Densification of WC-Fe-Ni-Co-Cr cemented carbides processed by HIP after sintering: effect of WC powder particle size

Shrinkage, liquid formation and mass losses of WC-19 vol% FeNiCoCr alloys during sintering have been inves- tigated in compositions either with coarse or submicron WC powders. Mass losses detected by thermogravimetry are compatible with carbothermal reduction of the different oxides present in the powder mixtures. Hardness and fracture toughness of materials based on submicron WC powders are within tolerances of those reported for WC- Co materials with similar microstructures. However, fracture strength is approx. 25% lower

Expressing Confidence in Models and in Model Transformation Elements.

The expression and management of uncertainty, both in the information and in the operations that manipulate it, is a critical issue in those systems that work with physical environments. Measurement uncertainty can be due to several factors, such as unreliable data sources, tolerance in the measurements, or the inability to determine if a certain event has actually happened or not. In particular, this contribution focuses on the expression of one kind of uncertainty, namely the confidence on the model elements, i.e., the degree of belief that we have on their occurrence, and on how such an uncertainty can be managed and propagated through model transformations, whose rules can also be subject to uncertainty

Usual dietary intake, nutritional adequacy and food sources of calcium, phosphorus, magnesium and vitamin D of spanish children aged one to dagger

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of age

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Why don&#x0027;t we treat chronic hepatitis C in HIV patients? Results from a cohort of HIV-HCV coinfected patients from the southeast of Spain

Purpose of the study: To know the different reasons why we decide not to treat or to delay the antiviral treatment against HCV in HIV coinfected patients. Methods: Prospective cohort of HIV and HCV coinfected patients, followed in the Infectious Diseases Department of the Santa Lucia Universitary Hospital (Cartagena, Spain) between 1/12/2011 and 28/02/2012 in which we made transitory elastography. We evaluated the main reasons that moved us to decide not to treat or to delay the antiviral treatment against HCV: social-familiar-laboral reasons; neuro-psychiatric severe diseases; patient decision; low grade hepatic fibrosis; previous failure to pegylated interferon (IFN) and ribavirin (RBV) in no-1 genotype patients; delay in the approval of the triple therapy with INF-RBV and a protease inhibitor (boceprevir or telaprevir) by the Regional Sanitary Authority; active alcohol abuse; active diseases that contraindicate the antiviral treatment, incomplete study of HCV (VL of HCV, genotype, ILB28, abdominal ecography); previous intolerance against IFN-RBV and severe thrombocytopenia (&#60;50&#x00D7;109/L). Summary of results: The cohort included 109 patients, being 27 of them females (25%) and 82 males (75%), with a median of age of 45.8 years (SD: 6.2). In 98 patients (90%) we decided not to treat or to delay the antiviral treatment against HCV for one or more of the following reasons: 37 (34%) presented low grade hepatic fibrosis (&#60;9.5 kpascal or F0-F2); 19 (17%) had neuro-psychiatric diseases; 18 (16.5%) were waiting for the approval of triple therapy by the Regional Sanitary Authority; 10 (9.2%) did not want to be treated; 10 (9.2%) had failure to IFN-RBV in no-1 genotype; 6 (5.5%) had social-familiar-laboral reasons; 6 (5.5%) presented active severe diseases; 4 (3.7%) were waiting to complete HCV study; 3 (2.8%) presented active alcohol abuse; 3 (2.8%) had previous intolerance against IFN-RBV treatment and 2 (2%) had severe thrombocytopenia. Conclusions: In our cohort of HIV-HCV coinfected patients it was decided to delay or not to treat chronic hepatitis C in a significant proportion of subjects. The low grade of hepatic fibrosis measured with transitory elastography was the main reason for delaying the HCV antiviral treatment. The neuro-psychiatric disease was the main clinical reason to not treat HCV. The delay of the approval of triple therapy treatment by the Regional Sanitary Authority was the most relevant non- clinical reason in our prospective study

Prolonged oral cannabinoid administration prevents neuroinflammation, lowers β-amyloid levels and improves cognitive performance in Tg APP 2576 mice

Background: Alzheimer’s disease (AD) brain shows an ongoing inflammatory condition and non-steroidal antiinflammatories diminish the risk of suffering the neurologic disease. Cannabinoids are neuroprotective and antiinflammatory agents with therapeutic potential. Methods: We have studied the effects of prolonged oral administration of transgenic amyloid precursor protein (APP) mice with two pharmacologically different cannabinoids (WIN 55,212-2 and JWH-133, 0.2 mg/kg/day in the drinking water during 4 months) on inflammatory and cognitive parameters, and on 18F-fluoro-deoxyglucose (18FDG) uptake by positron emission tomography (PET). Results: Novel object recognition was significantly reduced in 11 month old Tg APP mice and 4 month administration of JWH was able to normalize this cognitive deficit, although WIN was ineffective. Wild type mice cognitive performance was unaltered by cannabinoid administration. Tg APP mice showed decreased 18FDG uptake in hippocampus and cortical regions, which was counteracted by oral JWH treatment. Hippocampal GFAP immunoreactivity and cortical protein expression was unaffected by genotype or treatment. In contrast, the density of Iba1 positive microglia was increased in Tg APP mice, and normalized following JWH chronic treatment. Both cannabinoids were effective at reducing the enhancement of COX-2 protein levels and TNF-a mRNA expression found in the AD model. Increased cortical b-amyloid (Ab) levels were significantly reduced in the mouse model by both cannabinoids. Noteworthy both cannabinoids enhanced Ab transport across choroid plexus cells in vitro. Conclusions: In summary we have shown that chronically administered cannabinoid showed marked beneficial effects concomitant with inflammation reduction and increased Ab clearanceThis work was supported by the Spanish Ministry of Science and Technology (SAF 2005-02845 to M.L.C). A.M.M-M. was recipient a fellowship from the Ministry of Education and Scienc

Coronal voids and their magnetic nature

Context: Extreme ultraviolet (EUV) observations of the quiet solar atmosphere reveal extended regions of weak emission compared to the ambient quiescent corona. The magnetic nature of these coronal features is not well understood. // Aims: We study the magnetic properties of the weakly emitting extended regions, which we name coronal voids. In particular, we aim to understand whether these voids result from a reduced heat input into the corona or if they are associated with mainly unipolar and possibly open magnetic fields, similar to coronal holes. // Methods: We defined the coronal voids via an intensity threshold of 75% of the mean quiet-Sun (QS) EUV intensity observed by the high-resolution EUV channel (HRIEUV) of the Extreme Ultraviolet Imager on Solar Orbiter. The line-of-sight magnetograms of the same solar region recorded by the High Resolution Telescope of the Polarimetric and Helioseismic Imager allowed us to compare the photospheric magnetic field beneath the coronal voids with that in other parts of the QS. // Results: The coronal voids studied here range in size from a few granules to a few supergranules and on average exhibit a reduced intensity of 67% of the mean value of the entire field of view. The magnetic flux density in the photosphere below the voids is 76% (or more) lower than in the surrounding QS. Specifically, the coronal voids show much weaker or no network structures. The detected flux imbalances fall in the range of imbalances found in QS areas of the same size. // Conclusions: We conclude that coronal voids form because of locally reduced heating of the corona due to reduced magnetic flux density in the photosphere. This makes them a distinct class of (dark) structure, different from coronal holes

Coronal voids and their magnetic nature

Context. Extreme ultraviolet (EUV) observations of the quiet solar atmosphere reveal extended regions of weak emission compared to the ambient quiescent corona. The magnetic nature of these coronal features is not well understood.Aims. We study the magnetic properties of the weakly emitting extended regions, which we name coronal voids. In particular, we aim to understand whether these voids result from a reduced heat input into the corona or if they are associated with mainly unipolar and possibly open magnetic fields, similar to coronal holes. Methods. We defined the coronal voids via an intensity threshold of 75% of the mean quiet-Sun (QS) EUV intensity observed by the high- resolution EUV channel (HRIEUV) of the Extreme Ultraviolet Imager on Solar Orbiter. The line-of-sight magnetograms of the same solar region recorded by the High Resolution Telescope of the Polarimetric and Helioseismic Imager allowed us to compare the photospheric magnetic field beneath the coronal voids with that in other parts of the QS.Results. The coronal voids studied here range in size from a few granules to a few supergranules and on average exhibit a reduced intensity of 67% of the mean value of the entire field of view. The magnetic flux density in the photosphere below the voids is 76% (or more) lower than in the surrounding QS. Specifically, the coronal voids show much weaker or no network structures. The detected flux imbalances fall in the range of imbalances found in QS areas of the same size. Conclusions. We conclude that coronal voids form because of locally reduced heating of the corona due to reduced magnetic flux density in the photosphere. This makes them a distinct class of (dark) structure, different from coronal holes

Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients

Introduction: Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. Methods: Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. Results: The median [p25–p75] time from discharge to follow-up was 3.57 [2.77–4.92] months. Median age was 60 [53–67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO < 80% and 24% having DLCO < 60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO < 60% were chronic lung disease (CLD) (OR: 1.86 (1.18–2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37–1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18–1.63)), urea (OR: 1.16 (0.97–1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73–1.06)). Bacterial pneumonia (1.62 (1.11–2.35)) and duration of ventilation (NIMV (1.23 (1.06–1.42), IMV (1.21 (1.01–1.45)) and prone positioning (1.17 (0.98–1.39)) were associated with fibrotic lesions. Conclusion: Age and CLD, reflecting patients’ baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities