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.

背景与目标：

BACKGROUND & AIMS: :Several recent studies have shown that amphibian populations may exhibit high genetic subdivision in areas with recent fragmentation and urban development. Less is known about the potential for genetic differentiation in continuous habitats. We studied genetic differentiation of red-backed salamanders (Plethodon cinereus) across a 2-km transect through continuous forest in Virginia, USA. Mark-recapture studies suggest very little dispersal for this species, whereas homing experiments and post-Pleistocene range expansion both suggest greater dispersal abilities. We used six microsatellite loci to examine genetic population structure and differentiation between eight subpopulations of red-backed salamanders at distances from 200 m to 2 km. We also used several methods to extrapolate dispersal frequencies and test for sex-biased dispersal. We found small, but detectable differentiation among populations, even at distances as small as 200 m. Differentiation was closely correlated with distance and both Mantel tests and assignment tests were consistent with an isolation-by-distance model for the population. Extrapolations of intergenerational variance in spatial position (sigma(2)<15 m(2)) and pair-wise dispersal frequencies (4 Nm < 25 for plots separated by 300 m) both suggest limited gene flow. Additionally, tests for sex-biased dispersal imply that dispersal frequency is similarly low for both sexes. We suggest that these low levels of gene flow and the infrequent dispersal observed in mark-recapture studies may be reconciled with homing ability and range expansion if dispersing animals rarely succeed in breeding in saturated habitats, if dispersal is flexible depending on the availability of habitat, or if dispersal frequency varies across the geographic range of red-backed salamanders.

背景与目标： : 最近的几项研究表明，两栖动物种群在最近分裂和城市发展的地区可能表现出高度的遗传细分。对连续生境中遗传分化的潜力知之甚少。我们研究了红背sal (plethodn cinereus) 在美国弗吉尼亚州连续森林中穿越2公里样带的遗传分化。标记再捕获研究表明该物种的扩散很小，而归巢实验和更新世后范围的扩展都表明具有更大的扩散能力。我们使用六个微卫星基因座检查了距离为200 m至2千米的八个红背sal亚群之间的遗传种群结构和分化。我们还使用了几种方法来推断扩散频率并测试性别偏向的扩散。我们发现即使在小到200 m的距离下，人群之间也很小但可检测到的分化。分化与距离密切相关，Mantel测试和分配测试均与人群的隔离距离模型一致。空间位置的代际方差外推 (sigma(2)<15 m(2)) 和成对分散频率 (对于由300 m分隔的图，4 Nm <25) 都表明基因流有限。此外，对性别偏向的扩散的测试表明，男女的扩散频率同样较低。我们建议，如果分散的动物很少在饱和生境中成功繁殖，如果分散取决于栖息地的可用性，扩散是灵活的，那么在标记捕获研究中观察到的这些低水平的基因流和不频繁的扩散可能与归巢能力和范围扩大相协调，或者，如果散布频率在红背sal的地理范围内变化。

BACKGROUND & AIMS: :Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

背景与目标： : 纤溶酶原激活物抑制剂-1 (PAI-1) 是纤维蛋白溶解的抑制剂。血浆PAI-1水平的升高在心血管风险和与血栓形成相关的其他疾病的发病机理中起着至关重要的作用。PAI-1启动子区域的4G/5g多态性已在不同人群中进行了广泛研究。我们使用反向杂交PCR测定法研究了160个健康的无关黎巴嫩个体，以检测PAI-1基因的5G/5G，4G/5g和4G/4g基因型以及4g和5g等位基因的频率。我们发现4G/5g基因型最普遍 (45.6%)，其次是5G/5G (36.9%) 和4G/4G (17.5%)。4g和5g等位基因的频率分别计算为0.403和0.597。与其他种族社区相比，发现黎巴嫩人口的稀有4g等位基因患病率相对较高。反过来，这可能使该人群易患心血管疾病和其他血栓性临床疾病。这项研究有助于增进我们对黎巴嫩人口遗传特征的了解。

BACKGROUND & AIMS: :Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis with a very poor prognosis. We aimed at assessing risk factors related to the prognosis of patients with TBM.Forty-five inpatients with TBM in our institution from January 2013 to December 2015 were enrolled retrospectively. The good or poor prognosis in the patients was defined, based on Glasgow Outcome Scale System at discharge. Patients with a GOS score less than 5 were defined as "poor prognosis." Univariate and multivariate logistic regression analyses were performed to assess the predictors for TBM outcome.Among 45 TBM patients, 35 (77.8%) and 10 (22.2%) were in good, poor prognoses, respectively. Old age, disturbance of consciousness, moderate to severe electroencephalogram abnormality, hydrocephalus, remarkable increase of protein (≥ 236 mg/dL) and white blood cell counts (≥ 243 /μL) in cerebral spinal fluid were associated with poor prognosis. Multivariate analysis indicated that old age (odds ratio (OR) = 18.395, P = .036) and hydrocephalus (OR = 32.995, P = .049) were independent factors for a poor outcome of TBM.In conclusion, old age and hydrocephalus are the predictors for poor prognosis of TBM. Patients with these risk factors should be treated promptly with a special care paid to improve their outcomes.

背景与目标： 结核性脑膜炎 (TBM) 是中枢神经系统结核病的最常见形式，预后很差。我们旨在评估与TBM患者预后相关的危险因素。我们机构从2013年1月到2015年12月的45例TBM住院患者被回顾性纳入。根据出院时格拉斯哥结局量表系统，确定了患者的良好或不良预后。GOS评分小于5的患者被定义为 “不良预后”。进行单因素和多因素logistic回归分析以评估TBM结果的预测因素。在45例TBM患者中，分别有35例 (77.8% 例) 和10例 (22.2% 例) 预后良好。年龄大、意识障碍、中重度脑电图异常、脑积水、脑脊液中蛋白质 (≥ 236  mg/dL) 和白细胞计数 (≥ 243  /μ l) 均与预后不良相关。多因素分析显示，高龄 (优势比 (OR)  =   18.395，p   =  .036) 和脑积水 (OR   =   32.995，p   =  .049) 是TBM预后不良的独立因素。老年和脑积水是TBM预后不良的预测因素。具有这些危险因素的患者应及时接受特殊护理治疗，以改善其预后。