Long-Term Survival Rates after Resection for Locally Advanced Kidney Cancer: Memorial Sloan Kettering Cancer Center 1989 to 2012 Experience

Purpose: We analyzed the 23-year Memorial Sloan Kettering Cancer Center experience with surgical resection, and concurrent adrenalectomy and lymphadenectomy for locally advanced nonmetastatic renal cell carcinoma. Materials and Methods: We retrospectively reviewed the records of 802 patients who underwent nephrectomy with or without concurrent adrenalectomy or lymphadenectomy for locally advanced renal cell carcinoma, defined as stage T3 or greater and M0. Patients who received adjuvant treatment within 3 months of surgery or had fewer than 3 months of followup or bilateral renal masses at presentation were excluded from analysis. Five and 10-year progression-free and overall survival was estimated by the Kaplan-Meier method. Differences between groups were analyzed by the log rank test. Results: A total of 596 (74%) and 206 patients (26%) underwent radical and partial nephrectomy, respectively. Renal cell carcinoma progressed in 189 patients and 104 died of the disease. Median followup in patients without progression was 4.6 years. Symptoms at presentation, ASA (R) classification, tumor stage, histological subtype, grade and lymph node status were significantly associated with progression-free and overall survival. On multivariate analysis adrenalectomy use decreased with time but lymphadenectomy use increased (OR 0.82 vs 1.16 per year). Larger tumors were associated with a higher likelihood of concurrent adrenalectomy and lymphadenectomy. Conclusions: In our series of patients with locally advanced nonmetastatic renal cell carcinoma survival was favorable in those in good health who were asymptomatic at presentation with T3 tumors and negative lymph nodes. Further, there has been a trend toward more selective use of adrenalectomy and increased use of lymphadenectomy

Rapid Induction of Tumor-specific Type 1 T Helper Cells in Metastatic Melanoma Patients by Vaccination with Mature, Cryopreserved, Peptide-loaded Monocyte-derived Dendritic Cells

There is consensus that an optimized cancer vaccine will have to induce not only CD8+ cytotoxic but also CD4+ T helper (Th) cells, particularly interferon (IFN)-γ–producing, type 1 Th cells. The induction of strong, ex vivo detectable type 1 Th cell responses has not been reported to date. We demonstrate now that the subcutaneous injection of cryopreserved, mature, antigen-loaded, monocyte-derived dendritic cells (DCs) rapidly induces unequivocal Th1 responses (ex vivo detectable IFN-γ–producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II–restricted tumor peptides (melanoma-antigen [Mage]-3.DP4 and Mage-3.DR13) in the majority of 16 evaluable patients with metastatic melanoma. These Th1 cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4–specific Th1 cells IFN-γ was released even after direct recognition of viable, Mage-3–expressing HLA-DP4+ melanoma cells. The capacity of DCs to rapidly induce Th1 cells should be valuable to evaluate whether Th1 cells are instrumental in targeting human cancer and chronic infections

Comparing Open Radical Cystectomy and Robot-assisted Laparoscopic Radical Cystectomy: A Randomized Clinical Trial

Background: Open radical cystectomy (ORC) and urinary diversion in patients with bladder cancer (BCa) are associated with significant perioperative complication risk. Objective: To compare perioperative complications between robot-assisted radical cystectomy (RARC) and ORC techniques. Design, setting, and participants: A prospective randomized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy (RC), pelvic lymph node dissection (PLND), and urinary diversion. Patients were randomized to ORC/PLND or RARC/PLND, both with open urinary diversion. Patients were followed for 90 d postoperatively. Intervention: Standard ORC or RARC with PLND; all urinary diversions were performed via an open approach. Outcome measurements and statistical analysis: Primary outcomes were overall 90-d grade 2-5 complications defined by a modified Clavien system. Secondary outcomes included comparison of high-grade complications, estimated blood loss, operative time, pathologic outcomes, 3-and 6-mo patient-reported quality-of-life (QOL) outcomes, and total operative room and inpatient costs. Differences in binary outcomes were assessed with the chi-square test, with differences in continuous outcomes assessed by analysis of covariance with randomization group as covariate and, for QOL end points, baseline score. Results and limitations: The trial enrolled 124 patients, of whom 118 were randomized and underwent RC/PLND. Sixty were randomized to RARC and 58 to ORC. At 90 d, grade 2-5 complications were observed in 62% and 66% of RARC and ORC patients, respectively (95% confidence interval for difference, -21% to -13%; p = 0.7). The similar rates of grade 2-5 complications at our mandated interim analysis met futility criteria; thus, early closure of the trial occurred. The RARC group had lower mean intraoperative blood loss (p = 0.027) but significantly longer operative time than the ORC group (p \u3c 0.001). Pathologic variables including positive surgical margins and lymph node yields were similar. Mean hospital stay was 8 d in both arms (standard deviation, 3 and 5 d, respectively; p = 0.5). Three-and 6-mo QOL outcomes were similar between arms. Cost analysis demonstrated an advantage to ORC compared with RARC. A limitation is the setting at a single high-volume, referral center; our findings may not be generalizable to all settings. Conclusions: This trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing RC/PLND and urinary diversion. Similar 90-d complication rates, hospital stay, pathologic outcomes, and 3-and 6-mo QOL outcomes were observed regardless of surgical technique. Patient summary: Of 118 patients with bladder cancer who underwent radical cystectomy, pelvic lymph node dissection, and urinary diversion, half were randomized to open surgery and half to robot-assisted laparoscopic surgery. We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups. Trial Registration: ClinicalTrials. gov identifier NCT01076387, www.clinicaltrials.gov. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved

Laser-assisted collision effect on nonsequential double ionization of helium in a few-cycle laser pulse

Nonsequential double ionization (NSDI) of helium in an intense few-cycle laser pulse is investigated by applying the three-dimensional semi-classical re-scattering method. It is found that the momentum distribution of He$^{2+}$ shows a single-double-single peak structure as the pulse intensity increases. According to the different mechanisms dominating the NSDI process, the laser intensity can be classified into three regimes where the momentum distribution of He$^{2+}$ exhibits different characteristics. In the relatively high intensity regime, an NSDI mechanism named the "laser-assisted collision ionization" is found to be dominating the NSDI process and causing the single peak structure. This result can shed light on the study of non-sequential ionization of a highly charged ion in a relatively intense laser pulse

Eastern philosophies of education : Buddhist, Hindu, Daoist, and Confucian readings of Plato’s cave

This chapter provides readers with an understanding of some basic principles of selected Eastern traditions and their relation to philosophy of education. The attempt to characterize such diverse traditions and understandings of education raises numerous hermeneutical issues which can only be addressed through a pedagogical reduction as a vehicle for understanding. In this case, we have employed Plato’s cave allegory as that methodological and pedagogical vehicle. We explore aspects of the ontology, epistemology, and ethics of Buddhist, Hindu (focused on classical yoga), Daoist, and Confucian traditions, interpreting elements from Plato’s allegory in order to throw light onto the educational ideas and implications of those Eastern traditions

Numerical Investigation into the Effect of Splats and Pores on the Thermal Fracture of Air Plasma-Sprayed Thermal Barrier Coatings

The effect of splat interfaces on the fracture behavior of air plasma-sprayed thermal barrier coatings (APS-TBC) is analyzed using finite element modeling involving cohesive elements. A multiscale approach is adopted in which the explicitly resolved top coat microstructural features are embedded in a larger domain. Within the computational cell, splat interfaces are modeled as being located on a sinusoidal interface in combination with a random distribution of pores. Parametric studies are conducted for different splat interface waviness, spacing, pore volume fraction and fracture properties of the splat interface. The results are quantified in terms of crack nucleation temperature and total microcrack length. It is found that the amount of cracking in TBCs actually decreases with increased porosity up to a critical volume fraction. In contrast, the presence of splats is always detrimental to the TBC performance. This detrimental effect is reduced for the splat interfaces with high waviness and spacing compared to those with low waviness and spacing. The crack initiation temperature was found to be linearly dependent on the normal fracture properties of the splat interface. Insights derived from the numerical results aid in engineering the microstructure of practical TBC systems for improved resistance against thermal fracture

Non-specific low back pain in primary care in the Spanish National Health Service: a prospective study on clinical outcomes and determinants of management

BACKGROUND: The Spanish National Health Service is a universal and free health care system. Non-specific low back pain (LBP) is a prevalent disorder, generating large health and social costs. The objectives of this study were to describe its management in primary care, to assess patient characteristics that influence physicians' decisions, and to describe clinical outcome at 2 months. METHODS: A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians (out of 361 – 20.8%) working in 40 primary care centers in 10 of the 17 administrative regions in Spain, covering 693,026 out of the 40,499,792 inhabitants. Patients were assessed on the day they were recruited, and prospectively followed-up 14 and 60 days later. The principal patient characteristics that were analyzed were: sex, duration of the episode, history of LBP, working status, severity of LBP, leg pain and disability, and results of straight leg raising test. Descriptors of management were: performance of the straight leg raising test, ordering of diagnostic procedures, prescription of drug treatment, referral to physical therapy, rehabilitation or surgery, and granting of sick leave. Regression analysis was used to analyze the relationship between patients' baseline characteristics and physicians' management decisions. Only workers were included in the models on sick leave. RESULTS: Mean age (SD) of included patients was 46.5 (15.5) years, 367 (56.6%) were workers, and 338 (52.5%) were females. Median (25th–75th interquartile range) duration of pain when entering the study was 4 (2–10) days and only 28 patients (4.3%) had chronic low back pain. Diagnostic studies included plain radiographs in 43.1% of patients and CT or MRI scans in 18.8%. Drug medication was prescribed to 91.7% of patients, 19.1% were sent to physical therapy or rehabilitation, and 9.6% were referred to surgery. The main determinants of the clinical management were duration of the episode and, to a lesser extent, the intensity of the pain (especially leg pain), a positive straight leg raising test, and degree of disability. The main determinant of sick leave was the degree of disability, followed by the characteristics of the labor contract and the intensity of leg pain (but not low back pain). After at least 2 months of treatment, 37% of patients were still in pain and approximately 10% of patients had not improved or had worsened. CONCLUSION: Although the use of X-Rays is high, determinants of physicians' management of LBP in primary care made clinical sense and were consistent with patterns suggested by evidence-based recommendations. However, after 2 months of treatment more than one third of patients continued to have back pain and about 10% had worsened

The Intensity of IUGR-Induced Transcriptome Deregulations Is Inversely Correlated with the Onset of Organ Function in a Rat Model

A low-protein diet applied during pregnancy in the rat results in intrauterine growth restricted (IUGR) fetuses. In humans, IUGR is associated with increased perinatal morbidity, higher incidence of neuro-developmental defects and increased risk of adult metabolic anomalies, such as diabetes and cardiovascular disease. Development and function of many organs are affected by environmental conditions such as those inducing fetal and early postnatal growth restriction. This phenomenon, termed “fetal programming” has been studied unconnectedly in some organs, but very few studies (if any) have investigated at the same time several organs, on a more comparative basis. However, it is quite probable that IUGR affects differentially most organ systems, with possible persistent changes in gene expression. In this study we address transcriptional alterations induced by IUGR in a multi-organ perspective, by systematic analysis of 20-days rat fetuses. We show that (1) expressional alterations are apparently stronger in organs functioning late in foetal or postnatal life than in organs that are functioning early (2) hierarchical classification of the deregulations put together kidney and placenta in one cluster, liver, lungs and heart in another; (3) the epigenetic machinery is set up especially in the placenta, while its alterations are rather mild in other organs; (4) the genes appear deregulated in chromosome clusters; (5) the altered expression cascades varies from organ to organ, with noticeably a very significant modification of the complement and coagulation cascades in the kidney; (6) we found a significant increase in TF binding site for HNF4 proteins specifically for liver genes that are down-regulated in IUGR, suggesting that this decrease is achieved through the action of HNF transcription factors, that are themselves transcriptionnally induced in the liver by IUGR (x 1.84 fold). Altogether, our study suggests that a combination of tissue-specific mechanisms contributes to bring about tissue-driven modifications of gene cascades. The question of these cascades being activated to adapt the organ to harsh environmental condition, or as an endpoint consequence is still raised