Algebraic varieties with automorphism groups of maximal rank

We confirm, to some extent, the belief that a projective variety X has the largest number (relative to the dimension of X) of independent commuting automorphisms of positive entropy only when X is birational to a complex torus or a quotient of a torus. We also include an addendum to an early paper though it is not used in the present paper.Comment: Mathematische Annalen (to appear

The photometric properties of a vast stellar substructure in the outskirts of M33

We have surveyed $\sim40$sq.degrees surrounding M33 with CFHT MegaCam in the g and i filters, as part of the Pan-Andromeda Archaeological Survey. Our observations are deep enough to resolve the top 4mags of the red giant branch population in this galaxy. We have previously shown that the disk of M33 is surrounded by a large, irregular, low-surface brightness substructure. Here, we quantify the stellar populations and structure of this feature using the PAndAS data. We show that the stellar populations of this feature are consistent with an old population with $<[Fe/H]>\sim-1.6$dex and an interquartile range in metallicity of $\sim0.5$dex. We construct a surface brightness map of M33 that traces this feature to $\mu_V\simeq33$mags\,arcsec$^{-2}$. At these low surface brightness levels, the structure extends to projected radii of $\sim40$kpc from the center of M33 in both the north-west and south-east quadrants of the galaxy. Overall, the structure has an "S-shaped" appearance that broadly aligns with the orientation of the HI disk warp. We calculate a lower limit to the integrated luminosity of the structure of $-12.7\pm0.5$mags, comparable to a bright dwarf galaxy such as Fornax or AndII and slightly less than $1\$ of the total luminosity of M33. Further, we show that there is tentative evidence for a distortion in the distribution of young stars near the edge of the HI disk that occurs at similar azimuth to the warp in HI. The data also hint at a low-level, extended stellar component at larger radius that may be a M33 halo component. We revisit studies of M33 and its stellar populations in light of these new results, and we discuss possible formation scenarios for the vast stellar structure. Our favored model is that of the tidal disruption of M33 in its orbit around M31.Comment: Accepted for publication in ApJ. 17 figures. ApJ preprint forma

Effect of the patient information brochure in communicating the risks associated with crizotinib treatment to patients with non-small cell lung cancer (NSCLC) in Europe

Crizotinib (XALKORI®) is indicated for anaplastic lymphoma kinase-positive and ROS1-positive advanced non-small cell lung cancer. This study evaluated the distribution of the crizotinib patient information brochure (PIB) in Europe and patient knowledge of the key messages in the PIB. A cross-sectional survey was conducted in 10 European countries among patients who received crizotinib to ascertain whether each patient received and read the PIB, and his/her knowledge of its key messages on hepatotoxicity, interstitial lung disease/pneumonitis, QTc prolongation, bradycardia, and vision disorders. Of the 341 patients contacted, 40 responded (11.7%), and 39 patients were eligible. A total of 77% of respondents acknowledged receiving the PIB, of which, 93% reported reading it. Knowledge of the individual side effects ranged from 36% to 85%, and precautions for use ranged from 56% to 67%. Understanding the reasons for calling a physician ranged from 54% to 85%. Knowledge of each of the 6 key side effects was greater among readers of the PIB compared to non-readers or respondents who did not recall receiving the PIB. Approximately three-quarters of survey respondents recalled receiving the crizotinib PIB and respondents who read the PIB were more knowledgeable of the key side effects of crizotinib than those who did not read or receive. Caution should be taken in generalizing these results because of the potential for selection bias and small sample size. These survey results suggest that the crizotinib PIB may be an effective risk communication tool for crizotinib-treated patients in Europe

Beobachtungsstudie ärztlicher und pflegerischer Aktivitäten in der Notaufnahme

Background!#!Comprehensive and systematic assessments of nurse and physician activities in the emergency department (ED) are lacking for German-speaking countries.!##!Objectives!#!Assessment of work activities of ED nurses and physicians with particular focus on frequencies of direct patient contact as well as rates of activity changes.!##!Material and methods!#!We employed standardized assessments of work activities using participant observations (90 min each) among nurses and physicians during their regular shifts. The setting was an interdisciplinary ED of a Southern German academic hospital. Observed activities were classified according to an established system and recorded with time stamps. Overall, 160 observation sessions were conducted (with an observation time of approximately 240 h; 99 among nurses, 61 among physicians).!##!Results!#!Physicians spent 30% of their working time in direct patient contact, nurses 44%. Concerning individual activities, the largest proportions of physicians' work time were allocated to documentation and writing (29.3%), communication with ED staff (16.9%) and patients (13.6%). Nurses were engaged in therapeutic and treatment activities (27.6%) and internal communication (17.9%) most of the time. Individual activities were highly fragmented: On average, we recorded 41.3 activities per hour with an average duration of 1.5 min. Nurses had significantly shorter activity durations than ED physicians (F[df = 1] = 4.5, p = 0.04). Activity-specific subanalyses revealed differences that could be attributed to professional roles in ED work.!##!Conclusion!#!Our results provide reliable and comprehensive insights into the distribution and duration of physician and nurse activities in clinical care in a German ED. Future work and design projects should focus particularly on effects of ED work time allocation on performance and work stress of ED staff as well as on safety and quality of ED patient care

Microwave Surface Impedance of YBCO:123 crystals: Experiment and comparison to a d-wave model

We present measurements of the microwave surface resistance Rs and the penetration depth lambda of YBCO:123 crystals. At low T obeys lambda(T) a polynomial behavior, while Rs displays a characteristic non-monotonic T-dependence. A detailed comparison of the experimental data is made to a model of d-wave superconductivity which includes both elastic and inelastic scattering. While the model reproduces the general features of the experimental data, three aspects of the parameters needed are worth noting. The elastic scattering rate required to fit the data is much smaller than measured from the normal state, the scattering phase shifts have to be close to pi/2 and a strong coupling value of the gap parameter 2\Delta(0)/kTc = 6 is needed. On the experimental side the uncertainties regarding the material parameters lambda(0) and Rs,res(0) further complicate a quantitative comparison. For one sample does Rs,res(0) agree with the intrinsic value which results from the d-wave model.Comment: uuencoded tar.Z, 11 pages with 5 figures, used style files: elsart and graphicx, PS-file available at http://sagar.cas.neu.edu/preprints.htm

A randomized phase II study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel in second-line therapy of advanced non-small cell lung cancer (GALAXY-1)

Background: This trial was designed to evaluate the activity and safety of ganetespib in combination with docetaxel in advanced non-small cell lung cancer (NSCLC) and to identify patient populations most likely to benefit from the combination. Patients and methods: Patients with one prior systemic therapy for advanced disease were eligible. Docetaxel (75 mg/m&lt;sup&gt;2&lt;/sup&gt; on day 1) was administered alone or with ganetespib (150 mg/m&lt;sup&gt;2&lt;/sup&gt; on days 1 and 15) every 3 weeks. The primary end points were progression-free survival (PFS) in two subgroups of the adenocarcinoma population: patients with elevated lactate dehydrogenase (eLDH) and mutated KRAS (mKRAS). Results: Of 385 patients enrolled, 381 were treated. Early in the trial, increased hemoptysis and lack of efficacy were observed in nonadenocarcinoma patients (n = 71); therefore, only patients with adenocarcinoma histology were subsequently enrolled. Neutropenia was the most common grade ≥3 adverse event: 41% in the combination arm versus 42% in docetaxel alone. There was no improvement in PFS for the combination arm in the eLDH (N = 114, adjusted hazard ratio (HR) = 0.77, P = 0.1134) or mKRAS (N = 89, adjusted HR = 1.11, P = 0.3384) subgroups. In the intent-to-treat adenocarcinoma population, there was a trend in favor of the combination, with PFS (N = 253, adjusted HR = 0.82, P = 0.0784) and overall survival (OS) (adjusted HR = 0.84, P = 0.1139). Exploratory analyses showed significant benefit of the ganetespib combination in the prespecified subgroup of adenocarcinoma patients diagnosed with advanced disease &gt;6 months before study entry (N = 177): PFS (adjusted HR = 0.74, P = 0.0417); OS (adjusted HR = 0.69, P = 0.0191). Conclusion: Advanced lung adenocarcinoma patients treated with ganetespib in combination with docetaxel had an acceptable safety profile. While the study's primary end points were not met, significant prolongation of PFS and OS was observed in patients &gt;6 months from diagnosis of advanced disease, a subgroup chosen as the target population for the phase III study.</p

Expression of chemokine receptor CXCR4 in esophageal squamous cell and adenocarcinoma

BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor growth, dissemination and local immune escape in a limited number of malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor spread of esophageal cancer with a differentiated view of the two predominant histologic types – squamous cell and adenocarcinoma. METHODS: Esophageal cancer tissue samples were obtained from 102 consecutive patients undergoing esophageal resection for cancer with curative intent. The LSAB+ System was used to detect the protein CXCR4. Tumor samples were classified into two groups based on the homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and CXCR4s (= strong expression) was set at 1.5 (grouped 0 – 1.5 versus 2.0 – 3). Long-term survival rates were calculated using life tables and the Kaplan-Meier method. Using the Cox's proportional hazards analysis, a model of survival prediction was established. RESULTS: The overall expression rate for CXCR4 in esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's proportional hazards analysis identified the pM-category with a hazard ratio (HR) of 1.860 (95% CI: 1.014–3.414) (p = 0.045), the histologic tumor type (HR: 0.334; 95% CI: 0.180–0.618) (p = 0.0001) and the operative approach (transthoracic > transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324–0.920) (p = 0.023) as independent factors with a possible influence on the long-term prognosis in patients with esophageal carcinoma, whereas CXCR4 expression was statistically not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4 in esophageal cancer is of major relevance in both histologic entities – squamous cell and adenocarcinoma. Though with lack of statistical significance, strong CXCR4 expression revealed a poorer long-term prognosis following curative esophagectomy in both histologic subtypes. Thus, the exact biological functions of CXCR4 in terms of tumor dissemination of esophageal cancer is yet undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists might be a promising therapeutic option in the future

oA novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology

<p>Abstract</p> <p>Background</p> <p>Epidemiological and clinical studies, often including anthropometric measures, have established obesity as a major risk factor for the development of type 2 diabetes. Appropriate cut-off values for anthropometric parameters are necessary for prediction or decision purposes. The cut-off corresponding to the Youden-Index is often applied in epidemiology and biomedical literature for dichotomizing a continuous risk indicator.</p> <p>Methods</p> <p>Using data from a representative large multistage longitudinal epidemiological study in a primary care setting in Germany, this paper explores a novel approach for estimating optimal cut-offs of anthropomorphic parameters for predicting type 2 diabetes based on a discontinuity of a regression function in a nonparametric regression framework.</p> <p>Results</p> <p>The resulting cut-off corresponded to values obtained by the Youden Index (maximum of the sum of sensitivity and specificity, minus one), often considered the optimal cut-off in epidemiological and biomedical research. The nonparametric regression based estimator was compared to results obtained by the established methods of the Receiver Operating Characteristic plot in various simulation scenarios and based on bias and root mean square error, yielded excellent finite sample properties.</p> <p>Conclusion</p> <p>It is thus recommended that this nonparametric regression approach be considered as valuable alternative when a continuous indicator has to be dichotomized at the Youden Index for prediction or decision purposes.</p