False Discovery Rates for Rare Variants From Sequenced Data

The detection of rare deleterious variants is the preeminent current technical challenge in statistical genetics. Sorting the deleterious from neutral variants at a disease locus is challenging because of the sparseness of the evidence for each individual variant. Hierarchical modeling and Bayesian model uncertainty are two techniques that have been shown to be promising in pinpointing individual rare variants that may be driving the association. Interpreting the results from these techniques from the perspective of multiple testing is a challenge and the goal of this article is to better understand their false discovery properties. Using simulations, we conclude that accurate false discovery control cannot be achieved in this framework unless the magnitude of the variants' risk is large and the hierarchical characteristics have high accuracy in distinguishing deleterious from neutral variants.     

Determinants of Patient's Adherence to Hypertension Medications in a Rural Population of Kancheepuram District in Tamil Nadu,South India

Context:

Non-communicable diseases, no longer a disease of the rich, impose a great threat in the developing nations due to demographic and epidemiological transition. This increasing burden of non-communicable diseases and their risk factors is worrisome. Adherence to hypertension (HT) medication is very important for improving the quality of life and preventing complications of HT.

Aim:

To study the factors determining adherence to HT medication.

Settings and Design:

A community-based cross-sectional study was conducted in a rural area of Kancheepuram district, Tamil Nadu, with a total population of around 16,005.

Materials and Methods:

This study was carried out over a period of 6 months (February-July) using a pre-structured and validated questionnaire. All eligible participants were selected by house-to-house survey and individuals not available on three consecutive visits were excluded from the study. The questionnaire included information on demographic characteristics, lifestyle habits, adherence to HT medication, blood pressure, and body mass index (BMI). Caste was classified based on Tamil Nadu Public Service commission.

Statistical Analysis:

Data were entered in MS Excel and analyzed in SPSS version 16. P value <0.05 was considered statistically significant. Ethical Consideration: Informed verbal consent was obtained prior to data collection. The patient''s adherence to HT medication was assessed using the Morisky 4-Item Self-Report Measure of Medication-taking Behavior [MMAS-4].

Results:

We studied 473 hypertensive patients of which 226 were males and 247 were females. The prevalence of adherence was 24.1% (n = 114) in the study population. Respondents with regular physical activity, non-smokers and non-alcoholics were more adherent to HT medication as compared with respondents with sedentary lifestyle, smoking and alcohol intake (P < 0.005). Based on health belief model, the respondents who perceived high susceptibility, severity, benefit had better adherence compared with moderate and low susceptibility, severity, benefit.     

胃痞消对胃癌前病变大鼠血浆肿瘤坏死因子-α和白细胞介素-4表达的影响

【目的】观察胃痞消对脾虚证胃癌前病变(PLGC)大鼠血浆肿瘤坏死因子-α(TNF-α)和白细胞介素-4(IL-4)表达的影响。【方法】将SD大鼠分为6组:正常对照组,模型组,维酶素组(剂量为0.2 g·kg-1·d-1),胃痞消高、中、低剂量组(剂量分别为15、7.5、3.75 g·kg-1·d-1)。采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)溶液(200μg/m L)自由饮用、小承气汤(2 m L/只,生药1 g/m L)灌胃法及饥饱失常等多因素造模18周复制脾虚证胃癌前病变模型,观察各组大鼠的组织病理学及行为学变化,检测血浆TNF-α及IL-4含量。【结果】模型组血浆TNF-α、IL-4含量较正常组显著降低(P<0.05);维酶素组、胃痞消高剂量组、胃痞消低剂量组血浆TNF-α含量较模型组显著升高(P<0.05),模型组与胃痞消中剂量组比较差异无统计学意义(P>0.05);维酶素组、胃痞消高剂量组、胃痞消中剂量组、胃痞消低剂量组血浆IL-4含量与模型组比较均显著升高(P<0.05)。【结论】胃痞消改善脾虚证胃癌前病变大鼠组织学变化的机制可能通过调节血浆TNF-α、IL-4含量变化及胃黏膜间质淋巴细胞及单核细胞的动员而实现。     

实验性自身免疫性重症肌无力动物模型研究

研究表明,实验性自身免疫性重症肌无力（EAMG）与重症肌无力（MG）在症状、病理、免疫及组织学方面相似。EAMG 动物模型主要通过主动或被动免疫实验动物,制备与重症肌无力患者的临床表现、免疫组织学、电生理学等相似的动物模型,为临床诊断及治疗提供依据。但目前 EAMG 模型仍不完善,仍需进一步探索。     

肌肉因子irisin在舒张性心力衰竭大鼠中的表达及意义

目的 通过建立大鼠压力负荷诱导舒张性心力衰竭模型,探索新型肌肉因子irisin与舒张性心力衰竭(diastolic dysfunction, DHF)之间的联系,为临床应用提供依据。方法 采用腹主动脉缩窄(abdominalaortic constriction, AAC)的手术方式建立压力负荷诱导大鼠DHF的疾病模型。20只SD大鼠随机分入AAC手术组(n=10)和假手术(sham)组(n=10)。造模12周后测量心超、心室内压力、解剖结构评估造模效果。EILSA检测irisin两组间血清水平表达差异;利用Real-time PCR、Western印迹法、免疫组化染色分析irisin的剪切前体Ⅲ型纤维蛋白结构域5(FNDC5)在两组间表达差异,寻找irisin的分泌来源。结果 成功建立AAC-DHF的SD大鼠疾病模型。造模12周时,AAC组大鼠血清irisin水平逐渐升高,第12周时显著高于Sham组[(135.2± 28.9)ng/ml vs(64.9±34.0)ng/ml, P＜0.001]。Real-time PCR结果显示,FNDC5在AAC组的心脏组织(11.8±2.4 vs 1.88±1.2,P＜0.001)和肌肉组织中表达较高(15.1±1.6 vs 1.25±1.4,P＜0.001)。Western印迹法显示,AAC组FNDC5在心脏表达高于Sham组(P=0.021)。IHC染色显示,FNDC5主要表达于AAC组骨骼肌筋膜和心肌实质。结论 大鼠AAC模型证实血清irisin水平在DHF的情况下升高,其来源可能是由心肌和骨骼肌共同分泌的。     

基于蒙特卡罗数学模型两种脊柱全景X射线成像技术受检者辐射剂量的对比研究

目的 比较两种脊柱全景X射线成像技术对受检者产生的辐射剂量。方法 使用仿真体模进行实验,摸索出该体模在日本岛津Sonialvision safire17设备Slot scan脊柱全景成像的适宜成像条件,然后在GE Discovery XR650型DR系统上对该体模进行不同曝光条件的DR脊柱全景成像,3位有经验的放射科医生对两种成像技术的图像进行评分,选择图像质量评分均值最接近的对应成像参数为实验成像参数。将相关成像参数及X射线机信息输入PCXMC 2.0软件,计算受检者脊柱全景成像的器官吸收剂量和有效剂量。结果 Slot scan脊柱全景成像的适宜成像条件为高质量全景成像模式(HQ模式)、SID 150 cm、100 kVp和2 mAs, DR手动曝光模式脊柱全景成像相当图像质量的成像条件为SID 200 cm、100 kVp和3.2 mAs。Slot scan HQ模式、DR手动曝光模式和DR自动曝光模式脊柱全景成像的有效剂量(E)分别为(0.118 7±0.001 4)、(0.084 7±0.000 8)和(0.158 0±0.001 5) mSv,DR手动曝光模式的有效剂量明显低于其余2种模式(F=3 007.293,P<0.05);除乳腺以外,DR手动曝光模式的器官剂量均低于Slot scan HQ模式的器官剂量(P<0.05);除甲状腺、食管、肺以外,DR自动曝光模式的器官剂量均高于另外两种成像方式的器官剂量(P<0.05)。结论 两种手动全景成像技术的辐射剂量均处于较低水平,合理选择全景成像技术的曝光参数和模式可实现低剂量全景X射线成像。     

低管电压联合迭代模型重建技术在肝脏CT增强扫描中的可行性研究

目的 探讨低管电压联合迭代模型重建(IMR)技术在肝脏CT增强扫描中的可行性。方法 60例患者按随机数字表法分为A组和B组,每组30例。扫描方案A组动脉期100 kV,门静脉期120 kV,B组动脉期120 kV,门静脉期100 kV。各组管电流均固定为250 mAs。A组动脉期和B组门静脉期采用IMR,A组门静脉期和B组动脉期采用滤波反投影(FBP)重建,得到4组图像,包括A1组(动脉期,100 kV,IMR),B1组(动脉期,120 kV,FBP),A2组(门静脉期,120 kV,FBP)以及B2组(门静脉期,100 kV,IMR)。分别比较A1组和B1组,A2组和B2组的图像质量客观评价指标 [图像噪声、图像信噪比(SNR)、对比噪声比(CNR)] 和主观评价指标(低对比分辨力、病灶边缘锐利度、图像失真及诊断信心度),并计算有效剂量。结果 有效剂量A1组较B1组、B2组较A2组明显下降(t=11.05、11.64, P<0.01)。低对比分辨力、病灶边缘锐利度A1优于B1组、 B2优于A2组(Z=6.391、3.200、6.559、3.409, P<0.01),图像失真和诊断信心差异无统计学意义(P>0.05)。图像噪声A1组低于B1组,B2组低于A2组(t=12.889、15.163, P<0.01),SNR和CNR A1组高于B1组,B2组高于A2组(t=15.458、1.325、15.308、3.136, P<0.01)。结论 与常规管电压FBP重建相比,低管电压联合IMR重建可显著降低肝脏增强CT的辐射剂量,并提高其图像质量。     

菌（毒）种保藏管理信息系统的研究与开发

目的：为了最大程度地提高菌（毒）种保藏机构的管理效率及质量,建立一套菌（毒）种保藏管理信息系统。方法采用C／S架构,以Visual Basic6．0、SQL Server2000为开发平台,结合E-R模型第三范式建立了菌（毒）种信息数据库,应用面向对象的语言程序进行了系统开发。结果总结了系统需要的硬件设备,构建了菌（毒）种信息管理、科研项目管理、人员管理、系统维护等功能模块,在平台界面和数据库均设置了访问权限,最大限度地保证菌（毒）种信息安全。结论该信息系统实现了菌（毒）种从入库、分类、保存、领取、备案等的信息化流程管理,有机整合了保藏机构的各种资源,提高了菌（毒）种的管理效率,保障了菌（毒）种信息安全。