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High-Gradient accelerating cavities are one of the main research lines in the development of compact linear accelerators. However, the operation of such accelerating cavities is currently limited by non-linear electromagnetic effects that are intensified at high electric fields, such as RF breakdowns, dark currents and radiation. A novel normal-conducting High Gradient S-band Backward Travelling Wave accelerating cavity for medical application (v = 0.38c) has been designed and constructed at CERN with a design gradient of 50 MV/m. In this paper, the high-power performance studies of this novel design carried out at the IFIC high-power laboratory are presented, as well as the analysis of the conditioning parameters in combination with numerical simulations.

In this letter, we evaluate the potential of linear e+e− colliders to measure the top quark mass in radiative events and in a suitable short-distance scheme. We present a calculation of the differential cross section for production of a top quark pair in association with an energetic photon from initial state radiation, as a function of the invariant mass of the tt¯ system. This matched calculation includes the QCD enhancement of the cross section around the tt¯ production threshold and remains valid in the continuum well above the threshold. The uncertainty in the top mass determination is evaluated in realistic operating scenarios for the Compact Linear Collider (CLIC) and the International Linear Collider (ILC), including the statistical uncertainty and the theoretical and experimental systematic uncertainties. With this method, the top quark mass can be determined with a precision of 110 MeV in the initial stage of CLIC, with 1 ab−1 at s=380 GeV, and with a precision of approximately 150 MeV at the ILC, with L=4 ab−1 at s=500 GeV. Radiative events allow measurements of the top quark mass at different renormalization scales, and we demonstrate that such a measurement can yield a statistically significant test of the evolution of the MSR mass mtMSR(R) for scales R

We propose a new sequential jet reconstruction algorithm for future lepton colliders at the energy frontier. The Valencia algorithm combines the natural distance criterion for lepton colliders with the greater robustness against backgrounds of algorithms adapted to hadron colliders. Results on a detailed Monte Carlo simulation of tt¯ and ZZ production at future linear e+e− colliders (ILC and CLIC) with a realistic level of background overlaid, show that it achieves better performance in the presence of background than the classical algorithms used at previous e+e− colliders.

Background and Aims: Familial hypercholesterolemia (FH) is a monogenic disease characterized by high levels of low-density lipoprotein cholesterol and premature atherosclerotic cardiovascular disease. FH is caused by loss of function mutations in genes encoding LDL receptor (LDLR), and Apolipoprotein B (APOB) or gain of function (GOF) mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, we identified a novel variant in PCSK9, p.(Arg499His), located in the C-terminal domain, in two unrelated FH patients from Spain and Italy., Methods: We studied familial segregation and determined variant activity in vitro., Results: We determined PCSK9 expression, secretion and activity of the variant in transfected HEK293 cells; extracellular activity of the recombinant p.(Arg499His) PCSK9 variant in HEK 293 and HepG2 cells; PCSK9 affinity to the LDL receptor at neutral and acidic pH; the mechanism of action of the p.(Arg499His) PCSK9 variant by co-transfection with a soluble construct of the LDL receptor and by determining total PCSK9 intracellular accumulation when endosomal acidification is impaired and when an excess of soluble LDLr is present in the culture medium. Our results show high LDL-C concentrations and FH phenotype in p.(Arg499His) carriers. In vitro functional characterization shows that p.(Arg499His) PCSK9 variant causes a reduction in LDLr expression and LDL uptake. An intracellular activity for this variant is also shown when blocking the activity of secreted PCSK9 and by inhibiting endosomal acidification., Conclusions: We demonstrated that p.(Arg499His) PCSK9 variant causes a direct intracellular degradation of LDLr therefore causing FH by reducing LDLr availability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Genetic diagnosis of familial hypercholesterolemia (FH) has not been universally performed in the Canary Islands (Spain)., Objectives: This study aimed to genetically characterize a cohort of patients with FH in the island of Gran Canaria., Methods: Study subjects were 70 unrelated index cases attending a tertiary hospital in Gran Canaria, with a clinical diagnosis of FH, according to the criteria of the Dutch Lipid Clinic Network. Given that 7 of the first 10 cases with positive genetic study were carriers of a single mutation in the LDLR gene [p.(Tyr400_Phe402del)], a specific polymerase chain reaction-based assay was developed for the detection of this variant as a first screening step on the remaining subjects. In those without this mutation, molecular diagnosis was completed using a next-generation sequencing panel including LDLR, APOB, PCSK9, LDLRAP1, APOE, STAP1, and LIPA genes and incorporating copy number variation detection in LDLR., Results: On the whole, 44 subjects (62%) had a positive genetic study, of whom 30 (68%) were heterozygous carriers of the p.(Tyr400_Phe402del) variant. Eleven subjects carried other mutations in LDLR, including the novel mutation NM_000527.4: c.877dupG; NP_000518.1: p.(Asp293Glyfs*8). An unclassified PCSK9 gene variant was found in one subject [(NM_174936.3:c.1496G>A; NP_777596.2: p.(Arg499His)]. Other single patients had mutations in APOB (heterozygous) and in LIPA (homozygous). All identified variants co-segregated with the disease phenotype., Conclusions: These findings suggest a founder effect for the p.(Tyr400_Phe402del) LDLR mutation in Gran Canaria. A cost-effective local screening strategy for genetic diagnosis of FH could be implemented in this region., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain., Methods: Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed., Results: Seven patients with ARH were identified, 6 true homozygous and one compound heterozygous with a novel mutation: c.[863C>T];p.[Ser288Leu]. High genetic heterogeneity was found in this cohort. True homozygous subjects for LDLRAP1 have more severe phenotypes than the compound heterozygous patient, but similar to patients with homozygous familial hypercholesterolemia (HoFH). Cardiovascular disease was present in 14% of the ARH patients. LDL-C under treatment was above 185 mg/dl and the response to PCSK9 inhibitors was heterogeneous. Finally, the estimated prevalence in Spain is very low, with just 1 case per 6.5 million people., Conclusions: ARH is a very rare disease in Spain, showing high genetic heterogeneity, similarly high LDL-C concentrations, but lower incidence of ASCVD than HoFH., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Statin choice, an encounter decision aid (DA), was developed in the USA to facilitate shared decision making between patients and clinicians about the use of statins to reduce cardiovascular risk. We aimed to assess the efficacy of this DA, compared to usual primary care, in Spanish patients with type 2 diabetes., Methods: Cluster randomized trial with 29 clinicians and 168 patients. Knowledge of statins, cardiovascular risk perception, decisional conflict, anxiety and satisfaction with the decision making process were assessed immediately after intervention, and self-reported adherence at three months., Results: Intervention significantly improved knowledge (p=0.01), perception of the 10-year risk of myocardial infarction without (p=0.01) and with statins (p=0.08), and satisfaction (p=0.01). There were no significant differences in decisional conflict, anxiety, consultation time or adherence, although more intervention patients reported taking all pills during the last week (92.7% vs. 81%; p=0.19)., Conclusion: The statin choice DA improved the quality of decision making about statins., Practice Implications: This trial contributes to the body of evidence substantiating the efficacy of statin choice and extending it to Spanish clinicians and their patients with type 2 diabetes., Trial Registration: This trial is registered with the European Union Clinical Trials Register (EudraCT: 2010-023912-14)., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Background and Aim: Several working definitions of metabolic syndrome have been proposed for clinical use. However, individuals can be discordantly classified as having or not having metabolic syndrome depending on the choice of one or another definition. This study compared the cardiovascular risk profile of subjects concordantly and discordantly diagnosed by the criteria of the National Cholesterol Education Program (NCEP) and the criteria of the International Diabetes Federation (IDF)., Methods and Results: Nine hundred and twenty-nine non-diabetic adult subjects belonging to a cross-sectional population-based study in Gran Canaria island (Spain) were assessed. Participants completed a questionnaire and underwent physical examination, fasting blood analyses, and a standardized oral glucose tolerance test. Two hundred and four subjects (22%) had metabolic syndrome according to both definitions, 31 (3.3%) only by the IDF criteria, and 5 (0.5%) only by the NCEP criteria. Participants fulfilling both proposals showed more adverse age and sex-adjusted measures of BMI, waist, HDL cholesterol, triglycerides, post-load glucose, HOMA-IR and plasminogen inhibitor activator-1 (PAI-1) than individuals exclusively satisfying the IDF criteria. Moreover, in contrast to subjects meeting both criteria, those that fulfilled only the IDF criteria had levels of BMI, waist, total and HDL cholesterol, post-load glucose, glycated HbA1c, C-reactive protein, PAI-1 and fibrinogen not significantly different from those observed in subjects without metabolic syndrome., Conclusion: The IDF definition identifies a surplus of individuals whose cardiovascular risk profile, particularly regarding to some non-traditional cardiovascular risk factors, is less adverse than that observed in subjects also diagnosed by the NCEP definition.

Background and Aim: This study was aimed to identify additional components of metabolic syndrome from a set of cardiovascular risk markers., Methods and Results: The homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were assessed in a population-based sample of 902 nondiabetic adult subjects. Those biomarkers that were associated with metabolic syndrome were evaluated by multiple regression analysis, along with other traditional cardiovascular risk factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that both the established components of metabolic syndrome and the novel variables identified by the regression analysis were associated with a single underlying factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related to metabolic syndrome. CFA validated a one-factor model that included these variables. Moreover, the indices of goodness of fit were better for this expanded model than those obtained for a previously validated one-factor model that was restricted to the conventional elements of the syndrome., Conclusions: These findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. Their elevation is presumably another manifestation of the same pathophysiological mechanism that underlies the recognized traits of the syndrome.

In the last years, 'in situ' solid-state NMR has been applied to investigate the Beckmann rearrangement of oximes into amides using zeolites and mesoporous materials of different structure containing Brønsted acids or silanol groups as active sites. DFT methods have been applied to model the geometry of the complexes resulting from adsorption of reactants, reaction intermediates and products on clusters representing the zeolite centers, and their (15)N and (13)C NMR chemical shift calculated theoretically. This article reviews the results reported in the bibliography on the Beckmann rearrangement of various oximes (acetophenone oxime, cyclohexanone oxime and cyclododecanone oxime) mainly using 'in situ'(15)N NMR spectroscopy and theoretical calculations, and are compared with those obtained by 'in situ' infrared spectroscopy. The combination of experiment and theory has been shown to be very useful for the interpretation of the NMR spectra and the identification of the species present at different reaction temperatures.