Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

Background: Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Methods: Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. Results: 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery. Conclusions: The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy

Large Scale Detonation Testing: New Findings in the prediction of DDTs at large scales

PresentationA large vapor cloud explosion (VCE) followed by a fire is one of the most dangerous and high-consequence events that can occur at petrochemical facilities. As the size and complexity of facilities increase, designs must consider the potential adverse effects associated with vapor cloud explosions in large congested areas and understand the potential for more devastating deflagration-to-detonation transitions (DDTs) on these facilities. While the likelihood of DDTs is lower than deflagrations, they have been identified in some of the most recent large-scale explosion incidents including: 2005 Buncefield explosion, 2009 San Juan explosion, and 2009 Jaipur event. The consequences of DDTs can be orders of magnitude larger than deflagration because they have the ability to self-propagate outside the region of high congestion/confinement. Hence, it is critical to understand how a facility’s geometry or equipment layout can affect explosion consequences and assist in their mitigation and/or prevention. Due to the inability to predict such devastating phenomena on the large scale, owners and designers cannot evaluate installations for risk of DDTs and provide “inherently safer” layout or mitigation measures to significantly reduce or eliminate such hazards. However, there is a lack of data at the large scale to validate the necessary design tools used to predict the risk of DDT. One of the main goals of this research project is to provide large scale DDT explosion data and validate the tools necessary to predict vapor cloud explosions in early design phase. This paper will present the results of large scale testing being conducted in a newly developed test rig of 50,000 ft3 (1,500 m3 ) gross volume under award Subcontract 12121-6403-01 provided by the Research Partnership to Secure Energy for America (RPSEA). These tests involve evaluation of deflagrations and DDTs involving stoichiometric, lean and rich mixtures, with propane and methane fuels. The effectiveness of mitigation techniques such as solid inhibitors or deluge is evaluated for preventing DDTs

Mimicry in Cretaceous Bugs

This work is licensed under a Creative Commons Attribution 4.0 International License.Mimicry is ubiquitous in nature, yet understanding its origin and evolution is complicated by the scarcity of exceptional fossils that enable behavioral inferences about extinct animals. Here we report bizarre true bugs (Hemiptera) that closely resemble beetles (Coleoptera) from mid-Cretaceous amber. The unusual fossil bugs are described as Bersta vampirica gen. et sp. nov. and Bersta coleopteromorpha gen. et sp. nov. and are placed into a new family, Berstidae fam. nov. The specialized mouthparts of berstids indicate that they were predaceous on small arthropods. Their striking beetle-like appearance implies that they were either involved in defensive mimicry or mimicked beetles to attack unsuspecting prey. The latter would represent the first case of aggressive mimicry in the invertebrate fossil record. These findings enrich our understanding of the paleoecological associations and extinct behavioral strategies of Mesozoic insects.Strategic Priority Research Program of the Chinese Academy of Sciences (XDB26000000 and XDB18000000)National Natural Science Foundation of China (41672011 and 41688103)Second Tibetan Plateau Scientific Expedition and Research (2019QZKK0706

First-order synchronization transition in a large population of strongly coupled relaxation oscillators.

Onset and loss of synchronization in coupled oscillators are of fundamental importance in understanding emergent behavior in natural and man-made systems, which range from neural networks to power grids. We report on experiments with hundreds of strongly coupled photochemical relaxation oscillators that exhibit a discontinuous synchronization transition with hysteresis, as opposed to the paradigmatic continuous transition expected from the widely used weak coupling theory. The resulting first-order transition is robust with respect to changes in network connectivity and natural frequency distribution. This allows us to identify the relaxation character of the oscillators as the essential parameter that determines the nature of the synchronization transition. We further support this hypothesis by revealing the mechanism of the transition, which cannot be accounted for by standard phase reduction techniques

Landwirtschaftliche Beratungssysteme und Ernährungssicherheit in Tadschikistan

Tadschikistan hat das erste Millenniumsentwicklungsziel (MDG 1 = Halbierung der Anzahl mangel- und unterernährter Menschen bis 2015) weit verfehlt. Eine Verbesserung der Ernährungssicherung bedarf u.a. auch einer Förderung der Landwirtschaft - aufgrund der geographischen Gegebenheiten muss diese Unterstützung in Tadschikistan auch in Gebirgsregionen stattfinden, denn dort werden große Teile der lokalen und nationalen Grundnahrungsmittel eingebracht. Landwirtschaftliche Beratungssysteme bieten die Möglichkeit, über Wissenstransfer die Bodenproduktivität zu erhöhen und Klein- und Mittelbauern weitere unterstützende Dienstleistungen anzubieten. Staatliche Beratungsdienste in Tadschikistan funktionieren allerdings u.a. aufgrund der Haushaltsdefizite des Landwirtschaftsministeriums nicht, gebergeförderte Beratungssysteme stellen mit Ende der Förderungen ihre Dienste häufig ein. Kommerzielle Beratung, wie sie seit 2011 in den Baumwollanbaugebieten des Landes aufgebaut wird, scheint daher ein erfolgversprechender Ansatz, um qualitativ hochwertige, kundenorientierte Dienstleistungen gegen angemessene Bezahlung anzubieten. Erhebungen in Rascht und Muminabad 2014 deuten darauf hin, dass Bauern auch in Bergregionen mit schwierigeren Produktions- und Absatzbedingungen bereit und in der Lage wären, für solche Dienstleistungen und begleitende Angebote und Produktionsmittel zu zahlen. Kommerzielle Beratungsdienste sollten also verstärkt ein Element der Agrarförderung in Tadschikistan werden

Mastigocoleidae fam. nov., a New Mesozoic Beetle Family and the Early Evolution of Dryopoidea (Coleoptera)

With some 3,700 described species, Dryopoidea are a moderately diverse superfamily of beetles whose position within basal Polyphaga has been historically difficult to elucidate. Members of most extant dryopoid families are set apart from the majority of other polyphagans by their association with aquatic habitats, but little is known about the origin of these derived life habits and the phylogeny of the superfamily. Here we describe Mastigocoleidae Tihelka, Jäch, Kundrata & Cai fam. nov., a new family of Mesozoic dryopoids represented by fossils from the Cretaceous Yixian Formation in northeastern China (undescribed species; ~125 Ma), Crato Formation in northeastern Brazil (Mastigocoleus rhinoceros Tihelka & Cai gen. et sp. nov.; ~113 Ma), and amber from northern Myanmar (Mastigocoleus resinicola Tihelka & Cai gen. et sp. nov. and Cretaceocoleus saetosus Tihelka, Kundrata & Cai gen. et sp. nov.; ~99 Ma). Integrating the findings of recent molecular and morphological phylogenetic analyses, we recover Mastigocoleidae as an early-diverging dryopoid clade sister to the families Lutrochidae and Dryopidae, or less likely as a group of putative stem-dryopoids. Mastigocoleidae are most distinctly separated from all other dryopoid families by their whip-like antennae, with 11 antennomeres, reaching to the pronotal base, and with the scape broadest and longest, a short pedicel, and antennomeres II-XI more or less distinctively gradually tapering toward the apex. Mastigocoleidae indicate that the last common ancestor of Dryopoidea was likely terrestrial in the adult stage, and document character acquisitions associated with a specialization for aquatic life

Improvements to the APBS biomolecular solvation software suite

The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve the equations of continuum electrostatics for large biomolecular assemblages that has provided impact in the study of a broad range of chemical, biological, and biomedical applications. APBS addresses three key technology challenges for understanding solvation and electrostatics in biomedical applications: accurate and efficient models for biomolecular solvation and electrostatics, robust and scalable software for applying those theories to biomolecular systems, and mechanisms for sharing and analyzing biomolecular electrostatics data in the scientific community. To address new research applications and advancing computational capabilities, we have continually updated APBS and its suite of accompanying software since its release in 2001. In this manuscript, we discuss the models and capabilities that have recently been implemented within the APBS software package including: a Poisson-Boltzmann analytical and a semi-analytical solver, an optimized boundary element solver, a geometry-based geometric flow solvation model, a graph theory based algorithm for determining p$K_a$ values, and an improved web-based visualization tool for viewing electrostatics