Hypofractionated stereotactic radiotherapy in combination with whole brain radiotherapy for brain metastases

Background The efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) in combination with whole brain radiotherapy (WBRT), for the treatment of 1-4 brain metastases, using a non invasive fixation of the skull, was investigated. Methods Between 04/2001 and 01/2006 30 patients with 44 brain metastases underwent irradiation. Every patient received WBRT (10 x 3 Gy); 41/44 lesions received HSRT boost with a median dose fraction of 6 Gy, the fractionation schemes were 3 x 6 Gy and 4 x 8 Gy; a median total dose of 18 Gy was delivered to the tumor isocenter. Results The median survival period was 9.15 months, the actuarial 1-year overall survival and freedom from new brain metastases were 36.6% and 87.9%, respectively; at univariate analysis Karnofsky Performance Status (KPS) was statistically significant (P = 0.05); the actuarial 1-year local control for the 41/44 lesions was 86.1%. No patient had acute or late complications. Conclusions HSRT as a concomitant boost during WBRT is a safe and well tolerated treatment for selected patients with brain metastases

The Collaborative Development of New CFD Methods Adapted for Tilt Rotor Aircraft in the HiPerTilt Project

No abstract available

DES14X3taz: A Type I Superluminous Supernova Showing a Luminous, Rapidly Cooling Initial Pre-Peak Bump

We present DES14X3taz, a new hydrogen-poor superluminous supernova (SLSN-I) discovered by the Dark Energy Survey (DES) supernova program, with additional photometric data provided by the Survey Using DECam for Superluminous Supernovae. Spectra obtained using Optical System for Imaging and low-Intermediate-Resolution Integrated Spectroscopy on the Gran Telescopio CANARIAS show DES14X3taz is an SLSN-I at z = 0.608. Multi-color photometry reveals a double-peaked light curve: a blue and relatively bright initial peak that fades rapidly prior to the slower rise of the main light curve. Our multi-color photometry allows us, for the first time, to show that the initial peak cools from 22,000 to 8000 K over 15 rest-frame days, and is faster and brighter than any published core-collapse supernova, reaching 30% of the bolometric luminosity of the main peak. No physical 56Ni-powered model can fit this initial peak. We show that a shock-cooling model followed by a magnetar driving the second phase of the light curve can adequately explain the entire light curve of DES14X3taz. Models involving the shock-cooling of extended circumstellar material at a distance of ≃400 R⊙ are preferred over the cooling of shock-heated surface layers of a stellar envelope. We compare DES14X3taz to the few double-peaked SLSN-I events in the literature. Although the rise times and characteristics of these initial peaks differ, there exists the tantalizing possibility that they can be explained by one physical interpretation

Reviewing two decades of energy system analysis with bibliometrics

Acknowledgements Dominik Franjo Dominkovi´c was funded by the CITIES project nr. DSF1305-00027B and Cool-Data project nr. 0177-00066B, both funded by the Danish Innovationsfonden. Fabian Scheller kindly acknowledges the financial support of the European Union’s research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 713683 (COFUNDfellowsDTU). The authors also thank three anonymous reviewers for their helpful comments on an earlier version of this paper. The usual disclaimer applies.Peer reviewedPostprin

Reviewing two decades of energy system analysis with bibliometrics

Acknowledgements Dominik Franjo Dominkovi´c was funded by the CITIES project nr. DSF1305-00027B and Cool-Data project nr. 0177-00066B, both funded by the Danish Innovationsfonden. Fabian Scheller kindly acknowledges the financial support of the European Union’s research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 713683 (COFUNDfellowsDTU). The authors also thank three anonymous reviewers for their helpful comments on an earlier version of this paper. The usual disclaimer applies.Peer reviewedPostprin

The CRE-Like Element Inside the 5′-Upstream Region of the Rat Sodium/Iodide Symporter Gene Interacts with Diverse Classes of b-Zip Molecules that Regulate Transcriptional Activities through Strong Synergy with Pax-8

AbstractWe previously demonstrated that transcription of the rat sodium/iodide symporter (NIS) gene is regulated by NUE, an upstream enhancer located between nucleotides −2264 and −2495 of the 5′-flanking region. To elucidate the mechanism of TSH/cAMP-mediated regulation of NIS gene expression, we have characterized the putative cAMP response element (CRE)/activator protein (AP)-1 site (termed NUC) that is closely located between the two Pax-8 (paired box domain transcription factor-8) binding sites within NUE. In two different approaches using either gel supershift analyses or dominant-negative inhibitors of b-Zip molecules, we have shown that NUC can be recognized by several members of the AP-1 and CREB family transcription factors that modulate the transcriptional activity of NUE. Using tethered dimers of b-Zip molecules, we have also demonstrated that specific homo- or heterodimers of AP-1 can synergistically stimulate NUE activity in concert with Pax-8. To demonstrate further that NUC is a bona fide CRE, we made an artificial promoter with the five-time tandem repeat of this sequence (5xNUC). In comparison to the canonical CRE (5xCRE), 5xNUC manifested greater transcriptional activity and broader response to cAMP signaling. Hence, we postulate that the significance of this evolutionally conserved CRE-like site may lie in its broader cell type specificity

Differential expression of cyclooxygenases in hypertrophic scar and keloid tissues

Hypertrophic scar (HS) and keloid (KL) are two forms of an abnormal cutaneous scarring process, mainly characterized by excessive extracellular matrix deposition and fibroblast proliferation. Despite the increased understanding of the molecular and cellular events leading to HS and KL, the pathogenesis of these lesions remains poorly understood. A pivotal role in the formation of abnormal scars has been ascribed to transforming growth factor-β, whose activity appears to be mediated through a link with pathways acting via cyclooxygenases (COX-1 and COX-2). To date, there is no report on the in vivo expression of COX-1 and COX-2 in human HS and KL tissues. Therefore, using immunohistochemistry and Western blot analysis, we investigated 36 cases of KL, 32 cases of HS, and 25 cases of normal skin in order to define the localization and distribution of COX-1 and COX-2 in the tissues of these scar lesions and the overlying epidermis. The results mainly show the following: (a) a significant overexpression of COX-1 in HS tissues and the overlying epidermis as compared with normal skin and KL tissues and (b) a significant overexpression of COX-2 in KL tissue and the overlying epidermis in contrast to normal skin and HS tissues. Our data support the hypothesis that both COXs are involved in the pathogenesis of scar lesions in different ways and, particularly, COX-1 in the formation of HS and COX-2 in the formation of KL. In addition, the overexpression of COX-1 and COX-2 in the epidermis overlying HS and KL tissues, respectively, underlines the importance of epithelial- mesenchymal interactions in the pathogenesis of scar lesion

A Chemical Strategy for the Preparation of Multimodified Peptide Imaging Probes

Multimodality probes appear of great interest for innovative imaging applications in disease diagnosis. Herein, we present a chemical strategy enabling site-specific doublemodification and cyclization of a peptide probe exploiting native chemical ligation (NCL) and thiol-maleimide addition. The synthetic strategy is straightforward and of general applicability for the development of double-labeled peptide multimodality probes

Effect of antithrombotic therapy on postoperative outcome of 538 consecutive emergency laparoscopic cholecystectomies for acute cholecystitis. Two Italian center’s study

The risk of developing hemorrhagic complications during or after emergency cholecystectomy (EC) for acute cholecystitis (AC) in patients with antithrombotic therapy (ATT) remains uncertain. In this double-center study, we evaluated post-operative outcomes in patients with ATT undergoing EC. We retrospectively evaluated 538 patients who underwent laparoscopic EC for AC between May 2015 and December 2019 at two referral centers. 89 of them (17%) were on ATT. We defined postoperative complication rates, including bleeding, as our primary outcome. Mortality was higher in the ATT group. Morbidity was higher in the ATT group as well; however, the difference was not statistically significant. 12 patients (2%) experienced intraoperative blood loss over 500 ml and ten (2%) had postoperative bleeding complications. Two patients (< 1%) experienced both intraoperative and postoperative bleeding. On multivariate analysis, ATT was not significantly associated with worse postoperative outcomes. Antithrombotic therapy is not an independently associated factor of severe postoperative complications (including bleeding) or mortality. However, these patients still represent a challenging group and must be carefully managed to avoid postoperative bleeding complications