DESIGN AND FABRICATION OF A 64-QAM MODULATOR FOR ANALYSIS OF SIGNALS BETWEEN STAGES

AbstractThis paper proposes the design of a 64-QAM digital modulator on board based on chip technology, the developed board comprises two phase delay and two amplification stages , the modulator was developed using the software PCB Wizard and were established test points for each stage. The developed layout was built through a computer numerical control machine. Experimental results show a significant improvement of the accuracy based on a reached NMSE= -51 dB. The developed board offer a design tool for hardware developers where the intermodulation products can be evaluated, this digital modulator avoid parasitic inductances and capacitances between the lines. The results of the developed system are effective to add white Gaussian noise and probe the intermodulation products up to 3rd order that can be added, as well as the effect of spectral regrowth. The system is a hardware design tool able to show by stages the amplitude and phase changes that involves a 64-QAM modulation.Keywords: CNC, Intermodulation, Layout, 64-QAM.DISEÑO Y FABRICACIÓN DE UN MODULADOR DE 64 QAM PARA EL ANÁLISIS DE SEÑALES ENTRE ETAPASResumenEste trabajo propone el diseño de un modulador digital 64-QAM en tarjeta impresa basado en tecnología en chip, la tarjeta desarrollada consta de dos fases de retardo y dos fases de amplificación, el modulador fue desarrollado usando el software PCB Wizard y fueron establecidos puntos de prueba para cada etapa. El diseño desarrollado fue construido a través de una máquina de control numérico por computadora. Los resultados experimentales muestran una mejora significativa en la precisión alcanzada de NMSE de -51 dB. La tarjeta desarrollada ofrece una herramienta de diseño para desarrolladores de hardware donde los productos de intermodulación puedan ser evaluados, este modulador digital evita inductancias parásitas y capacitancias entre líneas. Los resultados del sistema desarrollado son efectivos para agregar ruido blanco Gaussiano y comprobar los los productos de intermodulación de hasta 3er orden que se pueden agregar, así como el efecto de recrecimiento espectral. El sistema es una herramienta de diseño de hardware capaz de mostrar por etapas los cambios en amplitud y fase que involucra una modulación de tipo QAM.Palabras Claves: CNC, Diseño, Intermodulación, 64-QAM

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

La terapia celular en la cardiopatía isquémica

La cardiopatía isquémica es la principal causa de muerte e insuficiencia cardiaca a nivel mundial. Esto hace de vital importancia el desarrollo de nuevas modalidades terapéuticas, que disminuyan la mortalidad y complicaciones a largo plazo en estos pacientes. Una de las principales líneas de investigación a nivel mundial es la regeneración miocárdica a partir de células progenitoras, con el fin de mejorar la función sistólica y diastólica de los pacientes con cardiopatía isquémica, además de incrementar su sobrevida. Con bases teóricas y fisiológicas sobre la función de estas células, se han llevado a cabo con gran entusiasmo a nivel mundial, estudios en animales y humanos para tratar de definir la utilidad del empleo de las células madre, en el manejo de los pacientes con cardiopatía isquémica. En la actualidad, la terapia regenerativa en la cardiopatía isquémica es considerada una herramienta terapéutica novedosa, de beneficios teóricos considerables y pocos efectos adversos. En esta revisión presentamos los fundamentos científicos básicos que apoyan el empleo de esta terapia, la evidencia clínica actual sobre su beneficio. Señalamos los puntos controversiales y las perspectivas sobre su empleo y utilidad a corto y largo plazo

Geographic differences in patients with acute myocardial infarction in the PARADISE‐MI trial

Introduction: The globalization of clinical trials has highlighted geographic differences in patient characteristics, treatments, and outcomes. We examined these differences in PARADISE-MI. Methods and results: 23.0% were randomized in Eastern Europe/Russia, 17.5% in Western Europe, 12.2% in Southern Europe, 10.1% in Northern Europe, 12.0% in Latin America (LA), 9.3% in North America (NA), 10.0% in East/South-East Asia and 5.8% in South Asia (SA). Those from Asia, particularly SA, were different from patients enrolled in the other regions, being younger and thinner. They also differed in terms of comorbidities (high prevalence of diabetes and low prevalence of AF), type of MI (more often STEMI), and treatment (low rate of primary PCI). By contrast, patients from LA did not differ meaningfully from those randomized in Europe or NA. Use of ACE-inhibitor/ARB (34.8%) and beta-blockers (65.5%) was low in SA, whereas MRA use was lowest in NA (22%) and highest in Eastern Europe/Russia (53%). Rates of the primary composite outcome of cardiovascular death or incident HF varied two-fold among regions, with the lowest rate in SA (4.6/100person-years) and the highest in LA (9.2/100person-years). Rates of incident HF varied almost six-fold among regions, with the lowest rate in SA (1.0/100person-years) and the highest in Northern Europe (5.9/100person-years). The effect of sacubitril/valsartan was not modified by region. Conclusion: In PARADISE-MI, there were substantial regional differences in patient characteristics, treatments and outcomes. Although the generalizability of these findings to a “real-world” unselected population may be limited, these findings underscore the importance of considering both regional and within-region differences when designing global clinical trials

Gender differences and management of stroke risk of nonvalvular atrial fibrillation in an upper middle-income country: Insights from the CARMEN-AF registry

Background: Atrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. Objective: To describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. Methods: A total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014–2017). They were categorized according to Gender. Results: Overall, 48.6% were women, mean age 70 ± 12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). Conclusions: CARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC. Keywords: Atrial fibrillation, Gender, Thromboembolic risk, Antithrombotic therapy, Stroke, Mexic

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of &lt;30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy