BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To assess whether interindividual variation in renal plasma flow or in its response to angiotensin II infusion is associated with interindividual differences in blood pressure in a population-based sample of 287 non-Hispanic whites (143 women and 144 men), aged 20-49.9 years.

METHODS:After seven days of eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg per min angiotensin II. Multiple linear regression methods were used to assess whether measures of the renal plasma flow and of its response to angiotensin II infusion were predictive of systolic or diastolic blood pressures measured prior to administration of the high-sodium diet, on day 6 of the high-sodium diet, or during the renal clearance procedure on day 7 prior to angiotensin II infusion.

RESULTS:There was some evidence that measures of the renal plasma flow and of its response to angiotensin II infusion during the high-sodium diet were statistically significant predictors of measures of blood pressure in women; there was less evidence for this for blood pressures in men. Interindividual variation in measures of the renal plasma flow and of its response to angiotensin II infusion explained less than 10% of the interindividual variation in any measure of the blood pressure in both sexes.

CONCLUSION:These results suggest that interindividual variation in renal plasma flow ad in its response to angiotensin II infusion during a high-sodium diet will be of limited utility in elucidating the basis for interindividual differences in blood pressure.

背景与目标： 目的 : 在基于人群的287非西班牙裔白人 (143名女性和144名男性) 样本中，评估肾血浆流量或对血管紧张素II输注的反应的个体差异是否与血压的个体差异相关，年龄在20-49.9岁之间。
方法 : 在食用高钠饮食 (260 mmol/天) 7天后，通过在每分钟输注3 ng/kg血管紧张素II之前和之后测量对氨基马尿酸盐的清除率来确定肾血浆流量。使用多元线性回归方法来评估肾血浆流量及其对血管紧张素II输注的反应的测量是否可以预测高钠饮食第6天在给予高钠饮食之前测得的收缩压或舒张压。钠饮食，或在输注血管紧张素II之前第7天的肾脏清除过程中。
结果 : 有证据表明，高钠饮食期间肾脏血浆流量的测量及其对血管紧张素II输注的反应是女性血压测量的统计学显着预测指标; 男性血压的证据较少。肾血浆流量测量及其对血管紧张素II输注的反应的个体差异解释了男女血压测量中个体间差异的10%。
结论 : 这些结果表明，在高钠饮食中对血管紧张素II输注的反应中，肾血浆流量ad的个体差异在阐明血压个体差异的基础方面将是有限的。

BACKGROUND & AIMS: :Cupriavidus necator JMP134(pJP4) harbors a catabolic plasmid, pJP4, which confers the ability to grow on chloroaromatic compounds. Repeated growth on 3-chlorobenzoate (3-CB) results in selection of a recombinant strain, which degrades 3-CB better but no longer grows on 2,4-dichlorophenoxyacetate (2,4-D). We have previously proposed that this phenotype is due to a double homologous recombination event between inverted repeats of the multicopies of this plasmid within the cell. One recombinant form of this plasmid (pJP4-F3) explains this phenotype, since it harbors two copies of the chlorocatechol degradation tfd gene clusters, which are essential to grow on 3-CB, but has lost the tfdA gene, encoding the first step in degradation of 2,4-D. The other recombinant plasmid (pJP4-FM) should harbor two copies of the tfdA gene but no copies of the tfd gene clusters. A molecular analysis using a multiplex PCR approach to distinguish the wild-type plasmid pJP4 from its two recombinant forms, was carried out. Expected PCR products confirming this recombination model were found and sequenced. Few recombinant plasmid forms in cultures grown in several carbon sources were detected. Kinetic studies indicated that cells containing the recombinant plasmid pJP4-FM were not selectable by sole carbon source growth pressure, whereas those cells harboring recombinant plasmid pJP4-F3 were selected upon growth on 3-CB. After 12 days of repeated growth on 3-CB, the complete plasmid population in C. necator JMP134 apparently corresponds to this form. However, wild-type plasmid forms could be recovered after growing this culture on 2,4-D, indicating that different plasmid forms can be found in C. necator JMP134 at the population level.

背景与目标： : Cupriavidus necatator JMP134(pJP4) 具有分解代谢质粒pJP4，该质粒赋予了在氯芳族化合物上生长的能力。在3-氯苯甲酸酯 (3-CB) 上重复生长导致选择重组菌株，该菌株可以更好地降解3-CB，但不再在2,4-二氯苯氧乙酸 (2,4-d) 上生长。我们先前已经提出，这种表型是由于该质粒在细胞内的多胞菌的反向重复之间发生了双重同源重组事件。这种质粒的一种重组形式 (pJP4-F3) 解释了这种表型，因为它包含两个拷贝的氯邻苯二酚降解tfd基因簇，这两个拷贝对于在3-CB上生长是必不可少的，但是已经失去了tfdA基因，编码2,4-d降解的第一步。另一个重组质粒 (pJP4-FM) 应该包含两个拷贝的tfdA基因，但没有拷贝的tfd基因簇。进行了分子分析，使用多重PCR方法将野生型质粒pJP4与其两种重组形式区分开。发现并测序了证实该重组模型的预期PCR产物。在几种碳源中生长的培养物中，几乎没有检测到重组质粒形式。动力学研究表明，含有重组质粒pJP4-FM的细胞不能通过唯一的碳源生长压力来选择，而那些具有重组质粒pJP4-F3的细胞在3-CB上生长时被选择。在3-CB上重复生长12天后，C. necator JMP134中的完整质粒群体显然对应于这种形式。但是，在2,4-d上生长该培养物后，可以恢复野生型质粒形式，这表明在种群水平上在C. necator JMP134中可以发现不同的质粒形式。

BACKGROUND & AIMS: :The yeast S. cerevisiae is a central model organism in eukaryotic cell studies and a major component in many food and biotechnological industrial processes. However, the wide knowledge regarding genetics and molecular biology of S. cerevisiae is based on an extremely narrow range of strains. Studies of natural populations of S. cerevisiae, not associated with human activities or industrial fermentation environments, are very few. We isolated a panel of S. cerevisiae strains from a natural microsite, "Evolution Canyon" at Mount Carmel, Israel, and studied their genomic biodiversity. Analysis of 19 microsatellite loci revealed high allelic diversity and variation in ploidy level across the panel, from diploids to tetraploids, confirmed by flow cytometry. No significant differences were found in the level of microsatellite variation between strains derived from the major localities or microniches, whereas strains of different ploidy showed low similarity in allele content. Maximum genetic diversity was observed among diploids and minimum among triploids. Phylogenetic analysis revealed clonal, rather than sexual, structure of the triploid and tetraploid subpopulations. Viability tests in tetrad analysis also suggest that clonal reproduction may predominate in the polyploid subpopulations.

背景与目标： : 酵母酿酒酵母是真核细胞研究中的中心模式生物，也是许多食品和生物技术工业过程中的主要组成部分。然而，关于酿酒酵母的遗传学和分子生物学的广泛知识是基于极其狭窄的菌株范围。与人类活动或工业发酵环境无关的酿酒酵母自然种群研究很少。我们从以色列卡梅尔山的自然微位点 “进化峡谷” 中分离了一组酿酒酵母菌株，并研究了它们的基因组生物多样性。对19个微卫星基因座的分析显示，从二倍体到四倍体，整个面板的等位基因多样性和倍性水平变化很高，通过流式细胞术证实。在来自主要地区或微型物种的菌株之间的微卫星变异水平上没有发现显着差异，而不同倍性的菌株在等位基因含量上显示出较低的相似性。在二倍体中观察到最大的遗传多样性，在三倍体中观察到最小。系统发育分析显示，三倍体和四倍体亚群的克隆而非性结构。tetrad分析中的生存力测试还表明，克隆繁殖可能在多倍体亚群中占主导地位。

BACKGROUND & AIMS: BACKGROUND:Little is known about the impact of the recent varicella vaccine shortage. To assess the temporal trend in varicella vaccine administration before 18 and 24 months of age in a community cohort of children prior to, during and after the recent varicella vaccine shortage. And to compare the temporal trends in varicella vaccinations to trends of an older, more widely accepted vaccine, the MMR. METHODS:Community population-based birth cohorts were identified who were eligible for the varicella vaccination before, during and after the 2001 to 2002 varicella vaccine shortage. Only children (84% of all) who remained in the community through their second birthday were included. For each child in the cohort, the medical records and immunization registry records from both medical facilities in the county were reviewed to identify the dates and sites for all varicella immunizations given. In addition to varicella immunizations, the dates of all MMR vaccinations were recorded. Additional data abstracted included the child's birth date, gender and dates of any recognized cases of chickenpox up through age 24 months. RESULTS:Of the 2,512 children in the birth cohorts, 50.8% were boys. In the three cohorts combined, 81.1% of the boys and 79.3% of the girls (p = 0.30) received the varicella vaccine by age 24 months. The pre-shortage community rate of varicella immunization was 79.7% by 24 months of age. During the varicella vaccine shortage, the rate of varicella immunization by 24 months fell to 77.2%. Only 6 additional children received a "catch-up" immunization by 36 months of age. In the post shortage period the community 24-month immunization rate rebounded to a level higher than the pre-shortage rate 84.0%. During the almost three years of observation, the MMR immunization rate by age 24 months was constant (87%). CONCLUSION:The varicella shortage was associated with an immediate drop in the 24-month varicella immunizations rate but rebounded quickly to above pre-shortage rates. In this community the only long term impact of the varicella vaccine shortage may be on the small number of children who still had not received catch-up varicella immunizations by 36 months of age.

背景与目标：

BACKGROUND & AIMS: :Insulin resistance affecting skeletal muscle metabolism is present in the prehypertensive state. The aim of our study was to test the hypothesis that blood pressure value is related to skeletal muscle composition, measured by (31)P magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring of hypertensive parents (OH) and healthy controls. Study groups consisted of 10 healthy young lean OH with normal glucose tolerance, confirmed with oral glucose tolerance test, and 13 controls matched for age, sex, and body mass index. Insulin action was estimated as glucose disposal (M), glucose metabolic clearance rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose tolerance test was calculated. (31)P MR spectroscopy was performed on a whole-body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and equipped with actively shielded gradient coils. There were no differences in common metabolic and anthropometric parameters between OH and controls except for the blood pressure, which was in the range of normal to high-normal level in OH. Mean blood pressure was significantly higher in OH (95.73 +/- 4.39 vs 83.76 +/- 3.95 mm Hg; P < .001). Trend toward insulin resistance was registered in OH with significantly lower M/I (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg x kg(-1) x min(-1) x mIU(-1) x L(-1); P < .05). There were no significant differences in total serum magnesium (sMg) levels between OH and controls, although a positive correlation exists between sMg and insulin sensitivity expressed as M (r = 0.63, P < .01), MCR (r = 0.54, P < .01), and M/I (r = 0.51, P < .05). No differences in signal intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters, inorganic phosphates (Pi), adenosine triphosphates (Patp and betaATP), and calculated concentrations of intracellular ionized magnesium (Mgi) and H(+) ions between the groups were detected. Systolic blood pressure correlates positively with PCr/Patp (r = 0.43, P < .05), Pi/Patp (r = 0.413, P < .05), and Pi/betaATP (r = 0.48, P < .05). Diastolic blood pressure correlates positively only with the ratio Pi/betaATP (r = 0.42, P < .05). The sum of immunoreactive insulin values correlates with PCr/betaATP (r = 0.53, P < .01) and with Pi/betaATP (r = 0.6, P < .01). In conclusion, increase in blood pressure and insulin resistance were confirmed in offspring of OH. Insulin sensitivity is related to sMg and the elevation of blood pressure is associated with the activation of energy metabolism in skeletal muscle. The relationship between muscle energetic characteristics and markers of insulin resistance suggests that the alteration of energy metabolism may be present in early stages of metabolic syndrome.

背景与目标： : 影响骨骼肌代谢的胰岛素抵抗在高血压前期存在。我们研究的目的是检验以下假设: 血压值与通过 (31)P磁共振 (MR) 光谱法测量的骨骼肌组成以及高血压父母 (OH) 和健康的后代的胰岛素敏感性有关对照。研究组由10个健康的年轻lean OH组成，葡萄糖耐量正常，经口服葡萄糖耐量试验证实，以及13个年龄，性别和体重指数相匹配的对照。在10小时的高胰岛素血症正常血糖钳夹中，胰岛素的作用估计为葡萄糖处置 (M)，葡萄糖代谢清除率 (MCR) 和胰岛素敏感性指数 (M/I)。计算了口服葡萄糖耐量试验的免疫反应性胰岛素值之和。(31) 在操作于1.5 T并配备有主动屏蔽梯度线圈的全身MR扫描仪 (Siemens Vision，Erlangen，德国) 上进行P MR光谱。OH和对照组之间的常见代谢和人体测量参数没有差异，但血压在OH的正常至正常水平范围内。OH中的平均血压显着更高 (95.73/- 4.39 vs 83.76/-3.95毫米Hg; P <.001)。在OH中记录了胰岛素抵抗的趋势，M/I显著降低 (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg × kg(-1) × min(-1) × mIU(-1) × L(-1); P <.05)。血清总镁 (sMg) 水平与对照组无显著差异，但sMg与胰岛素敏感性呈正相关，表现为M (r = 0.63，P <.01)，MCR (r = 0.54，P <.01)。和M/I (r = 0.51，P <.05)。检测到磷酸肌酸 (PCr)，磷酸单酯，磷酸二酯，无机磷酸盐 (Pi)，三磷酸腺苷 (Patp和 βatp) 的信号强度以及计算的细胞内离子镁 (Mgi) 和H () 离子浓度之间的差异。收缩压与PCr/Patp (r = 0.43，P <.05) 、Pi/Patp (r = 0.413，P <.05) 和Pi/betaATP (r = 0.48，P <.05) 呈正相关。舒张压仅与Pi/βatp比值正相关 (r = 0.42，P <.05)。免疫反应性胰岛素值的总和与PCr/betaATP (r = 0.53，P <.01) 和Pi/betaATP (r = 0.6，P <.01) 相关。总之，在OH的后代中证实了血压升高和胰岛素抵抗。胰岛素敏感性与sMg有关，血压升高与骨骼肌能量代谢的激活有关。肌肉能量特征与胰岛素抵抗标志物之间的关系表明，能量代谢的改变可能存在于代谢综合征的早期阶段。

BACKGROUND & AIMS: :In the present pilot study, the feasibility of a site-of-care cervicovaginal self-sampling methodology for HPV-based screening was tested in 346 women residing in underserved rural areas of Northern Greece. These women provided self-collected cervicovaginal sample along with a study questionnaire. Following molecular testing, using the cobas® HPV Test, Roche®, HPV positive women, were referred to colposcopy and upon abnormal findings, to biopsy and treatment. Participation rate was 100%. Regular pap-test examination was reported for 17.1%. Among hrHPV testing, 11.9% were positive and colposcopy/biopsy revealed 2 CIN3 cases. Non-compliance was the most prevalent reason for no previous attendance. Most women reported non-difficulty and non-discomfort in self-sampling (77.6% and 82.4%, respectively). They would choose self-sampling over clinician-sampling (86.2%), and should self-sampling being available, they would test themselves more regularly (92.3%). In conclusion, self-sampling is feasible and well-accepted for HPV-based screening, and could increase population coverage in underserved areas, helping towards successful prevention.

背景与目标： : 在本试点研究中，对居住在希腊北部服务不足的农村地区的346名妇女进行了基于HPV筛查的护理现场宫颈阴道自采样方法的可行性进行了测试。这些妇女提供了自我收集的宫颈阴道样本以及研究问卷。在分子测试之后，使用cobas®罗氏HPV检测®HPV阳性女性被转诊至阴道镜检查和异常发现后，进行活检和治疗。参与率为100%。报告定期进行17.1% 巴氏试验检查。在hrHPV检测中，11.9% 例为阳性，阴道镜/活检显示2例CIN3。不遵守是以前没有出席的最普遍原因。大多数妇女报告说，自我取样没有困难，也没有不适 (分别为77.6% 和82.4%)。他们将选择自采样而不是临床医生采样 (86.2%)，并且如果自采样可用，他们将更定期地测试自己 (92.3%)。总之，自我采样对于基于HPV的筛查是可行的且被广泛接受，并且可以增加服务不足地区的人口覆盖率，从而有助于成功预防。

BACKGROUND & AIMS: :In order to investigate the mode of interaction between the N-quarternized cytosine base and the aromatic amino acid, the crystal structure of the 3-methyl-cytidine-5'-monophosphate:tryptamine complex was analyzed by X-ray diffraction. The complex crystals were stabilized by extensive hydrogen bond formations in which eight independent water molecules per complex pair participated. A prominent stacking interaction, characterized by a parallel alignment of both rings with a separation distance of ca. 3.4 A, was observed between the cytosine base and the indole ring. Combining the present results with X-ray crystallographic data on the adenine--and guanine--aromatic amino acid interactions, we summarize the structural characteristics observed in the stacking interaction of the N-quarternized nucleic acid base with the aromatic amino acid and discuss their biological implications, especially in connection with the significance of N-protonation of nucleic acid base for selective recognition by protein.

背景与目标： : 为了研究N-四分之一化胞嘧啶碱与芳香族氨基酸之间的相互作用模式，通过x射线衍射分析了3-甲基胞苷-5 '-单磷酸: 色胺复合物的晶体结构。复杂的晶体通过广泛的氢键形成而稳定，其中每个复杂对有八个独立的水分子参与其中。在胞嘧啶碱和吲哚环之间观察到显著的堆叠相互作用，其特征是两个环平行排列，分离距离约3.4 A。结合目前的结果与腺嘌呤-和鸟嘌呤-芳香族氨基酸相互作用的x射线晶体学数据，我们总结了在N-四分之一化核酸碱基与芳香族氨基酸的堆叠相互作用中观察到的结构特征，并讨论了它们的生物学意义，特别是与核酸碱基的N-质子化对蛋白质选择性识别的意义有关。

BACKGROUND & AIMS: OBJECTIVE:Provoked deep venous thrombosis (DVT) is precipitated by a specific event. This paper compares the characteristics of provoked DVT in patients with transient risk (TR) factors and patients with continuous risk (CR) factors. METHODS:A retrospective review of records of all consecutive patients diagnosed with DVT between January 2013 and August 2014 was performed. Patients with provoked DVT were included in the TR group if the provoking event resolved in 2 weeks and they did not have ongoing risk of thrombosis. Patients in the CR group had a provoked DVT with ongoing risk of thrombosis due to individual factors deemed to be ongoing risks of thrombosis, such as cancer, hypercoagulable disorder, and prolonged immobilization. Demographics, risk factors, association with pulmonary embolism (PE) and its severity, risk of recurrent venous thromboembolism (VTE), and mortality were compared between the two groups. RESULTS:A total of 838 patients were diagnosed with DVT, and 50.7% (425) were provoked. There were 127 (29.9%) patients with TR and 298 (70.1%) with CR. TR patients were younger (60.4 ± 16.3 vs 65.9 ± 16.0; P = .001). TR was more likely to be provoked by surgery (70.9% vs 55.4%; P = .003), whereas CR was more likely to be provoked by immobilization (21.5% vs 12.6%; P = .032). CR patients were affected by cancer (48.7%) and hypercoagulable disorders (4.4%). TR patients were more likely to have calf DVTs (36.2% vs 26.2%; P = .047). There was a trend toward lower association with PE on presentation in TR (17.3% vs 21.1%; P = .072), but that did not reach statistical significance. However, TR factors were more likely to be associated with low-risk PE compared with CR factors (30.2% vs 54.6%; P = .040). After mean follow-up of 7.2 months, CR had higher risk of recurrent VTE (14.0% vs 6.8%; P = .045) and mortality (23.5% vs 7.1%; P < .0001). CONCLUSIONS:Provoked DVT with CR factors affects older patients and is associated with high recurrence of VTE and mortality compared with provoked DVT with TR factors.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:Patients with heartburn and normal upper gastrointestinal endoscopy, normal oesophageal acid exposure, no symptom-reflux association and who fail to respond to a proton-pump inhibitor are classified as having functional heartburn (FH). This study aimed (i) to characterize the symptoms and functional abnormalities of patients with FH and (ii) to describe their clinical outcome. MATERIALS AND METHODS:Among all patients referred for 24 h multichannel intraluminal impedance-pH (MII-pH), patients with FH were identified. The clinical characteristics and high-resolution oesophageal pressure topography recordings of FH patients were analyzed at the time of the 24-h MII-pH test. A symptom-related and health-related quality-of-life questionnaire was then sent to FH patients to assess the long-term outcome. RESULTS:Forty patients fulfilled the criteria for FH, representing 8.5% of the referred population. Twenty-two months after initial testing, 66% of patients still suffered from heartburn. The rate of mixed reflux (liquid/gas) was higher in patients with persisting heartburn at the final evaluation (63 vs. 50%, P=0.04). Sixty-six per cent of patients had one or more manometric abnormalities. Acid clearance time in MII-pH was significantly higher in patients with weak peristalsis than patients with normal peristalsis (60 ± 45 vs. 31 ± 19 s, P=0.03). A high rate of mixed reflux and/or a manometric abnormality were associated with a higher risk of persistent heartburn. CONCLUSION:FH is a chronic disorder with persisting symptoms in two-thirds of patients. An increased rate of mixed reflux and/or the presence of manometric abnormalities are associated with a higher risk of persisting symptoms and may help to identify the population with unmet therapeutic needs.

背景与目标：

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.

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