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

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

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

Distinct immunologic and radiographic patterns in etanercept-induced lung injury

Nonspecific clinical presentation of non-infectious, immune-mediated pulmonary complications of etanercept therapy makes the diagnosis difficult. While bronchoalveolar lavage fluid (BALF) cell analysis is frequently used in diagnosing drug-induced lung disease, BALF patterns in etanercept-induced lung injury (EILI) are not well established. Furthermore, previous reports of EILI diagnosis relied on transbronchial or surgical lung biopsies. Here, we report two patients who developed pulmonary toxicity after etanercept treatment. Both patients were diagnosed with EILI. While one patient presented with CD4(+)-predominant lymphocytic alveolitis (consistent with a sarcoid-like pattern), the other patient exhibited a CD8(+)-predominant pattern (consistent with hypersensitivity pneumonitis-like reaction). The different BAL patterns were accompanied by distinct radiographic findings. Both patients significantly improved after etanercept discontinuation and corticosteroid initiation. We propose that EILI can present with distinct immunologic and radiographic phenotypes. In addition, early BALF analysis with lymphocyte immunophenotyping can further define the underlying immunologic abnormalities, and thereby, avoid more invasive procedures

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

Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial

BACKGROUND: The study hypothesis is that administration of inhaled nitric oxide (NO) plus oxygen to subjects with submassive pulmonary embolism (PE) will improve right ventricular (RV) systolic function and reduce RV strain and necrosis, while improving patient dyspnea, more than treatment with oxygen alone. METHODS: This article describes the rationale and protocol for a registered (NCT01939301), nearly completed phase II, 3-center, randomized, double-blind, controlled trial. Eligible patients have pulmonary imaging-proven acute PE. Subjects must be normotensive, and have RV dysfunction on echocardiography or elevated troponin or brain natriuretic peptide and no fibrinolytics. Subjects receive NO plus oxygen or placebo for 24 hours (±3 hours) with blood sampling before and after treatment, and mandatory echocardiography and high-sensitivity troponin posttreatment to assess the composite primary end point. The sample size of N=78 was predicated on 30% more NO-treated patients having a normal high-sensitivity troponin (<14 pg/mL) and a normal RV on echocardiography at 24 hours with α=.05 and β=.20. Safety was ensured by continuous spectrophotometric monitoring of percentage of methemoglobinemia and a predefined protocol to respond to emergent changes in condition. Blinding was ensured by identical tanks, software, and physical shielding of the device display and query of the clinical care team to assess blinding efficacy. RESULTS: We have enrolled 78 patients over a 31-month period. No patient has been withdrawn as a result of a safety concern, and no patient has had a serious adverse event related to NO. CONCLUSIONS: We present methods and a protocol for the first double-blinded, randomized trial of inhaled NO to treat PE

Формирование и совершенствование оплаты труда на предприятии ООО «Томскнефтехим»

Объект исследования - предприятие ООО «Томскнефтехим». Предметом исследования является формирование оплаты труда на данном предприятии. Цель работы – исследование вопросов формирования и совершенствования оплаты труда на предприятии. В процессе исследования применялись научные и специальные методы экономических исследований, а именно диалектический метод, системный и процессный подходы, анализ литературных данных, обобщения, описания, расчетно – аналитический подход и сравнительно – сопоставительный методы. В качестве рекомендации предприятию в отношении экономических методов организации работы специалистов и руководителей и ее эффективности можно предложить ввести систему KPI (ключевых показателей эффективности) оценку способностей и качества работы персонала. Оценка результатов выступает основой для выплаты регулярных премий, то есть у сотрудников появляются возможности зарабатывать больше, а также оценка квалификации и потенциала работника может стать основой для принятия решений по его обучению, карьерному перемещению и эффективной работе на предприятии.The object of study - the enterprise of OOO "Tomskneftekhim". The subject of research is the formation of wage in the enterprise. The aim of this work is the study of questions of formation and improvement of labor payment at the enterprise. In the process of research used scientific and special methods of economic researches, namely the dialectical method, system and process approaches, the literary data analysis, generalization, description, analytical approach and comparative methods. As a recommendation to the enterprise in respect of economic methods of organization of work of specialists and managers and its effectiveness can introduce the KPI system (key performance indicators) the ability and quality of staff. Evaluation of results is the basis for the payment of regular premiums, then the employees have opportunities to earn more, as well as the qualification and potential of the employee can be the basis for decision-making in his training, career displacement and effective work at the enterprise

Isolated heart model demonstrates evidence of contractile and diastolic dysfunction in right ventricles from rats with sugen/hypoxia‐induced pulmonary hypertension

Although extensively used for the study of left ventricular function, limited experience exists with the isolated heart model in the evaluation of right ventricular (RV) function. In particular, no published experience exists with this tool in sugen/hypoxia‐induced pulmonary hypertension (SuHx‐PH), a frequently used model of severe and progressive PH. We sought to characterize markers of RV contractile and diastolic function in SuHx‐PH and to establish their relationship with markers of maladaptive RV remodeling. Hearts were excised from anesthetized Sprague Dawley rats with or without SuHx‐PH and perfused via the aorta using a Langendorff preparation. We explored the Frank–Starling relationship of RV function (RV developed pressure, dP/dt max, and dP/dt min; all normalized to RV mass) by increasing RV end‐diastolic pressure (RVEDP) from 0 to 40 mmHg. Functional studies were complemented by quantification of RV pro‐apoptotic signaling (bcl2/bax), procontractile signaling (apelin), and stress response signaling (p38MAPK activation). Pearson's correlation analysis was performed for functional and biochemical parameters. SuHx‐RVs exhibited severe RV dysfunction with marked hypertrophy and decreased echocardiographic cardiac output. For any given RVEDP, SuHx‐RVs demonstrated less developed pressure and lower dP/dt max, as well as less pronounced dP/dt min, suggestive of decreased contractile and diastolic function. SuHx‐RVs exhibited decreased bcl2/bax ratios, apelin expression, and p38MAPK activation. Bcl2/bax and apelin RNA abundance correlated positively with RV developed pressure and dP/dt max and negatively with dP/dt min. p38MAPK activation correlated positively with RV developed pressure. We conclude that SuHx‐RVs exhibit severe contractile and diastolic dysfunction. Increased pro‐apoptotic signaling and attenuated procontractile and stress response signaling may contribute to these functional alterations

Inhaled nitric oxide to treat intermediate risk pulmonary embolism: A multicenter randomized controlled trial

Objective To test the hypothesis that adjunctive inhaled NO would improve RV function and viability in acute PE. Methods This was a randomized, placebo-controlled, double blind trial conducted at four academic hospitals. Eligible patients had acute PE without systemic arterial hypotension but had RV dysfunction and a treatment plan of standard anticoagulation. Subjects received either oxygen plus 50 parts per million nitrogen (placebo) or oxygen plus 50 ppm NO for 24 h. The primary composite endpoint required a normal RV on echocardiography and a plasma troponin T concentration <14 pg/mL. The secondary endpoint required a blood brain natriuretic peptide concentration <90 pg/mL and a Borg dyspnea score ≤ 2. The sample size of N = 76 tested if 30% more patients treated with NO would achieve the primary endpoint with 80% power and alpha = 5%. Results We randomized 78 patients and after two withdrawals, 38 were treated per protocol in each group. Patients were well matched for baseline conditions. At 24 h, 5/38 (13%) of patients treated with placebo and 9/38 (24%) of patients treated with NO reached the primary endpoint (P = 0.375). The secondary endpoint was reached in 34% with placebo and 13% of the NO (P = 0.11). In a pre-planned post-hoc analysis, we examined how many patients with RV hypokinesis or dilation at enrollment resolved these abnormalities; 29% more patients treated with NO resolved both abnormalities at 24 h (P = 0.010, Cochrane's Q test). Conclusions In patients with severe submassive PE, inhaled nitric oxide failed to increase the proportion of patients with a normal troponin and echocardiogram but increased the probability of eliminating RV hypokinesis and dilation on echocardiography