Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved survival of children with neuroblastoma between 1979 and 2005: a report of the Italian Neuroblastoma Registry.

PURPOSE To describe treatment, clinical course, and survival of a cohort of Italian patients with neuroblastoma. PATIENTS AND METHODS The study includes data from 2,216 children (age 0 to 14 years) diagnosed between 1979 and 2005. Overall survival (OS) was analyzed by clinical and biologic features at presentation and periods of diagnosis: 1979 to 1984, 1985 to 1991, 1992 to 1998, and 1999 to 2005. The relative risk of second malignant neoplasm (SMN) was assessed by the standardized incidence ratio (SIR), with the Italian population selected as referent. RESULTS Yearly patient accrual increased over time from 58 to 102. Patients age 0 to 17 months represented 45.6% of the total population, and their incidence increased over time from 36.5% to 48.5%. The incidence of stage 1 patients increased over time from 5.8% to 23.2%. A total of 898 patients (40.5%) developed disease progression or relapse, 19 patients developed SMN, and two patients developed myelodysplasia. The cumulative risk of SMN at 20 years was 7.1%, for an SIR of 8.4 (95% CI, 5.1 to 13.2). A total of 858 patients (39%) died (779 of disease, 71 of toxicity, six of SMN, and two of tumor-unrelated surgical complications). Ten-year OS was 55.3% (95% CI, 53.0% to 57.6%) and increased over time from 34.9% to 65.0%; it was significantly better for females and patients age 0 to 17 months at diagnosis, with extra-abdominal primary, and stage 1 and 2 disease. OS improved significantly over time in stage 1 and 3 patients. In patients with stage 4 disease, the improvement occurred between the first and second time cohorts (6.7% v 23.5%), but not afterward. CONCLUSION The outcome of children with neuroblastoma has progressively improved. Long-term survivors bear a significant risk of SMN.
Epigenetic regulation of the endothelial nitric oxide synthase gene in persistent pulmonary hypertension of the newborn rat

Objective Persistent pulmonary hypertension of the newborn (PPHN) is a major clinical problem. Nitric oxide produced by endothelial nitric oxide synthase (eNOS) in endothelial cells plays an important role in the pathogenesis of PPHN. The eNOS expression in endothelial cells is controlled by epigenetic regulation. The aim of this study was to investigate the epigenetic regulatory mechanisms of the eNOS gene in PPHN. Methods The rat model of PPHN was induced by hypoxia and indomethacin. Pulmonary vascular endothelial cells were isolated from the fetal rat lungs by magnetic-activated cell sorting. Chromatin immunoprecipitation and bisulfite sequencing methods were used to analyze epigenetic regulation. Results The levels of acetylated histone H3 and acetylated histone H4 at the proximal promoter of the eNOS gene in pulmonary vascular endothelial cells from PPHN were significantly higher than those from the control group (P < 0.01, respectively). Total methylation percentage of the eNOS gene promoter in PPHN rat was slightly lower than that of control, but there was no statistically significant difference between the two groups (24.7 ± 2.0 vs. 27.3 ± 2.3%, P = 0.408). These changes of epigenetic modifications at the eNOS gene promoter were consistent with increased levels of eNOS mRNA and protein in PPHN. Conclusion The increased expression of eNOS in PPHN was associated with epigenetic regulation.
Pharmacology and Force Development of Single Freshly Isolated Bovine Carotid Artery Smooth Muscle Cells

Most studies of mammalian vascular smooth muscle cell mechanics and pharmacology have relied upon data from intact tissue preparations. The purpose of this study was to determine how single mammalian vascular smooth muscle cell pharmacological sensitivity to histamine and force development compared to the intact tissue from which it was derived. Thus, techniques were developed for isolating large numbers (5 × 105 cells/ml) of cells from bovine carotid arteries. Single cells were spindle-shaped with dimensions of 117 ± 11 (SE) μm in length by 7 ± 11 (SE) μm in diameter (n = 27). The effect of histamine concentration on cell length was studied in suspensions of freshly isolated cells. Histamine concentration-response curves revealed that single smooth muscle cells shortened to histamine concentrations in a graded fashion, and that shortening was mediated through histamine HI receptors. The threshold for 10% of maximum response occurred at 8.0 × 10−11 M histamine. This threshold was at least three orders of magnitude lower than the threshold for 10% of maximum tension in the intact tissue under isometric conditions. In addition to cellular pharmacology, mechanical studies were performed by tying a single cell to an ultrasensitive force transducer. Active stresses of 0.5 ± 0.1 × 105 N/m2 (n = 4) were measured in response to electrical stimulation for cells in low extracellular calcium (0.5 mM). These data suggest that histamine sensitivity and smooth muscle cell mechanics may best be determined in single cell studies that minimize diffusional barriers to agonist and avoid intercellular interactions that are present in the intact tissue.
Modelling seasonality in residential water demand: the case of Tunisia

This article proposes to model seasonal patterns of residential water demand using the techniques of seasonal integration and cointegration. The methodology is applied to quarterly aggregate time series data for Tunisia (1980–2007), applying the same increasing, multi-step pricing scheme in the whole country. First, a seasonal cointegration analysis demonstrates the relevance of a pricing policy that increases the size of the lower consumption block in summer. Second, the nonseasonal cointegration analysis reveals a relatively high price elasticity for the highest consumption block. Therefore, we also propose to increase the tariff progressivity to promote water savings. This modified pricing scheme will help to achieve goals of environmental protection and social equity.
Properties of human spinal interneurones: normal and dystonic control

The muscles that control wrist posture receive large inputs from reflexes driven by hand afferents. In several studies, we have investigated these reflexes by electrical stimulation of cutaneous (median nerve) and proprioceptive (ulnar nerve) afferents from the hand. Median stimulation produced short latency inhibition in all motor nuclei investigated, possibly through inhibitory propriospinal‐like interneurones. Ulnar stimulation produced similar inhibition but only in wrist extensors. In the other motor nuclei, ulnar stimulation produced short latency excitation mediated by group I motoneuronal drive through both monosynaptic and non‐monosynaptic pathways involving excitatory propriospinal‐like interneurones. This was followed by late excitations mediated through spinal group II and trans‐cortical group I pathways. These results show that these pathways are concerned with the integration of afferent inputs, proprioceptive and cutaneous, to control of wrist posture during hand movements. Patients with focal hand dystonia exhibit abnormal postures. To investigate whether these spinal pathways contribute to these conditions, the effects of ulnar stimulation on wrist muscle activity during voluntary tonic contraction were examined in patients who suffer writer's cramp. Ulnar‐induced inhibition of the wrist extensors was reduced on the dystonic side of patients compared with their normal side and controls. In patients who exhibited abnormal wrist posture, group II excitation of the wrist flexors was also modified on the dystonic side. Cutaneous stimuli, by contrast, increased wrist flexor EMG on both sides and only in patients who exhibited normal posture. We conclude that spinal interneurones have a significant role in integrating afferent inputs from the hand to control wrist posture during hand movements and that altered function in these spinal networks is associated with the complex pathophysiology of writer's cramp.
Clinical impact of new prostate-specific antigen WHO standardization on biopsy rates and cancer detection.

BACKGROUND Clinicians may be unaware that replacement of the historical total prostate-specific antigen (tPSA) standard with the WHO 96/670 international standard leads to difficulties in interpreting tPSA results. Our aim was to investigate the relationship between the Hybritech and WHO calibrations of the Beckman Coulter tPSA assay, and to assess the impact on prostate cancer (PCa) detection. METHODS tPSA concentrations were measured in 106 serum samples with both Hybritech and WHO calibrations. The established relationships were used for an in silico experiment with a cohort of 5865 men. Differences in prostate biopsy rates, PCa detection, and characteristics of missed cancers were calculated at biopsy thresholds of 3.0 and 4.0 microg/L. RESULTS A linear relationship was observed between the 2 calibrations, with a 20.3% decrease in tPSA values with the WHO standard compared with the Hybritech calibration. Applying the WHO calibration to the cohort of 5865 men yielded a 20% or 19% decrease in prostate biopsies and a 19% or 20% decrease in detected cancers compared with the Hybritech calibration, at a cutoff for biopsy of 3.0 or 4.0 microg/L, respectively. The decrease in detected cancers declined to 9% or 11% if an abnormal result in a digital rectal examination or a transrectal ultrasound evaluation was used as trigger for prostate biopsy (cutoff of 3.0 or 4.0 microg/L, respectively). CONCLUSIONS Application of the WHO standard for tPSA assays with commonly used tPSA thresholds leads to a significant decrease in PCa detection. Careful assessment of the relationship between the WHO standard and the thresholds used for prostate biopsy is hence necessary.
On the Pricing of Options in Incomplete Markets

In this paper we reconsider the pricing of options in incomplete continuous time markets.We first discuss option pricing with idiosyncratic stochastic volatility.This leads, of course, to an averaged Black-Scholes price formula.Our proof of this result uses a new formalization of idiosyncraticy which encapsulates other definitions in the literature.Our method of proof is subsequently generalized to other forms of incompleteness and systematic (i.e. non-idiosyncratic) information.Generally this leads to an option pricing formula which can be expressed as the average of a complete markets formula.
Are there Ethnic Enclaves/Ghettos in English Cities?

The residential segregation of ethnic groups in urban areas remains an issue of importance for policy-making in multicultural societies, such as England's, with levels of segregation frequently linked to questions of social exclusion and equal treatment. But how segregated are ethnic groups in England? Most studies answer this question using single indices which address one aspect only of a multidimensional concept. In this paper, an alternative approach is used which identifies residential area types according to the degree of ethnic mixing; we evaluate their relative importance in 18 English cities in the light of Boal and Peach's arguments regarding the processes and patterns involved in segregation. We find little evidence of significant segregation of Black ethnic groups, but more with regard to Asian groups-especially outside London.
MR imaging of tumor microcirculation: Promise for the new millenium

Dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI) is a method of imaging the physiology of the microcirculation. A series of recent clinical studies have shown that DCE MRI can measure and predict tumor response to therapy. Recent advances in MR technology provide the enhanced spatial and temporal resolution that allow the application of this methodology in the management of cancer patients. The September issue of this journal provided a microcirculation section to update readers on this exciting and challenging topic. Evidence is mounting that DCE MRI‐based measures correlate well with tumor angiogenesis. DCE MRI has already been shown in several types of tumors to correlate well with traditional outcome measures, such as histopathologic studies, and with survival. These new measures are sensitive to tumor physiology and to the pharmacokinetics of the contrast agent in individual tumors. Moreover, they can present anatomical images of tumor microcirculation at excellent spatial resolution. Several issues have emerged from recent international workshops that must be addressed to move this methodology into routine clinical practice. First, is complex modeling of DCE MRI really necessary to answer clinical questions reliably? Clinical research has shown that, for tumors such as bone sarcomas, reliable outcome measures of tumor response to chemotherapy can be extracted from DCE MRI by methods ranging from simple measures of enhancement to pharmacokinetic models. However, the use of similar methods to answer a different question—the differentiation of malignant from benign breast tumors—has yielded contradictory results. Thus, no simple, one‐size‐fits‐all‐tumors solution has yet been identified. Second, what is the most rational and reliable data collection procedure for the DCE MRI evaluation? Several groups have addressed population variations in some key variables, such as tumor T10 (T1 prior to contrast administration) and the arterial input function Ca(t) for contrast agent, and how they influence the precision and accuracy of DCE MRI outcomes. However, despite these potential complications, clinical studies in this section show that some tumor types can be assessed by relatively simple dynamic measures and analyses. The clinical scenario and tumor type may well determine the required complexity of the DCE MRI exam procedure and its analysis. Finally, we suggest that a consensus on naming conventions (nomenclature) is needed to facilitate comparison and analysis of the results of studies conducted at different centers. J. Magn. Reson. Imaging 10:903–907, 1999. © 1999 Wiley‐Liss, Inc.
Review of solid state transformer in the distribution system: From components to field application

The emergence of high power converters makes the modern power grid more active than it was before. One of the research directions in this area is the solid state transformer, which aims at replacing the traditional 50/60 Hz power transformer by means of high frequency isolated AC/AC solid state conversion techniques. This paper presents a systematical technology review essential for the development of solid state transformer in the distribution system, especially focusing on the following four areas: high voltage and high frequency power devices, high power and high frequency transformers, AC/AC converter topologies, and applications of solid state transformer in the distribution system. For each category, the state-of-art technologies are reviewed and possible research directions are presented. It is concluded that the solid state transformer is an emerging technology for the modernization of the future smart grid.
Disability as an outcome in MS clinical trials

Background: Inferences about long-term effects of therapies in multiple sclerosis (MS) have been based on surrogate markers studied in short-term trials. Preventing progressive disability is the key therapeutic goal but there remains no validated definition for its measurement in a trial context. Meanwhile, MS trials continue to shorten and to depend on unvalidated surrogates. Since there have been no treatment claims for improving unremitting disability, worsening of disability in the placebo/control arm must occur for effectiveness on this outcome to be shown. Methods: We examined widely-used clinical surrogates of long-term disability progression in individual patients with MS within a unique database from the placebo arms of 31 randomized clinical trials. Results: Detection of treatment effects in secondary progressive MS trials is undermined by noise in disability measurement. Whereas existing measures can be partially validated in secondary progressive MS, this is not the case in relapsing-remitting MS. Here, examination of widely used definitions of treatment failure demonstrated that disability progression was no more likely than similarly defined improvement. Existing definitions of disease progression in short-term intervention trials in relapsing-remitting patients reflect random variation, measurement error, and remitting relapses. Conclusion: Clinical surrogates of unremitting disability used in trials of relapsing-remitting multiple sclerosis cannot be validated. Trials have been too short or degrees of disability change too small to measure the key outcomes. These analyses highlight the difficulty in determining effectiveness of therapy in chronic diseases.
De-commodification and Welfare: Evaluating Housing Systems

This article adopts an operational definition of de-commodification that emphasises its significance for the welfare of individuals. It explores what the definition indicates about different forms of home ownership and renting found in industrialised countries. The evaluations are brought together to derive quantitative estimates of the degree of de-commodification found in the housing systems of Britain, Sweden and Germany. Deriving the degrees of de-commodification of particular forms of housing and of entire national housing systems is a complex process. They cannot be read-off from knowledge of, say, tenure, and conclusions may differ from those generally assumed.
SENSITIVITY AND SPECIFICITY OF DETECTING RETICULAR PSEUDODRUSEN IN MULTIMODAL IMAGING IN JAPANESE PATIENTS

Purpose: To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD. Methods: This study included 220 eyes from 114 patients with newly diagnosed age-related macular degeneration. Patients underwent fundus photography, IR, fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and SD-OCT in both eyes. Eyes were diagnosed with RPD if they showed reticular patterns on at least two of the seven imaging modalities. Results: Thirty-seven eyes were diagnosed with RPD. However, SD-OCT and IR had the highest sensitivity (94.6%), and at the same time, SD-OCT had a high specificity (98.4%). The blue channel of color fundus photography, confocal blue reflectance, and indocyanine green angiography had a specificity of 100% but had lower sensitivity than that of SD-OCT and IR. Conclusion: For detecting RPD, IR and SD-OCT had the highest sensitivity. Although SD-OCT had the highest sensitivity and specificity, RPD detection should be confirmed using more than one modality for increased accuracy.
Beyond the histamine receptor: effect of antihistamines on mast cells

Many antihistamines exhibit inhibition of mediator release from mast cells and basophils, in in vitro studies in addition to H1 antagonism. The underlying mechanism is unclear but is unrelated to H1‐receptor antagonism. Clinical studies of antihistamins in antigen challenge and seasonal allergy demonstrate reduction of mast cell mediators in nasal lavage. It is not known what mechanism(s) underly these observations, although the concentrations required in in vitro studies suggests that a direct effect on mast cells is unlikely. Furthermore, the therapeutic contribution of this effect is difficult to assess because of concomitant clinically significant H1 antagonism. This and other potential anti‐allergic effects may enhance the therapeutic benefit of antihistamines and long‐term studies are underway to explore this possibility.
On the market viability under proportional transaction costs

This paper studies the market viability with proportional transaction costs. Instead of requiring the existence of strictly consistent price systems as in the literature, we show that strictly consistent local martingale systems (SCLMS) can successfully serve as the dual elements such that the market viability can be verified. We introduce two weaker notions of no arbitrage conditions on market models named no unbounded profit with bounded risk (NUPBR) and no local arbitrage with bounded portfolios (NLABPs). In particular, we show that the NUPBR and NLABP conditions in the robust sense are equivalent to the existence of SCLMS for general market models. We also discuss the implications for the utility maximization problem.
The Staying Power of Leveraged Buyouts

This paper documents the organizational status over time of 183 large leveraged buyouts (LBOs) completed between 1979 and 1986. As of August 1990, 63% of the LaOs are privately owned, 14% are independent public companies, and 23% are owned by other public companies As time since the LBO increases, the percentage of LBOs that have returned to public ownership increases. The (unconditional) median time LBOs remain private equals 6.70 years. This evidence suggests that the majority of LBO organizations are neither short-lived nor permanent. In addition the moderate fraction of LBOs assets owned by other (potentially related) companies implies that asset sales play a role in, but are not the primarily force motivating LBO transactions. (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was borrowed from another version of this item.) (This abstract was (This abstract was borrowed from another version of this item.)
Public Policy Implications for Using Remote Monitoring Technology to Treat Diabetes

Daily medical practice in the United States is at the threshold of a significant and permanent change. The driving force is technologies that permit remote physiological monitoring of patients who have diabetes and other chronic diseases, along with widespread access to the Internet and the adoption of email as a primary means of communicating in our society. Utilization of these technologies not only improves the quality of patient care, it also reduces the need for frequent physician office appointments, costly emergency room visits, and unnecessary hospitalizations. The Remote Monitoring Access Act of 2007 will eliminate disincentives in current Medicare rules that only provide payment for face-to-face meetings between patients and their doctors.