BACKGROUND & AIMS: :Adolescents who are changing residence, as well as their social and economic circumstances may experience lifestyle changes that have an effect on body composition outcomes such as undernutrition, overweight or obesity. This paper uses data from Birth to Twenty, a birth cohort of South African urban children, to determine the relationship between residential mobility and body mass index (BMI) amongst Black adolescents aged 15 (n=1613), and to examine the role of changes in household socioeconomic status (SES). The prevalence of overweight and obesity in the sample was 25% in females and 8% in males. Amongst the females, a strong positive association between residential mobility and BMI was observed for those who also experienced an increase in household SES between birth and 15 years (β=0.42, SE=0.13), while no effect was identified for males. The study shows the potential for environmental change and increased resources to influence the risk for obesity. It also highlights the value in considering the range of social environmental factors and changes across the early life course that might play a part in evolving nutritional patterns in urban transitioning environments.

背景与目标： : 改变居住地以及他们的社会和经济环境的青少年可能会经历生活方式的改变，这些改变会影响身体成分的结果，例如营养不足，超重或肥胖。本文使用从出生到20岁的数据 (南非城市儿童的出生队列) 来确定居住流动性与15岁黑人青少年 (n = 1613) 的体重指数 (BMI) 之间的关系，并研究其作用在家庭社会经济地位 (SES) 中的变化。样本中超重和肥胖的患病率在女性中25%，在男性中8%。在女性中，对于那些在出生至15岁之间家庭SES增加的人 (β = 0.42，SE = 0.13)，观察到居住流动性与BMI之间存在很强的正相关关系，而对男性则没有发现影响。这项研究显示了环境变化的潜力和增加的资源来影响肥胖的风险。它还强调了在考虑社会环境因素的范围以及整个早期生活过程中可能在城市转型环境中不断变化的营养模式中发挥作用的价值。

BACKGROUND & AIMS: INTRODUCTION:Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS:BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS:Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION:Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

背景与目标：

BACKGROUND & AIMS: :The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

背景与目标： : 在普通人群中，缺铁性贫血 (IDA) 与骨质疏松症之间的因果关系尚未建立。因此，当前的纵向研究通过分析大量全国基于人群的样本来确定IDA作为骨质疏松症危险因素的作用。在从1998-2012中随机抽取的1,000,000个样本中。对台湾全民健康保险研究数据库、IDA患者 (病例组 (n = 35,751)) 和无IDA患者 (对照组 (n = 178,755)) 进行比较。年龄 <20岁且在诊断IDA之前已有骨质疏松症的患者被排除。每位IDA患者的年龄和性别与五名没有IDA的患者相匹配。通过血液检查结果和x射线骨密度法进一步确认IDA和骨质疏松症 (使用ICD-9CM编码) 的诊断，以确保诊断的准确性。与没有IDA的个体相比，IDA患者中更经常发生骨质疏松症 (2.27% vs. 1.32%，p <0.001)。Cox比例风险分析显示，该病例的骨质疏松症风险显着高于对照组 (风险比 (HR) = 1.74; 95% CI = 1.61-1.88)，并且在校正协变量后保持相似 (调整后HR = 1.81; 95% CI = 1.67-1.97)。与没有IDA的个体相比，接受静脉铁治疗的IDA患者的骨质疏松症风险更高 (调整后的HR = 2.21; 95% CI = 1.85-2.63)。相比之下，接受输血的IDA患者的骨质疏松症风险降低 (调整后的HR = 1.47; 95% CI = 1.20-1.80)。作为预测因素，先前的IDA是骨质疏松症发生的重要且独立的危险因素。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population. METHODS:Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and gastrointestinal stromal tumors) as a single agent or in combination with chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM®. RESULTS:The PKs of olaratumab were best described by a two-compartment PK model with linear clearance (CL). Patient body weight was found to have a significant effect on both CL and central volume of distribution (V 1), whereas tumor size significantly affected CL. A small subset of patients developed treatment-emergent anti-drug antibodies (TE-ADAs); however, TE-ADAs did not have any effect on CL or PK time course of olaratumab. There was no difference in the PKs of olaratumab between patients who received olaratumab as a single agent or in combination with chemotherapy. CONCLUSION:The PKs of olaratumab were best described by a model with linear disposition. Patient body weight and tumor size were found to be significant covariates. The PKs of olaratumab were not affected by immunogenicity or chemotherapeutic agents.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In the first population-based study of psychopathology conducted in Haiti, we documented earthquake-related experiences associated with risk for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) 2-4 months following the 2010 Haiti earthquake. METHODS:A population-based survey was conducted of 1,323 survivors randomly selected from the general nondisplaced community, internally displaced persons camps, and a community clinic. Respondents were from the Nazon area of Port-au-Prince, ∼20 miles from the epicenter. RESULTS:Respondents (90.5%) reported at least one relative/close friend injured/killed, 93% saw dead bodies, and 20.9% lost their job post-earthquake. The prevalence of PTSD (24.6%) and MDD (28.3%) was high. History of violent trauma was associated with risk of PTSD and MDD (adjusted odds ratio [AOR] 1.4, 95% confidence interval [CI], 1.0-1.9; AOR, 1.7, 95% CI 1.3, 2.2, respectively). Low social support (AOR, 1.7, 95% CI 1.2, 2.3; AOR 1.4, 95% CI 1.0, 1.9, respectively) increased risk of PTSD and MDD among women. Suffering damage to the home increased risk of MDD in males (AOR 2.8, 95% CI 1.5, 5.5). Associations between being trapped in rubble, major damage to house, job loss, and PTSD; and participation in rescue/recovery, friends/family injured/killed, and MDD varied based on prior history of violent trauma. CONCLUSIONS:Addressing mental health in a post-earthquake setting such as Haiti will require focusing resources on screening and treatment of identified vulnerable groups while targeting improvement of post-earthquake living conditions. Investment in sources of social support for women may make help mitigate the vulnerability of women to PTSD and MDD.

背景与目标：

BACKGROUND & AIMS: PURPOSE:Descriptive studies have indicated a rising trend in Hodgkin's lymphoma (HL) incidence in young adults, especially females. Increasing evidence has suggested that some risk factors associated with HL may vary by age or gender. Recent studies have reported an increased risk of HL associated with increasing body mass index (BMI), but the results have been inconsistent. The objectives of this study were to examine whether the associations between measures of body size (height, weight, and BMI) and HL risk vary by age and/or gender. METHODS:A population-based case-control study was conducted in Connecticut and Massachusetts. A total of 567 HL cases and 679 controls were recruited in 1997-2000. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS:Among younger women <35 years old, being overweight (25-29.9 kg/m(2)) versus normal weight (18.5-24.9 kg/m(2)) was significantly associated with an increased risk of HL (OR = 2.1, 95 % CI = 1.1-4.0). The risk increased with increasing weight and BMI (p trends <0.01). Among women ≥35 years old, by contrast, higher weight and BMI were associated with a reduced risk of HL (p trends <0.01). Conversely, there was no significant association between BMI and risk of HL in younger or older males. CONCLUSIONS:These findings show that the associations between body size and risk of HL vary by gender and age, and require confirmation in other populations.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Laparoscopic gastric bypass surgery (LGBS) has become the most widely used bariatric procedure due to its beneficial long-term outcomes for patients with morbid obesity. However, it is unclear whether racial differences in admission for LGBS have changed over time compared to racial differences in all other admissions. We aimed to investigate the trends and differences in the use of LGBS among white, African-American, and Hispanic patients from 2002 to 2008. METHODS:We performed a secondary analysis of data on obese adult patients operated between 2002 and 2008, using the Nationwide Inpatient Sample (NIS) database. The probability of being admitted for LGBS was estimated using logistic regression with race, year, and year by race interaction as predictors, controlling for numerous patient and hospital characteristics. RESULTS:Among 1,704,972 obese hospitalized patients captured through NIS from 2002 to 2008, 2.6 % underwent LGBS (2.8 % Whites, 1.7 % African-Americans, and 2.6 % Hispanics). In adjusted analysis, obese African-American (OR 0.48, p < 0.001) and Hispanic patients (OR 0.59, p < 0.001) were less likely to be admitted for LGBS than white patients in 2002. Race-year interactions showed that the odds of African-Americans undergoing LGBS significantly increased from 2002 to 2008 compared with Whites (annual OR 1.03, p < 0.001) while no such increase was detected for Hispanics (annual OR 1.02, p = 0.11). In 2008, African-American (OR 0.58, p < 0.001) and Hispanic patients (OR 0.65, p < 0.001) still had lower odds than white patients. CONCLUSIONS:This is the first study showing that the difference in the use of LGBS between obese African-American and white patients declined between 2002 and 2008. However, LGBS use still remained significantly lower for both African-American and Hispanic patients in 2008 compared with white patients.

背景与目标：

BACKGROUND & AIMS: :Adaptive radiations are an important source of biodiversity and are often characterized by many speciation events in very short succession. It has been proposed that the high speciation rates in these radiations may be fuelled by novel genetic combinations produced in episodes of hybridization among the young species. The role of such hybridization events in the evolutionary history of a group can be investigated by comparing the genealogical relationships inferred from different subsets of loci, but such studies have thus far often been hampered by shallow genetic divergences, especially in young adaptive radiations, and the lack of genome-scale molecular data. Here, we use a genome-wide sampling of SNPs identified within restriction site-associated DNA (RAD) tags to investigate the genomic consistency of patterns of shared ancestry and adaptive divergence among five sympatric cichlid species of two genera, Pundamilia and Mbipia, which form part of the massive adaptive radiation of cichlids in the East African Lake Victoria. Species pairs differ along several axes: male nuptial colouration, feeding ecology, depth distribution, as well as the morphological traits that distinguish the two genera and more subtle morphological differences. Using outlier scan approaches, we identify signals of divergent selection between all species pairs with a number of loci showing parallel patterns in replicated contrasts either between genera or between male colour types. We then create SNP subsets that we expect to be characterized to different extents by selection history and neutral processes and describe phylogenetic and population genetic patterns across these subsets. These analyses reveal very different evolutionary histories for different regions of the genome. To explain these results, we propose at least two intergeneric hybridization events (between Mbipia spp. and Pundamilia spp.) in the evolutionary history of these five species that would have lead to the evolution of novel trait combinations and new species.

背景与目标： : 适应性辐射是生物多样性的重要来源，通常以非常短的连续发生许多物种形成事件为特征。已经提出，这些辐射中的高物种形成率可能是由年轻物种之间杂交过程中产生的新型遗传组合推动的。可以通过比较从不同基因座子集推断出的系谱关系来研究此类杂交事件在群体进化史中的作用，但是到目前为止，此类研究经常受到浅遗传差异的阻碍，尤其是在年轻的适应性辐射中，以及缺乏基因组规模的分子数据。在这里，我们使用在限制性位点相关DNA (RAD) 标签中鉴定的snp的全基因组采样来研究Pundamilia和Mbipia这两个属的五个同族丽鱼科鱼物种之间共享祖先和适应性差异模式的基因组一致性，构成东非维多利亚湖丽鱼科鱼大规模适应性辐射的一部分。物种对沿几个轴不同: 雄性婚育颜色，摄食生态，深度分布以及区分两个属的形态特征和更细微的形态差异。使用异常值扫描方法，我们可以识别所有物种对之间不同选择的信号，其中许多基因座在属之间或雄性颜色类型之间的复制对比中显示平行模式。然后，我们创建了SNP子集，我们希望通过选择历史和中性过程对其进行不同程度的表征，并描述了这些子集的系统发育和种群遗传模式。这些分析揭示了基因组不同区域的进化历史非常不同。为了解释这些结果，我们在这五个物种的进化史中提出了至少两个属间杂交事件 (在Mbipia spp。和Pundamilia spp。之间)，这将导致新的性状组合和新物种的进化。

BACKGROUND & AIMS: OBJECTIVES:In a large population-based study among adults in northern Europe the relation between occupational exposure and new-onset asthma was studied. METHODS:The study comprised 13 284 subjects born between 1945 and 1973, who answered a questionnaire 1989-1992 and again 1999-2001. Asthma was defined as 'Asthma diagnosed by a physician' with reported year of diagnose. Hazard ratios (HR), for new-onset adult asthma during 1980-2000, were calculated using a modified job-exposure matrix as well as high-risk occupations in Cox regression models. The analyses were made separately for men and women and were also stratified for atopy. RESULTS:During the observation period there were 429 subjects with new-onset asthma with an asthma incidence of 1.3 cases per 1000 person-years for men and 2.4 for women. A significant increase in new-onset asthma was seen for men exposed to plant-associated antigens (HR = 3.6; 95% CI [confidence interval] = 1.4-9.0), epoxy (HR = 2.4; 95% CI = 1.3-4.5), diisocyanates (HR = 2.1; 95% CI = 1.2-3.7) and accidental peak exposures to irritants (HR = 2.4; 95% CI = 1.3-4.7). Both men and women exposed to cleaning agents had an increased asthma risk. When stratifying for atopy an increased asthma risk were seen in non-atopic men exposed to acrylates (HR = 3.3; 95% CI = 1.4-7.5), epoxy compounds (HR = 3.6; 95% CI = 1.6-7.9), diisocyanates and accidental peak exposures to irritants (HR = 3.0; 95% CI = 1.2-7.2). Population attributable risk for occupational asthma was 14% for men and 7% for women. CONCLUSIONS:This population-based study showed that men exposed to epoxy, diisocyanates and acrylates had an increased risk of new-onset asthma. Non-atopics seemed to be at higher risk than atopics, except for exposure to high molecular weight agents. Increased asthma risks among cleaners, spray painters, plumbers, and hairdressers were confirmed.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE:the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS:this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS:at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION:the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To obtain prevalence estimates of clinical features of obstructive sleep apnoea (OSA) and identify the dimensions of the public health problem requiring further investigation for an Australian population. METHODS:The South Australian Health Omnibus Survey is an annual representative population survey of South Australians aged≥15 years, conducted via interviewer-administered questionnaire. In 2009, 3007 participants were asked the STOP-BANG instrument measure of obstructive sleep apnoea risk, which includes symptoms of loud snoring, frequent tiredness during daytime, observed apnoea, and high blood pressure (STOP), and measured body mass index, age, neck circumference and gender (BANG). Three or more positive response categorises a person at high risk for OSA. RESULTS:Snoring was reported by 49.7% of adults. Tiredness after sleep more than 3 - 4 times per week was reported by 24.8%, and during wake-time by 27.7% of adults, with 8.8% reporting having fallen asleep while driving. Over half of the surveyed men (57.1%, n=566) and 19.3% (n=269) of the women were classified at high-risk of OSA with the STOP-BANG measure. In multivariable models, high risk was associated with less education, lower income, and residence in a regional rather than metropolitan area. CONCLUSION:The high prevalence of adults at risk for OSA suggests that the capacity currently available within the healthcare system to investigate and diagnose OSA is likely to be inadequate, particularly outside urban areas. This highlights an important public health problem that requires further detailed study and trials of new models of care.

背景与目标：

BACKGROUND & AIMS: :Over the course of its long history, Armenia has acted as both a source of numerous indigenous cultures and as a recipient of foreign invasions. As a result of this complex history among populations, the gene pool of the Armenian population may contain traces of historically well-documented ancient migrations. Furthermore, the regions within the historical boundaries of Armenia possess unique demographic histories, having hosted both autochthonous and specific exogenous genetic influences. In the present study, we analyze the Armenian population sub-structure utilizing 17 Y-chromosome short tandem repeat (Y-STR) loci of 412 Armenians from four geographically and anthropologically well-defined groups (Ararat Valley, Gardman, Lake Van and Sasun). To place the genetic composition of Armenia in a regional and historic context, we have compared the Y-STR profiles from these four Armenian collections to 18 current-day Eurasian populations and two ancient DNA collections. Our results illustrate regional trends in Armenian paternal lineages and locale-specific patterns of affinities with neighboring regions. Additionally, we observe a phylogenetic relationship between the Northern Caucasus and the group from Sasun, which offers an explanation for the genetic divergence of this group from other three Armenian collections. These findings highlight the importance of analyzing both general populations as well as geographically defined sub-populations when utilizing Y-STRs for forensic analyses and population genetics studies.

背景与目标： : 在其漫长的历史过程中，亚美尼亚既是众多土著文化的来源，也是外国入侵的接受者。由于人口之间的这种复杂历史，亚美尼亚人口的基因库可能包含历史上有据可查的古代迁徙的痕迹。此外，亚美尼亚历史边界内的地区拥有独特的人口统计学历史，既具有本土遗传影响，也具有特定的外源遗传影响。在本研究中，我们利用来自四个地理和人类学上明确定义的群体 (Ararat Valley，Gardman，Lake Van和Sasun) 的412名亚美尼亚人的17个Y染色体短串联重复序列 (y-str) 基因座来分析亚美尼亚人口亚结构)。为了将亚美尼亚的遗传组成放在区域和历史背景下，我们将这四个亚美尼亚收藏的y-str概况与18个当今的欧亚种群和两个古代DNA收藏进行了比较。我们的结果说明了亚美尼亚父系血统的区域趋势以及与邻近地区的特定区域亲和力模式。此外，我们观察到北高加索地区与Sasun组之间的系统发育关系，这为该组与其他三个亚美尼亚收藏的遗传差异提供了解释。这些发现突显了在利用y-str进行法医分析和群体遗传学研究时分析普通人群以及地理上定义的亚人群的重要性。

BACKGROUND & AIMS: OBJECTIVE:The epidemic of obesity and type 2 diabetes is evident in sub-Saharan Africa (SSA). However, their associations have hardly been examined in this region. METHODS:A hospital-based case-control study in urban Ghana consisting of 1221 adults (542 cases and 679 controls) investigated the role of anthropometric parameters for diabetes. Logistic regression was used for analysis. The discriminative power and population-specific cut-off points for diabetes were identified by receiver operating characteristic curves. RESULTS:The strongest association with diabetes was observed for waist-to-hip ratio: age-adjusted odds ratios per 1 standard deviation difference were 1.95 (95% confidence interval [CI]: 1.64-2.31) in women and 1.40 [1.01-1.94] in men. Also, among women, the odds of diabetes increased with higher waist circumference (1.35 [1.17-1.57]) and waist-to-height ratio (1.29 [1.12-1.50]). Among men, this was not discernible. Rather, hip circumference was inversely related (0.69 [0.50-0.95]). Body mass index was neither associated with diabetes in women (1.01 [0.88-1.15]) nor in men (0.74 [0.52-1.04]). Among both genders, waist-to-hip ratio showed the best discriminative ability for diabetes in this population and the optimal cut-off points were ≥ 0.88 in women and ≥ 0.90 in men. Recommended cut-off points for body mass index and waist circumference had a poor predictive ability. CONCLUSION:Our findings suggest that measures of central rather than general obesity relate to type 2 diabetes in SSA. It remains to be verified from larger population-based epidemiological studies whether anthropometric targets of obesity prevention in SSA differ from those in developed countries.

背景与目标：

BACKGROUND & AIMS: :Tumor necrosis factor superfamily member 4 (TNFSF4) plays a key role in the process of atherosclerosis, a common risk factor for both myocardial and cerebral infarctions. Recent studies indicate that the single nucleotide polymorphism (SNP) rs3850641 in TNFSF4 is associated with higher risk of myocardial infarction, but little is known about the association between TNFSF4 variation and cerebral infarction (CI). A case-control study involving 385 CI patients and 385 age-matched, sex-matched non-CI controls was conducted in a Chinese population, only the most common subtype, atherosclerosis CI, was recruited. Two SNPs of TNFSF4, rs3850641 and rs3861950, were genotyped by the TaqMan SNP genotyping method, and verified partly by genomic DNA sequencing. The results revealed a significant allelic association between rs3861950 and CI (Odds ration = 1.733, 95 % confidence interval = 1.333-2.254, P = 0.000). Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI (Odds ration = 2.896, 95 % confidence interval = 1.368-6.132), and it was associated with a significantly higher risk of ischemic stroke (Odds ration = 3.520, 95 % confidence interval = 1.546-8.015, P = 0.003) after adjusting for the other confirmed risk factors such as the history of hypertension, diabetes, CAD, smoking and alcohol drinking. While the odds ratio of the T allele to the C allele was 1.733 (95 % confidence interval: 1.333-2.254). However, there was no significant association between rs3850641 and CI (Odds ration = 1.288, 95 % confidence interval = 0.993-1.670, P = 0.056). TNFSF4 gene polymorphism rs3861950, but not rs3850641, is associated with the risk of atherosclerosis CI in a Chinese population.

背景与目标： : 肿瘤坏死因子超家族成员4 (TNFSF4) 在动脉粥样硬化过程中起关键作用，动脉粥样硬化是心肌和脑梗塞的常见危险因素。最近的研究表明，TNFSF4中的单核苷酸多态性 (SNP) rs3850641与心肌梗死的高风险相关，但对TNFSF4变异与脑梗死 (CI) 之间的关系知之甚少。在中国人群中进行了385例CI患者和385年龄匹配，性别匹配的非CI对照的病例对照研究，仅招募了最常见的亚型动脉粥样硬化CI。TNFSF4的两个SNP，rs3850641和rs3861950，通过TaqMan SNP基因分型方法进行了基因分型，并通过基因组DNA测序进行了部分验证。结果显示rs3861950和CI之间存在显着的等位基因关联 (赔率 = 1.733，95% 置信区间 = 1.333-2.254，P = 0.000)。基因型关联分析表明，rs3861950的CC基因型赋予CI易感性 (赔率 = 2.896，95% 置信区间 = 1.368-6.132)，并且与缺血性中风的风险显着增加相关 (赔率 = 3.520，95% 置信区间 = 1.546-8.015，P = 0.003) 在调整其他已确认的危险因素 (例如高血压，糖尿病，CAD，吸烟和饮酒史) 后。而T等位基因与C等位基因的比值比为1.733 (95% 置信区间: 1.333-2.254)。然而，rs3850641与CI之间没有显着关联 (赔率 = 1.288，95% 置信区间 = 0.993-1.670，P = 0.056)。TNFSF4基因多态性rs3861950 (而非rs3850641) 与中国人群动脉粥样硬化CI的风险相关。

BACKGROUND & AIMS: BACKGROUND:Frequent germ line cells mutations were previously demonstrated to be associated with aging. This suggests a higher incidence of childhood cancer among children of older parents. A population-based cohort study of parental ages and other prenatal risk factors for five main childhood cancers was performed with the use of a linkage between several national-based registries. METHODS:In total, about 4.3 million children with their parents, born between 1961 and 2000, were included in the study. Multivariate Poisson regression was used to obtain the incidence rate ratios (IRR) and 95% confidence interval (CI). Children <5 years of age and children 5-14 years of age were analysed independently. RESULTS:There was no significant result for children 5-14 years of age. For children <5 years of age, maternal age were associated with elevated risk of retinoblastoma (oldest age group's IRR = 2.39, 95%CI = 1.17-4.85) and leukaemia (oldest age group's IRR = 1.44, 95%CI = 1.01-2.05). Paternal age was significantly associated with leukaemia (oldest age group's IRR = 1.31, 95%CI = 1.04-1.66). For central nervous system cancer, the effect of paternal age was found to be significant (oldest age group's IRR = 1.69, 95%CI = 1.21-2.35) when maternal age was included in the analysis. CONCLUSION:Our findings indicate that advanced parental age might be associated with an increased risk of early childhood cancers.

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