Application of FFTBM with signal mirroring to improve accuracy assessment of MELCOR code

This paper deals with the application of Fast Fourier Transform Base Method (FFTBM) with signal mirroring (FFTBM-SM) to assess accuracy of MELCOR code. This provides deeper insights into how the accuracy of MELCOR code in predictions of thermal-hydraulic parameters varies during transients. The case studied was modeling of Station Black-Out (SBO) accident in PSB-VVER integral test facility by MELCOR code. The accuracy of this thermal-hydraulic modeling was previously quantified using original FFTBM in a few number of time-intervals, based on phenomenological windows of SBO accident. Accuracy indices calculated by original FFTBM in a series of time-intervals unreasonably fluctuate when the investigated signals sharply increase or decrease. In the current study, accuracy of MELCOR code is quantified using FFTBMSM in a series of increasing time-intervals, and the results are compared to those with original FFTBM. Also, differences between the accuracy indices of original FFTBM and FFTBM-SM are investigated and correction factors calculated to eliminate unphysical effects in original FFTBM. The main findings are: (1) replacing limited number of phenomena-based time-intervals by a series of increasing time-intervals provides deeper insights about accuracy variation of the MELCOR calculations, and (2) application of FFTBM-SM for accuracy evaluation of the MELCOR predictions, provides more reliable results than original FFTBM by eliminating the fluctuations of accuracy indices when experimental signals sharply increase or decrease. These studies have been performed in the framework of a research project, aiming to develop an appropriate accident management support tool for Bushehr nuclear power plant. 2016 Elsevier B.V. All rights reserved

Intractable Seizure Disorders: Efficacy of The Classic Ketogenic Diet

 ObjectiveThe ketogenic diet is a high-fat, low carbohydrate, adequate protein diet,developed in the 1920s for the management of intractable seizure disorders in children. To evaluate efficacy and tolerability of the classic  ketogenic diet, we analyzed records of the children started on the diet from 1999 to 2006 at the Mofid children's hospital.Materials & Methods The subjects were 87 children, mean age 55 months. Before initiation of the diet, 55% of the patients had seizures, at least 1-4 times per day, 36% - 5 or more per day and 9% - 2 to 4 times per week. Mean number of Anti Epileptic Drugs (AEDs) tried for them was 8 and 67% were receiving three or more drugs.Results The ketogenic diet showed drastic improvement, with at least 50% reduction in seizure frequency in 87% of our patients, 39% of whom showed complete seizure control in the third month. After one year, in 80% of the patients who returned, improvement  continued, with 26% of them being seizure free; besides, 23% had one AED decreased, 36% had two or three AEDs decreased, and 25% (one child) had all AEDs discontinued. Of the 30 improved cases, 20%, at the end of the first year, had improved behavior as  well, and 23% of them had become more alert. The median diet duration of the improved group was 15 months.Conclusion The improvement in our patients, low  side effects, and the duration of diet by families reveal that the ketogenic diet can still be a very useful alternative therapy in certain epileptic children.

VITAMIN B6 & TREATMENT OF INFANTILE SPASMS: A COMPARISON WITH STANDARD STEROID THERAPY

BackgroundConsidering the inadequacies of current therapeutic regimens for infantile spasms (IS), and the frequent and serious side effects of  Some regimens, the ongoing search for more enhanced protocols is understandable.Materials and Methods:We have compared the therapeutic and adverse effects of vitamin B6 given in high doses with those of prednisolone in a randomized controlled clinical trial. Vitamin B6 (40mg/kg/24hr) and prednisolone (1.5mg/kg/day) were given to in 22 and 15 patients respectively, and the patients were followed for at least 6 months.Results:Response to treatment was slightly better in the prednisolone group but the difference was not significant (p=0.4). On the other hand adverse effects were also seen more frequently with prednisolone.Conclusion:We conclude that high dose vitamin B6 should be considered as an alternative method of treatment; it seems that it can be safely used where there is contraindication to use other antiepileptic drugs or where they have failed; even in newly diagnosed cases of IS.Keywords:Vitamin B6, prednisolone, infantile spasm

Sodium Valproate and Phenobarbitol: Weight Complications of Treatment in Epileptic Children

Objective The aim of this study was to evaluate and compare the effects of Na Valproate and Phenobarbital on changes in the weight of epileptic patients following treatment for their condition using the drugs mentioned.Materials and methodsSixty epileptics were assigned into two groups of 30 patients each, the case and controls. The diagnosis was made on the basis of the International League Against Epilepsy (ILAE) characteristics. BMI was defined. In the case group, the patients received 20mg/kg/day of Na Valproate, while the 30 controls received 5mg/kg/day of Phenobarbital for 6 months. Using the Mc Nemar and Chi-2 tests, BMI changes were compared after 6 months between the groups. Fisher's exact test was used to evaluate the role of age, sex, and primary weight on the weight increase due to Na Valproate usage.ResultsThere were no specific changes in age, sex, primary BMI and fatness between the 2 groups; in the case group, 20 patients(66.7%) and in the controls 4(13.3%) gained weight (PConclusionThe results indicate that epileptic children, aged over 10 years, and those who are overweight have more chances of gaining weight or becoming fatter, following treatment with Na Valproate. Further studies investigating the issue are warranted

Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report

BACKGROUND: Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. CASE PRESENTATION: We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. CONCLUSION: This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach

Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Riociguat, a member of a new class of compounds (soluble guanylate cyclase stimulators), has been shown in previous clinical studies to be beneficial in the treatment of chronic thromboembolic pulmonary hypertension. METHODS: In this phase 3, multicenter, randomized, double-blind, placebo-controlled study, we randomly assigned 261 patients with inoperable chronic thromboembolic pulmonary hypertension or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy to receive placebo or riociguat. The primary end point was the change from baseline to the end of week 16 in the distance walked in 6 minutes. Secondary end points included changes from baseline in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, World Health Organization (WHO) functional class, time to clinical worsening, Borg dyspnea score, quality-of-life variables, and safety. RESULTS: By week 16, the 6-minute walk distance had increased by a mean of 39 m in the riociguat group, as compared with a mean decrease of 6 m in the placebo group (least-squares mean difference, 46 m; 95% confidence interval [CI], 25 to 67; P<0.001). Pulmonary vascular resistance decreased by 226 dyn · sec · cm-5in the riociguat group and increased by 23 dyn · sec · cm-5in the placebo group (least-squares mean difference, -246 dyn · sec · cm-5; 95% CI, -303 to -190; P<0.001). Riociguat was also associated with significant improvements in the NT-proBNP level (P<0.001) and WHO functional class (P = 0.003). The most common serious adverse events were right ventricular failure (in 3% of patients in each group) and syncope (in 2% of the riociguat group and in 3% of the placebo group). CONCLUSIONS: Riociguat significantly improved exercise capacity and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. (Funded by Bayer HealthCare; CHEST-1 and CHEST-2 ClinicalTrials.gov numbers, NCT00855465 and NCT00910429, respectively.) Copyright © 2013 Massachusetts Medical Society

Primary Central Nervous System Lymphoma

ObjectivePrimary central nervous system lymphoma (PCNSL) is an extremely rare condition in childhood. We report the first case of PCNSL in a child in Iran.Clinical presentationA nine-year-old boy was referred to Mofid Hospital with the history of headache of four months and seizure of 2 months duration. Magnetic resonance imaging of the brain revealed a hyper-intense lesion in left fronto-parietal area with secondary satellite lesions. Biopsy of the brain mass was performed. Pathologic findings showed brain lymphoma and immunohistochemistry confirmed this diagnosis. The treatment started with intrathecal and systemic chemotherapy in combination with radiotherapy

Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2

BACKGROUND: The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD). METHODS: Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability. RESULTS: In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population. CONCLUSIONS: Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD. TRIAL REGISTRATION NUMBERS: PATENT-1 (NCT00810693), PATENT-2 (NCT00863681)

Long-term safety and efficacy of imatinib in pulmonary arterial hypertension

Abstract BACKGROUND: Imatinib is an oral inhibitor of several protein kinases implicated in the pathophysiology of pulmonary hypertension. Treatment with imatinib resulted in improved hemodynamics and exercise capacity in a controlled trial (Imatinib [QTI571] in Pulmonary Arterial Hypertension, a Randomized Efficacy Study [IMPRES]), among pulmonary arterial hypertension (PAH) patients inadequately responsive to 2 to 3 PAH-specific therapies. METHODS: The long-term (up to 204 weeks) safety and efficacy of imatinib in this open-label extension study were reviewed until early study termination on April 16, 2014. Of 202 IMPRES-enrolled patients, 66 imatinib and 78 placebo recipients entered the extension. RESULTS: Overall, 93.8% (135 of 144) of patients discontinued the extension study; administrative issues (i.e., sponsor termination; 32.6%) and adverse events (31.3%) were the primary reasons for discontinuation. Nine patients completed the extension study before it was terminated. Serious and unexpected adverse events were frequent. These included 6 subdural hematomas in the extension study and 17 deaths during or within 30 days of study end. Although the patients who tolerated imatinib and remained in the extension for a longer duration did experience an improvement in functional class and walk distance, most discontinued the drug and the study. CONCLUSIONS: Severe adverse events, significant side effects, and a high discontinuation rate limit the utility of imatinib in the treatment of PAH. These risks outweigh any possible improvements in hemodynamics and walk distance seen in those patients able to remain on drug. The off-label use of this compound in PAH is discouraged

Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension

BACKGROUND: Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of aldosterone to the pathobiology of pulmonary arterial hypertension (PAH) and right ventricular (RV) heart failure is not fully understood. METHODS: The effects of Eplerenone (0.1% Inspra® mixed in chow) on pulmonary vascular and RV remodeling were evaluated in mice with pulmonary hypertension (PH) caused by Sugen5416 injection with concomitant chronic hypoxia (SuHx) and in a second animal model with established RV dysfunction independent from lung remodeling through surgical pulmonary artery banding. RESULTS: Preventive Eplerenone administration attenuated the development of PH and pathological remodeling of pulmonary arterioles. Therapeutic aldosterone antagonism - starting when RV dysfunction was established - normalized mineralocorticoid receptor gene expression in the right ventricle without direct effects on either RV structure (Cardiomyocyte hypertrophy, Fibrosis) or function (assessed by non-invasive echocardiography along with intra-cardiac pressure volume measurements), but significantly lowered systemic blood pressure. CONCLUSIONS: Our data indicate that aldosterone antagonism with Eplerenone attenuates pulmonary vascular rather than RV remodeling in PAH