This work evaluates the glass formation of selected alloys based on the Ti–Zr–Fe–Co system, assuming the synergy of two distinct criteria: minimum topological instability and average ...electronegativity plots. Combining the minimum topological instability and the average electronegativity values result in a plot in which the most probable good glass former compositions are identified. Ti–Zr rich alloys with Fe and Co additions were produced, compared against the final plot, and the best glass forming alloy composition was found to be very close the theoretically predicted ones on the Ti–Zr rich side, for both Ti–Zr–Fe and Ti–Zr–Co systems.
The illegal use of glucocorticoids (GCs) as growth-promoters (GPs) is prohibited in farm animals in the European Union because the strong pharmacological activity of most synthetic GCs produces ...residues that are dangerous for human consumption. Among the alternative methods proposed to increase the efficacy of official controls, histology was the technique of choice in Italy on account of its high performance level. The aim of this study was to evaluate the reliability of immunohistochemistry (IHC) using anti-cleaved-Lamin A antibody to enhance the performance of the histological test applied to GC-related microscopic changes in the thymus. Veal calves (VC) and beef cattle (BC) were raised and both underwent different growth-promoting protocols or were left untreated. The morphology of the thymus parenchyma was evaluated for cortical atrophy with concurrent adipose tissue infiltration, and a score of 1 to 3 was attributed. A semi-quantitative IHC analysis was also performed by counting the number of positive thymocytes in 5 randomly selected high-power fields (HPFs). The distribution of the thymus atrophy scores was significantly different among the subgroups in both BC and VC. The IHC values were higher in untreated than in treated animals, for both BC and VC. The association between thymus atrophy score and IHC positivity showed higher median values in control than in treated animals (independently of the treatment protocol), for both BC and VC. Our data shows that IHC against anti-cleaved-Lamin A antibody is a reliable marker to detect illegal GC treatments, administered either alone or in association with other growth promoters, in both BC and VC. Combining IHC with the thymus atrophy score improves the accuracy of the histological method in correctly identifying treated animals and could represent a valuable, reproducible method to be applied to large-scale screening programmes.
Acute alcohol consumption causes deficits in motor coordination and gait, suggesting an involvement of cerebellar circuits, which play a role in the fine adjustment of movements and in motor ...learning. It has previously been shown that ethanol modulates inhibitory transmission in the cerebellum and affects synaptic transmission and plasticity at excitatory climbing fiber (CF) to Purkinje cell synapses. However, it has not been examined thus far how acute ethanol application affects long-term depression (LTD) and long-term potentiation (LTP) at excitatory parallel fiber (PF) to Purkinje cell synapses, which are assumed to mediate forms of cerebellar motor learning. To examine ethanol effects on PF synaptic transmission and plasticity, we performed whole cell patch-clamp recordings from Purkinje cells in rat cerebellar slices. We found that ethanol (50 mM) selectively blocked PF-LTD induction, whereas it did not change the amplitude of excitatory postsynaptic currents at PF synapses. In contrast, ethanol application reduced voltage-gated calcium currents and type 1 metabotropic glutamate receptor (mGluR1)-dependent responses in Purkinje cells, both of which are involved in PF-LTD induction. The selectivity of these effects is emphasized by the observation that ethanol did not impair PF-LTP and that PF-LTP could readily be induced in the presence of the group I mGluR antagonist AIDA or the mGluR1a antagonist LY367385. Taken together, these findings identify calcium currents and mGluR1-dependent signaling pathways as potential ethanol targets and suggest that an ethanol-induced blockade of PF-LTD could contribute to the motor coordination deficits resulting from alcohol consumption.
Sympatric species are expected to differ in ecological requirements to minimize niche overlap and avoid competition. Here we assess the trophic interactions among three coexisting dolphin species ...from southern Brazil: the franciscana dolphin (Pontoporia blainvillei), the Guiana dolphin (Sotalia guianensis), and the Lahille's bottlenose dolphin (Tursiops truncatus gephyreus). We evaluated temporal variation in carbon (δ13C) and nitrogen (δ15N) isotope values of bone collagen to examine potential dietary shifts resulting from increased fishing activity over the past three decades. We estimated the degree of niche overlap among these species and the contribution of potential prey sources to their diet. δ15N values were consistent among species and across years, while δ13C values increased for Guiana dolphins and decreased for bottlenose dolphins, suggesting changes in diet and/or foraging habitats through time. The similar δ13C and δ15N values and the high niche overlap between Guiana and bottlenose dolphins indicate that these species are primarily feeding on demersal prey. The franciscana diet is primarily composed of pelagic prey, resulting in a lower niche overlap in comparison with the other dolphin species. Our study provides further information about the foraging ecology of this unique dolphin community in southern Brazil with implications for its management and conservation.
The southwestern Atlantic Ocean (SWA) represents an important foraging ground for loggerhead sea turtles (
Caretta caretta
). Most studies at the region have focused on adult females and juveniles, ...and little is known about males. Here, we present the first insights about origin and foraging ecology of male loggerheads from the SWA, by integrating genetic and stable isotope analysis (SIA). Skin samples were obtained from 26 males stranded along the southern coast of Brazil (from 31°21′S–51°05′W to 33°44′S–53°22′W), from February 2014 to March 2017. Samples of potential food sources (benthic and pelagic organisms) were also collected for SIA. A fragment of the mitochondrial DNA control region was sequenced and a Bayesian Mixed Stock Analysis was performed to estimate natal origins of male loggerheads. Bayesian Stable Isotope Mixing Models were fitted to assess the relative contribution of different food sources assimilated by males. Most males exhibit endemic haplotypes from Brazilian rookeries, followed by a low frequency of a haplotype from the North Atlantic and the Mediterranean Sea, as well as olive ridley (
Lepidochelys olivaea
) haplotype, showing hybridization. SIA showed life stage-related differences in feeding and habitat use by male loggerheads, with benthic invertebrates dominating the diet of adults, while pelagic prey items dominated the diet of juveniles. Our findings demonstrate the importance of southern Brazil neritic and oceanic habitats for male loggerheads and highlight the value of this area for the maintenance of SWA reproductive management units, which are the main contributors to these feeding aggregations.
Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose ...a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.
•We investigated levels of glucocorticoids in calf urine after prednisolone treatments.•Free 6β-hydroxyhydrocortisone was studied as possible biomarker of illicit treatment.•Urinary levels of ...prednisolone during the treatments never exceeded 1.1ngmL−1.•Similar prednisolone levels were found in samples of both treated and untreated calves.
Over the last few years, low levels of prednisolone have been reported in several cattle urine samples by a number of laboratories within the EU at an average concentration of 2.0ngmL−1. The occurrence of prednisolone residues together with increased levels of hydrocortisone and cortisone in urine and tissue samples of untreated animals seems to demonstrate that traces of this steroid can be produced endogenously during stressful situations. Therefore, the endogenous origin of prednisolone makes difficult to correlate positive samples to a potential illicit treatment. An experimental study was developed to investigate the presence of natural and synthetic glucocorticoids and to evaluate levels of excreted prednisolone following growth-promoting treatments. Urine samples from calves undergone oral treatment with prednisolone, alone and in association with dexamethasone, were analyzed by a LC–MS/MS method, validated according to the Commission Decision 2002/657/EC. We also investigated if urinary free 6β-hydroxyhydrocortisone/hydrocortisone ratio could be a reliable biomarker of illicit treatment with prednisolone and dexamethasone in calves. Our data revealed that urinary levels of prednisolone after both oral prednisolone treatments, never exceeded the value of 1.1ngmL−1. Similar prednisolone levels were found in urine samples of untreated calves. Moreover the presence of 6β-hydroxyhydrocortisone below the CCα value made possible to estimate the 6β-hydroxyhydrocortisone/hydrocortisone ratio only in a very limited number of samples. Obtained data suggest that further criteria have to be considered to allow correct decisions about the urinary presence of prednisolone during control activities.
Ti-6Al-7Nb alloys are being evaluated for biomedical applications, in substitution of the more conventional Ti-6Al-7V. Both types of alloys present a microstructure containing the alpha and the beta ...phases, which result in good compromise for mechanical applications. In the present work Ti-6Al-7Nb alloys were processed by High Pressure Torsion (HPT), varying the number of revolutions and thus the total imposed strain. X-Ray Diffraction (XRD) results revealed the formation of different crystallographic textures in samples subjected to HPT. Microhardness distribution, across the diameters of the disks, is rather homogeneous for all samples, with higher values for those subjected to 03 and 05 turns. Transmission electron microscopy (TEM) micrographs have showed that an ultra-fine grained microstructurc was obtained in all the samples.
Undetectable measurable residual disease (MRD) is a surrogate of prolonged survival in multiple myeloma. Thus, treatment individualization based on the probability of a patient achieving undetectable ...MRD with a singular regimen could represent a new concept toward personalized treatment, with fast assessment of its success. This has never been investigated; therefore, we sought to define a machine learning model to predict undetectable MRD at the onset of multiple myeloma.
This study included 487 newly diagnosed patients with multiple myeloma. The training (n = 152) and internal validation cohorts (n = 149) consisted of 301 transplant-eligible patients with active multiple myeloma enrolled in the GEM2012MENOS65 trial. Two external validation cohorts were defined by 76 high-risk transplant-eligible patients with smoldering multiple myeloma enrolled in the Grupo Español de Mieloma(GEM)-CESAR trial, and 110 transplant-ineligible elderly patients enrolled in the GEM-CLARIDEX trial.
The most effective model to predict MRD status resulted from integrating cytogenetic t(4;14) and/or del(17p13), tumor burden (bone marrow plasma cell clonality and circulating tumor cells), and immune-related biomarkers. Accurate predictions of MRD outcomes were achieved in 71% of cases in the GEM2012MENOS65 trial (n = 214/301) and 72% in the external validation cohorts (n = 134/186). The model also predicted sustained MRD negativity from consolidation onto 2 years maintenance (GEM2014MAIN). High-confidence prediction of undetectable MRD at diagnosis identified a subgroup of patients with active multiple myeloma with 80% and 93% progression-free and overall survival rates at 5 years.
It is possible to accurately predict MRD outcomes using an integrative, weighted model defined by machine learning algorithms. This is a new concept toward individualized treatment in multiple myeloma. See related commentary by Pawlyn and Davies, p. 2482.
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