We performed a time-resolved spectroscopic study of the VUV/UV scintillation of gaseous argon as a function of pressure and electric field, by means of a wavelength sensitive detector operated with ...different radioactive sources. Our work conveys new evidence of distinctive features of the argon light which are in contrast with the general assumption that, for particle detection purposes, the scintillation can be considered to be largely monochromatic at 128 nm (second continuum). The wavelength and time-resolved analysis of the photon emission reveal that the dominant component of the argon scintillation during the first tens of ns is in the range 160, 325 nm. This light is consistent with the third continuum emission from highly charged argon ions/molecules. This component of the scintillation is field-independent up to 25 V/cm/bar and shows a very mild dependence with pressure in the range 1, 16 bar. The dynamics of the second continuum emission is dominated by the excimer formation time, whose variation as a function of pressure has been measured. Additionally, the time and pressure-dependent features of electron-ion recombination, in the second continuum band, have been measured. This study opens new paths toward a novel particle identification technique based on the spectral information of the noble-elements scintillation light.
This multicentre, randomised, and phase II study evaluated mFOLFOX+cetuximab followed by maintenance mFOLFOX+cetuximab or single-agent cetuximab in metastatic colorectal cancer (mCRC) patients ...(NCT01161316).
Previously, untreated mCRC patients (wild-type KRAS) were randomised to receive cetuximab+mFOLFOX-6 (8 cycles for 2 weeks) followed by maintenance therapy: single-agent cetuximab (Arm-A) or mFOLFOX-6 + cetuximab (Arm-B) until progression. Primary endpoint was progression-free survival (PFS) at 9 months.
One hundred ninety-three patients (median range age 60 33–74 years) were randomised (2:1): 129 Arm-A versus 64 Arm-B. PFS at 9 months (95% confidence interval) showed non-inferiority between arms (Arm-A/Arm-B: 60 52, 69%/72 61, 83%, p non-inferiority<0.1). There were no statistically significant differences in the PFS (Arm-A/Arm-B: 9 95% CI 7, 10 months/10 7,13 months, hazard ratio HR = 1.19 0.80, 1.79) or overall survival (23 19, 28 months/27 18, 36 months, HR = 1.24 0.85, 1.79) between arms. The objective response rate was also similar (48 39, 57%/39 27, 52%). The safety profile was similar between arms, and all patients experienced at least one adverse event (AE) (Arm-A/Arm-B grade ≥III AEs: 70%/68%). The most common grade ≥III AEs were as follows: neutropenia (Arm-A/Arm-B: 28%/26%), rash acneiform (15%/24%) and sensory neuropathy (2%/15%) in any group. Arm-A was associated with less grade ≥III rash and sensory neuropathy and a lower rate of serious AEs (20%/27%).
This phase II exploratory trial with a non-inferiority design suggests that maintenance therapy with single-agent cetuximab following mFOLFOX+cetuximab induction could be a valuable option compared with mFOLFOX+cetuximab treatment continuation. We await phase III trials to confirm single-agent cetuximab as maintenance therapy in mCRC patients.
•Cetuximab alone could be a viable maintenance therapy option in metastatic colorectal cancer patients.•Progression-free survival (PFS) at 9 months was similar between cetuximab alone and FOLFOX+cetuximab.•PFS and overall survival were similar between cetuximab alone and FOLFOX+cetuximab.•Safety profile was similar between cetuximab alone and FOLFOX+cetuximab.
Abstract
Cerambyx welensii
Küster (Coleoptera: Cerambycidae) is a wood‐borer responsible for the decline of Mediterranean oaks in open woodlands.
To establish that contact pheromones are involved in ...mate recognition of
C. welensii
, we extracted the cuticular hydrocarbons by solid phase microextraction at pre‐reproductive, beginning and ending of the reproductive period, and by solvent extraction of prothorax and elytra. The extracts were analysed by GC–MS under electron impact and chemical ionization conditions. Cuticular hydrocarbon profiles varied according to the reproductive period, although differences between sexes were not significant. Two compounds, 11/13‐methylheptacosane and 11‐methylnonacosane were more abundant in females at the beginning and ending of the reproductive periods. Compound 11/13‐methylheptacosane was also more representative in female prothorax than in males, and 2‐methyloctacosane was richer in male elytra than in females.
We also studied the role of cuticular hydrocarbons in mate recognition in arena bioassays. Treatment of solvent‐washed dead females and glass dummies with one female equivalent (FE) of cuticular extract elicited mating responses in males, especially at the beginning of the reproductive period, with copulation attempts reaching 61.9% on solvent‐washed dead females and 23.8% on dummies. The successive treatment with synthetic compounds approaching a male cuticular profile inhibited male response.
Our results confirm that contact pheromones mediate mate recognition in
C. welensii
. Knowledge of the precise role played by the major compounds 11/13‐methylheptacosane and 11‐methylnonacosane and other minor compounds representative in female prothorax may contribute to the development of novel management strategies against
C. welensii
.
Resumen
Cerambyx welensii
Küster (Coleoptera: Cerambycidae) es un insecto xilófago que afecta a especies mediterráneas de
Quercus
.
Para estudiar si la estimulación química por contacto influye en el apareamiento de
C. welensii
se extrajeron los hidrocarburos cuticulares de ambos sexos. Para ello se realizó microextracción en fase sólida en los momentos previo, inicio y final del período reproductivo. Además, se llevó a cabo la extracción con disolvente de protórax y élitros. Los extractos fueron analizados por CG‐EM en impacto electrónico e ionización química. Los perfiles de hidrocarburos cuticulares variaron según el período reproductivo, aunque las diferencias entre sexos no resultaron significativas. El 11/13‐metilheptacosano y el 11‐metilnonacosano fueron los hidrocarburos más abundantes en hembras. En protórax de hembras, el 11/13‐metilheptacosano fue de nuevo el compuesto más representativo, mientras que el 2‐metiloctacosano lo fue en élitros de machos.
Se estudió también la actividad de los hidrocarburos cuticulares en bioensayos de apareamiento. La aplicación de un equivalente de extracto cuticular de hembras sobre carcasas de hembras lavadas con hexano y sobre señuelos de vidrio provocó intentos de cópula en los machos, especialmente al inicio del período reproductivo (61.9% y 23.8%, frente a carcasas y señuelos de vidrio, respectivamente).
Nuestros resultados confirman que feromonas de contacto pueden inducir el apareamiento en
C. welensii
. El conocimiento preciso del papel que desempeñan los principales hidrocarburos cuticulares 11/13‐metilheptacosano y 11‐metilnonacosano, junto a otros compuestos menores representativos del protórax de las hembras, podría contribuir a desarrollar nuevas estrategias de control para
C. welensii
.
In this work, we analyze the spectrum of solar cosmic rays flux during ground-level enhancements using the pair of lead-free and standard neutron monitors in the South Pole station. Using both ...monitor data, effects due to anisotropy are considerably reduced. We assume a power-law form for the solar particle spectrum at the top of the atmosphere. The spectral index was computed during all events for which data were available, regardless of the duration or the intensity of the GLE. Seventeen events were analyzed. In this paper, we show the efficiency of the method used, as well as a clear tendency of the spectral index behavior to the ratio between the observed increases in both monitors. It is also shown that the method can be used to calculate the solar cosmic ray spectrum at any required stage of the event. Our results show that the spectral index estimation depends on the choice of the yield function. For the three yield functions used in the analysis, the spectral index changes by about 10%.
Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus ...injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.
Display omitted
Fueyo and colleagues observed that anti-viral immune responses may have hindered the efficacy of virotherapy in clinical trials. To overcome this limitation, they generated a chimeric immune-stealth oncolytic adenovirus that evaded neutralizing antibodies from patients previously treated with parental oncolytic viruses and prolonged the survival of glioma-bearing mice.
We analysed 15,101 biological samples from patients presenting with superficial mycoses who attended outpatient services over a 10-year period. Scale samples were processed for direct microscopic ...examination with 15% KOH and cultured on Sabouraud glucose agar plus chloramphenicol and cycloheximide. Laboratory examination confirmed 4,709 cases of superficial mycosis (31.18%), of which 2,084 (44.26%) were dermatophytoses. The species most frequently encountered was Trichophyton rubrum (71.2%), followed by T. tonsurans (6.9%), T. mentagrophytes (5.5%), Microsporum canis (4.5%) and Epidermophyton floccosum (1.3%). The most frequent clinical form of dermatophytosis was tinea unguium (59.9%), followed by tinea pedis (24.5%). We demonstrate that the number of cases of T. rubrum is increasing in Mexico.
To validate externally the CACE-HF clinical prediction rule, which predicts 1-year mortality in patients with heart failure (HF).
We performed an external validation of the CACE-HF risk score in ...patients included in the RICA heart failure registry who had completed 1 year of follow-up, comparing the characteristics of the derivation and validation cohorts. The performance of the risk score was evaluated in terms of calibration, using calibration-in-the-large (a), calibration slope (b), and the Hosmer-Lemeshow test, and in terms of discrimination, using the area under the ROC curve.
In total, 3337 patients were included in the validation cohort. There were no significant differences between the derivation and validation cohorts in 1-year mortality (24.63% vs. 22.98%) or in the risk score and risk classes. The discrimination capacity in the validation cohort was slightly lower, 0.67 (95% CI: 0.65, 0.69), compared to that of the derivation cohort. Calibration results were a −0.05 (95% CI: −0.14, 0.03), indicating that the average predictions did not differ from the average outcome frequency, and b = 0.75 (95% CI: 0.64, 0.86), indicating a modest inconsistency in predictor effects. Observed mortality versus predicted mortality according to the deciles and risk classes were very similar in both cases, indicating good calibration.
The results of the external validation of the CACE-HF risk score show that although the capacity for discrimination was slightly lower than in the derivation cohort, the calibration was excellent. This tool, therefore, can assist in decision-making in the management of these patients.
•To improve our management of HF we need tools to optimize the available resources.•The prognostic models help us differentiate the life expectancy of the HF patients.•We have externally validated a risk model to predict 1-year mortality.•The model was developed and validated in real-world cohorts of HF patients.
PDF
