BACKGROUND & AIMS: Genotypes at five previously described polymorphic sites at the apolipoprotein(a) gene locus have been determined for the members of 27 families as well as for unrelated white Caucasian and Asian-Indian subjects, and their relationship with isoform size and plasma lipoprotein(a) concentrations investigated. There was strong linkage disequilibrium between sites at the 5'-region of the gene and also between this region and a site in the coding sequence for Kringle 4-37 on the other side of the polymorphic Kringle 4 repeat region. There was no evidence that changes at any of the sites had any direct effect upon lipoprotein(a) concentration. However, certain haplotypes were present almost exclusively on apolipoprotein(a) alleles within a restricted range of sizes and associated lipoprotein(a) concentrations. After correcting for the effect of allele size, there were clear differences between the lipoprotein(a) concentrations associated with alleles of different haplotypes, suggesting that there may be genetically distinct groups of apolipoprotein alleles of different size and different levels of expression. Factors that regulate expression apparently exchange at a rate similar to the rate of change of Kringle 4 repeat number.

背景与目标： 已经确定了载脂蛋白（a）基因位点五个先前描述的多态性位点的基因型，涉及27个家庭的成员以及无关的白人高加索人和亚裔印度人，及其与同工型大小和血浆脂蛋白（a）浓度的关系调查。在基因的5'区域的位点之间以及在该区域与多态性Kringle 4重复区域另一侧的Kringle 4-37的编码序列中的位点之间也存在强烈的连锁不平衡。没有证据表明任何位点的变化都对脂蛋白（a）的浓度有任何直接影响。但是，某些单倍型几乎完全存在于载脂蛋白（a）等位基因上，且大小和相关脂蛋白（a）的浓度范围有限。校正等位基因大小的影响后，与不同单倍型等位基因相关的脂蛋白（a）浓度之间存在明显差异，这表明可能存在遗传上不同的不同大小和表达水平的载脂蛋白等位基因组。调节表达的因子显然以类似于Kringle 4重复数变化率的速率交换。

BACKGROUND & AIMS: OBJECTIVE:Inflammatory mechanisms are involved in atherosclerotic plaque rupture and subsequent thrombin formation. Thrombin not only plays a central role in thrombus formation and platelet activation, but also in the induction of inflammatory processes. We assessed the hypothesis that melagatran, a direct thrombin inhibitor, attenuates plaque progression and promotes stability of advanced atherosclerotic lesions. METHODS AND RESULTS:Melagatran (500 micromol/kg/d) or control diet was administered to apolipoprotein E-deficient mice (n=54) with advanced atherosclerotic lesions. Treatment reduced lesion progression in brachiocephalic arteries (P<0.005). Morphometric analysis confirmed that thrombin inhibition promoted plaque stability and resulted in thicker fibrous caps (28.4+/-14.2 microm versus 20.8+/-12.0 microm; P<0.05), increased media thickness (29.3+/-9.6 microm versus 24.4+/-6.7 microm; P<0.05), and smaller necrotic cores (73,537+/-41,301 microm2 versus 126,819+/-51,730 microm2; P<0.0005). Electro mobility shift assays revealed reduced binding activity of nuclear factor kappaB (P<0.05) and activator protein-1 (P<0.05) in aortas of treated mice. Furthermore, immunohistochemistry demonstrated reduced staining for matrix metalloproteinase (MMP)-9 (P<0.05). Melagatran had no significant effect on early lesion formation in C57BL/6J mice. CONCLUSIONS:The direct thrombin inhibitor melagatran reduces lesion size and may promote plaque stability in apolipoprotein E-deficient mice, possibly through reduced activation of proinflammatory transcription factors and reduced synthesis of MMP-9.

背景与目标： 目的：炎症机制与动脉粥样硬化斑块破裂及随后的凝血酶形成有关。凝血酶不仅在血栓形成和血小板活化中起核心作用，而且在炎症过程的诱导中也起着重要作用。我们评估了一种假设，即直接凝血酶抑制剂melagatran会减轻斑块进程并促进晚期动脉粥样硬化病变的稳定性。
方法和结果：对患有晚期动脉粥样硬化病变的载脂蛋白E缺乏症小鼠（n = 54）给予美拉加群（500 micromol / kg / d）或对照饮食。治疗降低了头臂动脉的病变进展（P <0.005）。形态计量学分析证实，凝血酶抑制促进了斑块稳定性并导致较厚的纤维帽（28.4 /-14.2微米对20.8 /-12.0微米； P <0.05），介质厚度增加（29.3 /-9.6微米对24.4 /-6.7微米； P <0.05）和较小的坏死芯（73,537 / -41,301 microm2与126,819 / -51,730 microm2； P <0.0005）。电迁移率变化分析显示，在处理过的小鼠主动脉中核因子κB（P <0.05）和激活蛋白-1（P <0.05）的结合活性降低。此外，免疫组化显示基质金属蛋白酶（MMP）-9染色减少（P <0.05）。 Melagatran对C57BL / 6J小鼠的早期病变形成没有明显影响。
结论：直接凝血酶抑制剂美拉加群减少了载脂蛋白E缺乏症小鼠的病变大小，并可能增强了斑块稳定性，可能是通过减少促炎转录因子的激活和减少MMP-9的合成来实现的。

BACKGROUND & AIMS: :The environmental mobility of newly deposited radionuclides in surface soil is driven by complex biogeochemical relationships, which have significant impacts on transport pathways. The partition coefficient (Kd) is useful for characterizing the soil-solution exchange kinetics and is an important factor for predicting relative amounts of a radionuclide transported to groundwater compared to that remaining on soil surfaces and thus available for transport through erosion processes. Measurements of Kd for 238U are particularly useful because of the extensive use of 238U in military applications and associated testing, such as done at Los Alamos National Laboratory (LANL). Site-specific measurements of Kd for 238U are needed because Kd is highly dependent on local soil conditions and also on the fine soil fraction because 238U concentrates onto smaller soil particles, such as clays and soil organic material, which are most susceptible to wind erosion and contribute to inhalation exposure in off-site populations. We measured Kd for uranium in soils from two neighboring semiarid forest sites at LANL using a U.S. Environmental Protection Agency (EPA)-based protocol for both whole soil and the fine soil fraction (diameters<45 microm). The 7-d Kd values, which are those specified in the EPA protocol, ranged from 276-508 mL g-1 for whole soil and from 615-2249 mL g-1 for the fine soil fraction. Unexpectedly, the 30-d Kd values, measured to test for soil-solution exchange equilibrium, were more than two times the 7-d values. Rates of adsorption of 238U to soil from solution were derived using a 2-component (FAST and SLOW) exponential model. We found significant differences in Kd values among LANL sampling sites, between whole and fine soils, and between 7-d and 30-d Kd measurements. The significant variation in soil-solution exchange kinetics among the soils and soil sizes promotes the use of site-specific data for estimates of environmental transport rates and suggests possible differences in desorption rates from soil to solution (e.g., into groundwater or lung fluid). We also explore potential relationships between wind erosion, soil characteristics, and Kd values. Combined, our results highlight the need for a better mechanistic understanding of soil-solution partitioning kinetics for accurate risk assessment.

背景与目标： ：表层土壤中新沉积的放射性核素的环境迁移是由复杂的生物地球化学关系驱动的，这对运输途径有重大影响。分配系数（Kd）可用于表征土壤-溶液交换动力学，并且是预测与土壤表面上剩余的放射性核素相比相对放射性量的重要因素，因此可用于整个侵蚀过程。 238U的Kd测量特别有用，因为238U在军事应用和相关测试中得到了广泛使用，例如在洛斯阿拉莫斯国家实验室（LANL）进行的测试。需要对238U的Kd进行特定地点的测量，因为Kd高度依赖于当地土壤条件，还取决于土壤的细碎度，因为238U集中在较小的土壤颗粒（如粘土和土壤有机材料）上，这些颗粒最容易受到风蚀和风蚀的影响。导致异地人群的吸入暴露。我们使用基于美国环境保护局（EPA）的协议对全土壤和细土壤部分（直径<45微米）进行了测量，测量了LANL两个相邻半干旱森林站点土壤中铀的Kd。 7-d Kd值（在EPA协议中指定）对于整个土壤而言为276-508 mL g-1，对于精细土壤馏分而言为615-2249 mL g-1。出乎意料的是，为测试土壤溶液交换平衡而测量的30 d Kd值是7 d值的两倍以上。使用2成分（FAST和SLOW）指数模型，得出溶液中238U对土壤的吸附速率。我们发现在LANL采样点之间，整个土壤和细土壤之间以及在7天至30天的Kd测量值之间，Kd值存在显着差异。土壤之间和土壤大小之间土壤溶液交换动力学的显着变化促进了使用特定地点的数据来估算环境传输速率，并暗示了从土壤到溶液（例如，进入地下水或肺液）的解吸速率可能存在差异。我们还探讨了风蚀，土壤特性和Kd值之间的潜在关系。综合起来，我们的结果强调需要对土壤溶液分配动力学有更好的机械理解，以便进行准确的风险评估。

BACKGROUND & AIMS: OBJECTIVE:Bone loss and periosteal expansion is found after menopause. The accelerated early postmenopausal bone loss is not permanent but if the same accounts for the periosteal expansion is unknown. METHODS:Bone mineral density (BMD) and skeletal structure of the distal forearm were followed from menopause and on average 24 years (range 18-28) by single-photon absorptiometry at 12 occasions in a population-based sample of 81 Caucasian women with no medication or disease affecting bone metabolism. A Strength Index based on areal BMD and bone structure was calculated. Postmenopausal serum-estradiol levels and incident distal radius fractures were registered. Data are presented as means with 95% confidence interval (95% CI). RESULTS:The annual BMD loss in three periods, 0-8, 8-16 and 16-28 years after menopause, was 2.0% (1.6, 2.4), 1.0% (0.6, 1.4) and 1.0% (0.7, 1.3), respectively. The annual periosteal expansion was 1.0% (0.8, 1.3), 0.0% (-0.3, 0.3) and 0.0% (-0.2, 0.2), respectively. Mean post-menopausal oestrogen levels correlated moderately with annual loss in aBMD (r=0.51, p<0.001) but less with the annual changes in bone width (r= -0.22, p=0.06). CONCLUSION:Postmenopausal periosteal expansion in the distal forearm seems to occur only in the first postmenopausal decade.

背景与目标： 目的：更年期后发现骨丢失和骨膜扩张。绝经后早期加速的骨丢失不是永久性的，但未知是否导致骨膜扩张。
方法：采用单光子吸光光度法，在81例白人女性中，从更年期开始追踪平均绝经后平均24年（18-28岁）的骨矿物质密度（BMD）和平均年龄（18-28）。影响骨骼代谢的药物或疾病。计算出基于面积骨密度和骨骼结构的强度指数。记录绝经后血清雌二醇水平和incident骨远端骨折的发生率。数据以具有95％置信区间（95％CI）的平均值表示。
结果：绝经后0-8、8-16和16-28年这三个时期的年BMD损失分别为2.0％（1.6、2.4），1.0％（0.6、1.4）和1.0％（0.7、1.3），分别。每年的骨膜扩张分别为1.0％（0.8，1.3），0.0％（-0.3，0.3）和0.0％（-0.2，0.2）。绝经后的平均雌激素水平与aBMD的年度损失呈中等程度的相关性（r = 0.51，p <0.001），而与年度骨宽变化的相关性较小（r = -0.22，p = 0.06）。
结论：绝经后前臂远端的骨膜扩张似乎仅发生在绝经后的第一个十年中。

BACKGROUND & AIMS: :Samples sizes are calculated for case-control studies where 1:1 matching has been employed, and where the goal is the interval estimation of the odds ratio. The optimal sample size is defined to be the smallest value for which a 100(1 - alpha)% confidence interval for the log odds ratio will not exceed a specified width 2 delta with specified probability (1 - gamma). This approach is similar in spirit to the power-based approach for sample size determination when significance testing is the goal. Tables of sample sizes are presented for various choices of parameters. We also find considerable disagreement with a published method based on expected numbers of discordant pairs.

背景与目标： ：样本大小是为个案对照研究计算的，其中采用了1：1匹配，并且目标是比值比的区间估计。最佳样本大小定义为对数优势比的100（1-alpha）％置信区间不会以指定的概率（1- gamma）超过指定的宽度2 delta的最小值。当以显着性测试为目标时，该方法在本质上类似于确定样本大小的基于幂的方法。列出了各种参数选择的样本量表。我们还发现与基于预期的不一致对数的已发布方法存在很大的分歧。

BACKGROUND & AIMS: :It is not known how the volume of the cell nucleus is set, nor how the ratio of nuclear volume to cell volume (N/C) is determined. Here, we have measured the size of the nucleus in growing cells of the budding yeast Saccharomyces cerevisiae. Analysis of mutant yeast strains spanning a range of cell sizes revealed that the ratio of average nuclear volume to average cell volume was quite consistent, with nuclear volume being approximately 7% that of cell volume. At the single cell level, nuclear and cell size were strongly correlated in growing wild-type cells, as determined by three different microscopic approaches. Even in G1-phase, nuclear volume grew, although it did not grow quite as fast as overall cell volume. DNA content did not appear to have any immediate, direct influence on nuclear size, in that nuclear size did not increase sharply during S-phase. The maintenance of nuclear size did not require continuous growth or ribosome biogenesis, as starvation and rapamycin treatment had little immediate impact on nuclear size. Blocking the nuclear export of new ribosomal subunits, among other proteins and RNAs, with leptomycin B also had no obvious effect on nuclear size. Nuclear expansion must now be factored into conceptual and mathematical models of budding yeast growth and division. These results raise questions as to the unknown force(s) that expand the nucleus as yeast cells grow.

背景与目标： ：未知如何设置细胞核的体积，也不知道如何确定核体积与细胞体积的比值（N / C）。在这里，我们测量了芽孢酵母酿酒酵母生长细胞中细胞核的大小。对跨越一系列细胞大小的突变酵母菌株的分析表明，平均核体积与平均细胞体积之比非常一致，核体积约为细胞体积的7％。在单细胞水平上，通过三种不同的显微镜方法确定，在生长的野生型细胞中，核和细胞大小密切相关。即使在G1期，核体积也会增长，尽管它的增长速度不及总细胞体积。 DNA含量似乎对核大小没有任何直接的直接影响，因为在S期核大小没有急剧增加。维持核大小不需要连续生长或核糖体生物发生，因为饥饿和雷帕霉素治疗对核大小几乎没有立即影响。瘦霉素B阻止新的核糖体亚基以及其他蛋白质和RNA的核输出，对核大小也没有明显影响。现在必须将核扩展纳入萌芽的酵母生长和分裂的概念和数学模型中。这些结果引起了关于随着酵母细胞生长而使核膨胀的未知力的疑问。

BACKGROUND & AIMS: :Previously, expected satiety (ES) has been measured using software and two-dimensional pictures presented on a computer screen. In this context, ES is an excellent predictor of self-selected portions, when quantified using similar images and similar software. In the present study we sought to establish the veracity of ES as a predictor of behaviours associated with real foods. Participants (N=30) used computer software to assess their ES and ideal portion of three familiar foods. A real bowl of one food (pasta and sauce) was then presented and participants self-selected an ideal portion size. They then consumed the portion ad libitum. Additional measures of appetite, expected and actual liking, novelty, and reward, were also taken. Importantly, our screen-based measures of expected satiety and ideal portion size were both significantly related to intake (p<.05). By contrast, measures of liking were relatively poor predictors (p>.05). In addition, consistent with previous studies, the majority (90%) of participants engaged in plate cleaning. Of these, 29.6% consumed more when prompted by the experimenter. Together, these findings further validate the use of screen-based measures to explore determinants of portion-size selection and energy intake in humans.

背景与目标： ：以前，使用软件和在计算机屏幕上显示的二维图片来测量预期的饱腹感（ES）。在这种情况下，当使用相似的图像和相似的软件进行量化时，ES是自我选择部分的极佳预测指标。在本研究中，我们试图将ES的准确性确定为与真实食品相关的行为的预测指标。参与者（N = 30）使用计算机软件评估其ES和三种常见食物的理想部分。然后展示了一个真正的一碗食物（意大利面和酱汁），参与者自行选择了理想的份量。然后，他们随意消费了这部分。还采取了食欲，预期和实际喜好，新颖性和奖励的其他措施。重要的是，我们基于屏幕的预期饱腹感和理想部位大小的测量均与摄入量显着相关（p <.05）。相比之下，喜好的衡量指标相对较差（p> .05）。此外，与以前的研究一致，大多数（90％）参与者进行了印版清洁。其中，有29.6％的人在实验人员的提示下消耗了更多。在一起，这些发现进一步验证了基于屏幕的测量方法的使用，以探索决定人体部分尺寸选择和能量摄入的决定因素。

BACKGROUND & AIMS: :There is an unresolved debate in the scientific community about the shape of the quasistatic displacement pulse produced by nonlinear acoustic wave propagation in an elastic solid with quadratic nonlinearity. Early analytical and experimental studies suggested that the quasistatic pulse exhibits a right-triangular shape with the peak displacement of the leading edge being proportional to the length of the tone burst. In contrast, more recent theoretical, analytical, numerical, and experimental studies suggested that the quasistatic displacement pulse has a flat-top shape where the peak displacement is proportional to the propagation distance. This study presents rigorous mathematical analyses and numerical simulations of the quasistatic displacement pulse. In the case of semi-infinite solids, it is confirmed that the time-domain shape of the quasistatic pulse generated by a longitudinal plane wave is not a right-angle triangle. In the case of finite-size solids, the finite axial dimension of the specimen cannot simply be modeled with a linear reflection coefficient that neglects the nonlinear interaction between the combined incident and reflected fields. More profoundly, the quasistatic pulse generated by a transducer of finite aperture suffers more severe divergence than both the fundamental and second order harmonic pulses generated by the same transducer.

背景与目标： ：关于由非线性声波在具有二次非线性的弹性固体中传播产生的准静态位移脉冲的形状，科学界尚无定论。早期的分析和实验研究表明，准静态脉冲呈现出直角三角形的形状，其前沿的峰值位移与音调脉冲串的长度成正比。相反，最近的理论，分析，数值和实验研究表明，准静态位移脉冲具有平顶形状，其中峰值位移与传播距离成正比。这项研究提出了准静态位移脉冲的严格数学分析和数值模拟。在半无限固体的情况下，已确认由纵向平面波产生的准静态脉冲的时域形状不是直角三角形。对于有限尺寸的固体，不能简单地使用线性反射系数来建模样本的有限轴向尺寸，而线性反射系数会忽略入射场和反射场之间的非线性相互作用。更深刻地讲，与相同的换能器产生的基波和二阶谐波脉冲相比，有限孔径的换能器产生的准静态脉冲遭受更严重的发散。

BACKGROUND & AIMS: :Intra-group social stability is important for the long-term productivity and health of social organisms. We evaluated the effect of group size on group stability in the face of repeated social perturbations using a cooperatively breeding fish, Neolamprologus pulcher In a laboratory study, we compared both the social and physiological responses of individuals from small versus large groups to the repeated removal and replacement of the most dominant group member (the breeder male), either with a new male (treatment condition) or with the same male (control condition). Individuals living in large groups were overall more resistant to instability but were seemingly slower to recover from perturbation. Members of small groups were more vulnerable to instability but recovered faster. Breeder females in smaller groups also showed greater physiological preparedness for instability following social perturbations. In sum, we discover both behavioral and physiological evidence that living in larger groups helps to dampen the impacts of social instability in this system.

背景与目标： ：群体内部的社会稳定对社会有机体的长期生产力和健康至关重要。我们使用合作繁殖的鱼类Neolamprologus pulcher评估了面对反复的社会动荡时，群体规模对群体稳定性的影响。在一项实验室研究中，我们比较了小型和大型群体个体的社会和生理反应与重复去除和用新的雄性（治疗条件）或相同的雄性（对照条件）替换最主要的组成员（育种雄性）。整体而言，生活在较大群体中的个体对不稳定的抵抗力更大，但从动荡中恢复的速度似乎较慢。小组成员更容易受到不稳定的影响，但恢复得更快。较小群体的母鸡也表现出更大的生理上的准备，以应对社会动荡后的不稳定性。总之，我们发现行为和生理证据都表明，生活在较大的群体中有助于减轻该系统中社会不稳定的影响。

BACKGROUND & AIMS: OBJECTIVES:We aimed to establish which of sitting height (SH) and total height (Ht) is most appropriately used in the scaling of adult body mass (BM), waist circumference (WC), and forced vital capacity (FVC), considering likely explanations and proposing a suitable index for each. METHODS:Data were from the US Third National Health and Nutrition Survey for white and black American women and men aged 20 to 50 years. Statistical analysis involved mainly correlation coefficients, the multiple regression of BM, WC, or FVC on SH and leg length (LL), and fitting of allometric regression equations relating each of BM, WC, and FVC to SH or Ht. RESULTS:BM and WC correlated more strongly with SH than with Ht, and FVC correlated more strongly with Ht. Associations with LL were negative for WC, negative or nonsignificant for BM, and positive for FVC. Using round-number exponents for Ht and SH, the allometric relationships indicated that appropriate indices are BM/SH3 , WC/SH, and FVC/Ht2 . CONCLUSIONS:Contrary to usual practice, BM and WC are better scaled in relation to SH than to Ht. FVC is slightly better scaled in relation to Ht, as is conventional. Interpretations involve the small influence of LL on BM and the influence both of gluteo-femoral fatness on measured SH and of childhood health and nutrition on adult LL, WC, and FVC. It is evident that SH should be measured more often for research purposes.

背景与目标： 目的：考虑到可能的情况，我们旨在确定最适合用于成人体重（BM），腰围（WC）和强迫肺活量（FVC）缩放的坐高（SH）和总身高（Ht）中的哪一个解释并为每个提出合适的索引。
方法：数据来自美国第三次全国健康与营养调查，调查对象为20至50岁的美国白人和黑人。统计分析主要涉及相关系数，BM，WC或FVC在SH和腿长（LL）上的多元回归，以及将BM，WC和FVC分别与SH或Ht相关的异速回归方程的拟合。
结果：BM和WC与SH的相关性比与Ht的相关性强，而FVC与Ht的相关性则更强。与LL的关联对WC呈阴性，对BM呈阴性或不显着，对FVC呈阳性。使用Ht和SH的整数指数，异速关系表明合适的指数是BM / SH3，WC / SH和FVC / Ht2。
结论：与通常的做法相反，相对于SH，BM和WC的缩放比例要好于Ht。与传统技术相比，FVC相对于Ht具有更好的缩放比例。解释涉及LL对BM的影响较小，以及臀股脂肪对测得的SH的影响以及儿童健康和营养对成年LL，WC和FVC的影响。显然，出于研究目的，应更频繁地测量SH。

BACKGROUND & AIMS: PURPOSE:Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We present a population modeling framework identifying and quantifying such relationships, based on longitudinal data collected in patients with metastatic colorectal cancer (mCRC) to evaluate the value of tumor size and CTC counts as predictors of OS. EXPERIMENTAL DESIGN:A pharmacometric approach (i.e., population pharmacodynamic modeling) was used to characterize the changes in tumor size and CTC count and evaluate them as predictors of OS in 451 patients with mCRC treated with chemotherapy and targeted therapy in a prospectively randomized phase III study (CAIRO2). RESULTS:A tumor size model of tumor quiescence and drug resistance was used to characterize the tumor size time-course, and was, in addition to the total normalized dose (i.e., of all administered drugs) in a given cycle, related to the CTC counts through a negative binomial model (CTC model). Tumor size changes did not contribute additional predictive value when the mean CTC count was a predictor of OS. Treatment reduced the typical mean count from 1.43 to 0.477 (HR = 3.94). The modeling framework was applied to explore whether dose modifications (increased and reduced) would result in a CTC count below 1/7.5 mL after 1 to 2 weeks of treatment. CONCLUSIONS:Time-varying CTC counts can be useful for early predicting OS in patients with mCRC, and may therefore have potential for model-based treatment individualization. Although tumor size was connected to CTC, its link to OS was weaker.

背景与目标： 目的：缺乏治疗引起的肿瘤大小变化和循环肿瘤细胞（CTC）计数之间的定量关系，以及它们与总生存期（OS）的联系。我们基于在转移性结直肠癌（mCRC）患者中收集的纵向数据，以鉴定和量化这种关系的人群建模框架，以评估肿瘤大小和CTC计数作为OS预测因子的价值。
实验设计：在一项前瞻性随机III期研究中，使用药理学方法（即群体药效学模型）表征了451名接受化疗和靶向治疗的mCRC患者的肿瘤大小和CTC计数变化，并将其评估为OS的预测指标（CAIRO2）。
结果：使用肿瘤静止和耐药性的肿瘤大小模型来表征肿瘤大小的时程，并且除了给定周期中的总归一化剂量（即所有给药药物）外，还与CTC相关通过负二项式模型（CTC模型）进行计数。当平均CTC计数是OS的预测指标时，肿瘤大小的变化并没有提供其他预测价值。治疗使典型平均计数从1.43降低到0.477（HR = 3.94）。应用该建模框架来研究剂量修改（增加和减少）在治疗1至2周后是否会导致CTC计数低于1 / 7.5 mL。
结论：随时间变化的CTC计数可用于早期预测mCRC患者的OS，因此可能具有基于模型的治疗个体化的潜力。尽管肿瘤大小与CTC相关，但其与OS的联系较弱。

BACKGROUND & AIMS: BACKGROUND:Necropsy studies demonstrate that coronary artery disease (CAD) is frequently complex and eccentric. However, angiography provides only a silhouette of the vessel lumen. Intravascular ultrasound is a new tomographic imaging method for evaluation of coronary dimensions and wall morphology. Few data exist regarding intravascular ultrasound in patients with CAD, and no data exist for subjects with normal coronaries. METHODS AND RESULTS:We used a multielement 5.5F, 20-MHz ultrasound catheter to examine eight normal subjects and 43 patients with CAD. We assessed the safety of coronary ultrasound and the effect of vessel eccentricity on comparison of minimum luminal diameter by angiography and ultrasound. Normal and atherosclerotic wall morphology and stenosis severity were also evaluated by intravascular ultrasound. The only untoward effect was transient coronary spasm in five patients. At 33 sites in normal subjects, the lumen was nearly circular, yielding a close correlation between angiographic and ultrasonic minimum diameter (r = 0.92). At 90 sites in patients with CAD, ultrasound demonstrated a concentric cross section; correlation was also close (r = 0.93). However, at 72 eccentric sites, correlation was not as close (r = 0.77). For 41 stenoses, correlation between angiography and ultrasound for area reduction was moderate (r = 0.63). In normal subjects, wall morphology revealed a thin (0.30 mm or less) intimal leading edge and subadjacent sonolucent zone (0.20 mm or less). Patients with CAD exhibited increased thickness and echogenicity of the leading edge, thickened sonolucent zones, and/or attenuation of ultrasound transmission. CONCLUSIONS:These data establish that intravascular ultrasound is feasible and safe and yields luminal measurements that correlate generally with angiography. Differences between angiographic and ultrasound measures of lumen size in eccentric vessels probably reflect the dissimilar perspectives of tomographic and silhouette imaging techniques. Intravascular ultrasound provides detailed images of normal and abnormal wall morphology not previously possible in vivo.

背景与目标： 背景：尸检研究表明，冠状动脉疾病（CAD）常常很复杂而且很古怪。然而，血管造影仅提供血管腔的轮廓。血管内超声是一种新的层析成像成像方法，可用于评估冠状动脉尺寸和壁形态。很少有关于冠心病患者血管内超声的数据，而对于冠状动脉正常的受试者则没有数据。
方法和结果：我们使用多元素5.5F，20 MHz超声导管检查了八名正常受试者和43例CAD患者。我们通过血管造影和超声评估了冠状动脉超声的安全性和血管偏心率对最小管腔直径比较的影响。还通过血管内超声评估了正常和动脉粥样硬化壁的形态和狭窄的严重程度。唯一令人不快的作用是五名患者的短暂性冠状动脉痉挛。在正常受试者的33个部位，管腔几乎呈圆形，在血管造影和超声最小直径之间具有密切的相关性（r = 0.92）。在CAD患者的90个部位，超声显示出同心的横截面。相关性也很接近（r = 0.93）。但是，在72个偏心部位，相关性不那么紧密（r = 0.77）。对于41例狭窄的患者，血管造影和超声检查对减少面积的相关性中等（r = 0.63）。在正常受试者中，壁形态显示内膜前缘较薄（0.30毫米或更小）和声纳区下方（0.20毫米或更小）。患有CAD的患者表现出前缘的厚度和回声增加，声纳区变厚和/或超声传输减弱。
结论：这些数据证实血管内超声是可行和安全的，并产生与血管造影通常相关的腔内测量。偏心管腔大小的血管造影和超声测量之间的差异可能反映了层析成像和轮廓成像技术的不同观点。血管内超声可提供以前在体内不可能的正常和异常壁形态的详细图像。

BACKGROUND & AIMS: STUDY OBJECTIVE:The aim was to demonstrate the ability of diltiazem to protect the ischaemic myocardium in the course of coronary reperfusion, and to establish if an interaction with neutrophils is implied. DESIGN:Ischaemia was induced by occluding the left anterior descending coronary artery for 90 min followed by 6 h of reperfusion with a residual critical stenosis left in place. Three groups were studied: group 1 (control) received a saline perfusion; group 2 was given a bolus injection of 400 micrograms.kg-1 of diltiazem 10 min before reperfusion, followed by 4 micrograms.kg-1.min-1 perfusion until termination of experiment; group 3 was made neutropenic by injecting a neutrophil antiserum produced in rabbits and was then treated with diltiazem, as in the second group. SUBJECTS:60 mongrel dogs of either sex were allocated at random into one of the three groups the day before the experiment. MEASUREMENTS AND MAIN RESULTS:Diltiazem plasma concentrations ranged from 68.6(SEM 10.0) to 102.5(15.2) micrograms.litre-1 during the study. Transmural collateral blood flow, measured with 153Gd microspheres 15 min after occlusion, and area at risk, evaluated by Evans blue perfusion, did not differ among the three groups. Infarct size, estimated by triphenyltetrazolium staining of heart slices and expressed as a percentage of area at risk, was less (p less than 0.05) in the diltiazem [20.5(5.2)%] and diltiazem plus neutropenia [17.6(5.4)%] groups compared to controls [39.8(6.9)%] but neutropenia added no significant benefit to diltiazem alone. The animals treated with diltiazem alone had lower serum creatine kinase levels than controls, at 5719(891) v 14,333(2885) IU.litre-1, p less than 0.05. The neutrophilia seen in controls was virtually absent in diltiazem dogs. Myocardial neutrophil accumulation estimated by scintigraphy of 111In labelled autologous neutrophils was much less in diltiazem than in control dogs, at 3948(1228) v 11,021(2081) 111In-neutrophil.g-1 of infarct, p less than 0.02. CONCLUSIONS:Diltiazem given during reperfusion reduces infarct size by a mechanism that includes an inhibition of neutrophil accumulation in the post-ischaemic myocardium.

背景与目标： 目的：证明地尔硫卓在冠状动脉再灌注过程中保护缺血性心肌的能力，并确定是否暗示与中性粒细胞的相互作用。
设计：缺血是通过阻塞左冠状动脉前降支90分钟，然后再灌注6小时，并留有残留的严重狭窄。研究了三组：第一组（对照组）接受盐水灌注；第二组（对照组）接受盐水灌注。第2组在再灌注前10分钟大剂量注射400微克.kg-1的地尔硫卓，然后再进行4微克.kg-1.min-1的灌注，直到实验终止。通过注射在兔中产生的嗜中性白细胞抗血清，使第3组中性粒细胞减少，与第二组一样，用地尔硫卓治疗。
研究对象：实验前一天，将60只性别不一的杂种狗随机分为三组。
测量和主要结果：在研究过程中地尔硫卓的血浆浓度范围从68.6（SEM 10.0）到102.5（15.2）micrograms.litre-1。闭塞后15分钟用153Gd微球测量的透壁侧支血流和通过埃文斯蓝灌注评估的危险区域在三组之间没有差异。地尔硫卓[20.5（5.2）％]和地尔硫卓加中性粒细胞减少症[17.6（5.4）％]组中，通过心脏切片的三苯基四唑鎓染色估计的梗塞面积（表示为危险区域的百分比）较小（p小于0.05）。与对照组相比[39.8（6.9）％]，但嗜中性白血球减少症对单独使用地尔硫卓没有明显的益处。单独用地尔硫卓治疗的动物的血清肌酸激酶水平低于对照组，分别为5719（891）v 14,333（2885）IU.litre-1，p小于0.05。对照组中见到的中性粒细胞缺乏实际上在地尔硫卓的狗中。闪烁显像法通过111In标记的自体中性粒细胞的闪烁显像估计地尔硫卓的心肌中性粒细胞蓄积比对照组犬少得多，在3948（1228）v 11,021（2081）111In-neutrophil.g-1梗死，p小于0.02。
结论：再灌注期间给予地尔硫卓可通过一种机制来减少梗死面积，该机制包括抑制缺血后心肌中的中性粒细胞积聚。

BACKGROUND & AIMS: BACKGROUND:Calcium may be mobilized from the maternal skeleton during pregnancy, which may be influenced by several factors. OBJECTIVE:The objective was to investigate changes in bone mineral status and size during pregnancy and to consider the influences of body weight and calcium intake. DESIGN:Thirty-four British women were studied before pregnancy and 2 wk postpartum (Preg). Eighty-four nonpregnant, nonlactating (NPNL) women were studied over a corresponding time. Bone mineral content (BMC), bone area (BA), areal bone mineral density (aBMD), and BA-adjusted BMC of the whole-body, lumbar spine, radius, and hip were measured by dual-energy X-ray absorptiometry. RESULTS:The Preg group experienced significant decreases in BMC, aBMD, and BA-adjusted BMC at the whole-body, spine, and total hip of between 1% and 4%. Whole-body BMC increased in the NPNL group, and aBMD and BA-adjusted BMC decreased at the spine and hip by 0.5% to 1%. Whole-body BMC decreased in the Preg group by -2.16 +/- 0.46%, equivalent to -2.71 +/- 0.43% relative to the NPNL group (P < or = 0.001). Weight change was a positive predictor of skeletal change at the spine, hip, and radius in both groups. Differences between the Preg and NPNL groups in change in BA-adjusted BMC, after correction for weight change and other influences, were as follows (P < or = 0.01): whole-body, -1.70 +/- 0.25%; spine, -3.03 +/- 0.72%; and total hip, -1.87 +/- 0.60%. Calcium intake was not a significant predictor of skeletal change in either group. CONCLUSIONS:Pregnancy is associated with decreases in whole-body and regional bone mineral status sufficient to make a sizeable contribution to maternal and fetal calcium economy. Calcium intake is not a significant predictor of the skeletal response to pregnancy in well-nourished women.

背景与目标： 背景：孕妇在怀孕期间可能会从母体骨骼中吸收钙，这可能受到多种因素的影响。
目的：研究怀孕期间骨矿物质状态和大小的变化，并考虑体重和钙摄入量的影响。
设计：对34名英国妇女在怀孕前和产后2周进行了研究（Preg）。在相应的时间里研究了84名未怀孕，不哺乳（NPNL）的妇女。通过双能X射线吸收法测量全身，腰椎，radius骨和臀部的骨矿物质含量（BMC），骨面积（BA），面骨矿物质密度（aBMD）和BA调整后的BMC。
结果：Preg组的全身，脊柱和全髋关节的BMC，aBMD和BA调整后的BMC明显降低了1％至4％。 NPNL组的全身BMC升高，而脊柱和髋部的aBMD和BA调整后的BMC降低了0.5％至1％。 Preg组的全身BMC相对于NPNL组降低了-2.16 /-0.46％，相当于-2.71 /-0.43％（P <或= 0.001）。体重变化是两组脊柱，臀部和radius骨骨骼变化的积极预测指标。校正体重变化和其他影响后，Breg调整后的BMC的Preg组和NPNL组之间的变化差异如下（P <或= 0.01）：全身，-1.70 /-0.25％；脊柱-3.03 /-0.72％;和整个臀部，-1.87 /-0.60％。钙摄入量不是两组中骨骼变化的重要预测指标。
结论：妊娠与全身和区域性骨矿物质状态的降低有关，足以为母体和胎儿的钙经济做出可观的贡献。钙摄入量不是营养丰富的女性对怀孕骨骼反应的重要预测指标。

BACKGROUND & AIMS: :Brief exposure to moderate intensity static magnetic fields has been shown to produce a transient alteration in physiological function in a variety of biological systems, primarily those related to changes in intracellular Ca(2+). In the present study GH3 cells were cultured during continuous exposure to a 0.5 T field, for periods of up to 5 weeks. Following a 1-week exposure, cell growth declined by 22% and returned to control levels in 1 week. This was not statistically significant but, with a 4-week exposure, a statistically significant decline in growth of 51% was observed and return to control levels did not occur for 4 weeks. Cell diameter, on the other hand, significantly increased following 3 weeks of exposure and did not return to control levels for 3 weeks after termination of exposure. Ca(2+)-dependent changes in the dynamic reorganization of the actin cytoskeleton are suggested as the probable explanation for these observations.

背景与目标： ：短暂暴露于中等强度的静磁场已显示在多种生物系统中，主要是与细胞内Ca（2）的变化有关的生理功能中，产生暂时性的生理变化。在本研究中，在连续暴露于0.5 T场的过程中培养GH3细胞长达5周。暴露1周后，细胞生长下降了22％，并在1周内恢复到对照水平。这在统计学上不显着，但是在暴露4周后，观察到生长增长在统计学上显着下降51％，并且在4周内未出现恢复到对照水平的情况。另一方面，细胞直径在接触3周后显着增加，并且在接触终止后3周未恢复到对照水平。 Ca（2）依赖变化的肌动蛋白细胞骨架的动态重组被建议为这些观察结果的解释。