physician use and health equity were observed. Furthermore, physician use and health varied among the groups by age. The diverse background of older Asian Americans and the differential effects of the ageing process point to the need for novel interventions to promote health among this population.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Epidemiology of gastric cancer

胃的癌症的发生和死亡在过去的几十年在美国并且在其它地方戏剧性地掉落了。尽管如此，胃的癌症作为第四很普通的癌症和世界范围的癌症死亡的第二个领先的原因仍然是一个主要公共卫生问题。人口统计的趋势由肿瘤地点和组织学不同。当在远侧的、肠的类型有显著衰落时胃的癌症，胃的贲门的近似、弥漫的类型腺癌的发生一直在增加，特别地在西方的国家。由肿瘤亚地点的发生也基于地理地点，种族，和社会经济的地位广泛地变化。而近似肿瘤在发达国家，并且在更高社会经济的班上是更普通的，远侧的胃的癌症在发展，并且在更低的社会经济的组支配国家，在黑人之中，在白人之中。在由肿瘤地点的胃的癌症的发生的分叉的趋势建议他们可以与不同病原学代表二疾病。为远侧的胃的癌症的主要风险因素包括 Helicobacter pylori (H pylori ) 感染和饮食的因素，而胃的食道的倒流疾病和肥胖在近似的胃癌症的发展起重要作用。这评论的目的是检验胃的癌症的传染病学和风险因素，并且为主要预防讨论策略。

Towards an Artificial Intelligence Framework for Data-Driven Prediction of Coronavirus Clinical Severity

The virus SARS-CoV2,which causes the Coronavirus disease COVID-19 has become a pandemic and has spread to every inhabited continent.Given the increasing caseload,there is an urgent need to augment clinical skills in order to identify from among the many mild cases the few that will progress to critical illness.We present a first step towards building an artificial intelligence(AI)framework,with predictive analytics(PA)capabilities applied to real patient data,to provide rapid clinical decision-making support.COVID-19 has presented a pressing need as a)clinicians are still developing clinical acumen given the disease’s novelty,and b)resource limitations in a rapidly expanding pandemic require difficult decisions relating to resource allocation.The objectives of this research are:(1)to algorithmically identify the combinations of clinical characteristics of COVID-19 that predict outcomes,and(2)to develop a tool with AI capabilities that will predict patients at risk for more severe illness on initial presentation.The predictive models learn from historical data to help predict specifically who will develop acute respiratory distress syndrome(ARDS),a severe outcome in COVID-19.Our experimental results based on two hospitals in Wenzhou,Zhejang,China identify features most predictive of ARDS in COVID-19 initial presentation which would not have stood out to clinicians.A mild increase in elevated alanine aminotransferase(ALT)(a liver enzyme)),a presence of myalgias(body aches),and an increase in hemoglobin,in this order,are the clinical features,on presentation,that are the most predictive.Those two centers’COVID-19 case series symptoms on initial presentation can help predict severe outcomes.Predictive models that learned from historical data of patients from two Chinese hospitals achieved 70%to 80%accuracy in predicting severe cases.

Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan

AIM: To evaluate the effects of OGG1(Ser326Cys, 11657A/G, and Arg154His) and APE1(Asp148Glu, and T-656G) polymorphisms on colorectal cancer(CRC) risk.METHODS: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses onthe basis of sex, age at diagnosis, and tumor subsite and stage were performed.RESULTS: The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype(OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage Ⅲ + Ⅳ cancer(OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657 G allele carriers had a 41% reduced CRC risk among stage 0-Ⅱ patients(OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele(OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656 G haplotype was also associated with a significant CRC risk in females(OR = 1.36, 95%CI: 1.03-1.78).CONCLUSION: OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwan Residents population.

High school sports programs differentially impact participation by sex

背景:研究表明,参加体育活动可降低儿童和青少年肥胖的风险。学校是促进儿童和青少年参加体育活动的理想环境,但目前尚不清楚体育活动的"获得"和"选择"如何影响学生的参与度,也不清楚学校体育课的特点对学生参与体育的影响是否存在性别差异。本研究旨在评价高中体育运动项目的特点,并确定这些体育课程对男女生参与运动队的影响程度。方法:用电话采访的方式纵向调查了1,244名新罕布什尔州和佛蒙特州的学生。学生自述他们小学至高中阶段参与运动队的情况。通过调查高中职员了解体育机会。在本研究中,"体育机会"是指每100名学生所对应的学校提供的体育项目种类《选择)和学校提供的体育种类中不限制参加人数的体育项目的比例(获得)。结果:约70%的儿童参加了至少一个体育运动队,男生为73%,女生为66%。研究发现在性别和两个体育机会变量之间存在显著交互影响。控制小学生参与体育活动和其他协变量后,发现如果学校不限制最受欢迎的体育项目的参与人数,男生会参加更多的体育运动队(RR=1.12,p<0.01)。相反,如果学校提供广泛的体育项目,女生会参加更多的体育运动队(RR=1 47,p<0.001)。结论:前人研究表明,参加体育活动能带来许多健康效益。对公共卫生工作包括预防肥胖而言,学校体育课可能是一个重要而有效但未被充分利用的对象。要使青少年参加更多的体育活动,就应综合考虑学校体育项目的获得和选择。学校可运用不同策略,促使男生和女生更多地参加体育活动。

Interaction models of CYP1A1, GSTMl polymorphisms and tobacco smoking in intestinal gastric cancer

AIM: To explore the interaction models of the cytochrome P-450 (CYP) 1A1 Valv ariant and glutathione S-transferase (GST)M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer.METHODS: A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblingsin-law who had no history of digestive system cancer.Logistic regression was used to estimate the interaction models.RESULTS: The frequency of the CYP1A1 Val variant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 (95% confidence interval [95%CI]: 1.2-3.1, P＜0.01). It showed a significant type 2 form of interaction model when both CYP1A1 Val variant allele and former tobacco smoking existed (i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYP1A1 variant alone). The interaction index γ was 2.8, and OReg (95%CI)was 5.0 (1.9-13.4). GSTM1 null genotype and former tobacco smoking were significant in a type 4 interaction model (i.e.,the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects).The interaction index γ and OReg (95%CI) were 3.4 and 8.4 (3.4-20.9), respectively.CONCLUSION: Different interaction models of CYP1A1 Val variant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.

prevalence of colorectal neoplasms in young, average risk individuals: A turning tide between East and West

AIM To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations. METHODS We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma(AA) and colorectal cancer(CRC) were determined in the 40's and 50's age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations.RESULTS We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men(p < 0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups.CONCLUSION The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population.

Analysis of YouTube^(TM) videos related to bowel preparation for colonoscopy

AIM: To examine YouTubeTM videos about bowel preparation procedure to better understand the quality of this information on the Internet. METHODS: YouTubeTM videos related to colonoscopy preparation were identified during the winter of 2014; only those with ≥ 5000 views were selected for analysis(n = 280). Creator of the video, length, date posted, whether the video was based upon personal experience, and theme was recorded. Bivariate analysis was conducted to examine differences between consumers vs healthcare professionals-created videos. RESULTS: Most videos were based on personal experience. Half were created by consumers and 34% were ≥ 4.5 min long. Healthcare professional videos were viewed more often(> 19400, 59.4% vs 40.8%,P = 0.037, for healthcare professional and consumer, respectively) and more often focused on the purgative type and completing the preparation. Consumer videos received more comments(> 10 comments, 62.2% vs 42.7%, P = 0.001) and more often emphasized the palatability of the purgative, disgust, and hunger during the procedure. Content of colonoscopy bowel preparation YouTube? videos is influenced by who creates the video and may affect views on colon cancer screening. CONCLUSION: The impact of perspectives on the quality of health-related information found on the Internet requires further examination.

Implications of multigene testing for hereditary breast cancer in primary care

Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a proportion in which a gene mutation can be the cause of the predisposition for breast cancer. A careful assessment of family and clinical history should be performed in these women in order to determine if a genetic counseling referral is indicated. In cases of hereditary breast cancer, genetic testing with a multigene panel can identify specific genetic mutations in over 100 genes. The most common genes mutated in hereditary breast cancer are the high-penetrance BRCA1 and BRCA2 genes. In addition, other mutations in high-penetrance genes in familial cancer syndromes and mutations in DNA repair genes can cause hereditary breast cancer. Mutations in low-penetrance genes and variants of uncertain significance may play a role in breast cancer development, but the magnitude and scope of risk in these cases remain unclear, thus the clinical utility of testing for these mutations is uncertain. In women with high-penetrance genetic mutations or lifetime risk of breast cancer > 20%, risk-reducing interventions, such as intensive screening, surgery, and chemoprevention, can decrease the incidence and mortality of breast cancer.

Cardiovascular effects of hemoglobin response in patients receiving epoetin alfa and oral iron in heart failure with a preserved ejection fraction

BackgroundPrevious 数据从一最近在社区住所之中进行了未来的、单个盲目使随机化的临床的试用有有保存喷射部分( HFPEF )和贫血症的心失败的更老的病人与 epoetin A 使随机化到治疗(刺激红血球生成的代理人， ESA )对安慰剂没证明治疗考虑的重要好处留给室( LV )生活( QOL )的结构，功能的能力，或质量。然而，几个病人使随机化到治疗手臂是有血红素的非最优的增加的非应答者。在试用的所有病人也收到了口头的铁的 gluconate，它能在在收到安慰剂的那些观察的血红素贡献了增加。因此，我们执行了把病人分开成应答者对非应答者以便决定在贫血症的测量改进是否将在 56 个病人全部的临床的 endpoints.MethodsA 上有任何效果的分析(年龄 77 ±；11 年， 68% 女性) 被招募有的贫血症定义为 ≤ 的血红素；12 g/dL (平均， 10.4 ±；1 g/dL ) 与定义为有 NHANES-CHF 的 HFPEF (国家健康和营养检查调查：充血的心失败) 标准 ≥ 得分；3 并且 > 的喷射部分；40%( 平均 EF =63%±；15%) 。病人们随机被分配仅仅收到 ESA 和铁的 gluconate 或铁的 gluconate。在这分析，当有在 trial.ResultsNineteen 题目的开始的 4 个星期内的 1 g/dL 的增加的一个病人与 33 非应答者相比作为应答者被分类，一个应答者被定义。当平均血红素为应答者在 6 个月的结束显著地增加了时(1.8 ±；0.3 对 0.8 ±；0.2 g/dL， P = 0.004 ) ，分到 ESA 的 50% 题目是非应答者。左室的功能包括喷射部分(P = 0.32 ) 并且结束心脏舒张的体积(P = 0.59 ) 在与非应答者相比的应答者是未改变的。应答者也没在纽约心协会(NYHA ) 班，六极小的散步测试(6 MWT ) 和山峰 VO 2 上显示出重要改进。尽管 QOL 在每个组以内显著地改善了，对有 ESA 和口头的铁的贫血症治疗的重要血红素反应不导致的 two.ConclusionsA 之间没有差别在改变的 LV 的差别，功能的地位，或 QOL。另外，有 HFPEF 和贫血症的更老的成年人的一个重要百分比不对 ESA 治疗作出回应。给这小试用的结果，当在有 HFPEF 的更老的成年题目的一个标记没有重要临床的用途，它出现好像在贫血症使用客观改进。

A Genetic Susceptibility Study of Lung Cancer Risk Potentially Associated with Polycyclic Aromatic Hydrocarbon Inhalation Exposure

To establish a genetic susceptibility assessment model of lung cancer risk potentially associated with polycyclic aromatic hydrocarbon(PAH) inhalation exposure among non-smokers in China,a total of 143 patients with lung adenocarcinoma and 143 cancer-free individuals were recruited.Sixty-eight genetic polymorphisms in 10 pathways related to PAH metabolism and tumorigenesis were selected and examined.It was observed that 3 genetic polymorphisms,along with 10 additional genetic polymorphisms via gene-gene interactions,significantly influenced lung cancer risk potentially associated with PAH inhalation exposure.Most polymorphisms were associated with PAH metabolism.According to the established genetic susceptibility score(GSS),lung cancer risk increased with a rise in the GSS level,thereby indicating a positive dose-response relationship.

影响三地居民黄曲霉毒素B_1-白蛋白加合物的相关因素分析

[目的]分析影响存在肝癌发病率梯度的三地居民个体黄曲霉毒素生物效应的相关因素。[方法]对广西扶挼两个自然村农民、南宁和四川成都城市居民采用酶联免疫法检测血浆黄曲霉毒素B1-白蛋白加合物(AFB1-AlbuminAdducts,AAA)水平、肝炎病毒(hepatitisvirus,HV)标志物(HBV两对半,HCV、HDV、HEV和HGV抗体)及肝功能。[结果]扶挼47.2%(42/89)的居民至少1种HV感染标志物阳性;南宁和成都分别为15.8%(31/196)和22.7%(27/119)。Log(AAA)水平(n,x±s)为扶挼(89,2.44±0.16)和南宁(196,2.45±0.15)均高于成都(118,2.20±0.24),(P=0.000);但扶挼与南宁间差别无显著性(P=0.859)。南宁(P=0.023)、成都(P=0.026)两地男性AAA水平均高于女性。扶挼和成都两地HV感染者AAA水平均高于非感染者(P分别为0.447和0.041)。HV(-)组中,AAA水平与年龄(r=-0.199,P=0.000)和BMI(r=-0.158,P=0.006)负相关。HV(+)组AAA分别与白蛋白(P=0.000)、球蛋白(P=0.012)和天冬氨酸转氨酶(P=0.052)相关,而HV(-)组AAA分别与直接胆红素、间接胆红素、白蛋白、γ-谷氨酰转肽酶、总胆汁酸和碱性磷酸酶相关(P<0.05)。[结论]AFB1暴露的生物效应可能受肝炎病毒感染、性别、年龄和代谢等因素的影响。AAA与肝功能指标的相关性提示AFB1对肝脏实质或胆道细胞的损害作用。

麦冬不同部位降血糖作用实验研究

目的 比较麦东不同极性部位对α-葡萄糖苷酶和α淀粉酶的抑制作用,评价活性部位对糖尿病小鼠血糖的影响。方法 制备了麦冬水提物、70%乙醇提取物、正丁醇部位、石油醚部位、二氯甲烷部位、乙酸乙酯部位,评价不同提取物对α-葡萄糖苷酶和α-淀粉酶的抑制作用。腹腔注射链脲佐菌素构建糖尿病小鼠模型,验证活性部位的降血糖作用。结果 α-葡萄糖苷酶活性抑制作用大小依次为水提物>70%乙醇提取物>正丁醇部位>石油醚部位>二氯甲烷部位>乙酸乙酯部位;α-淀粉酶活性抑制作用大小依次为水提物>乙酸乙酯部位>正丁醇部位>二氯甲烷部位>70%乙醇提取物>石油醚部位。其中,体外活性最强的部位为麦冬水提物,灌胃给予糖尿病小鼠后能显著降低空腹血糖值。结论 麦冬水提物对α-葡萄糖苷酶和α-淀粉酶活性的抑制作用最强,并具有显著的体内降血糖作用。

Global hypomethylation in hepatocellular carcinoma and its relationship to aflatoxin B_1 exposure

AIM:To determine global DNA methylation in paired hepatocellular carcinoma(HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers,including that of aflatoxin B 1 exposure.METHODS:Using the radio labeled methyl acceptance assay as a measure of global hypomethylation,as well as two repetitive elements,including satellite 2(Sat2) by MethyLight and long interspersed nucleotide elements(LINE1),by pyrosequencing.RESULTS:By all three assays,mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues.Methyl acceptance assay log(mean ± SD) disintegrations/min/ng DNA are 70.0 ± 54.8 and 32.4 ± 15.6,respectively,P = 0.040;percent methylation of Sat2 42.2 ± 55.1 and 117.9 ± 88.8,respectively,P < 0.0001 and percent methylation LINE1 48.6 ± 14.8 and 71.7 ± 1.4,respectively,P < 0.0001.Aflatoxin B 1 albumin(AFB 1-Alb) adducts,a measure of exposure to this dietary carcinogen,were inversely correlated with LINE1 methylation(r =-0.36,P = 0.034).CONCLUSION:Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods.AFB 1 exposure is associated with DNA global hypomethylation,suggesting that chemical carcinogens may influence epigenetic changes in humans.

个体化动态治疗方案和多重方案随机序贯试验在精神卫生研究中的应用(英文)

动态治疗方案(Dynamic treatment regimens,DTRs)是一种序贯决策规则,是根据每个患者随时间变化而变化的特征和先前观察到的中间结果而量身定制的临床决策。精神障碍具有慢性和复杂性的特点,精神障碍患者具有异质性特点。这就要求随时间推移,根据个体对治疗反应的不同而分析出最佳的治疗方案,并动态地应用到患者之后的治疗中。多重方案随机序贯试验(Sequential Multiple Assignment Randomized Trial,SMARTs)的设计可以估计DTRs的治疗效应。SMARTs收集到大量的个体化变量和中间结果,在此基础上应用已有的现代统计工具可以优化DTRs。这些统计方法也可为今后的SMARTs研究设计推荐量身定制的变量。本文通过两个精神卫生研究案例介绍了DTRs和SMARTs,讨论了从SMARTs数据估算出最佳DTR的两种不同的计算机自动分析方法,并使用模拟数据演示这两种统计方法的性能。

Blood DNA methylation markers in prospectively identifiedhepatocellular carcinoma cases and controls from Taiwan

AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNAmethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA as biomarkers of HCC susceptibility but should be replicated in additional prospective studies.