Causal Analysis of India’s Energy-led Growth and CO2 Emission (1960-2010)

For any developing nation, GDP growth and CO2 emission goes hand-in-hand. GDP growth affects the CO2 emission level and vice versa. EKC hypothesis ensures the interaction between income level and environmental degradation. Based on this foundation, bi-directional causal relationship between these two factors for India has been obtained in this paper. For empirical analysis, data for GDP growth of and CO2 emission over the period 1960-2010 has been considered. Vector Error Correction model using lag-augmented VAR model has been employed for the analysis. The result obtained is new in the considering the existing body of literature

Experimental Performance Analysis of Diesel Engine without Ceramic Coating on Cylinder Liner

Automobile industries faces big problem related to fuel economy, engine efficiency and emission which is harmful to the environment as well as human. In diesel engine one–third fuel energy is converted into the useful work otherwise diesel engine rejects about two third of heat energy of fuel i.e. one third to exhaust and one third to coolant. Due to rise of fuel cost major challenges for automobile industry is to decrease the fuel consumption, exhaust emissions without compromising efficiency. The performance of internal combustion engine can be improve by reducing frictional losses as well as reduction in specific fuel consumption of fuel during the engine operation. Exhaust emission can be reduced by complete combustion of fuel which is obtained by complete combustion of fuel due to high combustion temperature inside the combustion chamber. These things can be obtain by ceramic materials which have low thermal conductivity, less weight, corrosion resistance, wear resistance and shock resistance etc. the objective is to improve the performance of four stroke single cylinder diesel engine by providing ceramic coating on cylinder liner to know the effect of coating on the performance of diesel engine

Twenty years of the Fabry Outcome Survey (FOS): insights, achievements, and lessons learned from a global patient registry

Agalsidase alfa; Cardiovascular outcomes; Renal outcomesAgalsidasa alfa; Resultados cardiovasculares; Resultados renalesAgalsidasa alfa; Resultats cardiovasculars; Resultats renalsBackground Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the effects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of affected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS studies have made in understanding FD. Results FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confirmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been published in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term effectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its effects on morbidity and mortality, as well as the benefits of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agalsidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specific populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. Conclusion FOS over the last 20 years has substantially increased the scientific knowledge around improved patient management of FD and continues to expand our understanding of this rare disease.FOS is funded by Takeda Pharmaceuticals International AG, which also assisted in analyzing the data and preparing the manuscript. Takeda Development Center Americas, Inc. provided funding to Excel Medical Affairs for support in writing and editing this manuscript

Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease

Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm3). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187

A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide

Background: Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifesta‑ tions and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. Methods: The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of beneft, in selected countries, through donation of ERT to nonproft organiza‑ tions, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. Results: As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. Conclusions: The response rate for follow-up data at 1 year was high, with data collected for>90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These fndings suggest that the program can beneft selected patients previously unable to access disease-specifc treatments. Further inno‑ vative solutions and eforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world

Role of serum N-terminal pro-brain natriuretic peptide measurement in diagnosis of cardiac involvement in patients with anderson-fabry disease

Enzyme replacement therapy has the potential to delay or reverse adverse cardiac remodeling in Anderson-Fabry disease (AFD); however, the current indications for enzyme replacement therapy rely on detecting relatively advanced features of the disease. We aimed to determine the relation between the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and cardiac abnormalities in patients with AFD. We hypothesized that it might help to detect early disease. NT-proBNP was measured under at rest conditions in 117 patients with AFD (age 48 ± 15 years, 46.2% men). All patients underwent clinical evaluation with electrocardiography and echocardiography. The median NT-proBNP concentration was 24 pmol/L (range <5 to 6,059). Of the 117 patients, 67 (57%) had elevated, age-corrected, NT-proBNP levels. In the 56 patients (48%) with normal echocardiographic findings, the NT-proBNP levels were greater than the age-predicted cutoffs in 10 of 25 patients with abnormal electrocardiographic findings and 3 of 31 patients with normal electrocardiographic findings (p <0.05). On multiple regression analysis, age, creatinine, left atrial volume index, E/Ea, and the presence of abnormal electrocardiographic findings were independently associated with log NT-proBNP (R(2) = 0.67, p <0.05). In conclusion, NT-proBNP concentrations were elevated in patients with AFD and early cardiac involvement, suggesting its measurement could assist in decisions regarding the timing of enzyme replacement therapy

Formal Scenario-Based Testing of Autonomous Vehicles: From Simulation to the Real World

We present a new approach to automated scenario-based testing of the safety of autonomous vehicles, especially those using advanced artificial intelligence-based components, spanning both simulation-based evaluation as well as testing in the real world. Our approach is based on formal methods, combining formal specification of scenarios and safety properties, algorithmic test case generation using formal simulation, test case selection for track testing, executing test cases on the track, and analyzing the resulting data. Experiments with a real autonomous vehicle at an industrial testing facility support our hypotheses that (i) formal simulation can be effective at identifying test cases to run on the track, and (ii) the gap between simulated and real worlds can be systematically evaluated and bridged.Comment: 9 pages, 6 figures. Full version of an ITSC 2020 pape

P-475: Uncontrolled hypertension in Fabry disease

Fabry disease is a x-linked lysosomal storage disease leading to early death related to renal, cardiac, and cerebrovascular disease. Therefore, proper diagnosis and therapy of elevated blood pressure may improve morbidity and mortality of these patients. However, the prevalence of uncontrolled hypertension in Fabry disease is unknown. We examined blood pressure of patients with Fabry disease using a large international database, the Fabry Outcome Survey (FOS). We defined uncontrolled hypertension as a systolic blood pressure (SBP) ≥130, and/or a diastolic blood pressure (DBP) ≥ 80 mmHg (threshold for blood pressure control in renal disease, JNC7). We used the short MDRD-GFR formula for assessment of renal function, and we classified chronic kidney disease according to K/DOQI. Among 459 patients with Fabry disease, 306 had blood pressure readings entered in the database. Mean SBP was 124.6 ± 16.9 mmHg and mean DBP was 73.6 ± 11.7 mmHg (mean age: 38.4 ± 15.6 years, 142 females, 164 males). Fourty-three percent of men and and 28% of women showed uncontrolled hypertension. In 291 patients both, blood pressure readings and GFR estimates, were available. In patients with normal GFR (>90 ml/min/1.73m2) mean SBP was 119.5 ± 15.6 mmHg and mean DBP was 69.7 ± 11.1 mmHg (n=120). In patients with mild decreased GFR (60-89 ml/min/1.73m2) mean SBP was 126.7 ± 15.9 mmHg and mean DBP was 75.0 ± 11.0 mmHg (n=110). In patients with moderate decreased GFR (30-59 ml/min/1.73m2) mean SBP was 132.7 ± 20.8 mmHg and mean DBP was 79.0 ± 13.3 mmHg (n=41). In 70 patients blood pressure readings were available before start of enzyme replacemen therapy (ERT) with agalsidase alfa (Replagal, TKT 5S Europe, 0.2 mg/kg bodyweight fortnightly i.v.), in 87 at 12 months and in 76 at 24 months of therapy. At baseline, at 12 and at 24 months of ERT, 39%, 30% and 42%of the patients presented with uncontrolled hypertension, respectively. Our study revealed a high prevalence of uncontrolled hypertension among patients with Fabry disease. Thus, there is need for improvement of blood pressure control in these patients. Am J Hypertens (2004) 17, 206A-206A; doi: 10.1016/j.amjhyper.2004.03.54