Tailoring chitosan/collagen scaffolds for tissue engineering: Effect of composition and different crosslinking agents on scaffold properties.

Chitosan/collagen (Chit/Col) blends have demonstrated great potential for use in tissue engineering (TE) applications. However, there exists a lack of detailed study on the influence of important design parameters (i.e, component ratio or crosslinking methods) on the essential properties of the scaffolds (morphology, mechanical stiffness, swelling, degradation and cytotoxicity). This work entailed a systematic study of these essential properties of three Chit/Col compositions, covering a wide range of component ratios and using different crosslinking methods. Our results showed the possibility of tailoring these properties by changing component ratios, since different interactions occurred between Chit/Col: samples with Chit-enriched compositions showed a hydrogen-bonding type complex (HC), whereas a self-crosslinking phenomenon was induced in Col-enriched scaffolds. Additionally, material and biological properties of the resultant matrices were further adjusted and tuned by changing crosslinking conditions. In such way, we obtained a wide range of scaffolds whose properties were tailored to meet specific needs of TE applications.The authors are grateful to Dr. von Kobbe (Chimera Pharma of Bionostra Group) for the gift of MCF7 cells. The financial support of the Ministerio de Ciencia e Innovación of Spain (FIS PS09/01513), and the FPI grant from UCM to A. Martínez are gratefully acknowledged.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.carbpol.2015.06.08

Electrocardiographic changes in normal and abnormal canine pregnancy

The aim of this study was to describe the canine electrocardiographic changes in the course of normal and abnormal pregnancy. Twenty-three Brucellosis-negative pregnant bitches were retrospectively classified as normal (n=12) or abnormal (n=11). A control group of non-pregnant dioestrous bitches (n=10) was also included. Normal pregnant females delivered healthy puppies at term while abnormal animals interrupted their pregnancy between days 52-60 (from estimated luteinizing hormone peak) or presented perinatal litter death higher than 60%. All the bitches were electrocardiographically evaluated every 10days from day 0 to day 65 of the oestrous cycle, to parturition or abortion. Percentage heart rate change increased 31.3% from day 40 to 60 in normal gestation while it decreased -1.8% in dioestrous bitches, although it did not change in the abnormal group (p<0.01). In the abnormal pregnant group but not in the others, percentage QRSa change fell to -34% on day 60 (p<0.01). At the same time point, percentage QRSd change was 6.2% vs -4.9% in normal gestations and dioestrous animals, respectively (p<0.05). Corrected QT interval augmented from day 40 onwards up to 9.9% and 4.3% in the normal pregnant and dioestrous groups, respectively, while it remained unchanged in abnormal gestations (p<0.05). It is concluded that during normal canine pregnancy, some electrocardiographic parameters begin changing from day 40 onwards, and that pathological gestations differ from normality from day 30. The use of electrocardiography in canine obstetrics might contribute to identify abnormal outcomes before they become clinically evident.Fil: Blanco, Paula Graciela. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Batista, Pablo Rodrigo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Re, N. E.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Mattioli, Guillermo Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Ciencias Básicas. Laboratorio de Nutrición Mineral y Fisiología Reproductiva; ArgentinaFil: Arias, Daniel Osvaldo. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Gobello, María Cristina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

The ILIUM forward modelling algorithm for multivariate parameter estimation and its application to derive stellar parameters from Gaia spectrophotometry

I introduce an algorithm for estimating parameters from multidimensional data based on forward modelling. In contrast to many machine learning approaches it avoids fitting an inverse model and the problems associated with this. The algorithm makes explicit use of the sensitivities of the data to the parameters, with the goal of better treating parameters which only have a weak impact on the data. The forward modelling approach provides uncertainty (full covariance) estimates in the predicted parameters as well as a goodness-of-fit for observations. I demonstrate the algorithm, ILIUM, with the estimation of stellar astrophysical parameters (APs) from simulations of the low resolution spectrophotometry to be obtained by Gaia. The AP accuracy is competitive with that obtained by a support vector machine. For example, for zero extinction stars covering a wide range of metallicity, surface gravity and temperature, ILIUM can estimate Teff to an accuracy of 0.3% at G=15 and to 4% for (lower signal-to-noise ratio) spectra at G=20. [Fe/H] and logg can be estimated to accuracies of 0.1-0.4dex for stars with G<=18.5. If extinction varies a priori over a wide range (Av=0-10mag), then Teff and Av can be estimated quite accurately (3-4% and 0.1-0.2mag respectively at G=15), but there is a strong and ubiquitous degeneracy in these parameters which limits our ability to estimate either accurately at faint magnitudes. Using the forward model we can map these degeneracies (in advance), and thus provide a complete probability distribution over solutions. (Abridged)Comment: MNRAS, in press. This revision corrects a few minor errors and typos. A better formatted version for A4 paper is available at http://www.mpia.de/home/calj/ilium.pd

Stellar atmosphere parameters with MAx, a MAssive compression of x^2 for spectral fitting

MAx is a new tool to estimate parameters from stellar spectra. It is based on the maximum likelihood method, with the likelihood compressed in a way that the information stored in the spectral fluxes is conserved. The compressed data are given by the size of the number of parameters, rather than by the number of flux points. The optimum speed-up reached by the compression is the ratio of the data set to the number of parameters. The method has been tested on a sample of low-resolution spectra from the Sloan Extension for Galactic Understanding and Exploration (SEGUE) survey for the estimate of metallicity, effective temperature and surface gravity, with accuracies of 0.24 dex, 130K and 0.5 dex, respectively. Our stellar parameters and those recovered by the SEGUE Stellar Parameter Pipeline agree reasonably well. A small sample of high-resolution VLT-UVES spectra were also used to test the method and the results have been compared to a more classical approach. The speed and multi-resolution capability of MAx combined with its performance compared with other methods indicates that it will be a useful tool for the analysis of upcoming spectral surveys.Comment: 17 pages, 10 figures, minor changes after the chief language editor. A&A, in pres

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE) : study protocol for a randomized controlled trial

Peer reviewedPublisher PD

The expected performance of stellar parametrization with Gaia spectrophotometry

Gaia will obtain astrometry and spectrophotometry for essentially all sources in the sky down to a broad band magnitude limit of G=20, an expected yield of 10^9 stars. Its main scientific objective is to reveal the formation and evolution of our Galaxy through chemo-dynamical analysis. In addition to inferring positions, parallaxes and proper motions from the astrometry, we must also infer the astrophysical parameters of the stars from the spectrophotometry, the BP/RP spectrum. Here we investigate the performance of three different algorithms (SVM, ILIUM, Aeneas) for estimating the effective temperature, line-of-sight interstellar extinction, metallicity and surface gravity of A-M stars over a wide range of these parameters and over the full magnitude range Gaia will observe (G=6-20mag). One of the algorithms, Aeneas, infers the posterior probability density function over all parameters, and can optionally take into account the parallax and the Hertzsprung-Russell diagram to improve the estimates. For all algorithms the accuracy of estimation depends on G and on the value of the parameters themselves, so a broad summary of performance is only approximate. For stars at G=15 with less than two magnitudes extinction, we expect to be able to estimate Teff to within 1%, logg to 0.1-0.2dex, and [Fe/H] (for FGKM stars) to 0.1-0.2dex, just using the BP/RP spectrum (mean absolute error statistics are quoted). Performance degrades at larger extinctions, but not always by a large amount. Extinction can be estimated to an accuracy of 0.05-0.2mag for stars across the full parameter range with a priori unknown extinction between 0 and 10mag. Performance degrades at fainter magnitudes, but even at G=19 we can estimate logg to better than 0.2dex for all spectral types, and [Fe/H] to within 0.35dex for FGKM stars, for extinctions below 1mag.Comment: MNRAS, in press. Minor corrections made in v

The chemical signature of the Galactic spiral arms revealed by Gaia DR3

Taking advantage of the recent Gaia Data Release 3 (DR3), we map chemical inhomogeneities in the Milky Way's disc out to a distance of $\sim$ 4 kpc from the Sun, using different samples of bright giant stars. The samples are selected using effective temperatures and surface gravities from the GSP-Spec module, and are expected to trace stellar populations of different typical age. The cool (old) giants exhibit a relatively smooth radial metallicity gradient with an azimuthal dependence. Binning in Galactic azimuth $\phi$, the slope gradually varies from $d$[M/H]$/dR \sim -0.054$ dex kpc$^{-1}$ at $\phi \sim -20^{\circ}$ to $\sim -0.035$ dex kpc$^{-1}$ at $\phi \sim 20^{\circ}$. On the other hand, the relatively hotter (and younger) stars present remarkable inhomogeneities, apparent as three (possibly four) metal-rich elongated features in correspondence of the spiral arms' locations in the Galactic disc. When projected onto Galactic radius, those features manifest themselves as statistically significant bumps on top of the observed radial metallicity gradients with amplitudes up to $\sim 0.05-0.1$ dex, making the assumption of a linear radial decrease not applicable to this sample. The strong correlation between the spiral structure of the Galaxy and the observed chemical pattern in the young sample indicates that the spiral arms might be at the origin for the detected chemical inhomogeneities. In this scenario, the spiral arms would leave in the younger stars a strong signature, which progressively disappears when cooler (and older) giants are considered.Comment: 9 pages, 6 figures. Accepted for publication in A&A Letter

Influence of dose and route of administration on the outcome of infection with the virulent Neospora caninum isolate Nc-Spain7 in pregnant sheep at mid-gestation

Experimental infections in pregnant sheep have been focused on studying the effect of the time of challenge on the outcome of N. caninum infection, whereas the impact of the dose and route of challenge has not been studied in depth. Therefore, clinical outcome, immune responses, parasite detection and burden, and lesion severity in placental tissues and foetal brains were investigated in 90-day-pregnant sheep inoculated intravenously with 105 (G1), 104 (G2), 103 (G3), or 102 (G4) tachyzoites or subcutaneously with 104 (G5) tachyzoites of the virulent Nc-Spain7 isolate and an uninfected group (G6). Comparing challenge doses, G1 was the only group that had 100% abortion. Likewise, IFN¿ levels in G1 increased earlier than those in other intravenously infected groups, and IgG levels on day 21 post-infection (pi) were higher in G1 than those in other intravenously infected groups. Concerning vertical transmission, G1 shows a higher parasite burden in the foetal brain than did G2 and G3. Comparing routes of administration, no differences in foetal survival rate or parasite load in the foetal brain were found. Although G2 had higher IFN¿ levels than G5 on day 10 pi, no differences were found in humoral immune responses. Because the outcome after intravenous infection with 105 tachyzoites was similar to that observed after intravenous infection with 106 tachyzoites used in a previous work (100% abortion and vertical transmission), we conclude that it may be reasonable to use 105 tachyzoites administered by the intravenous route in further experiments when assessing drugs or vaccine candidates

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14&nbsp;weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48&nbsp;weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching