• 【局限性前列腺癌的自然病程。以个人观点审阅已发表的论文。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Hugosson J,Aus G
    BACKGROUND & AIMS: :The course of untreated localized prostate cancer after 10 years of follow-up is at large unknown. As curative treatment is usually only offered patients with a life expectancy exceeding 10 Years, the expected course of the disease if left untreated is of the utmost interest. This paper aims to describe the outcome for patients who survive for more than 10 years when treated without curative intent. The results indicate that cancer specific mortality in patients with localized prostate cancer increases steadily over time and is approximately 50% after 15 years. This is a much higher figure than in reported series on radical prostatectomy. Even if many deaths occur at an old age, prostate cancer death is shown to be associated with a significant morbidity, need for palliative treatment, hospital care and cost. Preventing prostate cancer death is therefore not only a matter of saving year of life but also to prevent suffering caused by the disease. Modern diagnostic tools, such as prostate specific antigen, seem to detect clinically significant cancers in the vast majority of patients. Over diagnosis seems to be uncommon if diagnostic procedures are restricted to patients with a long life expectancy. Localized prostate cancer is a slow-growing but progressive neoplastic disease. When diagnosed in a man with a longer life expectancy it should be handled as such.
    背景与目标: :十年随访后未经治疗的局限性前列腺癌的病程目前还不得而知。由于通常仅为预期寿命超过10年的患者提供治愈性治疗,因此,如果不及时治疗,预期的病程将是最重要的。本文旨在描述未经治疗而存活超过10年的患者的预后。结果表明,局部前列腺癌患者的癌症特异性死亡率随时间稳定增加,并且在15年后约为50%。这是一个比已报道的前列腺癌根治术系列高得多的数字。即使许多死亡发生在老年,前列腺癌的死亡也被证明与明显的发病率,姑息治疗的需要,医院护理和费用有关。因此,预防前列腺癌的死亡不仅是挽救生命的一年,而且是预防由该疾病引起的痛苦的问题。现代诊断工具,例如前列腺特异性抗原,似乎可以在绝大多数患者中检测出具有临床意义的癌症。如果诊断程序仅限于预期寿命较长的患者,则过度诊断似乎不常见。局限性前列腺癌是一种生长缓慢但正在进行的肿瘤性疾病。当诊断为预期寿命较长的男性时,应照此处理。
  • 【小鼠第6号染色体上自然杀手基因复合物的2-Mb YAC重叠群和物理图谱。】 复制标题 收藏 收藏
    DOI:10.1006/geno.1997.4721 复制DOI
    作者列表:Brown MG,Fulmek S,Matsumoto K,Cho R,Lyons PA,Levy ER,Scalzo AA,Yokoyama WM
    BACKGROUND & AIMS: :We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode > 17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.
    背景与目标: :我们在小鼠染色体6上构建了一个大于2-Mb区域的物理图,其中包含自然杀伤基因复合体(NKC)。该图包括14个重叠的酵母人工染色体的重叠群,我们在其上定位了25个NKC标记。 NKC遗传连锁基因编码> 17种蛋白质,这些蛋白质直接控制先天NK细胞介导的肿瘤溶解和疾病抵抗力。在本文中,我们显示Nkrp1基因聚集在A2m和Cd69基因侧翼的区域中,而大多数Ly49基因聚集在距离-1 Mb远的区域中。重要的是,保留了包含NKC的小鼠6号染色体和人类12p号染色体的同音间隔。 NKC物种保守性表明,人NKC可能含有小鼠病毒疾病抗性基因Cmv1和Rmp1的直向同源物。高分辨率的NKC图谱将有助于NKC基因调控的研究和表型定义的基因产物的鉴定,这些产物赋予NK细胞防御病毒病原体的能力。
  • 【参与胚胎干细胞生物学的Rhox簇的鼠特异性扩增处于自然选择之下。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2164-7-212 复制DOI
    作者列表:Jackson M,Watt AJ,Gautier P,Gilchrist D,Driehaus J,Graham GJ,Keebler J,Prugnolle F,Awadalla P,Forrester LM
    BACKGROUND & AIMS: BACKGROUND:The rodent specific reproductive homeobox (Rhox) gene cluster on the X chromosome has been reported to contain twelve homeobox-containing genes, Rhox1-12. RESULTS:We have identified a 40 kb genomic region within the Rhox cluster that is duplicated eight times in tandem resulting in the presence of eight paralogues of Rhox2 and Rhox3 and seven paralogues of Rhox4. Transcripts have been identified for the majority of these paralogues and all but three are predicted to produce full-length proteins with functional potential. We predict that there are a total of thirty-two Rhox genes at this genomic location, making it the most gene-rich homoeobox cluster identified in any species. From the 95% sequence similarity between the eight duplicated genomic regions and the synonymous substitution rate of the Rhox2, 3 and 4 paralogues we predict that the duplications occurred after divergence of mouse and rat and represent the youngest homoeobox cluster identified to date. Molecular evolutionary analysis reveals that this cluster is an actively evolving region with Rhox2 and 4 paralogues under diversifying selection and Rhox3 evolving neutrally. The biological importance of this duplication is emphasised by the identification of an important role for Rhox2 and Rhox4 in regulating the initial stages of embryonic stem (ES) cell differentiation. CONCLUSION:The gene rich Rhox cluster provides the mouse with significant biological novelty that we predict could provide a substrate for speciation. Moreover, this unique cluster may explain species differences in ES cell derivation and maintenance between mouse, rat and human.
    背景与目标: 背景:据报道,X染色体上的啮齿动物特异性生殖同源盒(Rhox)基因簇含有十二个包含同源盒的基因,Rhox1-12。
    结果:我们在Rhox簇中鉴定出一个40 kb的基因组区域,该区域串联重复八次,导致存在八个Rhox2和Rhox3旁系同源物和七个Rhox4旁系同源物。已为大多数这些旁系同源物确定了转录本,除三个外,均预测会产生具有功能潜力的全长蛋白质。我们预测在该基因组位置总共有32个Rhox基因,使其成为任何物种中鉴定到的最丰富的基因同源盒簇。从八个重复的基因组区域之间95%的序列相似性以及Rhox2、3和4个旁系同源物的同义取代率,我们预测重复发生在小鼠和大鼠分化后,并且代表了迄今确定的最年轻的同源盒簇。分子进化分析表明,该簇是一个活跃进化的区域,在选择多样化的情况下,Rhox2和4个旁系同源物,而Rhox3则是中性进化的。通过鉴定Rhox2和Rhox4在调节胚胎干(ES)细胞分化的初始阶段中的重要作用,强调了这种重复的生物学重要性。
    结论:富含基因的Rhox簇为小鼠提供了重要的生物学新奇,我们预测可以为物种形成提供底物。而且,这种独特的簇可以解释小鼠,大鼠和人之间ES细胞衍生和维持中的物种差异。
  • 【来自“进化峡谷”的酿酒酵母自然种群中的分子遗传生物多样性:微卫星多态性,倍性和有争议的性状态。】 复制标题 收藏 收藏
    DOI:10.1534/genetics.106.062745 复制DOI
    作者列表:Ezov TK,Boger-Nadjar E,Frenkel Z,Katsperovski I,Kemeny S,Nevo E,Korol A,Kashi Y
    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: :酿酒酵母是真核细胞研究中的中心模型生物,在许多食品和生物技术工业过程中都是主要成分。但是,关于酿酒酵母的遗传学和分子生物学的广泛知识是基于非常狭窄的菌株。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天然微型站点“进化峡谷”中分离出一组酿酒酵母菌株,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,整个等位基因组中的高等位基因多样性和倍性水平存在差异,这已通过流式细胞仪进行了确认。在来自主要地区或微生态位的菌株之间,微卫星变异水平没有发现显着差异,而具有不同倍性的菌株在等位基因含量上的相似性很低。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的遗传多样性。系统发育分析显示三倍体和四倍体亚群的克隆结构,而不是有性结构。四元分析中的生存力测试还表明,在多倍体亚群中克隆繁殖可能占主导地位。
  • 【评估英国肾脏移植的资源。】 复制标题 收藏 收藏
    DOI:10.1016/s0140-6736(85)91508-9 复制DOI
    作者列表:Sells RA,Macpherson S,Salaman JR
    BACKGROUND & AIMS: :Statistics on treatment rates for patients with end stage renal disease (ESRD) show that the number of ESRD patients per million population in the United Kingdom has increased slowly in recent years. The British Transplantation Society issued questionnaires in 1983 and 1984 to determine the number of patients transplanted, the number of suitable patients, and the facilities needed to enable all suitable patients to receive treatment. While there is a high transplant rate, the percentage of ESRD patients on dialysis is low, and there is a "socially unacceptable deficit" with respect to treatment of diabetics and the elderly.
    背景与目标: :晚期肾病(ESRD)患者治疗率的统计数据表明,近年来英国每百万人口中ESRD患者的人数增长缓慢。英国移植学会在1983年和1984年发布了调查表,以确定移植的患者数量,合适的患者数量以及使所有合适的患者都能接受治疗所需的设施。尽管移植率很高,但接受透析的ESRD患者的比例却很低,并且在糖尿病患者和老年人的治疗方面存在“社会上无法接受的缺陷”。
  • 【用于经直肠自然孔腔内腔镜手术的新型可拆卸闭塞气囊装置。】 复制标题 收藏 收藏
    DOI:10.3109/13645706.2012.732080 复制DOI
    作者列表:Xu H,Ohdaira T,Nagao Y,Tsutsumi N,Mori M,Uemura M,Toyoda K,Ieiri S,Hashizume M
    BACKGROUND & AIMS: INTRODUCTION:Transrectal natural orifice translumenal endoscopic surgery (NOTES) requires a good endoluminal view and adequate intrarectal bacterial clearance in the working area. We developed a new occlusion balloon unit with an easily detachable inflation device, which allows the surgeon a clear working area distal to the balloon. MATERIAL AND METHODS:The effectiveness of the sealing balloon and the extent of macroscopic and histopathological injury to the bowel wall at the site of balloon placement were examined in 12 pigs. RESULTS:The mean time to place and inflate the balloon unit was 12.0 ± 3.5 min, effective air-tightness lasted for 21.0 ± 12.0 min. There was no leakage of dye (methylene blue) past the balloon when pressure was maintained >6.70 ± 0.08 kPa (6.62-6.78 kPa). After gut irrigation, good visibility was maintained in the working area for six hours, and adequate bacterial clearance was maintained for three hours. There were no macroscopic signs of intestinal wall damage at the site of balloon placement. Histopathological examination showed only patchy mucosal damage and submucosal thrombus at the site of balloon placement. CONCLUSION:This newly-developed occlusion balloon unit helps to establish good visibility and adequate bacterial clearance for endoluminal surgical procedures.
    背景与目标: 简介:经直肠自然孔腔内镜手术(NOTES)需要良好的腔内视野,并在工作区域内有足够的直肠内细菌清除率。我们开发了一种带有易于拆卸的充气装置的新型阻塞球囊装置,使外科医生在球囊远端有一个清晰的工作区域。
    材料与方法:检查了12只猪的密封球囊的有效性以及球囊放置部位肠壁的宏观和组织病理学损伤程度。
    结果:气囊装置的平均放置时间和充气时间为12.0±3.5分钟,有效气密性持续21.0±12.0分钟。当压力保持> 6.70±0.08 kPa(6.62-6.78 kPa)时,没有染料(亚甲蓝)通过球囊泄漏。灌肠后,在工作区域内保持六个小时的可见度,并在三个小时内保持足够的细菌清除率。在球囊放置部位没有肉眼可见的肠壁损伤迹象。组织病理学检查仅在球囊放置部位发现斑块状的粘膜损伤和粘膜下的血栓。
    结论:这种新开发的闭塞气囊装置有助于为腔内外科手术建立良好的可见性和足够的细菌清除率。
  • 【分化型早期胃癌非治愈性内镜切除的自然过程。】 复制标题 收藏 收藏
    DOI:10.1055/s-0032-1325676 复制DOI
    作者列表:Ahn JY,Jung HY,Choi JY,Kim MY,Lee JH,Choi KS,Kim DH,Choi KD,Song HJ,Lee GH,Kim JH,Park YS
    BACKGROUND & AIMS: BACKGROUND AND STUDY AIMS:Following noncurative endoscopic resection of early gastric cancer (EGC), the patient should be observed when the underlying disease is severe, the patient is elderly, or the patient refuses further treatment. The aim of this study was to analyze the clinical outcomes of patients with differentiated EGC who underwent noncurative endoscopic resection without additional treatment. PATIENTS AND METHODS:Included patients underwent noncurative endoscopic resection for differentiated EGC without additional treatment at the Asan Medical Center between July 1994 and January 2009. Clinical and oncological outcomes were analyzed. RESULTS:A total of 159 patients were included in the analysis. The median follow-up period was 33 months (interquartile range [IQR] 22 - 52 months). In total, 40 patients died (25.2 %) - 3 due to stomach cancer, 34 due to other causes, and 3 from unknown causes; the median survival time after endoscopic treatment for these patients was 27.5 months (IQR 13.8 - 48.3 months). Multivariate analysis showed that the rates of underlying disease (P < 0.001) and lymphovascular invasion (P = 0.005) were higher among the 40 patients who died than among the 119 survivors. The overall 3-  and 5-year survival rates were 82.9 % and 77.1 %, respectively; the rates of the patients with lymphovascular invasion were 61.9 % and 42.4 %, respectively, and the rates of patients without lymphovascular invasion were 86.1 % and 81.8 %, respectively (P < 0.001). CONCLUSIONS:Additional treatment provides fewer benefits to patients who do not have long life expectancies. Additional surgery can be considered for patients with lymphovascular invasion because of its high mortality rate; however, the benefits and risks of surgery should be considered carefully.
    背景与目标: 背景与研究目的:在早期胃癌(EGC)的非根治性内镜切除术之后,应在基础疾病严重,患者年老或患者拒绝进一步治疗时对患者进行观察。这项研究的目的是分析未经治疗的内镜下切除术而无需额外治疗的分化型EGC患者的临床结局。
    患者与方法:1994年7月至2009年1月间,在Asan医疗中心对其中包括分化型EGC的患者进行了非根治性内镜切除术,未进行进一步的治疗。分析了临床和肿瘤学结局。
    结果:总共159例患者被纳入分析。中位随访期为33个月(四分位间距[IQR] 22±52个月)。共有40例患者(25.2 %%)died- 3因胃癌死亡,34因其他原因死亡,3因不明原因死亡;这些患者经内镜治疗后的中位生存时间为27.5个月(IQR 13.8±48.3个月)。多因素分析显示,死亡的40例患者的基础疾病(P(<0.001)和淋巴管浸润(P invasion = 0.005)的发生率高于119名幸存者。 3年和5年总生存率分别为82.9%和77.1%。淋巴管浸润患者的发生率分别为61.9%和42.4%,无淋巴管浸润的患者分别为86.1%和81.8%(P <0.001)。
    结论:额外治疗对没有预期寿命的患者提供的益处较少。由于其高死亡率,可以考虑对淋巴管侵犯的患者进行额外的手术。但是,应仔细考虑手术的益处和风险。
  • 【人为和自然资源对大气甲烷变化的贡献。】 复制标题 收藏 收藏
    DOI:10.1038/nature05132 复制DOI
    作者列表:Bousquet P,Ciais P,Miller JB,Dlugokencky EJ,Hauglustaine DA,Prigent C,Van der Werf GR,Peylin P,Brunke EG,Carouge C,Langenfelds RL,Lathière J,Papa F,Ramonet M,Schmidt M,Steele LP,Tyler SC,White J
    BACKGROUND & AIMS: :Methane is an important greenhouse gas, and its atmospheric concentration has nearly tripled since pre-industrial times. The growth rate of atmospheric methane is determined by the balance between surface emissions and photochemical destruction by the hydroxyl radical, the major atmospheric oxidant. Remarkably, this growth rate has decreased markedly since the early 1990s, and the level of methane has remained relatively constant since 1999, leading to a downward revision of its projected influence on global temperatures. Large fluctuations in the growth rate of atmospheric methane are also observed from one year to the next, but their causes remain uncertain. Here we quantify the processes that controlled variations in methane emissions between 1984 and 2003 using an inversion model of atmospheric transport and chemistry. Our results indicate that wetland emissions dominated the inter-annual variability of methane sources, whereas fire emissions played a smaller role, except during the 1997-1998 El Niño event. These top-down estimates of changes in wetland and fire emissions are in good agreement with independent estimates based on remote sensing information and biogeochemical models. On longer timescales, our results show that the decrease in atmospheric methane growth during the 1990s was caused by a decline in anthropogenic emissions. Since 1999, however, they indicate that anthropogenic emissions of methane have risen again. The effect of this increase on the growth rate of atmospheric methane has been masked by a coincident decrease in wetland emissions, but atmospheric methane levels may increase in the near future if wetland emissions return to their mean 1990s levels.
    背景与目标: :甲烷是一种重要的温室气体,自工业化前以来,其大气浓度几乎增加了两倍。大气甲烷的增长率取决于表面排放与主要大气氧化剂羟基自由基对光化学的破坏之间的平衡。值得注意的是,自1990年代初以来,这一增长率已明显下降,而甲烷的水平自1999年以来一直保持相对稳定,从而导致其对全球气温的预计影响向下修正。从一年到下一年,大气中甲烷的增长率也出现了较大的波动,但其原因仍然不确定。在这里,我们使用大气传输和化学反演模型对控制1984年至2003年甲烷排放量变化的过程进行了量化。我们的结果表明,除1997-1998年厄尔尼诺事件外,甲烷排放源的年际变化主要是湿地排放,而火灾排放的作用较小。这些对湿地和火灾排放变化的自上而下的估算与基于遥感信息和生物地球化学模型的独立估算非常吻合。在更长的时间尺度上,我们的结果表明,1990年代期间大气甲烷增长的下降是由于人为排放量的下降引起的。但是,自1999年以来,它们表明人为排放的甲烷再次增加。湿地排放量的同时减少掩盖了这种增加对大气中甲烷增长率的影响,但是如果湿地排放量恢复到1990年代的平均水平,那么大气中的甲烷水平在不久的将来可能会增加。
  • 【天然搪瓷龋齿:生化容积的比较组织学研究。】 复制标题 收藏 收藏
    DOI:10.1159/000345378 复制DOI
    作者列表:Barbosa de Sousa F,Dias Soares J,Sampaio Vianna S
    BACKGROUND & AIMS: :This study aimed to test the hypothesis that organic volume is the main variable for explaining the optical properties and predictive degree of diffusion of enamel histological points at zones of natural enamel caries (NEC; surface layer, SL, n = 30, and body of the lesion, BL, n = 58) and normal enamel (NE, n = 131). Molars with either NEC or NE were quantitatively analyzed regarding the mineral, organic and water volumes (considered as effective pore volume), opacity (predicted in 94% of cases by water volume in NEC), and water volume more easily available for diffusion, αd (squared water volume divided by the nonmineral volume; related to permeability). NEC presented lower mineral volumes and higher organic volumes, effective pore volume and opacity than NE. External origin of organic volume in NEC was evidenced by an organic gradient decreasing from the surface inward (R2 = -0.7), which was not detected in teeth with NE only; αd values of the SL and NE were similar and both were lower (p < 0.0001) than that of the BL. Comparing the SL from both NEC and artificial enamel caries (AEC; published data; n = 71), with similar mineral volumes, against developing enamel (published data), AEC showed more effective pore volume (3 times higher), higher αd and opacity than NEC mainly due to differences in organic volumes. Our results reasonably matched widely known features of NEC histological zones, and confirmed the organic volume as the main variable for explaining optical properties and αd (related to permeability).
    背景与目标: :这项研究旨在检验以下假设:有机物体积是解释天然釉质龋齿(NEC;表面层,SL,n = 30,以及牙体)的光学特性和牙釉质组织学点扩散的预测程度的主要变量。病变,BL,n = 58)和正常牙釉质(NE,n = 131)。对具有NEC或NE的磨牙定量分析了矿物质,有机物和水的体积(视为有效孔体积),不透明度(由NEC中的水体积预测为94%的情况)以及更易于扩散的水体积αd (平方水量除以非矿物质量;与渗透率有关)。与NEC相比,NEC具有更低的矿物质量和更高的有机量,有效的孔隙率和不透明度。 NEC中有机物体积的外部来源通过从表面向内减小的有机梯度来证明(R2 = -0.7),仅在具有NE的牙齿中未检测到有机梯度。 SL和NE的αd值相似,均低于BL的(p <0.0001)。比较来自NEC和人造牙釉质的SL(AEC;已发表的数据; n = 71),具有相似的矿物质量,与发育中的牙釉质(已发表的数据)相比,AEC显示出更有效的孔体积(高3倍),更高的αd和不透明度比NEC主要是由于有机量的差异。我们的结果合理地匹配了NEC组织学区域的广为人知的特征,并确认了有机物体积是解释光学性质和αd(与渗透率有关)的主要变量。
  • 【提示导致的平滑追随加速度的速度缩放服从自然运动的约束。】 复制标题 收藏 收藏
    DOI:10.1007/s00221-007-0988-y 复制DOI
    作者列表:Ladda J,Eggert T,Glasauer S,Straube A
    BACKGROUND & AIMS: :Information about the future trajectory of a visual target is contained not only in the history of target motion but also in static visual cues, e.g., the street provides information about the car's future trajectory. For most natural moving targets, this information imposes strong constraints on the relation between velocity and acceleration which can be exploited by predictive smooth pursuit mechanisms. We questioned how cue-induced predictive changes in pursuit direction depend on target speed and how cue- and target-induced pursuit interact. Subjects pursued a target entering a +/-90 degrees curve and moving on either a homogeneous background or on a low contrast static band indicating the future trajectory. The cue induced a predictive change of pursuit direction, which occurred before curve onset of the target. The predictive velocity component orthogonal to the initial pursuit direction started later and became faster with increasing target velocity. The predictive eye acceleration increased quadratically with target velocity and was independent of the initial target direction. After curve onset, cue- and target-induced pursuit velocity components were not linearly superimposed. The quadratic increase of eye acceleration with target velocity is consistent with the natural velocity scaling implied by the two-thirds power law, which is a characteristic of biological controlled movements. Comparison with linear pursuit models reveals that the ratio between eye acceleration and actual or expected retinal slip cannot be considered a constant gain factor. To obey a natural velocity scaling, this acceleration gain must linearly increase with target or pursuit velocity. We suggest that gain control mechanisms, which affect target-induced changes of pursuit velocity, act similarly on predictive changes of pursuit induced by static visual cues.
    背景与目标: :关于视觉目标的未来轨迹的信息不仅包含在目标运动的历史中,而且还包含在静态视觉线索中,例如,街道提供有关汽车未来轨迹的信息。对于大多数自然运动目标,此信息对速度和加速度之间的关系施加了严格的约束,可以通过预测性平滑跟踪机制加以利用。我们质疑线索诱导的追踪方向预测性变化如何取决于目标速度以及线索与目标诱导的追踪之间如何相互作用。受试者追踪进入/ -90度曲线的目标,并在均质背景或指示未来轨迹的低对比度静态波段上移动。提示引起了追踪方向的预测性变化,该变化发生在目标曲线开始之前。与初始跟踪方向正交的预测速度分量开始较晚,并且随着目标速度的增加而变得更快。预测眼加速度随目标速度呈二次方增加,并且与初始目标方向无关。曲线开始后,提示和目标诱导的追击速度分量未线性叠加。眼球加速度随目标速度的二次增加与三分之二幂定律所暗示的自然速度定标一致,这是生物控制运动的特征。与线性追踪模型的比较表明,眼加速度与实际或预期的视网膜滑移之间的比率不能视为恒定的增益因子。为了服从自然速度比例,该加速度增益必须随目标速度或跟踪速度线性增加。我们建议增益控制机制,影响目标诱导的追踪速度变化,类似地作用于静态视觉提示所诱导的追踪预测变化。
  • 【我们对早产的自然结果了解多少?对早产无宫缩抑制剂的女性进行系统的回顾和荟萃分析。】 复制标题 收藏 收藏
    DOI:10.1111/ppe.12070 复制DOI
    作者列表:Hackney DN,Olson-Chen C,Thornburg LL
    BACKGROUND & AIMS: BACKGROUND:Current knowledge of the natural outcomes of untreated women in preterm labour is both incomplete and outcomes vary significantly between the available studies. The aim of this study was to systematically review outcomes of preterm labour without tocolysis and determine if outcome variation could be accounted for by differences in study populations. Such data could potentially assist in the interpretation of intervention trials that do not include a no-treatment arm. METHODS:Included studies reported outcomes of women in clinically diagnosed preterm labour without tocolytic treatment between 1950 and 2011. Studies that were limited to preterm prelabour rupture of membranes, recurrent preterm labour or in which the women without tocolysis represented a potentially biased subgroup, or were not tocolysed because of contraindications were excluded. Study quality, design, and population characteristics were abstracted. Outcomes included pregnancy prolongation and the proportion of women undelivered at 48-72 h, 7 days, and term. Study characteristics associated with differing odds of preterm birth were explored through logistic regression. RESULTS:Three hundred and eighty-five citations were initially identified, of which 26 were included encompassing 1383 women. The percentage of patients who were undelivered at 48-72 hours was 62.8%, at 7 days 53.4% and 40.4% delivered at term, though the range was very wide. Characteristics associated with decreased odds of delivery were not consistent among reported outcome measures. CONCLUSIONS:Most women without tocolysis do not deliver within 7 days, although the range is very wide. The majority of this variation is unrelated to reported differences in study design or reported population characteristics.
    背景与目标: 背景:目前对未接受治疗的早产妇女自然结局的了解还不完整,可用研究之间的结局差异很大。这项研究的目的是系统地审查无宫缩抑制剂的早产结局,并确定结果差异是否可以由研究人群的差异来解释。此类数据可能有助于解释不包括不治疗组的干预试验。
    方法:纳入的研究报告了1950年至2011年之间未经子宫溶栓治疗的临床诊断早产妇女的结局。研究仅限于胎膜早破,反复早产或未接受子宫溶解的妇女代表潜在的亚组,或因禁忌症而未接受治疗的人被排除在外。研究质量,设计和人口特征被抽象出来。结果包括妊娠延长和在48-72小时,7天和足月分娩时未分娩的妇女比例。通过逻辑回归研究了与早产几率不同相关的研究特征。
    结果:最初确定了385条被引用,其中26条被包括1383名女性。在48-72小时未分娩的患者百分比为62.8%,在7天时足月分娩的比例分别为53.4%和40.4%,尽管范围很广。在报告的结果指标中,与分娩几率降低相关的特征不一致。
    结论:尽管未溶栓的范围很广,但大多数妇女都不会在7天之内分娩。这种变化的大部分与研究设计的报告差异或报告的人群特征无关。
  • 【慢性HBV感染自然过程中不同免疫阶段的免疫特性。】 复制标题 收藏 收藏
    DOI:10.5754/hge12907 复制DOI
    作者列表:Ren YY,Liu YZ,Ding YP,Song G,Li SH,Wang GQ
    BACKGROUND & AIMS: BACKGROUND/AIMS:The hepatitis B virus (HBV) infection course is divided into 4 immune phases which were mainly characterized by clinical markers. We investigated the immune markers, especially inhibitory receptors, cytokine and chemokine expressions among the immune phases especially between immune tolerance (IT) phase and immune control (IC) phase. METHODOLOGY:Blood and serum samples of 64 patients and serum samples of 22 healthy controls were obtained. We used flow cytometric methods for measurements of PD-1, PD-L1 and flow fluorescence immunoassay for the serum cytokines and chemokines concentrations. IL-27 was measured by ELISA and the receptor IL-27R was detected too. RESULTS:The proportions of PD1 positive cells in CD4+, CD4+CD45RO+, and CD8+ T-cell subsets in IC phase were greater than in IC phase. The frequencies of PD1 expressions in CD8+pentamer+ and CD8+CD45RA-pentamer+ T cells were higher in IC phase than in IT and ICC phases. The serum concentration of IL-27 in IT group was higher than in IC, ICC and HC groups. Concentrations of cytokines TNF-α and IL-10 and chemokines RANTES, IL-8 and IP-10 were higher in HBV infected patients. CONCLUSIONS:The reduction of percentages of PD-1 positive cells may contribute to estimate entering the IC phase and decide the opportune moment to start antivirus therapy.
    背景与目标: 背景/目的:乙肝病毒(HBV)感染过程分为四个免疫阶段,主要以临床标志物为特征。我们调查了免疫阶段,尤其是免疫耐受(IT)阶段和免疫控制(IC)阶段之间的免疫标志物,特别是抑制性受体,细胞因子和趋化因子的表达。
    方法:获得64例患者的血液和血清样本以及22例健康对照者的血清样本。我们使用流式细胞仪方法测量PD-1,PD-L1,并使用流式荧光免疫法测定血清细胞因子和趋化因子的浓度。通过ELISA测量IL-27,并且也检测到受体IL-27R。
    结果:IC期CD4,CD4,CD45RO和CD8 T细胞亚群中PD1阳性细胞的比例大于IC期。 CD8五聚体和CD8 CD45RA-五聚体T细胞中PD1表达的频率在IC期高于IT和ICC期。 IT组的血清IL-27浓度高于IC,ICC和HC组。 HBV感染患者的细胞因子TNF-α和IL-10以及趋化因子RANTES,IL-8和IP-10的浓度较高。
    结论:PD-1阳性细胞百分比的降低可能有助于估计进入IC阶段并决定开始抗病毒治疗的时机。
  • 【压力和应对的社会模式:处于不利地位的社会地位会带来更大的压力和更少的应对资源吗?】 复制标题 收藏 收藏
    DOI:10.1016/j.socscimed.2008.03.012 复制DOI
    作者列表:Meyer IH,Schwartz S,Frost DM
    BACKGROUND & AIMS: :Despite its centrality to social stress theory, research on the social patterning of stress exposure and coping resources has been sparse and existing research shows conflicting results. We interviewed 396 gay, lesbian and bisexual, and 128 heterosexual people in New York City to examine variability in exposure to stress related to sexual orientation, gender, and race/ethnicity. Multiple linear regressions showed clear support for the social stress hypothesis with regard to race/ethnic minority status, somewhat mixed support with regard to sexual orientation, and no support with regard to gender. We discuss this lack of parsimony in social stress explanations for health disparities.
    背景与目标: :尽管它在社会压力理论中处于中心地位,但对压力暴露和应对资源的社会模式的研究却很少,现有研究显示出相互矛盾的结果。我们采访了纽约市396名男同性恋,女同性恋和双性恋者以及128位异性恋者,以研究他们暴露于与性取向,性别和种族/民族有关的压力中的变异性。多元线性回归显示出对种族/族裔少数群体地位的社会压力假说的明确支持,对性取向的支持有些混杂,而对性别的支持则没有。我们在针对健康差异的社会压力解释中讨论了缺乏简约性的问题。
  • 【PARP1自然多态性V762A和PARP1抑制剂减少的ADP-核糖基化作用增强了乙型肝炎病毒的复制。】 复制标题 收藏 收藏
    DOI:10.1111/jvh.12100 复制DOI
    作者列表:Ko HL,Ng HJ,Goh EH,Ren EC
    BACKGROUND & AIMS: :HepG2 and Huh7 cell lines are frequently used as models to study viral hepatitis and hepatocellular carcinoma. However, they exhibit significantly different capacities in their ability to support hepatitis B virus (HBV) replication. To investigate the basis for this, transcription factor-binding motifs at the HBV core promoter (HBVCP) were tested in luciferase reporter constructs to identify the possible role of host factors. Among the transcription factors screened: PARP1, SP1, HNF4α, HNF3, hB1F and HNF1, deletion of the PARP1 binding motif abrogated transcriptional activity at the HBVCP in HepG2 but not Huh7 cells. Sequencing of the PARP1 gene revealed that HepG2 cells carried an Ala762 allele which has low ADP-ribosylation activity, which was shown to have increased PARP1 binding affinity to its cognate motif thus resulting in higher transcriptional activity. PARP1 inhibitors that are being developed as broad cancer therapeutics also target PARP1 ADP-ribosylation enzymatic function. Four PARP1 inhibitors: PJ-34, ABT888, AZD2281 and AG014699 were tested for their effect on HBV replication. All four small molecules effectively enhanced HBV replication in vitro, confirming the role of PARP1 in HBV replication and that alteration of ADP-ribosylation by mutation or drugs can affect HBV replication. Our data demonstrate that natural polymorphisms in the host affecting proteins such as PARP1 can have a significant effect on HBV replication. Hence, patients who are infected with HBV and are on clinical trials involving PARP1 inhibitors may be at risk from unintended side-effects such as exacerbation of HBV replication.
    背景与目标: :HepG2和Huh7细胞系经常用作研究病毒性肝炎和肝细胞癌的模型。但是,它们在支持乙型肝炎病毒(HBV)复制的能力上表现出明显不同的能力。为了研究其基础,在萤光素酶报告基因构建物中测试了HBV核心启动子(HBVCP)上的转录因子结合基序,以确定宿主因子的可能作用。在筛选的转录因子中:PARP1,SP1,HNF4α,HNF3,hB1F和HNF1,PARP1结合基序的缺失废除了HepG2细胞中HBVCP的转录活性,而没有废除Huh7细胞中的转录活性。 PARP1基因的测序表明,HepG2细胞带有一个Ala762等位基因,该等位基因的ADP-核糖基化活性较低,这表明PARP1与其关联基序的结合亲和力增强,从而导致更高的转录活性。被开发为广泛的癌症治疗剂的PARP1抑制剂也靶向PARP1 ADP-核糖基化酶功能。测试了四种PARP1抑制剂:PJ-34,ABT888,AZD2281和AG0​​14699对HBV复制的影响。所有这四个小分子在体外均有效地增强了HBV复制,这证实了PARP1在HBV复制中的作用,以及通过突变或药物改变ADP-核糖基化可以影响HBV复制。我们的数据表明,宿主中影响蛋白(例如PARP1)的天然多态性可能对HBV复制产生重大影响。因此,被HBV感染并正在接受PARP1抑制剂临床试验的患者可能有意料之外的副作用,例如加剧HBV复制的危险。
  • 【在阿尔茨海默氏病病例中,痴呆症的行为和心理症状已通过自然药物成功治疗:与促性腺激素有关。】 复制标题 收藏 收藏
    DOI:10.1111/psyg.12010 复制DOI
    作者列表:Niitsu T,Okamoto H,Iyo M
    BACKGROUND & AIMS: :Pharmacotherapies for the behavioural and psychological symptoms of dementia are limited; novel agents for the symptoms are still needed. Herein, we report the case of an 80-year-old male patient with Alzheimer's disease whose severe agitation, insomnia and sexual delusions were successfully treated with a traditional natural Japanese (Kampo) medicine, keishi-ka-ryukotsu-borei-to. We found that administrating keishi-ka-ryukotsu-borei-to increased his serum luteinizing hormone level, which could be inversely associated with his behavioural and psychological symptoms. This report suggests that keishi-ka-ryukotsu-borei-to is a possible alternative treatment for the behavioural and psychological symptoms of dementia, especially sexual delusions.
    背景与目标: :痴呆症的行为和心理症状的药物治疗有限;仍然需要用于症状的新型药物。在此,我们报告了一名80岁的老年痴呆症男性患者的病例,该患者患有严重的躁动,失眠和性妄想,已成功使用传统的日本天然药物(Kampo)keishi-ka-ryukotsu-borei-to治疗。我们发现,服用keishi-ka-ryukotsu-borei-可以提高他的血清黄体生成素水平,这可能与他的行为和心理症状呈负相关。该报告表明,keishi-ka-ryukotsu-borei-to是痴呆症(尤其是性妄想)的行为和心理症状的可能替代疗法。

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