A geometrical view of scalar modulation instability in optical fibers

Full models of scalar modulation instability (MI) in optical fibers available in the literature usually involve complex formulations. In this paper, we present a novel approach to the analysis of MI in optical fibers by means of a simple geometrical description in the power vs. frequency plane. This formulation allows to relate the shape of the MI gain to any arbitrary dispersion profile of the medium, thus providing a simple insight. As a result, we derive a straightforward explanation of the non-trivial dependence of the cutoff power on high-order dispersion and derive explicitly the power that maximizes the gain. Our approach puts forth a tool to synthesize a desired MI gain with the potential application to a number of parametric-amplification and supercontinuum-generation devices whose initial-stage dynamics rely upon modulation instability.Fil: Hernandez, Santiago Martin. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Fierens, Pablo Ignacio. Instituto Tecnológico de Buenos Aires; ArgentinaFil: Bonetti, Juan Ignacio. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Sánchez, Alfredo Daniel. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Grosz, Diego Fernando. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Instituto Tecnológico de Buenos Aires; Argentin

Measuring self-steepening with the photon-conserving nonlinear Schrödinger equation

We propose an original, simple, and direct method to measure self-steepening (SS) in nonlinear waveguides. Our proposal is based on results derived from the recently introduced photon-conserving nonlinear Schrödinger equation (NLSE) and relies on the time shift experienced by soliton-like pulses due to SS upon propagation. In particular, a direct measurement of this time shift allows for a precise estimation of the SS parameter. Furthermore, we show that such an approach cannot be tackled by resorting to the NLSE. The proposed method is validated through numerical simulations, in excellent agreement with the analytical model, and results are presented for relevant spectral regions in the near infrared, the telecommunication band, and the mid infrared, and for realistic parameters of available laser sources and waveguides. Finally, we demonstrate the robustness of the proposed scheme against deviations expected in real-life experimental conditions, such as pulse shape, pulse peak power, pulsewidth, and/or higher-order linear and nonlinear dispersion.Fil: Linale, Nicolás Martín. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comision Nacional de Energia Atomica. Gerencia D/area Invest y Aplicaciones No Nucleares. Gerencia de Des. Tec. y Proyectos Especiales. Departamento de Ingenieria En Telecomunicaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Fierens, Pablo Ignacio. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonetti, Juan Ignacio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comision Nacional de Energia Atomica. Gerencia D/area Invest y Aplicaciones No Nucleares. Gerencia de Des. Tec. y Proyectos Especiales. Departamento de Ingenieria En Telecomunicaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Sánchez, Alfredo Daniel. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comision Nacional de Energia Atomica. Gerencia D/area Invest y Aplicaciones No Nucleares. Gerencia de Des. Tec. y Proyectos Especiales. Departamento de Ingenieria En Telecomunicaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Hernandez, Santiago Martin. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Grosz, Diego Fernando. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comision Nacional de Energia Atomica. Gerencia D/area Invest y Aplicaciones No Nucleares. Gerencia de Des. Tec. y Proyectos Especiales. Departamento de Ingenieria En Telecomunicaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin

Variação espaço-temporal do ictioplâncton em um trecho do río Paraná

El objetivo del estudio fue determinar la ocurrencia de desoves y su variación espacio-temporal a partir de la abundancia de ictioplancton en un tramo del río Paraná aguas abajo de la represa de Yacyretá, provincia de Corrientes, Argentina. Se tomaron muestras con frecuencia quincenal con una red cilindro-cónica de 500μm de apertura de malla durante tres ciclos anuales consecutivos (septiembre a abril). En todos los ciclos se observaron picos de abundancia de ictioplancton, evidenciándose una correlación positiva entre los diferentes sitios de muestreo. Los resultados indicarían que los desoves se producen aproximadamente en el mismo período y estrechamente relacionados a los aumentos de los regímenes hidrológicos. La presencia de ictioplancton en tres ciclos anuales consecutivos permite determinar la existencia de buena actividad reproductiva, aunque las variaciones temporales de la densidad ictioplanctónica reflejan la ocurrencia de mecanismos desencadenantes de los desoves fuertemente relacionados al régimen hidrológico.The aim of this study was to determine the occurrence of spawning and its spatial-temporal variation, from the ichthyoplankton abundance in a section of the Paraná River downstream of the Yacyretá dam, Corrientes province, Argentina. Samples were collected every two weeks with a 500µm mesh cylindro-conical net during three consecutive annual cycles (September to April). In all cycles, ichthyoplankton abundance peaks were observed, showing a positive correlation between the different sampled sites. The results indicate that spawning occurs at approximately the same period and is closely related to the flood period. The presence of ichthyoplankton in three consecutive annual cycles determines the existence of important reproductive activity, although the temporal variation of ichthyoplankton density reflects the occurrence of spawning trigger mechanisms closely related to the hydrological regime.O objetivo do estudo foi determinar a ocorrência de desovas do ictioplâncton e sua variação espaço-temporal a partir da abundância de ovos e larvas de peixes, em um trecho do rio Paraná abaixo da represa de Yacyretá, província de Corriente, Argentina. Recolheram-se amostras com frequência quincenal utilizando uma rede cilindro-cônica de 500μm de abertura da malha durante três ciclos anuais consecutivos (setembro até abril). En todos los ciclos foram observados picos de abundância de ictioplâncton, evidenciando-se una correlação positiva entre os diferentes locais de amostragem. Os resultados poderiam indicar que as desovas acontecem aproximadamente no mesmo período e estão fortemente relacionadas ao aumento dos regimes hidrológicos. A presença de ictioplâncton em três ciclos anuais consecutivos permite determinar a existência de uma boa atividade reprodutiva, embora as variações temporais da densidade ictioplanctônica revelem a ocorrência de mecanismos desencadeantes de desovas fortemente relacionadas ao regime hidrológico.Fil: González, Alfredo Oscar. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias. Instituto de Ictiología del Nordeste; ArgentinaFil: Roux, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias. Instituto de Ictiología del Nordeste; ArgentinaFil: Hernandez, David Roque. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias. Instituto de Ictiología del Nordeste; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Sánchez, Sebastián. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias. Instituto de Ictiología del Nordeste; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

Structure of a Luminescent MOF-2 Derivative with a Core of Zn(II)-Terephthalate-Isoquinoline and Its Application in Sensing of Xylenes

Articulo de investigación publicado en revista indexada.A new blue photoluminescent 2D metal–organic framework, 1, with formula {[Zn2( 2-BDC)2 (iQ)2]}1 has been synthesized in a high yield under solvothermal conditions by reacting Zn(II) ions with 1,4-benzenedicarboxylic acid (H2BDC) and isoquinoline (iQ) in DMF. Compound 1 was thoroughly characterized by single-crystal X-ray di raction, solid-state cross-polarization magic-angle spinning 13C NMR, X-ray powder di raction, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), and thermoanalysis. The crystal structure of 1 showed interpenetrated 2D frameworks consisting of dinuclear paddle-wheel cores Zn2; moreover, this material possessed thermostability up to 310 C. The CPMAS 13C-NMR spectrum of 1 is consistent with the symmetry of the crystal structure. Luminescence studies showed that 1 strongly enhances its fluorescence emission in the presence of xylene isomers with a pronounced selectivity to p-xylene.Universidad Autónoma del Estado de México (Project 4995/2020CIB

Rationale and design of the pragmatic clinical trial tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT).

There is a lack of evidence regarding the benefits of β-blocker treatment after invasively managed acute myocardial infarction (MI) without reduced left ventricular ejection fraction (LVEF). The tREatment with Beta-blockers after myOcardial infarction withOut reduced ejection fracTion (REBOOT) trial is a pragmatic, controlled, prospective, randomized, open-label blinded endpoint (PROBE design) clinical trial testing the benefits of β-blocker maintenance therapy in patients discharged after MI with or without ST-segment elevation. Patients eligible for participation are those managed invasively during index hospitalization (coronary angiography), with LVEF >40%, and no history of heart failure (HF). At discharge, patients will be randomized 1:1 to β-blocker therapy (agent and dose according to treating physician) or no β-blocker therapy. The primary endpoint is a composite of all-cause death, non-fatal reinfarction, or HF hospitalization over a median follow-up period of 2.75 years (minimum 2 years, maximum 3 years). Key secondary endpoints include the incidence of the individual components of the primary composite endpoint, the incidence of cardiac death, and incidence of malignant ventricular arrhythmias or resuscitated cardiac arrest. The primary endpoint will be analysed according to the intention-to-treat principle. The REBOOT trial will provide robust evidence to guide the prescription of β-blockers to patients discharged after MI without reduced LVEF.REBOOT is a non-commercial trial whose main sponsor is the Spanish National Center for Cardiovascular Research (CNIC). The study also received partial funding from the BI group through the CIBERCV network.S

Reduced Stability and Increased Dynamics in the Human Proliferating Cell Nuclear Antigen (PCNA) Relative to the Yeast Homolog

Proliferating Cell Nuclear Antigen (PCNA) is an essential factor for DNA replication and repair. PCNA forms a toroidal, ring shaped structure of 90 kDa by the symmetric association of three identical monomers. The ring encircles the DNA and acts as a platform where polymerases and other proteins dock to carry out different DNA metabolic processes. The amino acid sequence of human PCNA is 35% identical to the yeast homolog, and the two proteins have the same 3D crystal structure. In this report, we give evidence that the budding yeast (sc) and human (h) PCNAs have highly similar structures in solution but differ substantially in their stability and dynamics. hPCNA is less resistant to chemical and thermal denaturation and displays lower cooperativity of unfolding as compared to scPCNA. Solvent exchange rates measurements show that the slowest exchanging backbone amides are at the β-sheet, in the structure core, and not at the helices, which line the central channel. However, all the backbone amides of hPCNA exchange fast, becoming undetectable within hours, while the signals from the core amides of scPCNA persist for longer times. The high dynamics of the α-helices, which face the DNA in the PCNA-loaded form, is likely to have functional implications for the sliding of the PCNA ring on the DNA since a large hole with a flexible wall facilitates the establishment of protein-DNA interactions that are transient and easily broken. The increased dynamics of hPCNA relative to scPCNA may allow it to acquire multiple induced conformations upon binding to its substrates enlarging its binding diversity

Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.P.G.-G. (Pablo García-González) is supported by CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into ISCIII (Instituto de Salud Carlos III). I.d.R is supported by a national grant from the Instituto de Salud Carlos III FI20/00215. A.C. (Amanda Cano) acknowledges the support of the Spanish Ministry of Science, Innovation, and Universities under the grant Juan de la Cierva (FJC2018-036012-I). M.B. (Mercé Boada) and A.R. (Agustín Ruiz) are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240, and PI19/01301. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación—and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”). Genotyping of the ACE MCI-EADB samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND). Partial funding for open access charge: Universidad de Málag

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk

The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome. Methods: We performed a cross-sectional analysis of the PREDIMED-Plus trial. Consumption of any category of olive oil and olive pomace oil was assessed through a validated food-frequency questionnaire. Multivariable linear regression models were fitted to assess associations between olive oil consumption and ABI. Additionally, ABI ≤1 was considered as the outcome in logistic models with different categories of olive oil and olive pomace oil as exposure. Results: Among 4330 participants, the highest quintile of total olive oil consumption (sum of all categories of olive oil and olive pomace oil) was associated with higher mean values of ABI (beta coefficient: 0.014, 95% confidence interval [CI]: 0.002, 0.027) (p for trend = 0.010). Logistic models comparing the consumption of different categories of olive oils, olive pomace oil and ABI ≤1 values revealed an inverse association between virgin olive oils consumption and the likelihood of a low ABI (odds ratio [OR] 0.73, 95% CI [0.56, 0.97]), while consumption of olive pomace oil was positively associated with a low ABI (OR 1.22 95% CI [1.00, 1.48]). Conclusions: In a Mediterranean population at high cardiovascular risk, total olive oil consumption was associated with a higher mean ABI. These results suggest that olive oil consumption may be beneficial for peripheral artery disease prevention, but longitudinal studies are needed

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline