Failure detection and isolation investigation for strapdown skew redundant tetrad laser gyro inertial sensor arrays

The degree to which flight-critical failures in a strapdown laser gyro tetrad sensor assembly can be isolated in short-haul aircraft after a failure occurrence has been detected by the skewed sensor failure-detection voting logic is investigated along with the degree to which a failure in the tetrad computer can be detected and isolated at the computer level, assuming a dual-redundant computer configuration. The tetrad system was mechanized with two two-axis inertial navigation channels (INCs), each containing two gyro/accelerometer axes, computer, control circuitry, and input/output circuitry. Gyro/accelerometer data is crossfed between the two INCs to enable each computer to independently perform the navigation task. Computer calculations are synchronized between the computers so that calculated quantities are identical and may be compared. Fail-safe performance (identification of the first failure) is accomplished with a probability approaching 100 percent of the time, while fail-operational performance (identification and isolation of the first failure) is achieved 93 to 96 percent of the time

Emerging role of angiogenesis in adaptive and maladaptive right ventricular remodeling in pulmonary hypertension

Right ventricular (RV) function is the primary prognostic factor for both morbidity and mortality in pulmonary hypertension (PH). RV hypertrophy is initially an adaptive physiological response to increased overload; however, with persistent and/or progressive afterload increase, this response frequently transitions to more pathological maladaptive remodeling. The mechanisms and disease processes underlying this transition are mostly unknown. Angiogenesis has recently emerged as a major modifier of RV adaptation in the setting of pressure overload. A novel paradigm has emerged that suggests that angiogenesis and angiogenic signaling are required for RV adaptation to afterload increases and that impaired and/or insufficient angiogenesis is a major driver of RV decompensation. Here, we summarize our current understanding of the concepts of maladaptive and adaptive RV remodeling, discuss the current literature on angiogenesis in the adapted and failing RV, and identify potential therapeutic approaches targeting angiogenesis in RV failure

Propagation of the surface plasmon polaritons through gradient index and periodic structures

We study the propagation of surface electromagnetic waves along the metallic surface covered by various layered dielectric structures. We show that strong radiative losses typical for the scattering of the surface wave can be considerably suppressed when single dielectric step is substituted by gradient index or periodic layered structure

High Rate Of Right Ventricular Dysfunction After Negative Computed Tomographic Pulmonary Angiography

Background: Prior work found that 20% of patients with persistent dyspnea have right ventricular (RV) dysfunction. Many patients with suspected pulmonary embolism (PE) who have a negative CTPA have persistent yet unexplained dyspnea. We hypothesized that a substantial proportion of these patients have unrecognized RV dysfunction. We sought to estimate this proportion and develop criteria to predict RV dysfunction on echocardiography after CTPA negative for PE. Methods: This was a four-center, prospective study of patients with ≥one symptom or sign and ≥one risk factor for PE, and CTPA scan performed. To assess potential predictors of RV dysfunction, we recorded 82 clinical predictors in real time. These included clinical findings, 12-lead electrocardiography (ECG), exhaled volumetric CO2/O2, plasma D-dimer and fibrinogen measurements. Patients underwent echocardiography within one week. Isolated RV dysfunction was defined as normal LV function with either moderate-severe RV hypokinesis, or estimated RV systolic pressure >35 mmHg. To assess if RV dysfunction led to symptoms that prompted reevaluation, we compared the frequency of repeat CTPA within 90 days. CTPA scans were interpreted by two independent radiologists. Predictors of RV dysfunction were assessed using a univariate (P<0.1)-multivariate (P<0.05) statistical approach. Results: 647 patients were enrolled; 120 with CPTA positive for PE were excluded, and 97 were excluded because of lack of persistent dyspnea. Of the 430 remaining patients, 184 underwent echocardiography, which demonstrated isolated RV dysfunction in 34% (95% CI: 30-41%). 27% of patients with isolated RV dysfunction had repeat CTPA within 90 days, a significantly higher rate than in patients without echocardiography (4%, P=0.03, Chi Square) or a normal echocardiogram (5%, P=0.02). No repeat CTPA scan showed PE. Of 82 candidate predictors of examined, univariate analysis found only 6 significant: active malignancy, normal CTPA, right bundle branch block on ECG, T-wave inversion in V1-V2 on ECG, history of COPD, and fibrinogen concentration. Of these six, multivariate logistic regression analysis found only normal CTPA as a significant predictor of isolated RV dysfunction. Conclusion: Patients with persistent dyspnea who have a normal CTPA performed for suspected PE have a high rate of unexplained isolated RV dysfunction on echocardiography. These patients are more likely to have persistent symptoms leading to unnecessary repeat CTPA in the short term. These findings form the starting point for a screening protocol to select patients with negative CTPA scanning for formal echocardiography and specialist referral to evaluate for pulmonary hypertension or other treatable causes of RV dysfunction

Allergy approach to a dog population from a veterinary dermatology consultation at the tropical inland city of Londrina, Paraná, Brazil

Background: Prevalence of allergy in dogs is also increasing associated with better living conditions and medical care. Indoor life is more often related to mite and mold sensitization and allergy, while an outdoor environment would favor a pollinic response with seasonal worsening. On the other hand, food allergy tends to present as a perennial condition. The particular frame of a tropical climate may in turn introduce environmental factors associated either with the concentration of available airborne allergens or skin barrier conditions. This study aimed to characterize the allergy frame of a dog population attending the State University of Londrina and Veterinary Clinics Life Space dermatology outpatient consultation, situated in the tropical inland region of Paraná, Brazil. Methods: A 111 allergic patient population (60 males and 51 females) was selected by clinical evaluation and submitted to food allergy restriction measures from 2015 to 2018. Thirty five patients (33.3%) belonged to predisposed breeds, 74.8% were indoor and 25.2% outdoor. Results: First signs started between 1-3 years of age in 55% of the patients and after the 3 years in 45%. Several comorbidities were found in 47.5% of the 1-3 years group and in 60% of the above group. Atopic dermatitis (AD) was diagnosed in 90.9% and food allergy (FA) in 23.7%, with 12.6% of simultaneous AD+FA. Malassezia overgrowth (MO) was diagnosed in 49.6% of the patients, mostly in the AD group. Flea allergy dermatitis was simultaneously diagnosed in 14.4% of the patients and otitis and conjunctivitis in 36% and 18.9%, respectively. Skin barrier disruption with seborrhea was diagnosed in 59% of the patients. The fourth version of the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4) showed 13.5%, 33.3% and 53.2% of Light, Moderate and Severe scores, respectively, and pretty similar in the group of predisposed-breeds. Positive correlation was found between CADESI-4 scores and FA (p=0.03), seborrhea (p<0.00001), MO (p=0.00003) and otitis (p=0.01). Malassezia overgrowth correlated positively with indoor living (p=0.02) and otitis (p<0.00001) despite 29% of MO without otitis. Simultaneous flea allergy correlated negatively with MO (p=0.0079), otitis (p=0.001) and conjunctivitis (p<0.00001). Conclusion: A clear clinical worsening trend was found associated with seborrhea, FA, indoor living and otitis and MO in this tropical population. Malassezia overgrowth is probably more severe in this wet tropical environment

Hypoxia Upregulates Estrogen Receptor β in Pulmonary Artery Endothelial Cells in a HIF-1α-Dependent Manner

17β-Estradiol (E2) attenuates hypoxia-induced pulmonary hypertension (HPH) through estrogen receptor (ER)-dependent effects, including inhibition of hypoxia-induced endothelial cell proliferation; however, the mechanisms responsible for this remain unknown. We hypothesized that the protective effects of E2 in HPH are mediated through hypoxia-inducible factor 1α (HIF-1α)-dependent increases in ERβ expression. Sprague-Dawley rats and ERα or ERβ knockout mice were exposed to hypobaric hypoxia for 2-3 weeks. The effects of hypoxia were also studied in primary rat or human pulmonary artery endothelial cells (PAECs). Hypoxia increased expression of ERβ, but not ERα, in lungs from HPH rats as well as in rat and human PAECs. ERβ mRNA time dependently increased in PAECs exposed to hypoxia. Normoxic HIF-1α/HIF-2α stabilization increased PAEC ERβ, whereas HIF-1α knockdown decreased ERβ abundance in hypoxic PAECs. In turn, ERβ knockdown in hypoxic PAECs increased HIF-2α expression, suggesting a hypoxia-sensitive feedback mechanism. ERβ knockdown in hypoxic PAECs also decreased expression of the HIF inhibitor prolyl hydroxylase 2 (PHD2), whereas ERβ activation increased PHD2 and decreased both HIF-1α and HIF-2α, suggesting that ERβ regulates the PHD2/HIF-1α/HIF-2α axis during hypoxia. Whereas hypoxic wild-type or ERα knockout mice treated with E2 demonstrated less pulmonary vascular remodeling and decreased HIF-1α after hypoxia compared with untreated hypoxic mice, ERβ knockout mice exhibited increased HIF-2α and an attenuated response to E2 during hypoxia. Taken together, our results demonstrate a novel and potentially therapeutically targetable mechanism whereby hypoxia, via HIF-1α, increases ERβ expression and the E2-ERβ axis targets PHD2, HIF-1α, and HIF-2α to attenuate HPH development

Effect of Exercise on Right Ventricle Inflammation in a Rat Model of Severe Monocrotaline-Induced Pulmonary Arterial Hypertension

poster abstractPulmonary arterial hypertension (PAH) is a devastating disease of progressive remodeling of small and mid-size pulmonary arteries that leads to elevated pulmonary pressure. The work of the right heart is increased due to the elevated pulmonary pressures and can lead to maladaptive cardiac wall hypertrophy, right heart failure and then eventually death. Whether exercise-induced cardiac stress also promotes detrimental right ventricle (RV) inflammation in PAH has not been thoroughly examined. The purpose of this study is to determine if treadmill exercise at low relative intensity in a rat model of severe PAH without promoting greater RV inflammation. Adult male Sprague- Dawley rats were injected with monocrotaline (60mg/kg, subcutaneously, n=14) or saline (healthy controls, n=4). RV tissue was obtained from these rats following a 6 week, 5 times/week treadmill training program at a low intensity of 50% of measured aerobic capacity (VO2max) and compared to tissue obtained from sedentary counterparts. RV immunofluorescent staining for CD45, a lymphocyte marker, was performed to evaluate the inflammatory response due to chronic exercise training. The experiment is still underway and the expected result is that there is no greater exercised induced RV inflammation in PAH rats compared to healthy rats

Derivation of a screening tool to identify patients with right ventricular dysfunction or tricuspid regurgitation after negative computerized tomographic pulmonary angiography of the chest

Many dyspneic patients who undergo computerized tomographic pulmonary angiography (CTPA) for presumed acute pulmonary embolism (PE) have no identified cause for their dyspnea yet have persistent symptoms, leading to more CTPA scanning. Right ventricular (RV) dysfunction or overload can signal treatable causes of dyspnea. We report the rate of isolated RV dysfunction or overload after negative CTPA and derive a clinical decision rule (CDR). We performed secondary analysis of a multicenter study of diagnostic accuracy for PE. Inclusion required persistent dyspnea and no PE. Echocardiography was ordered at clinician discretion. A characterization of isolated RV dysfunction or overload required normal left ventricular function and RV hypokinesis, or estimated RV systolic pressure of at least 40 mmHg. The CDR was derived from bivariate analysis of 97 candidate variables, followed by multivariate logistic regression. Of 647 patients, 431 had no PE and persistent dyspnea, and 184 (43%) of these 431 had echocardiography ordered. Of these, 64 patients (35% [95% confidence interval (CI): 28%-42%]) had isolated RV dysfunction or overload, and these patients were significantly more likely to have a repeat CTPA within 90 days (P = .02, [Formula: see text] test). From univariate analysis, 4 variables predicted isolated RV dysfunction: complete right bundle branch block, normal CTPA scan, active malignancy, and CTPA with infiltrate, the last negatively. Logistic regression found only normal CTPA scanning significant. The final rule (persistent dyspnea + normal CTPA scan) had a positive predictive value of 53% (95% CI: 37%-69%). We conclude that a simple CDR consisting of persistent dyspnea plus a normal CTPA scan predicts a high probability of isolated RV dysfunction or overload on echocardiography

A novel de novo TBX5 mutation in a patient with Holt-Oram syndrome leading to a dramatically reduced biological function

BACKGROUND: The Holt-Oram syndrome (HOS) is an autosomal dominant disorder affecting 1/100.000 live births. It is defined by upper limb anomalies and congenital heart defects with variable severity. We describe a dramatic phenotype of a male, 15-month-old patient being investigated for strict diagnostic criteria of HOS. ----- METHODS AND RESULTS: Genetic analysis revealed a so far unpublished TBX5 mutation, which occurs de novo in the patient with healthy parents. TBX5 belongs to the large family of T-box transcription factors playing major roles in morphogenesis and cell-type specification. The mutation located in the DNA-binding domain at position 920 (C→A) leads to an amino acid change at position 85 (proline → threonine). Three-dimensional analysis of the protein structure predicted a cis to trans change in the respective peptide bond, thereby probably provoking major conformational and functional alterations of the protein. The p.Pro85Thr mutation showed a dramatically reduced activation (97%) of the NPPA promoter in luciferase assays and failed to induce NPPA expression in HEK 293 cells compared to wild-type TBX5 protein. The mutation did not interfere with the nuclear localization of the protein. ----- CONCLUSION: These results suggest that the dramatic functional alteration of the p.Pro85Thr mutation leads to the distinctive phenotype of the patient

Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner

INTRODUCTION: There is a sex difference in the risk of ischemic acute kidney injury (AKI), and estrogen mediates the protective effect of female sex. We previously demonstrated that preprocedural chronic restoration of physiologic estrogen to ovariectomized female mice ameliorated AKI after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). In the present study, we hypothesized that male mice and aged female mice would benefit from estrogen administration after CA/CPR. We tested the effect of estrogen in a clinically relevant manner by administrating it after CA/CPR. METHODS: CA/CPR was performed in young (10-15 weeks), middle-aged (43-48 weeks), and aged (78-87 weeks) C57BL/6 male and female mice. Mice received intravenous 17β-estradiol or vehicle 15 min after resuscitation. Serum chemistries and unbiased stereological assessment of renal injury were completed 24 h after CA. Regional renal cortical blood flow was measured by a laser Doppler, and renal levels of estrogen receptor alpha (ERα) and G protein-coupled estrogen receptor (GPER) were evaluated with immunoblotting. RESULTS: Post-arrest estrogen administration reduced injury in young males without significant changes in renal blood flow (percentage reduction compared with vehicle: serum urea nitrogen, 30 %; serum creatinine (sCr), 41 %; volume of necrotic tubules (VNT), 31 %; P < 0.05). In contrast, estrogen did not affect any outcomes in young females. In aged mice, estrogen significantly reduced sCr (80 %) and VNT (73 %) in males and VNT (51 %) in females. Serum estrogen levels in aged female mice after CA/CPR were the same as levels in male mice. With age, renal ERα was upregulated in females. CONCLUSIONS: Estrogen administration after resuscitation from CA ameliorates renal injury in young males and aged mice in both sexes. Because injury was small, young females were not affected. The protective effect of exogenous estrogen may be detectable with loss of endogenous estrogen in aged females and could be mediated by differences in renal ERs. Post-arrest estrogen administration is renoprotective in a sex- and age-dependent manner