Amostragem de indivíduos representativos em uma população de animais da raça Canchim aparentados e genotipados.

O objetivo neste estudo foi avaliar diferentes métodos para selecionar uma amostra de uma população contendo animais aparentados, representando estratos de famílias, de forma que os animais selecionados representem toda a população. Utilizaram-se duas fontes de informação para o estudo. A primeira foi o arquivo de pedigree (animal, pai e mãe) constituído de 6.801 animais da raça Canchim, sendo 400 animais genotipados . A segunda foi a matriz de parentesco constituída pelos coeficientes de parentesco dos 400 animais genotipados, organizados na forma de matriz, com os animais nas linhas e colunas e os correspondentes coeficientes de parentesco dentro da matriz (BOURDON, 2000)

Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases.

We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs

Comparing Mobile Laser Scanner and manual measurements for dendrometric variables estimation in a black pine (Pinus nigra Arn.) plantation

The growing demand of ecosystem services provided by forests increased the need for fast and accurate field survey. The recent technological innovations fostered the application of geomatic tools and processes to different fields of the forestry sector. In this study we compared the efficiency and the accuracy of Mobile Laser Scanner (MLS), combined with Simultaneous Localization and Mapping (SLAM) technology, and traditional field survey for the mensuration of main forest dendrometric variables like stem diameter at breast height (DBH), individual tree height (H), crown base height (CBH) and branch-free stem volume (VOL). With ground truth measurements taken from 50 felled trees, we tested the applicability of MLS technology for individual tree parameters esti-mation in a conifer plantation in central Italy. Our results showed no bias of DBH estimates and the corre-sponding RMSE was equal to 10.8% (2.7 cm). H and CBH measured with MLS were underestimated compared to the ground truth (bias of-8.6% for H and-13.3% for CBH). VOL values showed a bias and a RMSE of-4.1% (-0.01 m(3)) and 12.4% (0.04 m3) respectively. Tree height is not perfectly estimated due to laser obstruction by crowns layer, but the acquisition speed of this survey, joined with a suitable accuracy of parameters extraction, suggests sufficient suitability of the method for operational applications in simple forest structures (e.g. one-layered stands)

Millennium-long summer temperature variations in the European Alps as reconstructed from tree rings

This paper presents a reconstruction of the summer temperatures over the Greater Alpine Region (44.05A degrees-47.41A degrees N, 6.43A degrees-13A degrees E) during the last millennium based on a network of 38 multi-centennial larch and stone pine chronologies. Tree ring series are standardized using an Adaptative Regional Growth Curve, which attempts to remove the age effect from the low frequency variations in the series. The proxies are calibrated using the June to August mean temperatures from the HISTALP high-elevation temperature time series spanning the 1818-2003. The method combines an analogue technique, which is able to extend the too short tree-ring series, an artificial neural network technique for an optimal non-linear calibration including a bootstrap technique for calculating error assessment on the reconstruction. About 50% of the temperature variance is reconstructed. Low-elevation instrumental data back to 1760 compared to their instrumental target data reveal divergence between (warmer) early instrumental measurements and (colder) proxy estimates. The proxy record indicates cool conditions, from the mid-11th century to the mid-12th century, related to the Oort solar minimum followed by a short Medieval Warm Period (1200-1420). The Little Ice Age (1420-1830) appears particularly cold between 1420 and 1820 with summers that are 0.8 A degrees C cooler than the 1901-2000 period. The new record suggests that the persistency of the late 20th century warming trend is unprecedented. It also reveals significant similarities with other alpine reconstructions

Cost-effectiveness analysis of Vaborem in Carbapenem-resistant Enterobacterales (CRE) -Klebsiella pneumoniae infections in Italy

Background: Vaborem is a fixed dose combination of vaborbactam and meropenem with potent activity against target Carbapenem-resistant Enterobacterales (CRE) pathogens, optimally developed for Klebsiella pneumoniae carbapenemase (KPC). The study aims to evaluate the cost-effectiveness of Vaborem versus best available therapy (BAT) for the treatment of patients with CRE-KPC associated infections in the Italian setting. Methods: A cost-effectiveness analysis was conducted based on a decision tree model that simulates the clinical pathway followed by physicians treating patients with a confirmed CRE-KPC infection in a 5-year time horizon. The Italian National Health System perspective was adopted with a 3% discount rate. The clinical inputs were mostly sourced from the phase 3, randomised, clinical trial (TANGO II). Unit costs were retrieved from the Italian official drug pricing list and legislation, while patient resource use was validated by a national expert. Model outcomes included life years (LYs) and quality adjusted life years (QALYs) gained, incremental costs, incremental cost- effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Deterministic and probabilistic sensitivity analyses were also performed. Results: Vaborem is expected to decrease the burden associated with treatment failure and reduce the need for chronic renal replacement therapy while costs related to drug acquisition and long-term care (due to higher survival) may increase. Treatment with Vaborem versus BAT leads to a gain of 0.475 LYs, 0.384 QALYs, and incremental costs of €3549, resulting in an ICER and ICUR of €7473/LY and €9246/QALY, respectively. Sensitivity analyses proved the robustness of the model and also revealed that the probability of Vaborem being cost-effective reaches 90% when willingness to pay is €15,850/QALY. Conclusions: In the Italian setting, the introduction of Vaborem will lead to a substantial increase in the quality of life together with a minimal cost impact, therefore Vaborem is expected to be a cost-effective strategy compared to BAT

Universal photonic processors in a glass-based femtosecond laser writing platform

Femtosecond laser writing (FLW) can open new perspectives on universal photonic processors (UPPs). We propose here two building blocks for the realization of FLW-UPPs and we show the preliminary results obtained on a 6-mode device

Universal photonic processors fabricated by femtosecond laser writing

Universal photonic processors (UPPs) are reconfigurable photonic integrated circuits able to implement arbitrary unitary transformations on an input photonic state. Femtosecond laser writing (FLW) allows for rapid and cost-effective fabrication of circuits with low propagation losses. A FLW process featuring thermal isolation allows for a dramatic reduction in dissipated power and crosstalk in integrated thermally-reconfigurable Mach-Zehnder interferometers (MZIs), especially when operated in vacuum, with 0.9 mW dissipation for full reconfiguration and 0.5% crosstalk at 785 nm wavelength. To demonstrate the potential of this technology we fabricated and characterized a 6-mode FLW-UPP in a rectangular MZI mesh with 30 thermal shifters

What proportion of patients with chronic heart failure are eligible for sacubitril-valsartan?

AIMS: The PARADIGM-HF trial showed that sacubitril-valsartan, an ARB-neprilysin inhibitor, is more effective than enalapril for some patients with heart failure (HF). It is uncertain what proportion of patients with HF would be eligible for sacubitril-valsartan in clinical practice. METHODS AND RESULTS: Between 2001 and 2014, 6131 patients consecutively referred to a community HF clinic with suspected HF were assessed. The criteria required to enter the randomized phase of PARADIGM-HF, including symptoms, NT-proBNP, and current treatment with or without target doses of ACE inhibitors or ARBs, were applied to identify the proportion of patients eligible for sacubitril-valsartan. Recognizing the diversity of clinical opinion and guideline recommendations concerning this issue, entry criteria were applied singly and in combination. Of 1396 patients with reduced left ventricular ejection fraction (≤40%, HFrEF) and contemporary measurement of NT-proBNP, 379 were on target doses of an ACE inhibitor or ARB at their initial visit and, of these, 172 (45%) fulfilled the key entry criteria for the PARADIGM-HF trial. Lack of symptoms (32%) and NT-proBNP <600 ng/L (49%) were common reasons for failure to fulfil criteria. A further 122 patients became eligible during follow-up (n = 294, 21%). However, if background medication and doses were ignored, then 701 (50%) were eligible initially and a further 137 became eligible during follow-up. CONCLUSIONS: Of patients with HFrEF referred to a clinic such as ours, only 21% fulfilled the PARADIGM-HF randomization criteria, on which the ESC Guidelines are based; this proportion rises to 60% if background medication is ignored