bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Assessing Tumor Vascularity and Vascular Effects of Targeted Therapies in Renal Cell Carcinoma
Authors: Rosen Mark A. , Schnall Mitchell D. 
Published: January 2007

Abstract
Traditional cross-sectional tumor imaging focuses solely on tumor morphology. With the introduction of targeted biological therapies in human trials, morphologic change may lag behind other physiologic measures of response on clinical images. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a new imaging method for assessing the physiologic state of tumor vascularity in vivo. DCE-MRI, which uses available imaging techniques and contrast agents, assays the kinetics of tumor enhancement during bolus i.v. contrast administration. Modeling of the temporal enhancement pattern yields physiologic variables related to tumor blood flow and microvessel permeability. Changes in these variables after vascular-targeted therapy can then be quantified to evaluate the tumor vascular response. As these responses may precede morphologic tumor shrinkage, DCE-MRI might serve as a noninvasive means of monitoring early tumor response to vascular-targeted therapy. Renal cell carcinoma provides an excellent model for assessing the effect on DCE-MRI in clinical trials. The vascular richness of renal tumors provides a large dynamic scale of DCE-MRI measures. Patients with disseminated renal cell carcinoma frequently present with one or several large tumors, creating an easy imaging target for DCE-MRI evaluation. Finally, renal cell carcinoma is clearly susceptible to therapies that target tumor angiogenesis. DCE-MRI can be used to monitor the vascular changes induced by such therapies. Future efforts must be directed to standardizing image acquisition and analysis techniques to quantify tumor vascular responses.
The Role of Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal Cancer
Authors: Cho Daniel , Signoretti Sabina , Regan Meredith , Mier James W. , Atkins Michael B. 
Published: January 2007

Abstract
Inhibitors of the mammalian target of rapamycin (mTOR) have shown promising efficacy in early-stage trials in patients with advanced renal cell carcinoma (RCC). Most RCCs have been shown to possess biallelic alterations in the von Hippel-Lindau (VHL) gene, resulting in accumulation of hypoxia-inducible factors 1α and 2α, as well as their downstream targets including vascular endothelial growth factor (VEGF). The observed clinical efficacy of mTOR inhibitors in patients with RCC may be mediated in part by the dependence of efficient hypoxia-inducible factor translation on the mTOR pathway. mTOR inhibitors have entered more advanced phase clinical trials either as single agents or in combination with other targeted agents or IFN, which might ultimately result in regulatory approval of one or more agents. Given the likely nonoverlapping mechanism of action of mTOR inhibitors and VEGF pathway–targeted agents, mTOR inhibitors may prove useful if administered in combination or after resistance to VEGF inhibitors. With an increasing number of active agents for treatment of patients with RCC, efforts must continue to develop patient selection models based on predictive biomarkers to direct therapy to appropriate patients.
A Phase I Study of Immunization Using Particle-Mediated Epidermal Delivery of Genes for gp100 and GM-CSF into Uninvolved Skin of Melanoma Patients
Authors: Cassaday Ryan D. , Sondel Paul M. , King David M. , Macklin Michael D. , Gan Jacek , Warner Tom F. , Zuleger Cindy L. , Bridges Alan J. , Schalch Heidi G. , Kim Kyung Mann , Hank Jacquelyn A. , Mahvi David M. , Albertini Mark R. 
Published: January 2007

Abstract
Purpose: We examined in vivo particle-mediated epidermal delivery (PMED) of cDNAs for gp100 and granulocyte macrophage colony-stimulating factor (GM-CSF) into uninvolved skin of melanoma patients. The aims of this phase I study were to assess the safety and immunologic effects of PMED of these genes in melanoma patients.
Experimental Design: Two treatment groups of six patients each were evaluated. Group I received PMED with cDNA for gp100, and group II received PMED with cDNA for GM-CSF followed by PMED for gp100 at the same site. One vaccine site per treatment cycle was biopsied and divided for protein extraction and sectioning to assess transgene expression, gold-bead penetration, and dendritic cell infiltration. Exploratory immunologic monitoring of HLA-A2+ patients included flow cytometric analyses of peripheral blood lymphocytes and evaluation of delayed-type hypersensitivity to gp100 peptide.
Results: Local toxicity in both groups was mild and resolved within 2 weeks. No systemic toxicity could be attributed to the vaccines. Monitoring for autoimmunity showed no induction of pathologic autoantibodies. GM-CSF transgene expression in vaccinated skin sites was detected. GM-CSF and gp100 PMED yielded a greater infiltration of dendritic cells into vaccine sites than did gp100 PMED only. Exploratory immunologic monitoring suggested modest activation of an antimelanoma response.
Conclusions: PMED with cDNAs for gp100 alone or in combination with GM-CSF is well tolerated by patients with melanoma. Moreover, pathologic autoimmunity was not shown. This technique yields biologically active transgene expression in normal human skin. Although modest immune responses were observed, additional investigation is needed to determine how to best utilize PMED to induce antimelanoma immune responses.
Phase 2 Studies of Sunitinib and AG013736 in Patients with Cytokine-Refractory Renal Cell Carcinoma
Authors: George Daniel J. 
Published: January 2007

Abstract
Frequent loss of the von Hippel-Lindau (VHL) gene product in conventional-type renal cell carcinoma results in constitutive expression of proangiogenic growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). VEGF and PDGF function in a paracrine manner to stimulate tumor angiogenesis that results in a hypervascular phenotype. Dependency on this hypervascularity is underscored by the recent clinical efficacy shown by inhibition of the VEGF pathway. Most strategies that primarily target the VEGF pathway (neutralizing antibodies or receptor tyrosine kinase inhibitors) result in objective tumor responses in ≤10% of cases but show a significant delay in time to disease progression. In contrast, two multitargeted receptor tyrosine kinase inhibitors that target both VEGF and PDGF receptors (sunitinib and AG013736) have shown ≥40% objective responses with clinically important duration. Several hypotheses may explain the discrepancy of these response rates from other strategies in the class, including the synergistic effects of dual inhibition of VEGF and PDGF receptors, supported by preclinical studies. Ultimately, further clinical investigations with pharmacodynamic and correlative science end points are needed to clarify the mechanisms of action and resistance to build on the biological and clinical effects of these multitargeted agents.
Developing a Rational Tumor Vaccine Therapy for Renal Cell Carcinoma: Immune Yin and Yang
Authors: Ernstoff Marc S. , Crocenzi Todd S. , Seigne John D. , Crosby Nancy A. , Cole Bernard F. , Fisher Jan L. , Uhlenhake Jill C. , Mellinger Diane , Foster Cathy , Farnham Conrad J. , Mackay Kathleen , Szczepiorkowski Zbigniew M. , Webber Susan M. , Schned Alan R. , Harris Robert D. , Barth Richard J. , Heaney John A. , Noelle Randolph J. 
Published: January 2007

AbstractIn patients with progressive malignancy, the natural balance between proinflammatory (Yang) and inhibitory (regulatory or Yin) immune pathways is disrupted and favors cancer-specific immune suppression. Therapy with interleukin 2 (IL-2) can mobilize immune effector cells that recognize and destroy cancer. High-dose IL-2 is the only therapy that has consistently induced complete durable remissions in patients with metastatic renal cell carcinoma (RCC) but only in a few of them. The lack of benefit in most metastatic RCC patients is likely due to the ineffective manipulation of other immune circuits critical in regulating tumor cytotoxic pathways. The limited clinical activity of IL-2, RCC vaccines, and other immune therapies to date leads us to postulate that effective clinical treatment strategies will need to simultaneously enhance proinflammatory pathways and disrupt regulatory pathways. We present preliminary studies in RCC patients to highlight the complexity of the regulatory pathways and our approach to shifting the balance of proinflammatory and regulatory immune pathways using dendritic cell–tumor lysate vaccine followed by cytokine therapy.
Multimodal Approaches in the Management of Locally Advanced and Metastatic Renal Cell Carcinoma: Combining Surgery and Systemic Therapies to Improve Patient Outcome
Authors: Wood Christopher G. 
Published: January 2007

Abstract
Patients with locally advanced renal cell carcinoma are at high risk of metastatic relapse following surgery. Patients with metastatic disease have a poor prognosis and few systemic therapy options. Radiation, chemotherapy, hormonal therapy, vaccines, and immunotherapy have all been tested as adjuvant therapy without benefit. Neoadjuvant therapy in the metastatic setting holds promise as a new treatment paradigm. It can serve as a litmus test to allow proper patient selection for aggressive surgical intervention and may provide limited downstaging of primary tumors in selected cases. It can also provide a histologic assessment of the effect of targeted therapy. Application of this paradigm may have merit in the locally advanced setting as well. Effective adjuvant therapy for renal cell carcinoma remains elusive. The benefit of new targeted therapies has yet to be tested in this setting. Neoadjuvant strategies that integrate aggressive surgical intervention with systemic therapy may hold promise as a treatment paradigm.
Intercomparison of Water Vapor Data Measured with Lidar during IHOP_2002. Part I: Airborne to Ground-Based Lidar Systems and Comparisons with Chilled-Mirror Hygrometer Radiosondes
Authors: Behrendt Andreas , Wulfmeyer Volker , Bauer Hans-Stefan , Schaberl Thorsten , Di Girolamo Paolo , Summa Donato , Kiemle Christoph , Ehret Gerhard , Whiteman David N. , Demoz Belay B. , Browell Edward V. , Ismail Syed , Ferrare Richard , Kooi Susan , Wang Junhong 
Published: January 2007

AbstractThe water vapor data measured with airborne and ground-based lidar systems during the International H2O Project (IHOP_2002), which took place in the Southern Great Plains during 13 May–25 June 2002 were investigated. So far, the data collected during IHOP_2002 provide the largest set of state-of-the-art water vapor lidar data measured in a field campaign. In this first of two companion papers, intercomparisons between the scanning Raman lidar (SRL) of the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC) and two airborne systems are discussed. There are 9 intercomparisons possible between SRL and the differential absorption lidar (DIAL) of Deutsches Zentrum für Luft- und Raumfahrt (DLR), while there are 10 intercomparisons between SRL and the Lidar Atmospheric Sensing Experiment (LASE) of the NASA Langley Research Center. Mean biases of (−0.30 ± 0.25) g kg−1 or −4.3% ± 3.2% for SRL compared to DLR DIAL (DLR DIAL drier) and (0.16 ± 0.31) g kg−1 or 5.3% ± 5.1% for SRL compared to LASE (LASE wetter) in the height range of 1.3–3.8 km above sea level (450–2950 m above ground level at the SRL site) were found. Putting equal weight on the data reliability of the three instruments, these results yield relative bias values of −4.6%, −0.4%, and +5.0% for DLR DIAL, SRL, and LASE, respectively. Furthermore, measurements of the Snow White (SW) chilled-mirror hygrometer radiosonde were compared with lidar data. For the four comparisons possible between SW radiosondes and SRL, an overall bias of (−0.27 ± 0.30) g kg−1 or −3.2% ± 4.5% of SW compared to SRL (SW drier) again for 1.3–3.8 km above sea level was found. Because it is a challenging effort to reach an accuracy of humidity measurements down to the ∼5% level, the overall results are very satisfactory and confirm the high and stable performance of the instruments and the low noise errors of each profile.
Effects of Tides on Maximum Tsunami Wave Heights: Probability Distributions*
Authors: Mofjeld Harold O. , González Frank I. , Titov Vasily V. , Venturato Angie J. , Newman Jean C. 
Published: January 2007

Abstract
A theoretical study was carried out to understand how the probability distribution for maximum wave heights (ηm) during tsunamis depends on the initial tsunami amplitude (A) and the tides. It was assumed that the total wave height is the linear sum of the tides and tsunami time series in which the latter is decaying exponentially in amplitude with an e-folding time of 2.0 days, based on the behavior of observed Pacific-wide tsunamis. Direct computations were made to determine the statistics of maximum height for a suite of different arrival times and initial tsunami amplitudes. Using predicted tides for 1992 when the lunar nodal f factors were near unity during the present National Tidal Datum Epoch 1983–2001, the results show that when A is small compared with the tidal range the probability density function (PDF) of the difference ηm − A is closely confined in height near mean higher high water (MHHW). The ηm − A PDF spreads in height and its mean height ηo − A decreases, approaching the PDF of the tides and MSL, respectively, when A becomes large compared with the tidal range. A Gaussian form is found to be a close approximation to the ηm − A PDF over much of the amplitude range; associated parameters for 30 coastal stations along the U.S. West Coast, Alaska, and Hawaii are given in the paper. The formula should prove useful in probabilistic mapping of coastal tsunami flooding.
A Blended Satellite Total Precipitable Water Product for Operational Forecasting
Authors: Kidder Stanley Q. , Jones Andrew S. 
Published: January 2007

AbstractTotal precipitable water (TPW), the amount of water vapor in a column from the surface of the earth to space, is used by forecasters to predict heavy precipitation. In this paper, a process for blending TPW values retrieved from two satellite sources is detailed: the Advanced Microwave Sounding Unit (AMSU) instruments on three NOAA satellites, and the Special Sensor Microwave Imager (SSM/I) instruments on three Defense Meteorological Satellite Program (DMSP) satellites. The process starts with a blending algorithm, which matches the cumulative probability distribution functions of TPW retrievals from the two instruments to lessen their differences. The data are then mapped to a map projection useful to forecasters and composited for 12 h to make a global map. These maps are produced hourly using Data Processing and Error Analysis System (DPEAS) software and made available to forecasters online.
Trend Identification in Twentieth-Century U.S. Snowfall: The Challenges
Authors: Kunkel Kenneth E. , Palecki Michael A. , Hubbard Kenneth G. , Robinson David A. , Redmond Kelly T. , Easterling David R. 
Published: January 2007

Abstract
There is an increasing interest in examining long-term trends in measures of snow climatology. An examination of the U.S. daily snowfall records for 1900–2004 revealed numerous apparent inconsistencies. For example, long-term snowfall trends among neighboring lake-effect stations differ greatly from insignificant to +100% century−1. Internal inconsistencies in the snow records, such as a lack of upward trends in maximum seasonal snow depth at stations with large upward trends in snowfall, point to inhomogeneities. Nationwide, the frequency of daily observations with a 10:1 snowfall-to-liquid-equivalent ratio declined from 30% in the 1930s to a current value of around 10%, a change that is clearly due to observational practice. There then must be biases in cold-season liquid-equivalent precipitation, or snowfall, or both. An empirical adjustment of snow-event, liquid-equivalent precipitation indicates that the potential biases can be statistically significant.
Examples from this study show that there are nonclimatic issues that complicate the identification of and significantly change the trends in snow variables. Thus, great care should be taken in interpretation of time series of snow-related variables from the Cooperative Observer Program (COOP) network. Furthermore, full documentation of optional practices should be required of network observers so that future users of these data can properly account for such practices.
Sexual health knowledge, attitudes and behaviours among an ethnically diverse sample of young people in the UK
Authors: Coleman Lester , Testa Adrienne 
Published: January 2007

Objective To provide evidence about the sexual health knowledge, attitudes and behaviours of an ethnically diverse sample of young people from Secondary/High schools in London. Design Cross-sectional questionnaire-based survey. The sample consisted of students in school Years 11 to 13 (aged 15–18 years), present in school on the day of questionnaire administration. Setting Sixteen Secondary/High schools in London where the Black and Minority Ethnic (BME) population exceeded two-thirds of the intake. Questionnaires were completed by 2602 students aged 15 to 18, who self-defined their ethnicity as follows: White British ( n= 559), White Other ( n = 256), Black ( n = 710) and Asian ( n = 1077). Method Self-administered 30-minute questionnaire completed under ‘exam’ conditions, distributed and collected by a team of ethnically diverse fieldworkers. This questionnaire recorded socio-demographic information, sexual health knowledge, sexual health attitudes, experience of sexual intercourse, and sexual risk behaviour and outcomes. Results BME groups, relative to White British, generally reported poorer sexual health knowledge. Low level knowledge regarding STIs was particularly evident. The White British students were generally the most liberal in their attitudes to sex. With 65 per cent of Black Caribbean males reporting experience of sexual intercourse, and 48 per cent reporting first intercourse under the age of 16, this group is possibly the most at risk of poor sexual health. Although less likely to report sexual inter-course than Black Caribbeans, Black African females and Asian males and females also reported risk behaviour. Conclusion The findings demonstrate diverse sexual health knowledge, sexual attitudes and sexual behaviours among ethnic groups. This diversity demonstrates the importance of tailoring health education and promotion to meet the specific needs of ethnic groups.
Cardiovascular and metabolic effects of CPAP in obese males with OSA
Authors: Coughlin S. R. , Mawdsley L. , Mugarza J. A. , Wilding J. P. H. , Calverley P. M. A. 
Published: January 2007

Obstructive sleep apnoea is associated with increased blood pressure and other features of the metabolic syndrome. The aim of the present study was to determine the relative effectiveness of continuous positive airway pressure (CPAP) in modifying these outcomes.A randomised placebo-controlled blinded crossover trial comparing cardiovascular and metabolic outcomes after 6 weeks of therapeutic and sham CPAP was performed in 34 CPAP-naïve patients (mean±sdbody mass and respiratory disturbance indices were 36.1±7.6 and 39.7±13.8, respectively).Mean waking systolic and diastolic blood pressure fell by 6.7 and 4.9 mmHg, respectively, when compared with sham CPAP. No change was observed in glucose, lipids, insulin resistance or the proportion of patients with metabolic syndrome. In CPAP-compliant patients the fall in blood pressure was greater and the baroreceptor sensitivity improved significantly but no metabolic variable changed.In obese Caucasians with untreated obstructive sleep apnoea, continuous positive airways pressure can improve baroreceptor responsiveness and reduce waking blood pressure within 6 weeks, but this treatment period was insufficient to modify insulin resistance or change the metabolic profile. The mechanisms underlying this difference in the time course of blood pressure and metabolic response to continuous positive airway pressure in obstructive sleep apnoea requires further exploration.
Indacaterol, a novel inhaled β2-agonist, provides sustained 24-h bronchodilation in asthma
Authors: Beeh K. M. , Derom E. , Kanniess F. , Cameron R. , Higgins M. , van As A. 
Published: January 2007

The present study examined the bronchodilator and safety profiles of single-dose indacaterol in intermittent or persistent asthma.In the present double-blind crossover study, 42 patients were randomised to receive single doses of indacaterol (50, 100, 200 and 400 µg) or placeboviaa hydrofluoroalkane pressurised metered-dose inhaler. The primary efficacy comparisons were the per cent changes in forced expiratory volume in one second (FEV1) between indacaterol and placebo 30 min and 21 h post-dose.All doses resulted in prolonged bronchodilation, with indacaterol 200 and 400 µg meeting pre-specified efficacy criteria. The mean percentage increases in FEV1from placebo with indacaterol 200 and 400 µg were 7.6 and 14.9%, respectively, at 30 min, and 7.5 and 10.4%, respectively, at 21 h post-dose. At these doses, changes in mean FEV1relative to placebo were statistically significant from 5 min to 25 h, inclusive. At 5 min, the geometric least squares mean values for FEV1were 3.08 and 3.22 L for the 200 and 400 µg doses, respectively, compared with 2.99 L for placebo. At 24 h after dosing, the baseline-adjusted geometric least square mean FEV1was 3.13, 3.11, 3.24 and 3.30 L for indacaterol 50, 100, 200 and 400 µg, respectively, and 2.98 L for placebo. All treatments were well tolerated.Once-daily indacaterol at doses of 200 and 400 µg provided sustained 24-h bronchodilation, with a rapid onset and a good tolerability and safety profile.
Serological test and chest computed tomography findings in patients withMycobacterium aviumcomplex lung disease
Authors: Kitada S. , Nishiuchi Y. , Hiraga T. , Naka N. , Hashimoto H. , Yoshimura K. , Miki K. , Miki M. , Motone M. , Fujikawa T. , Kobayashi K. , Yano I. , Maekura R. 
Published: January 2007

The present authors have previously reported the usefulness of a serodiagnostic test to detect serum glycopeptidolipid (GPL) core antibody in diagnosingMycobacterium aviumcomplex (MAC) lung disease in immunocompetent patients. The aim of the present study was to investigate correlations between the levels of antibody against GPL core and chest computed tomography (CCT) findings in patients with MAC lung disease.A total of 47 patients with MAC-positive culture from their sputum and who had radiographic abnormalities were investigated. Thirty-three patients met the American Thoracic Society criteria for MAC disease; 14 did not. All patients underwent both CCT examination and the serodiagnostic test for MAC at the same time.Small nodular shadows were seen on CCT in all 47 patients and bronchiectasis shadows were seen in 39 (83%) of them. There was a significant positive correlation between the extent of the disease and the level of GPL core immunoglobulin (Ig)A antibody. The levels of GPL core IgA antibody were significantly elevated in patients who had nodular shadows (10–30 mm) compared with patients who had small nodular shadows (<10 mm).The present results document that the levels of immunoglobulin A antibody against glycopeptidolipid core correlate with the chest computed tomography findings ofMycobacterium aviumcomplex lung disease.