Frequency selective surfaces for Terahertz applications

This thesis presents both theoretical and experimental investigations of the performance and capabilities of frequency selective surfaces (FSS) applied at THz frequencies. The aim is to explore and extend the use of FSS, traditionally limited to microwave frequencies, towards the THz regime of the spectrum, where interesting applications such as imaging, sensing and communications exist. The contribution of this work lies in three main areas within the scope of THz FSS, namely, performance, prototyping and applications. Unlike microwave FSS where extensive research has been performed to evaluate the performance of different FSS designs, particular problems arise at THz frequencies, significantly, the ohmic losses. While a few notable studies can be found on the issue of ohmic losses, part of this thesis investigates, for the first time, the power dissipation due to the presence of both ohmic and dielectric losses, in relation to the power stored in the vicinity of the FSS, the currents induced in the elements of the array and the array’s terminal impedance. By doing so, a better understanding of the performance of THz FSS has been given in terms of their quality factor, allowing for design guidelines previously unavailable. In order to demonstrate multiband operation experimentally, a novel fabrication process has been designed and developed to manufacture capacitive or dipole-based THz FSS on a dielectric layer. Dry deep-reactive ion etching has been employed in order to avoid the use of wet etching to provide better control of etch characteristics. Various FSS operating around 15THz have been demonstrated experimentally. In addition, THz FSS have been investigated theoretically in the realm of three different applications, namely, multiband operation, sensing capability and reconfigurability. Multiband characteristics using single-screen FSS have been achieved by perturbed dipole FSS exhibiting up to four resonances due to the excitation of even and odd current modes. After studying the near-fields in perturbed FSS, it has been found that this type of FSS represent a very attractive candidate for sensing applications due to the revealed near-field enhancement phenomena related to the excitation of the odd mode, where currents flow in opposite directions. Finally, a novel tunability approach to reach frequency reconfigurability by varying the near-field coupling between two closely spaced layers in a dual-layer configuration has been proposed. A MEMS movable four-arm membrane has been suggested to vary the distance between the two layers mechanically, leading to the frequency tuning effect. This approach has been shown to be particularly suitable for THz frequencies, and has been applied to demonstrate theoretically tunable FSS and other periodic structures, such as artificial magnetic conductors and dielectric gratings

Does Socioeconomic Status Influence the Risk of Subclinical Atherosclerosis?: A Mediation Model

BACKGROUND: Socioeconomic status (SES)-education, income level, and occupation-is associated with cardiovascular risk. OBJECTIVES: This study aimed to investigate the association between SES and subclinical atherosclerosis and the potential mechanisms involved. METHODS: SES, lifestyle habits (smoking, dietary patterns, physical activity, and hours of sleep), traditional risk factors, and subclinical atherosclerosis extent were prospectively assessed in 4,025 individuals aged 40 to 54 years without known cardiovascular disease enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) study. After factors associated with atherosclerosis were identified, a multiple mediation model was created to quantify the effect of SES on subclinical atherosclerosis as explained by lifestyle behaviors. RESULTS: Although education level was significantly associated with the presence of atherosclerosis, no differences were found according to income level in this population. Participants with lower education presented with a higher risk of generalized atherosclerosis than those with higher education (odds ratio: 1.46; 95% confidence interval: 1.15 to 1.85; p = 0.002). Lifestyle behaviors associated with both education level and atherosclerosis extent were: smoking status, number of cigarettes/day, and dietary pattern, which explained 70.5% of the effect of SES on atherosclerosis. Of these, tobacco habit (smoking status 35% and number of cigarettes/day 32%) accounted for most of the explained differences between groups, whereas dietary pattern did not remain a significant mediator in the multiple mediation model. CONCLUSIONS: Despite the relative economic homogeneity of the cohort, lower education level is associated with increased subclinical atherosclerosis, mainly mediated by the higher and more frequent tobacco consumption. Smoking cessation programs are still needed, particularly in populations with lower education level.The PESA study is cofunded equally by the Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; and Banco Santander, Madrid, Spain. The study also receives funding from the Institute of Health Carlos III (PI15/02019) and the European Regional Development Fund. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No707642; and from the American Heart Association under grantnumber14SFRN20490315. Dr. Bueno has received research funding from the Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; has received consulting fees from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speaking fees or support for attending scientific meetings from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Ferrer, Novartis, Servier, and MEDSCAPE-the heart.org.S

Predicting Subclinical Atherosclerosis in Low-Risk Individuals Ideal Cardiovascular Health Score and Fuster-BEWAT Score

BACKGROUND The ideal cardiovascular health score (ICHS) is recommended for use in primary prevention. Simpler tools not requiring laboratory tests, such as the Fuster-BEWAT (blood pressure [B], exercise [E], weight [W], alimentation [A], and tobacco [T]) score (FBS), are also available. OBJECTIVES The purpose of this study was to compare the effectiveness of ICHS and FBS in predicting the presence and extent of subclinical atherosclerosis. METHODS A total of 3,983 participants 40 to 54 years of age were enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) cohort. Subclinical atherosclerosis was measured in right and left carotids, abdominal aorta, right and left iliofemoral arteries, and coronary arteries. Subjects were classified as having poor, intermediate, or ideal cardiovascular health based on the number of favorable ICHS or FBS. RESULTS With poor ICHS and FBS as references, individuals with ideal ICHS and FBS showed lower adjusted odds of having atherosclerotic plaques (ICHS odds ratio [OR]: 0.41; 95\% confidence interval [CI]: 0.31 to 0.55 vs. FBS OR: 0.49; 95\% CI: 0.36 to 0.66), coronary artery calcium (CACS) >= 1 (CACS OR: 0.41; 95\% CI: 0.28 to 0.60 vs. CACS OR: 0.53; 95\% CI: 0.38 to 0.74), higher number of affected territories (OR: 0.32; 95\% CI: 0.26 to 0.41 vs. OR: 0.39; 95\% CI: 0.31 to 0.50), and higher CACS level (OR: 0.40; 95\% CI: 0.28 to 0.58 vs. OR: 0.52; 95\% CI: 0.38 to 0.72). Similar levels of significantly discriminating accuracy were found for ICHS and FBS with respect to the presence of plaques (C-statistic: 0.694; 95\% CI: 0.678 to 0.711 vs. 0.692; 95\% CI: 0.676 to 0.709, respectively) and for CACS >= 1 (C-statistic: 0.782; 95\% CI: 0.765 to 0.800 vs. 0.780; 95\% CI: 0.762 to 0.798, respectively). CONCLUSIONS Both scores predict the presence and extent of subclinical atherosclerosis with similar accuracy, highlighting the value of the FBS as a simpler and more affordable score for evaluating the risk of subclinical disease. (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.The PESA study was co-funded by Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Banco Santander. Funding was also provided by Institute of Health Carlos III (PI15/02019) and European Regional Development Fund. CNIC is supported by the Ministry of Economy, Industry and Competitiveness and Pro CNIC Foundation; and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work is part of a project that received funding from the European Union Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant 707642 and American Heart Association grant 14SFRN20490315. Dr. Bueno has received research funding from Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; is a consultant for Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speakers fees and travel and attendance support from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Ferrer, Novartis, Servier, and Medscape. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Matthew Budoff, MD, served as Guest Editor for this paper.S

Association Between a Social-Business Eating Pattern and Early Asymptomatic Atherosclerosis

BACKGROUND The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. OBJECTIVES This study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults. METHODS The PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63\% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style-related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information. RESULTS Most PESA participants follow a Mediterranean (40\% of participants) or a Western (41\%) dietary pattern. A new pattern, identified among 19\% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95\% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet. CONCLUSIONS A new social-business eating pattern, characterized by high consumption of red and processed meat, alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy life-style, is associated with an increased prevalence, burden, and multisite presence of subclinical atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318) (C) 2016 by the American College of Cardiology Foundation.This study was supported by a noncompetitive unrestricted grant shared between the National Center for Cardiovascular Research Carlos III (CNIC) and the Bank of Santander. The PESA study is a noncommercial study independent of the health care and pharmaceutical industry. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Vedanthan is supported by the Fogarty International Center of the National Institutes of Health under award K01 TW 009218-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Bueno has received advisory/speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and Servier; has received a research grant from AstraZeneca; has received advisory fees from Abbott; and has received speaking fees from Ferrer. Frank B. Hu, MD, served as Guest Editor for this paper

Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited. OBJECTIVES: The purpose of this study was to characterize vascular inflammation by hybrid 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS: Carotid, aortic, and ilio-femoral 18F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary calcification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18F-FDG uptake) and plaques with or without inflammation (coincident 18F-FDG uptake). RESULTS: Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflammation than in those without (p < 0.01). The number of plaques and 18F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001). CONCLUSIONS: Arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis. Large-scale multiterritorial PET/MRI allows characterization of atherosclerosis-related arterial inflammation and demonstrates 18F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).The PESA study is cofunded equally by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Banco Santander. The study also receives funding from the Instituto de Salud Carlos III (PI15/02019) and the European Regional Development Fund (ERDF) “A way to make Europe.” The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Sanchez-González is an employee of Philips Healthcare. Dr. Bueno has received research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; has received consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speaking fees or support for attending scientific meetings from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and MEDSCAPE-the heart.org.S

Investigating Local Patterns of Mumps Virus Circulation, Using a Combination of Molecular Tools

Mumps is a vaccine-preventable disease caused by the mumps virus (MuV). However, MuV has re-emerged in many countries with high vaccine coverage. The World Health Organization (WHO) recommends molecular surveillance based on sequencing of the small hydrophobic (SH) gene. Additionally, the combined use of SH and non-coding regions (NCR) has been described in different studies, proving to be a useful complement marker to discriminate general patterns of circulation at national and international levels. The aim of this work is to test local-level usefulness of the combination of SH and MF-NCR sequencing in tracing hidden transmission clusters and chains during the last epidemic wave (2015-2020) in Spain. A database with 903 cases from the Autonomous Community of Madrid was generated by the integration of microbiological and epidemiological data. Of these, 453 representative cases were genotyped. Eight different SH variants and thirty-four SH haplotypes were detected. Local MuV circulation showed the same temporal pattern previously described at a national level. Only two of the thirteen previously identified outbreaks were caused by more than one variant/haplotype. Geographical representation of SH variants allowed the identification of several previously undetected clusters, which were analysed phylogenetically by the combination of SH and MF-NCR, in a total of 90 cases. MF-NCR was not able to improve the discrimination of geographical clusters based on SH sequencing, showing limited resolution for outbreak investigations.A.M.G. was funded by CIBER de Epidemiología y Salud Pública (CIBERESP), ISCIII. This work was supported by the “Instituto de Salud Carlos III” (PI15CIII/00023 and PI19ICIII/0041).S

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry.

Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8(+) T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance.This work was supported by the Cooperative Research Thematic Network (RTICCs; RD06/0020/0006 and G03/136), Instituto de Salud Carlos III/ Subdirección General de Investigación Sanitaria (FIS: PI060339; 06/1354; 02/0905; 01/0089/01-02; PS09/01897/01370) and Consejeria de Educacion (GR37) and Consejería de Sanidad, Junta de Castilla y León, Valladolid, Spain (557/A/10). The authors also thank the Fundación Carolina-BBVA for supporting and promoting the exchange of medical researchers from Latin America to Spai

DNA Methylation Profiles and Their Relationship with Cytogenetic Status in Adult Acute Myeloid Leukemia

Background: Aberrant promoter DNA methylation has been shown to play a role in acute myeloid leukemia (AML) pathophysiology. However, further studies to discuss the prognostic value and the relationship of the epigenetic signatures with defined genomic rearrangements in acute myeloid leukemia are required. Methodology/Principal Findings: We carried out high-throughput methylation profiling on 116 de novo AML cases and we validated the significant biomarkers in an independent cohort of 244 AML cases. Methylation signatures were associated with the presence of a specific cytogenetic status. In normal karyotype cases, aberrant methylation of the promoter of DBC1 was validated as a predictor of the disease-free and overall survival. Furthermore, DBC1 expression was significantly silenced in the aberrantly methylated samples. Patients with chromosome rearrangements showed distinct methylation signatures. To establish the role of fusion proteins in the epigenetic profiles, 20 additional samples of human hematopoietic stem/ progenitor cells (HSPC) transduced with common fusion genes were studied and compared with patient samples carrying the same rearrangements. The presence of MLL rearrangements in HSPC induced the methylation profile observed in the MLL-positive primary samples. In contrast, fusion genes such as AML1/ETO or CBFB/MYH11 failed to reproduce the epigenetic signature observed in the patients. Conclusions/Significance: Our study provides a comprehensive epigenetic profiling of AML, identifies new clinical markers for cases with a normal karyotype, and reveals relevant biological information related to the role of fusion proteins on the methylation signatur

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study.

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all-cause mortality and hospitalization due to cardiovascular events in a high-risk population. This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008-2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/HDL-Cholesterol: 8.94, 15.09, 6.92. In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers.S