Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

Aflibercept; Càncer colorectal; Perfil del pacientAflibercept; Cáncer colorrectal; Perfil del pacienteAflibercept; Colorectal cancer; Patient profileColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment

Biofilm formation displays intrinsic offensive and defensive features of Bacillus cereus

Biofilm formation is a strategy of many bacterial species to adapt to a variety of stresses and has become a part of infections, contaminations, or beneficial interactions. In this study, we demonstrate that profound physiological changes permit Bacillus cereus to switch from a floating to a sessile lifestyle, to undergo further maturation of the biofilm and to differentiate into the offensive or defensive features. We report that floating and biofilm cells are populations that differentiate metabolically, with members of each subpopulation developing different branches of certain metabolic pathways. Secondly, biofilm populations rearrange nucleotides, sugars, amino acids, and energy metabolism. Thirdly, this metabolic rearrangement coexists with: the synthesis of the extracellular matrix, sporulation, reinforcement of the cell wall, activation of the ROS detoxification machinery and production of secondary metabolites. This strategy contributes to defend biofilm cells from competitors. However, floating cells maintain a fermentative metabolic status that ensures a higher aggressiveness against hosts, evidenced by the production of toxins. The maintenance of the two distinct subpopulations is an effective strategy to face different environmental conditions found in the life styles of B. cereus

Multi-Etiological Nature of Tuberculosis-Like Lesions in Condemned Pigs at the Slaughterhouse.

Tuberculosis-like lesions (TBL) in pigs have been associated with microorganisms other than mycobacteria. In this work a histopathological and microbiological evaluation of TBL in pigs is shown. A total of 352 samples belonging to 171 pigs totally condemned at slaughterhouse due to generalized TBL were sampled and selected for analysis. Pyogranulomatous (56.2%) and granulomatous lesions (20.2%) were observed in all analysed organs. Most of the granulomas observed in both lymph nodes and lungs belonged to more advanced stages of development (stages III and IV) whereas in the liver and the spleen most of lesions belonged to intermediate stages (stages II and III). Different microorganisms were simultaneously detected from TBL in the 42.7% of the animals. Mycobacterium tuberculosis complex (MTC) (38%), coryneform bacteria (40.3%) and streptococci (28.1%) were the main groups of microorganisms detected after bacteriological analysis, with Trueperella pyogenes and Streptococcus suis as the most frequently isolated species. Mycobacteria belonging to MTC were the most frequently detected pathogens in granulomatous and pyogranulomatous lesions in submandibular lymph nodes (32.7%) and coryneform bacteria were the microorganisms more frequently isolated from lungs (25.9%) and spleen samples (37.2%). These results may provide new insights into the pathogenesis and diagnosis of this pathology. The importance of coryneform bacteria and streptococci in such processes must be evaluated in future studies

Multi-Etiological Nature of Tuberculosis-Like Lesions in Condemned Pigs at the Slaughterhouse

Tuberculosis-like lesions (TBL) in pigs have been associated with microorganisms other than mycobacteria. In this work a histopathological and microbiological evaluation of TBL in pigs is shown. A total of 352 samples belonging to 171 pigs totally condemned at slaughterhouse due to generalized TBL were sampled and selected for analysis. Pyogranulomatous (56.2%) and granulomatous lesions (20.2%) were observed in all analysed organs. Most of the granulomas observed in both lymph nodes and lungs belonged to more advanced stages of development (stages III and IV) whereas in the liver and the spleen most of lesions belonged to intermediate stages (stages II and III). Different microorganisms were simultaneously detected from TBL in the 42.7% of the animals. Mycobacterium tuberculosis complex (MTC) (38%), coryneform bacteria (40.3%) and streptococci (28.1%) were the main groups of microorganisms detected after bacteriological analysis, with Trueperella pyogenes and Streptococcus suis as the most frequently isolated species. Mycobacteria belonging to MTC were the most frequently detected pathogens in granulomatous and pyogranulomatous lesions in submandibular lymph nodes (32.7%) and coryneform bacteria were the microorganisms more frequently isolated from lungs (25.9%) and spleen samples (37.2%). These results may provide new insights into the pathogenesis and diagnosis of this pathology. The importance of coryneform bacteria and streptococci in such processes must be evaluated in future studie

Влияние механической активации гидрида титана на его взаимодействие с азотом и кислородом

Показано, что размол гидрида титана в планетарной мельнице приводит к повышению удельной поверхности порошка, росту микроискажений кристаллической решетки, уменьшению содержания в нем водорода и повышению химической активности, что позволяет получать нитрид титана из него в среде азота уже при температуре 500 °С. За счет кислорода, адсорбирован ного механически активированным порошком при нагревании в атмосфере азота, происходят реакции окисления атомов титана, в результате чего образуется низший оксид Tі2О.Показано, що подрібнення гідриду титану в планетарному млині приводить до підвищення питомої поверхні порошку, зростанню дефектів кристалічної ґратки, зменшенню вмісту в ній водню і підвищенню хімічної активності. Це дає змогу досягти повного перетворення механічно активованого гідриду в нітрид титану вже за температури 500 °С і витримці упродовж однієї години в середовищі азоту. За рахунок кисню, адсорбованого механічно активованим порошком при нагрівання в атмосфері азоту, проходять реакції окиснення, в результаті чого утворюється нижчий оксид Ti2O.Milling of titanium hydride in planetary mill is shoun to increase the speci surface area of powder, to decrease the hydrogen content in it and to intensity chemical activity. This makesit possible to obtain titanium nitride from the titanium hydride in a nitrogen atmosphere at as low temperature as 500 °C . Thanks to the presence of oxygen adsorbed by mechanically activated powder under heating in a nitrogen atmosphere? Reaction of intramolecular oxidation -reduction, of titanium takes place, which results in forming the lower oxide Ti2O

Simplified Interval Observer Scheme: A New Approach for Fault Diagnosis in Instruments

There are different schemes based on observers to detect and isolate faults in dynamic processes. In the case of fault diagnosis in instruments (FDI) there are different diagnosis schemes based on the number of observers: the Simplified Observer Scheme (SOS) only requires one observer, uses all the inputs and only one output, detecting faults in one detector; the Dedicated Observer Scheme (DOS), which again uses all the inputs and just one output, but this time there is a bank of observers capable of locating multiple faults in sensors, and the Generalized Observer Scheme (GOS) which involves a reduced bank of observers, where each observer uses all the inputs and m-1 outputs, and allows the localization of unique faults. This work proposes a new scheme named Simplified Interval Observer SIOS-FDI, which does not requires the measurement of any input and just with just one output allows the detection of unique faults in sensors and because it does not require any input, it simplifies in an important way the diagnosis of faults in processes in which it is difficult to measure all the inputs, as in the case of biologic reactors

Fermilab E791

Fermilab E791, a very high statistics charm particle experiment, recently completed its data taking at Fermilab's Tagged Photon Laboratory. Over 20 billion events were recorded through a loose transverse energy trigger and written to 8mm tape in the the 1991-92 fixed target run at Fermilab. This unprecedented data sample containing charm is being analysed on many-thousand MIP RISC computing farms set up at sites in the collaboration. A glimpse of the data taking and analysis effort is presented. We also show some preliminary results for common charm decay modes. Our present analysis indicates a very rich yield of over 200K reconstructed charm decays.Comment: 4 pages, 1 figure, LaTe

Identification of the Begomoviruses Squash Leaf Curl Virus and Watermelon Chlorotic Stunt Virus in Various Plant Samples in North America

Geminiviruses are a group of plant-infecting viruses with single-stranded DNA genomes. Within this family, viruses in the genus Begomovirus are known to have a worldwide distribution causing a range of severe diseases in a multitude of dicotyledonous plant species. Begomoviruses are transmitted by the whitefly Bemisia tabaci, and their ssDNA genomes can be either monopartite or bipartite. As part of a viral survey, various plants including those in the families Alliaceae, Amaranthaceae, Apiaceae, Asteraceae, Brassicaceae, Cactaceae, Cucurbitaceae, Lamiaceae, Lauraceae, Malvaceae, Oleaceae and Solanaceae were sampled and screened for begomoviruses using both a high-throughput sequencing and a begomovirus-specific primer pair approach. Based on the sequences derived using these approaches, the full-length genome of various begomoviruses were amplified from plants using abutting primers. Squash leaf curl virus (SLCV) and watermelon chlorotic stunt virus (WCSV) were identified in Cactaceae (n = 25), Solanaceae (n = 7), Cucurbitaceae (n = 2) and Lamiaceae (n = 1) samples. WCSV is an Old World bipartite begomovirus that has only recently been discovered infecting watermelons in the Americas. Our discovery of WCSV in the USA is the first indication that it has reached this country and indicates that this virus might be widespread throughout North America. Phylogenetic analysis suggests WCSV was introduced to the New World twice. The detection of begomoviruses in cactus plants suggests possible spillover events from agricultural areas into native vegetation. Since WCSV and SLCV have previously been found in mixed infections, pseudo-recombination infection experiments were conducted. We demonstrate that WCSV DNA-B is successfully trans-replicated by SLCV DNA-A despite very low degree of similarity between the replication-associated iterative sequences present in their common region, an essential feature for binding of the replication associated protein. This study highlights the importance of viral surveys for the detection of spillover events into native vegetation, but also suggests the need for more surveillance of WCSV in the USA, as this virus is a serious threat to watermelon cultivation in the Middle East