El examen serológico con muestras de sangre obtenidas en papel de filtro

Se ha puesto a punto una técnica de obtención de sangre total en papel filtro para el muestreo serológico de enfermedades de los conejos tales como: Enfermedad Hemorrágica Viral (RHVD); Encephalitozoonosis; Chlamydia psittaci y Mixomatosis. Se propone como alternativa de muestreo para la determinación de anticuerpos, por ser un método sencillo que no requiere muchos cuidados en el envío al laboratorio. Se evaluaron 94 muestras de suero de conejos llegados al laboratorio para el diagnóstico de las entidades antes citadas. Los resultados serológicos de la muestras de sangre total obtenida por venipuntura y en papel filtro, fueron comparados. Los métodos empleados incluyeron: Inmunofluorescencia Indirecta (IFI) para detectar IgG, Carbón inmunoensayo (CIA) e Inhibición de la Hemoaglutinación (IHA) para la evaluación de anticuerpos totales. Los resultados de sensibilidad, especificidad, índice de concordancia y valores predictivos positivos y negativos obtenidos en este trabajo fueron satisfactorios y nos permitieron decir que la toma y el transporte de muestras de sangre en papel de filtro es una técnica útil con sensibilidad y especificidad adecuada para realizar estudios seroepidemiológicos en conejos

Genetic variability of functional longevity in five rabbit lines

The objectives of this study were to analyse the differences in the genetic determination of functional longevity in five Spanish lines of rabbits and to check how different systematic factors might affect this genetic determination. Four of the lines were maternal (lines A, V, H and LP), these lines were established selecting base generation animals according to different criteria, but in the subsequent generations all of them were selected for litter size at weaning. The other is the paternal line R, this line was constituted by selecting animals with an outstanding daily growth rate. The trait analysed, length of productive life, was the time in days between the date of the first positive pregnancy test and the date of culling or death of a doe. Four models extended from the Cox proportional hazard model were used to analyse data of each line separately and jointly. The complete model (Model 1) included the fixed effect of year-season (YS) combination, positive palpation order (OPP), that is, reproductive cycle, physiological status of the doe (PS) at service and number of kits born alive (NBA) in each kindling as time-dependent factors. The inbreeding coefficient was fitted as a continuous covariate and the animal’s additive genetic effect was also fitted to the model (Model 1). The other models were identical to Model 1 but excluding OPP (Model 2) or PS (Model 3) or NBA (Model 4), which were explored to assess the consequence on additive variance estimates of not correcting for these animal-dependent factors. Estimated effective heritabilities of longevity were 0.07 ± 0.03, 0.03 ± 0.02, 0.14 ± 0.09, 0.05 ± 0.04, 0.02 ± 0.01 and 0.04 ± 0.01 for lines A, V, H, LP, R and for the merged data set, respectively. Removing the PS from the model led to an increase in the estimated additive genetic variance in all lines (0.17 ± 0.05, 0.05 ± 0.03, 0.29 ± 0.19, 0.29 ± 0.20, 0.07 ± 0.04 and 0.05 ± 0.02 for lines A, V, H, LP, R and the merged data set, respectively). The highest hazard of death and/or culling was observed during the first two parities and decreased as the order of parity progressed. Does non-pregnant-non-lactating had the highest risk of death or culling. The does that had zero kits born alive incurred the highest risk, and this risk decreased as the NBA increased. In conclusion, the consideration of longevity as selection criterion for the studied rabbit lines is not recommended.info:eu-repo/semantics/acceptedVersio

Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

IntroductionEffective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population.MethodsBOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints.ResultsFinal study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials.ConclusionThe addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655

Recent Technological Developments on LGAD and iLGAD Detectors for Tracking and Timing Applications

This paper reports the last technological development on the Low Gain Avalanche Detector (LGAD) and introduces a new architecture of these detectors called inverse-LGAD (iLGAD). Both approaches are based on the standard Avalanche Photo Diodes (APD) concept, commonly used in optical and X-ray detection applications, including an internal multiplication of the charge generated by radiation. The multiplication is inherent to the basic n++-p+-p structure, where the doping profile of the p+ layer is optimized to achieve high field and high impact ionization at the junction. The LGAD structures are optimized for applications such as tracking or timing detectors for high energy physics experiments or medical applications where time resolution lower than 30 ps is required. Detailed TCAD device simulations together with the electrical and charge collection measurements are presented through this work.Comment: Keywords: silicon detectors, avalanche multiplication, timing detectors, tracking detectors. 8 pages. 8 Figure

The hVPS34-SGK3 pathway counteracts inhibition of the PI3K-Akt to maintain mTORC1 and tumour growth

We explore mechanisms that enable cancer cells to tolerate PI3K or Akt inhibitors. Prolonged treatment of breast cancer cells with PI3K or Akt inhibitors leads to increased expression and activation of a kinase termed SGK3 that is related to Akt. Under these conditions, SGK3 is controlled by hVps34 that generates PtdIns(3)P, which binds to the PX domain of SGK3 promoting phosphorylation and activation by its upstream PDK1 activator. Furthermore, under conditions of prolonged PI3K/Akt pathway inhibition, SGK3 substitutes for Akt by phosphorylating TSC2 to activate mTORC1. We characterise 14h, a compound that inhibits both SGK3 activity and activation in vivo, and show that a combination of Akt and SGK inhibitors induced marked regression of BT‐474 breast cancer cell‐derived tumours in a xenograft model. Finally, we present the kinome‐wide analysis of mRNA expression dynamics induced by PI3K/Akt inhibition. Our findings highlight the importance of the hVps34‐SGK3 pathway and suggest it represents a mechanism to counteract inhibition of PI3K/Akt signalling. The data support the potential of targeting both Akt and SGK as a cancer therapeutic

Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655