Three-dimensional assessment of MR imaging-guided percutaneous cryotherapy using multi-performer repeated segmentations: the value of supervised learning

RATIONALE AND OBJECTIVES: Accurate and reproducible segmentations of two-dimensional images are an important prerequisite for assessing tumor ablations three dimensionally (3D). We evaluated whether supervised learning methods would improve multiperformer repeated segmentations of magnetic resonance images (MRI) obtained before and after MRI-guided cryotherapy of renal cell carcinoma. MATERIALS AND METHODS: Three medical students independently performed five manual segmentations of a biopsy-proven renal cell carcinoma that was treated with percutaneous MRI-guided cryotherapy. Using pretreatment (T2-weighted fast recovery fast spin echo [FRFSE]) and posttreatment (T1-weighted, fat-suppressed, dynamically enhanced) MRIs, regions of tumor cryonecrosis were segmented. The same tasks were repeated after an experienced abdominal radiologist provided supervised learning. Segmentation sensitivity was compared with an estimated 3D-ground truth via voxel counts for regions of tumor, both before and after treatment, and for the regions of cryonecrosis. The sensitivity of each repeated segmentation was compared against the estimated ground truth using sensitivity, overlap index, and volume (mL). RESULTS: Supervised learning significantly improved posttreatment segmentation sensitivity (P = .03). With supervised learning, the ranges of the performance metrics over the segmentation performers were: pretreated tumor, sensitivity 0.902-0.999, overlap index 0.935-0.961, and volume 19.15-23.71 mL; posttreated tumor, sensitivity 0.923-0.991, overlap index 0.952-0.981, and volume 20.67-22.70 mL; in the ablation zone, sensitivity 0.938-0.969, overlap index 0.940-0.962, and volume 31.79-32.36 mL. CONCLUSIONS: Supervised learning improved multiperformer repeated segmentations of MRIs obtained before and after MRI-guided percutaneous cryotherapy of renal cell carcinoma. These methods may prove useful in aiding the 3D assessment of percutaneous tumor ablations.     

Differential effects of aging and insulin-like growth factor-1 on synapses in CA1 of rat hippocampus

Aging-related impairments of learning and memory can be ameliorated by 28 days of intracerebroventricular (icv) infusion of insulin-like growth factor-1 (IGF-1) in old rats. The present study investigated whether there is an aging-related synaptic decline in the stratum radiatum of hippocampal CA1 and whether IGF-1 can ameliorate that decline. Five young (4 months), five middle-aged (18 months) and five old (29 months) Fischer 344xBrown Norway rats received saline infusion; five old (29 months) rats received IGF-1 infusion for 28 days preceding sacrifice. Pyramidal neurons, total synaptic profiles as well as synaptic profiles in multiple spine bouton (MSB) complexes in CA1 were quantified stereologically with the physical disector technique and the postsynaptic density (PSD) length was determined as well. The results indicated a decrease of total synapses between middle and old age but a maintenance of PSD length and MSB synapses throughout life. IGF-1 infusion in old rats did not reverse the aging-related decline in total synapses but did increase PSD length and the number of MSB synapses. These changes in synaptic configurations are morphological correlates of enhanced synaptic efficacy. Thus, aging and IGF-1 affect different, but complementary, aspects of synapses in hippocampal CA1.     

Anterior urethral injuries.

Seventeen patients are reviewed who presented at the Birmingham Accident Hospital over a 20-year period with injuries to the anterior urethra. Fourteen of the injuries resulted from isolated direct blows to the perineum, while 3 were associated with multiple injuries. The clinical features and management of these patients are discussed in conjunction with a review of the relevant literature. A protocol for the management of this type of injury is outlined.     

A statistical model for high-resolution mapping of quantitative trait loci determining HIV dynamics

Are there specific genes that control the pathogenesis of HIV infection? This question, which is of fundamental importance in designing personalized strategies of gene therapy to control HIV infection, can be examined by genetic mapping approaches. In this article, we present a new statistical model for unravelling the genetic mechanisms for the dynamic change of HIV that causes AIDS by marker‐based linkage disequilibrium (LD) analyses. This new model is the extension of our functional mapping theory to integrate viral load trajectories within a genetic mapping framework. Earlier studies of HIV dynamics have led to various mathematical functions for modelling the kinetic curves of plasma virions and CD4 lymphocytes in HIV patients. Through incorporating these functions into the LD‐based mapping procedure, we can identify and map individual quantitative trait loci (or QTL) responsible for viral pathogenesis. We derive a closed‐form solution for estimating QTL allele frequency and marker‐QTL linkage disequilibrium in the context of EM algorithm and implement the simplex algorithm to estimate the mathematical parameters describing the curve shapes of HIV pathogenesis. We performed different simulation scenarios based on currently used clinical designs in AIDS/HIV research to illustrate the utility and power of our model for genetic mapping of HIV dynamics. The implications of our model for genetic and genomic research into AIDS pathogenesis are discussed. Copyright © 2004 John Wiley & Sons, Ltd.     

Effect of treatment sequence with radiotherapy and the antiestrogen EM 800 on the growth of ZR 75 1 human mammary carcinoma in nude mice

We demonstrated previously that continuous administration of EM-800, a SERM having pure antiestrogenic activity in the mammary gland and endometrium in combination with monthly radiotherapy caused a greater inhibition of human ZR 75 1 tumor growth in nude mice than either therapy used alone. To further optimize therapy, we have now examined the effect of various treatment sequences to determine the optimal treatment regimen in the same model. EM 800 was given at the maximally effective oral dose of 300 microg daily. External beam radiation therapy (RTX) was carried out (2 Gy/tumor/day, 5 days per week for 3 weeks) for a total of 30 Gy/tumor delivered directly to the tumor while shielding the rest of the animal body. There was no evidence of RTX-related morbidity. Continuous treatment with EM 800 was initiated either 3 weeks before or at the same time as RTX, immediately after RTX, or 3 weeks before and immediately after RTX. After 156 days of treatment, EM 800 alone caused a 75% decrease in average tumor area, an effect equivalent to that achieved by ovariectomy. RTX alone, on the other hand, caused a transient 30% decrease in tumor area regardless of treatment sequence, whereas combined treatment with EM 800 and RTX was superior to either treatment alone. Combined treatment with EM 800 and RTX both started on Day 1 caused the greatest (88%), most rapid (50% in 2 weeks) and sustained decrease in tumor size. The present data indicate that optimal reduction in breast tumor size is achieved by continuous administration of EM 800 and RTX started simultaneously on Day 1.     

白花蛇舌草LC—MS指纹图谱的研究

目的：建立白花蛇舌草的LC—MS指纹图谱。方法：采用LC—MS法，检测不同产地同一季节采收的10批样品色谱特征，与此同时和黄毛耳草（两者都属于茜草科耳草属植物）进行比较。结果：建立白花蛇舌草指纹图谱。结论：LC—MS指纹图谱具有特异性，可以评价和全面控制白花蛇舌草质量。     

Estimating causal contrasts involving intermediate variables in the presence of selection bias

An important goal across the biomedical and social sciences is the quantification of the role of intermediate factors in explaining how an exposure exerts an effect on an outcome. Selection bias has the potential to severely undermine the validity of inferences on direct and indirect causal effects in observational as well as in randomized studies. The phenomenon of selection may arise through several mechanisms, and we here focus on instances of missing data. We study the sign and magnitude of selection bias in the estimates of direct and indirect effects when data on any of the factors involved in the analysis is either missing at random or not missing at random. Under some simplifying assumptions, the bias formulae can lead to nonparametric sensitivity analyses. These sensitivity analyses can be applied to causal effects on the risk difference and risk‐ratio scales irrespectively of the estimation approach employed. To incorporate parametric assumptions, we also develop a sensitivity analysis for selection bias in mediation analysis in the spirit of the expectation–maximization algorithm. The approaches are applied to data from a health disparities study investigating the role of stage at diagnosis on racial disparities in colorectal cancer survival. Copyright © 2016 John Wiley & Sons, Ltd.     

小蓟水提液对4种癌细胞生长抑制作用的研究

目的:研究小蓟水提液对癌细胞生长的抑制作用。方法:细胞形态观察、活细胞计数法和克隆形成率法研究小蓟水提液对人白血病细胞K562、肝癌细胞HepG2、宫颈癌细胞Hela、胃癌细胞BGC823生长的抑制作用。结果:小蓟水提液可使4种癌细胞形态上发生皱缩、变圆、脱壁、裂碎等变化,生长受到明显抑制,抑制率最高可达86.03%。结论:小蓟有确切的抑癌作用。     

Is there protective haplotype of dysbindin gene (DTNBP1) 3 polymorphisms for major depressive disorder

Dysbindin gene has been repeatedly associated with psychiatric disorders and schizophrenia in particular. This study aimed to investigate the variants of dysbindin gene in major depressive disorder (MDD). One hundred and eighty eight patients with MDD and 350 controls were investigated for 4 variants within the dysbindin gene (rs3213207 A/G, rs1011313 C/T, rs760761 C/T, and rs2619522 A/C). Haplotype analyses revealed a significant association with MDD (p=0.0007, protective A-C-T-A and A-C-C-C haplotypes), in particular the effect was due to the rs760761 (C/T) and rs2619522 (A/C) haplotype (p=0.000026). These results suggest a protective effect of some dysbindin gene haplotypes on the development of MDD. Coupled with previous findings on schizophrenia, our finding suggests that dysbindin gene variants may have a role in the susceptibility to MDD. Adequately powered further studies in different ethnic groups are warranted.     

胎鼠MEE细胞与腭裂发生关系的组织学研究

为探讨ＭＥＥ细胞与腭裂发生的关系，对１８４例ＮＩＨ胎鼠腭器官发生期不同阶段的头颅标本进行了组织胚胎学研究。结果表明，两组ＭＥＥ细胞于胎龄１４（１８）ｄ（ｈ）的标本中开始出现差异，正常组ＭＥＥ细胞逐渐由二层变为一层；给药组ＭＥＥ细胞有３种存在形式：①二层细胞；②假复层纤毛柱状上皮；③复层扁平鳞状上皮。１５（０）～１６（１８）ｄ（ｈ），正常组两腭突基底层ＭＥＥ细胞逐渐接触融合，最后中胚层组织也接触融合，ＭＥＥ细胞消失；给药组的腭裂标本ＭＥＥ细胞转归为口腔上皮。证明ＭＥＥ细胞的异常转归可导致腭裂畸形