BACKGROUND & AIMS: :Approaches to control epilepsy, one of the most important idiopathic brain disorders, are of great importance for public health. We have previously shown that in sympathetic neurons the neuronal isoform of the serum and glucocorticoid-regulated kinase (SGK1.1) increases the M-current, a well-known target for seizure control. The effect of SGK1.1 activation on kainate-induced seizures and neuronal excitability was studied in transgenic mice that express a permanently active form of the kinase, using electroencephalogram recordings and electrophysiological measurements in hippocampal brain slices. Our results demonstrate that SGK1.1 activation leads to reduced seizure severity and lower mortality rates following status epilepticus, in an M-current-dependent manner. EEG is characterized by reduced number, shorter duration, and early termination of kainate-induced seizures in the hippocampus and cortex. Hippocampal neurons show decreased excitability associated to increased M-current, without altering basal synaptic transmission or other neuronal properties. Altogether, our results reveal a novel and selective anticonvulsant pathway that promptly terminates seizures, suggesting that SGK1.1 activation can be a potent factor to secure the brain against permanent neuronal damage associated to epilepsy.

背景与目标： : 控制癫痫的方法是最重要的特发性脑部疾病之一，对公共卫生至关重要。我们以前已经表明，在交感神经元中，血清和糖皮质激素调节激酶 (SGK1.1) 的神经元同工型会增加M电流，这是控制癫痫发作的众所周知的靶标。在表达激酶永久活性形式的转基因小鼠中，使用脑电图记录和电生理测量在海马脑切片中研究了SGK1.1激活对海藻酸盐诱导的癫痫发作和神经元兴奋性的影响。我们的结果表明，SGK1.1激活以M电流依赖性方式导致癫痫持续状态后癫痫发作严重程度降低和死亡率降低。脑电图的特征是海马和皮层海藻酸盐诱发的癫痫发作的数量减少，持续时间缩短和提前终止。海马神经元表现出与M电流增加相关的兴奋性降低，而没有改变基底突触传递或其他神经元特性。总之，我们的结果揭示了一种新颖的选择性抗惊厥途径，可迅速终止癫痫发作，这表明SGK1.1激活可能是确保大脑免受与癫痫相关的永久性神经元损伤的有效因素。

BACKGROUND & AIMS: :Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2LRR-1 associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2LRR1 as a key regulated step during DNA replication termination. Interestingly, however, CMG persists on chromatin until prophase in worms that lack CUL-2LRR-1, but is then removed by a mitotic pathway that requires the CDC-48 cofactor UBXN-3, orthologous to the human tumour suppressor FAF1. Partial inactivation of lrr-1 and ubxn-3 leads to synthetic lethality, suggesting future approaches by which a deeper understanding of CMG disassembly in metazoa could be exploited therapeutically.

背景与目标： : repisome拆卸是真核生物中DNA复制的最后一步，涉及CMG解旋酶 (CDC45-MCM-GINS) 的泛素化和CDC48-dependent溶解。使用秀丽隐杆线虫早期胚胎和非洲爪蟾卵提取物，我们表明E3连接酶CUL-2LRR-1与复制体结合，并驱动CMG的泛素化和分解，以及CDC-48辅因子的UFD-1和NPL-4。从青蛙卵提取物中的染色质中去除CMG需要CUL2染色，我们的数据确定CUL2LRR1的染色质募集是DNA复制终止过程中的关键调节步骤。然而，有趣的是，CMG在染色质上持续存在，直到缺乏CUL-2LRR-1的蠕虫中出现前期，但随后被需要CDC-48辅因子UBXN-3 (与人类肿瘤抑制因子faf1同源) 的有丝分裂途径去除。lrr-1和ubxn-3的部分失活会导致合成的杀伤力，这表明了未来的方法，通过这些方法可以在治疗上更深入地了解后生动物中CMG的分解。

BACKGROUND & AIMS: :A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may influence breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

背景与目标： : 母乳喂养医学研究院的中心目标是制定临床方案，以管理可能影响母乳喂养成功的常见医学问题。这些协议仅作为母乳喂养母亲和婴儿护理的指南，并不划定专属疗程或作为医疗护理标准。根据个别患者的需要，治疗的变化可能是适当的。

BACKGROUND & AIMS: :Tectonics and climate-driven surface processes govern the evolution of Earth's surface topography. Topographic change in turn influences lithospheric deformation, but the elementary scale at which this feedback can be effective is unclear. Here we show that it operates in a single weather-driven erosion event. In 2009, typhoon Morakot delivered ~ 3 m of precipitation in southern Taiwan, causing exceptional landsliding and erosion. This event was followed by a step increase in the shallow (< 15 km depth) earthquake frequency lasting at least 2.5 years. Also, the scaling of earthquake magnitude and frequency underwent a sudden increase in the area where mass wasting was most intense. These observations suggest that the progressive removal of landslide debris by rivers from southern Taiwan has acted to increase the crustal stress rate to the extent that earthquake activity was demonstrably affected. Our study offers the first evidence of the impact of a single weather-driven erosion event on tectonics.

背景与目标： : 构造和气候驱动的表面过程控制着地球表面地形的演变。地形变化反过来会影响岩石圈变形，但是这种反馈有效的基本尺度尚不清楚。在这里，我们表明它在单个天气驱动的侵蚀事件中运行。2009年，台风莫拉克 (Morakot) 在台湾南部地区产生了约3 m的降水，造成了异常的滑坡和侵蚀。此事件之后，持续至少2.5年的浅 (<15千米深度) 地震频率逐步增加。此外，在大规模浪费最严重的地区，地震震级和频率的规模突然增加。这些观察结果表明，台湾南部河流对滑坡碎片的逐步清除已导致地壳应力速率增加，以至于地震活动受到明显影响。我们的研究提供了单个天气驱动的侵蚀事件对构造的影响的第一个证据。

BACKGROUND & AIMS: :In Ordinary Least Square regression, researchers often are interested in knowing whether a set of parameters is different from zero. With complete data, this could be achieved using the gain in prediction test, hierarchical multiple regression, or an omnibus F test. However, in substantive research scenarios, missing data often exist. In the context of multiple imputation, one of the current state-of-art missing data strategies, there are several different analogous multi-parameter tests of the joint significance of a set of parameters, and these multi-parameter test statistics can be referenced to various distributions to make statistical inferences. However, little is known about the performance of these tests, and virtually no research study has compared the Type 1 error rates and statistical power of these tests in scenarios that are typical of behavioral science data (e.g., small to moderate samples, etc.). This paper uses Monte Carlo simulation techniques to examine the performance of these multi-parameter test statistics for multiple imputation under a variety of realistic conditions. We provide a number of practical recommendations for substantive researchers based on the simulation results, and illustrate the calculation of these test statistics with an empirical example.

背景与目标： : 在普通的最小二乘回归中，研究人员通常对知道一组参数是否与零不同感兴趣。使用完整的数据，可以使用预测测试中的增益，分层多元回归或综合f检验来实现。然而，在实质性研究场景中，经常存在缺失的数据。在当前最先进的缺失数据策略之一的多重插补的背景下，对一组参数的联合显著性有几种不同的类比多参数检验，这些多参数检验统计量可以参考各种分布进行统计推断。然而，对这些测试的性能知之甚少，并且几乎没有研究研究在行为科学数据的典型场景 (例如，小到中等样本等) 中比较了这些测试的类型1错误率和统计能力。本文使用蒙特卡洛模拟技术来检验这些多参数测试统计量在多种现实条件下的多次插补的性能。我们根据模拟结果为实质性研究人员提供了一些实用的建议，并通过一个实证示例说明了这些测试统计量的计算。

BACKGROUND & AIMS: :Impetigo herpetiformis is a rare variant of generalized pustular psoriasis that occurs during pregnancy or is triggered by pregnancy, often in association with hypocalcemia. This condition is associated with increased maternal and fetal morbidity and mortality. We report a 29-year-old pregnant woman who presented to hospital at the gestational age of 20 weeks with widespread erythema covered with pustules that coalesced to form lakes of pus. She did not respond to corticosteroids, immunosuppressants, or phototherapy. Finally, intra-amniotic injection of ethacridine lactate was administered to terminate the pregnancy, and the patient showed complete recovery in 3 months. Insight from this case report may facilitate optimal management of this relatively rare entity.

背景与目标： : 脓疱疮是一种罕见的广泛性脓疱型牛皮癣，发生在怀孕期间或由怀孕触发，通常与低钙血症有关。这种情况与孕产妇和胎儿的发病率和死亡率增加有关。我们报告了一名29岁的孕妇，她在20周的胎龄就诊，出现了广泛的红斑，上面覆盖着脓疱，并合并形成了脓湖。她对皮质类固醇，免疫抑制剂或光疗无反应。最后，羊膜内注射乳酸依沙啶终止妊娠，患者在3个月内完全康复。从该病例报告中获得的见解可能有助于对该相对罕见的实体进行最佳管理。

BACKGROUND & AIMS: We present here four nonparametric statistics for linkage analysis that test whether pairs of affected relatives share marker alleles more often than expected. These statistics are based on simulating the null distribution of a given statistic conditional on the unaffecteds' marker genotypes. Each statistic uses a different measure of marker sharingthe SimAPM statistic uses the simulation-based affected-pedigree-member measure based on identity-by-state (IBS) sharing. The SimKIN (kinship) measure is 1.0 for identity-by-descent (IBD) sharing, 0.0 for no IBD status sharing, and the kinship coefficient when the IBD status is ambiguous. The simulation-based IBD (SimIBD) statistic uses a recursive algorithm to determine the probability of two affecteds sharing a specific allele IBD. The SimISO statistic is identical to SimIBD, except that it also measures marker similarity between unaffected pairs. We evaluated our statistics on data simulated under different two-locus disease models, comparing our results to those obtained with several other nonparametric statistics. Use of IBD information produces dramatic increases in power over the SimAPM method, which uses only IBS information. The power of our best statistic in most cases meets or exceeds the power of the other nonparametric statistics. Furthermore, our statistics perform comparisons between all affected relative pairs within general pedigrees and are not restricted to sib pairs or nuclear families.

背景与目标： 我们在这里提供了四个用于连锁分析的非参数统计数据，这些统计数据测试了受影响的亲戚对是否比预期的更频繁地共享标记等位基因。这些统计信息基于模拟给定统计信息的空分布，条件是未受影响的标记基因型。每个统计量使用不同的标记共享度量SimAPM统计量使用基于身份状态 (IBS) 共享的基于模拟的受影响谱系成员度量。SimKIN (亲属关系) 度量对于按血统身份 (IBD) 共享是1.0的，0.0对于没有IBD状态共享，并且当IBD状态不明确时是亲属系数。基于模拟的IBD (SimIBD) 统计量使用递归算法来确定两个情感共享特定等位基因IBD的概率。SimISO统计量与SimIBD相同，不同之处在于它还测量了未受影响的对之间的标记相似性。我们评估了在不同的两基因座疾病模型下模拟的数据的统计数据，并将我们的结果与其他几种非参数统计数据进行了比较。与仅使用IBS信息的SimAPM方法不同，使用IBD信息会大大提高功率。在大多数情况下，我们最好的统计量的能力达到或超过其他非参数统计量的能力。此外，我们的统计数据在一般谱系内所有受影响的相对对之间进行比较，并且不仅限于同胞对或核心家庭。

BACKGROUND & AIMS: OBJECTIVE:The Transtheoretical Model proposes that clients' stage of change will predict their engagement in therapy. This study tested the hypotheses that clients with high Precontemplation scores would prematurely terminate from therapy and that clients with high Action scores would attend a greater number of sessions and establish a more positive therapeutic alliance. DESIGN:Using a within-subjects design, baseline measures of stage of change were used to predict the number of sessions attended, premature drop-out from therapy, and the therapeutic alliance after sessions one and three. METHODS:Sixty clients completed the Stages of Change Scales and the Brief Symptom Inventory prior to therapy. The therapeutic alliance was assessed after the first and third therapy session using the Agnew Relationship Measure. RESULTS:The specific hypotheses were not supported. Premature termination from therapy was predicted by high level of initial symptom severity and low Contemplation scores. Positive therapeutic alliance at session one and session three was predicted by high Contemplation at baseline. CONCLUSIONS:These results suggest that the Transtheoretical Model, which was developed in the context of interventions for behavioural change, may not be directly generalizable to outpatient psychotherapy populations. However, Contemplation did predict premature termination and engagement. This implies that with adaptation the model may be a useful adjunct to psychotherapy assessment.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Approximately 12% of active duty US servicewomen have an unintended pregnancy each year; however, little is known about contraception use during deployment. STUDY DESIGN:From April to November 2010, we conducted an online survey with a convenience sample of 281 servicewomen who had been deployed overseas to assess access to and use of contraception for deployment. RESULTS:Sixty-three percent of respondents used birth control for part or all of their last deployment. Although military health insurance covers most contraceptive methods, one third reported that they were unable to access a method they might want for deployment, and 59% did not speak with a military provider about contraceptive options prior to deployment. Certain methods were reportedly discouraged or not available for some women, including intrauterine devices and sterilization, and 41% of women requiring refills found them difficult to obtain. CONCLUSIONS:Given the high prevalence of unintended pregnancy among servicewomen, efforts should focus on improving contraceptive counseling prior to deployment and ensuring refill access during deployment, as well as expanding access to long-acting reversible methods.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:This study aims to (1) evaluate the probability and timing of termination of pregnancy for fetal anomaly (TOPFA) for all congenital heart defects (CHD) and categories of CHD and (2) assess clinical and socioeconomic predictors of TOPFA for isolated CHD excluding ventricular septal defects (VSD). METHODS:Using population-based data from the Paris Registry of Congenital Malformations, we assessed the probability of TOPFA and gestational age at TOPFA. We used logistic regression to estimate the adjusted effects of maternal characteristics, clinical factors (CHD type, fetal growth restriction, nuchal translucency measurement and gestational age at prenatal diagnosis) on the odds of TOPFA. RESULTS:The proportion of TOPFA for prenatally diagnosed CHD was 46% for all CHD combined, 82% for CHD associated with chromosomal anomalies and 27% for isolated CHD-VSD excluded. Isolated CHD-VSD excluded diagnosed before 22 weeks of gestational age had a 3.2-fold higher odds of TOPFA (adjusted OR 3.2, 95%CI 1.4-7.1). Maternal occupation was not associated with the odds of TOPFA. Women of African origin had a tenfold lower odds of TOPFA than women of French origin (adjusted OR 0.1, 95%CI 0.02-0.4). CONCLUSION:In addition to severity of CHD, early prenatal diagnosis and maternal characteristics were highly associated with the probability of TOPFA for CHD.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The relationship between perinatal psychiatric disorders and the use of effective contraceptive methods among postpartum women served by primary care clinics has not been established. STUDY DESIGN:This was a prospective cohort study with 831 pregnant women recruited from 10 primary care clinics of the public sector in São Paulo followed up to 18 months after delivery. RESULTS:Among 701 postpartum women, 644 women (91.8%) had resumed sexual activity. Two hundred fifty-three women (39.2%) were classified as using a less effective contraception method (LECM). The presence of perinatal psychiatric disorder (in pregnancy and/or postpartum) was not associated with LECM. Resumption of sexual life 3 months or beyond after delivery was associated with LECM (odds ratio=1.28, 95% confidence interval: 1.02-1.56). DISCUSSION:Although the use of an LECM after delivery is common, contraception choice is not associated with perinatal depressive/anxiety symptoms. However, women who delay the resumption of sexual activity after delivery should be counseled on the use of available contraceptive methods.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:The New Zealand government has made a commitment to reducing inequalities in health among its population through the New Zealand Health Strategy. Termination of Pregnancy (TOP) services are an important part of women's health services, and equity in access to services must be ensured. OBJECTIVE:Assess geographic accessibility to first trimester termination of pregnancy services in New Zealand, and discuss implications for equity in access to services. METHODS:TOP service information was obtained nationwide through online resources, and approximate driving distances between all major centres and the closest TOP service to which patients are referred to were calculated for each region. Census data and Statistics NZ data are used to compare population characteristics between regions with reduced geographic accessibility of TOP services. RESULTS:Women who live in regions that do not offer local TOP services must travel on average 221 km to access TOP services. This equates to an average return-trip distance of 442 km. Three of the five regions that do not have local TOP services available have a higher than average proportion of Maori population. CONCLUSIONS:The results of this study demonstrate that first-trimester TOP services are relatively difficult to access for over one-sixth of the women in New Zealand.

背景与目标：

BACKGROUND & AIMS: :The trp RNA-binding attenuation protein (TRAP) regulates expression of the Bacillus subtilis trpEDCFBA operon by transcription attenuation and translational control mechanisms. Both mechanisms require binding of tryptophan-activated TRAP to 11 (G/U)AG repeats in the trp leader transcript. trpE translational control involves formation of a TRAP-dependent RNA structure that sequesters the trpE Shine-Dalgarno (SD) sequence (the SD blocking hairpin). By comparing expression levels from trpE'-'lacZ translational fusions controlled by the wild-type leader or by a leader that cannot form the SD blocking hairpin, we found that translational control requires a tryptophan concentration higher than that required for transcription attenuation. We also found that inhibition of trpE translation by the SD blocking hairpin does not alter the stability of the downstream message. Since the coding sequences for trpE and trpD overlap by 29 nucleotides, we examined expression levels from trpED'-'lacZ translational fusions to determine if these two genes are translationally coupled. We found that introduction of a UAA stop codon in trpE resulted in a substantial reduction in expression. Since expression was partially restored in the presence of a tRNA suppressor, our results indicate that trpE and trpD are translationally coupled. We determined that the coupling mechanism is TRAP independent and that formation of the SD blocking hairpin regulates trpD translation via translational coupling. We also constructed a rho mutation to investigate the role of Rho-dependent termination in trp operon expression. We found that TRAP-dependent formation of the SD blocking hairpin allows Rho access to the nascent transcript, causing transcriptional polarity.

背景与目标： : trp RNA结合衰减蛋白 (TRAP) 通过转录衰减和翻译控制机制调节枯草芽孢杆菌trpEDCFBA操纵子的表达。两种机制都需要色氨酸激活的TRAP与trp前导转录物中的11个 (G/U)AG重复序列结合。trpE翻译控制包括形成依赖于trpE Shine-Dalgarno (SD) 序列 (SD阻断发夹) 的RNA结构。通过比较trpE的表达水平-由野生型领导者或不能形成SD阻塞发夹的领导者控制的lacz翻译融合，我们发现翻译控制需要比转录衰减所需的色氨酸浓度更高。我们还发现SD阻断发夹对trpE翻译的抑制不会改变下游信息的稳定性。由于trpE和trpD的编码序列重叠了29个核苷酸，我们检查了trpED'-'lacZ翻译融合的表达水平，以确定这两个基因是否在翻译上耦合。我们发现在trpE中引入UAA终止密码子导致了表达的大幅降低。由于在tRNA抑制剂的存在下部分恢复了表达，我们的结果表明trpE和trpD是翻译耦合的。我们确定耦合机制是陷阱独立的，并且SD阻断发夹的形成通过翻译耦合调节trpD翻译。我们还构建了一个rho突变来研究Rho依赖性终止在trp操纵子表达中的作用。我们发现陷阱-SD阻塞发夹的依赖形成使Rho可以访问新生的转录本，导致转录极性。

BACKGROUND & AIMS: :Revertants of the cyc1-512 transcription termination mutant of the yeast Saccharomyces cerevisiae were isolated and subjected to a detailed genetic analysis. The cyc1-512 mutation previously was shown to be a 38-base pair deletion that causes only 10% of the normal steady-state levels of CYC1 mRNA and of the CYC1 gene product, iso-1-cytochrome c. Forty-one cyc1-512 revertants were classified by their content of iso-1-cytochrome c and by their genetic properties in meiotic crosses. Many of the revertants contain local genetic changes that either partially or completely restore the level of iso-1-cytochrome c. One revertant was shown to contain an unlinked extragenic suppressor, designated sut1, that causes partial suppression of the transcription termination defect. Four revertants of cyc1-512 contain chromosomal rearrangements with breakpoints that are tightly linked to the CYC1 locus; these include one duplication, one possible inversion, and two reciprocal translocations. Detailed genetic mapping demonstrated that one of the reciprocal translocations is between the right arms of chromosomes X and XII, with a breakpoint mapping 3' to the CYC1 locus. These results indicate that the defect in transcription termination in cyc1-512 can be restored in a variety of ways, including the translocation of different chromosomal regions to the 3' end of the CYC1 locus, local changes presumably at or near the original defect, and by mutation at another locus distinct from CYC1.

背景与目标： : 分离酿酒酵母的cyc1-512转录终止突变体的回复子，并进行详细的遗传分析。先前显示cyc1-512突变是38个碱基对缺失，仅引起cyc1mrna和CYC1基因产物的正常稳态水平的10%，iso-1-cytochrome c。41个cyc1-512回复子根据它们的iso-1-cytochrome c含量和它们在减数分裂杂交中的遗传特性进行分类。许多回复剂含有部分或完全恢复iso-1-cytochrome c水平的局部遗传变化。一种回复剂被证明含有未连接的基因外抑制子，称为sut1，其导致部分抑制转录终止缺陷。cyc1-512的四个回复剂包含具有与CYC1基因座紧密相连的断点的染色体重排; 这些包括一个重复，一个可能的反转和两个相互易位。详细的遗传图谱表明，相互易位之一是在X和XII染色体的右臂之间，断点将3' 映射到CYC1基因座。这些结果表明，cyc1-512转录终止的缺陷可以通过多种方式恢复，包括不同的染色体区域易位到CYC1基因座的3' 末端，可能在原始缺陷处或附近发生局部变化，以及通过不同于CYC1的另一个基因座的突变。

BACKGROUND & AIMS: :Acceptability and social characteristics of a cohort of Norplant, IUD, pill and depo-med-roxyprogesterone acetate (DMPA) acceptors who were seen at the University of Ilorin Family Planning Clinic over a 10-week period of the pre-introductory clinical trial of Norplant, are compared. Findings indicate that Norplant and DMPA are adopted as an alternative to sterilization by women advanced in reproductive age and of high parity. The pill and IUD are adopted mainly as birth-spacing methods. Women's education, but not previous use of a contraceptive method, influenced the adoption of Norplant. The continuation rate at 12 months, a measure of acceptability, was highest, 93.7 per 100 women, for Norplant and 77.9, 46.7 and 27.7 per 100 women for the IUD, DMPA and the pill, respectively. The need to address the high family size norms in the African subregion is discussed.

背景与目标： : 在伊洛林大学计划生育诊所进行的为期10周的Norplant，IUD，pill和depo-med-roxygesterone acetate (DMPA) 受体队列的可接受性和社会特征。比较了Norplant的入门临床试验。调查结果表明，育龄高，高胎次的妇女采用Norplant和DMPA作为绝育的替代方法。避孕药和宫内节育器主要用作生育间隔方法。妇女的教育，但以前没有使用避孕方法，影响了Norplant的采用。12个月时的可接受性指标Norplant最高，每100名妇女93.7例，IUD、DMPA和药丸分别为每100名妇女77.9例、46.7例和27.7例。讨论了解决非洲次区域高家庭规模规范的必要性。