Authority Approval Research Articles

The adaptation of sustainable biojet fuels and its effect on aircraft engine maintenance

Aviation industries are looking into several resources for renewable and sustainable energy. Among those attention is focused in biojet fuel. This paper engages the issue of biojet fuel emissions that increase the environmental concern in the air transport sector. The paper presents the use of biojet fuel and its effect on aircraft engine maintenance through preliminary data collections, and a review of its development process in operations for time and goal. As conclusion, airlines management needs to adapt and adopt the transition to alternative fuels, especially given the global biofuel trend emerging due to the authority approval.

О ЦЕЛОСТНОЙ СБАЛАНСИРОВАННОЙ ТЕОРЕТИЧЕСКИ И РЕАЛЬНО ВОЗМОЖНОЙ МОДЕЛИ МАКРОЭКОНОМИЧЕСКОЙ СИСТЕМЫ

The author´s model, which is close to the interpretation of econophysical" direction leniyu in modern economic theory (the Carnot cycle in the thermodynamic) resulting economic system specific amount of public expenditure and investments always result in the ideal case ("zero-loss" maximum mally possible social efficiency of public spending and investments) to the maximum possible rate of economic growth. The result of the model developed by the author of a balanced open economy is to overcome the barrier of the alleged lack of economic system of quantitative constants, so it is very different from the physical systems (with full awareness of the limitations of its author: irreducibility public the progress of human development to increase income or augmenting material wealth, economic growth). Holistic macroeconomic model proposed above, following the introduction of her in the preparation, negotiation, approval and implementation of the budget analysis relevant government authorities allow, in our opinion "sighted", and not blindly justify the scientific and strictly control the effectiveness of direction tions of macroeconomic development, their deviation from ideal.

Setting up clinical research studies in the National Health Service in England

Starting and conducting clinical trials in England can be a complicated and time-consuming process. Before your study can begin it is necessary to gain approval from the appropriate regulatory bodies. Prior to March 2016, studies required National Health Service (NHS) permission (also referred to as Research and Development (R&D) approval) obtained via the National Institute for Health Research (NIHR) Coordinated System for gaining NHS Permission (CSP). Since March 2016, a new streamlined system has been introduced with the aim of making it easier to gain regulatory approvals. Now studies must go through the process of Health Research Authority (HRA) approval. In this article we review the process of gaining HRA approval in England. The article is aimed at junior researchers to help them understand the application process, and to give tips on how to succeed in gaining approval.

THE ALZHEIMER’S PREVENTION INITIATIVE'S (API’S) EVOLVING PERSPECTIVE ON OUTCOMES IN PRECLINICAL TRIALS

The choice of outcomes for clinical trials in preclinical AD is influenced by factors such as trial goals (e.g., proof-of-concept, target engagement, demonstrating efficacy), participant characteristics, type of intervention, available infrastructure, data available to assess potential performance, Health Authority input). API and its partners have confronted these issues in conceiving and implementing its two active trials. API first proposed preclinical trials in cognitively unimpaired PSEN1 E280Amutation carriers and APOE4 homozygotes using biomarker outcomes to make go-no-go decisions. Based on input from prospective industry partners and Health Authorities, the focus was broadened to include clinical outcomes. We used existing prospective datasets to empirically derive a composite cognitive test score as a primary endpoint to track change in the ADAD trial, serving as a single measure of multiple cognitive domains, reducing the risk of Type 1 error. The primary aim of the API APOE4 homozygote clinical trial is to assess time to MCI or dementia due to AD and/or change in a different composite cognitive test score defined specifically for this trial. External to this trial, efforts will be undertaken to validate the clinical meaningfulness of change in the composite test scores. In both trials, key secondary clinical outcomes were selected, and biomarker aims were modified to address possible prognostic, predictive and theragnostic utility. The sample size for the API Colombia trial, conducted with the Neurosciences Group of Antioquia and Genentech/Roche, is 200 carriers and, to maintain genotype blind, 100 noncarriers; that for the 4-arm APOE4 homozygote trial, conducted in partnership with Novartis/Amgen, is approximately 1340. Sample size estimates will be provided for biomarker outcomes. In order to receive Health Authority approval, experimental therapies in preclinical trials are required to show a clinical effect. There is no consensus regarding the optimal approaches to do so. API and its partners are testing assumptions and refining methods, and are addressing the future potential for biomarker outcomes to serve as “reasonably likely“ therapeutic surrogates for decision-making in drug development. We hope these findings, which will be shared, will help advance the field’s efforts to find ways to assess clinically meaningful change in preclinical trials.

Predictive technology and natural hazards: risk for Australian planning authorities?

Purpose The purpose of this paper is to examine whether the improvements in technology that enhance community understanding of the frequency and severity of natural hazards also increased the risk of potential liability of planning authorities in negligence. In Australia, the National Strategy imposes a resilience-based approach to disaster management and stresses that responsible land-use planning can reduce or prevent the impact of natural hazards upon communities. Design/methodology/approach This paper analyses how the principles of negligence allocate responsibility for loss suffered by a landowner in a hazard-prone area between the landowner and local government. Findings The analysis in this paper concludes that despite being able to establish a causal link between the loss suffered by a landowner and the approval of a local authority to build in a hazard-prone area, it would be in the rarest of circumstances that a negligence action may be proven. Research limitations/implications The focus of this paper is on planning policies and land development, not on the negligent provision of advice or information by the local authority. Practical implications This paper identifies the issues a landowner may face when seeking compensation from a local authority for loss suffered because of the occurrence of a natural hazard known or predicted to be possible in the area. Originality/value The paper establishes that as risk managers, local authorities must place reliance upon scientific modelling and predictive technology when determining planning processes to fulfil their responsibilities under the National Strategy and to limit any possible liability in negligence.

Regulatory science of new technology: tendency of medical professionals' interests on silicone breast implants.

New technology related to artificial organs is most attractive for worldwide researchers. We believe they must contribute for the future patients against untreatable diseases. Regulatory science is a new science to establish 'social acceptance' of new technology into the clinical market as soon as possible. In the history of silicone breast implants, we could recognize risks many times; however, we missed such chances to prevent a subsequent crisis. We analyzed the trend of published literature related to silicone breast implants to review the medical professionals' interests on such risks. This trend showed, despite issues of a social acceptance of silicone breast implants in a few countries, other countries' medical professionals had no interest. Our hypothesis is 'medical professionals face the government and do not have contributed to re-establish the social acceptance of new technologies for patients'. Any technology does not have the complete evidence of safety, efficacy and quality, despite regulatory authorities' review and approval with clinical evidences. medical professionals need to conduct subsequently the epidemiological study, to take a meta-analysis periodically and to create/update the guidance for their patients under their professional ethics after the marketing of new technologies. We need to take seriously the 'lesson learned' from the history of silicone breast implants for all kind of new technologies existed in the present.

Recommendations for Urban Freight Policy Development in Gdynia

The purpose of this paper was to provide practical recommendations on how to develop Gdynia's urban freight policy based on actual planning experience and characteristics of potential measures. Freight policy scheme was developed as a result of three interrelated factors: a) the general procedure of the urban freight planning, b) the city's current planning stage analysis and, c) characteristics of urban freight objectives and related measures which allowed do compare existing planning competence with practical implementation requirements. Three phases of policy development were identified: preparation phase, implementation and follow up. On this basis, urban freight component of the Sustainable Urban Mobility Plan for Gdynia was proposed as a part of CIVITAS Dynamo project implementation. The SUMP's objectives were then described with the set of concrete measures. However final structure of the SUMP depends on the city's authorities approval, presented recommendations are intended to serve as a practical support for local decision makers.

THE INTEGRITY BALANCED THEORETICAL AND ACTUAL CAPABILITIES OF THE MODEL UNIVERSAL MACROECONOMIC SYSTEM

Numerical indicators of the level and pace of economic and social development are essential to evaluate the effectiveness of the country's economic policy, its subsequent changes, management of public development generally. The most common model among economists P.Samuelsona conclusions dit alleged direct link between large amounts of savings and the corresponding consumption level, the economic law of increasing additional cost, decreasing the efficiency and performance / yields, savings in oil headquarters, etc. The development of modern developing and developed economies often contradict this model of economic choice. The author's model, which is close to the interpretation of econophysical direction leniyu in modern economic theory (the Carnot cycle in the thermodynamic) resulting economic system specific amount of public expenditure and investments always result in the ideal case (zero-loss maximum mally possible social efficiency of public spending and investments) to the maximum possible rate of economic growth. The result of the model developed by the author of a balanced open economy is to overcome the barrier of the alleged lack of economic system of quantitative constants, so it is very different from the physical systems (with full awareness of the limitations of its author: irreducibility public the progress of human development to increase income or augmenting material wealth, economic growth). Holistic macroeconomic model proposed above, following the introduction of her in the preparation, negotiation, approval and implementation of the budget analysis relevant government authorities allow, in our opinion sighted, and not blindly justify the scientific and strictly control the effectiveness of direction tions of macroeconomic development, their deviation from ideal.

Conjugation to a Carrier Renders a Self Molecule Immunogenic besides Imparting Immuno-Prophylactic Benefit

Conjugation of hCGβ subunit with tetanus toxoid generates simultaneously independent set of antibodies against both hCG and tetanus. The former are competent to neutralise the bioactivity of hCG, and the latter impart immunoprophylactic benefit against tetanus. Similarly the decapeptide hormone LHRH which is common to both males and females can be rendered immunogenic by linking it to a carrier. It is conserved across species and is common to humans, rodents and dogs. Given to male rats, it causes a drastic reduction of testosterone and atrophy of testes and ventral prostate. Monoclonal antibody against LHRH can be employed to suppress the seasonal estrus in dogs With due approval of the Regulatory Authorities and Ethics Committees, the LHRH-DT (diphtheria toxoid) vaccine has undergone clinical trial in 28 patients of Carcinoma of Prostate in India and Austria. The vaccine was effective in reduction of testosterone and PSA (prostate specific antigen). It reduced the cancerous tissues and benefited the patients clinically. Keywords:

Abstract PL04-03: Basket studies: Lessons learned and future directions

Abstract Dramatic improvements in the ability to test for all classes of potentially actionable alterations in hundreds or even thousands of genes simultaneously, along with the rapidly expanding portfolio of therapeutic agents targeting a variety of cell signaling networks, have converged to create an unparalleled opportunity to pursue precision medicine in oncology. One obstacle to realizing the full potential of precision medicine in the clinic is the low prevalence of many potentially actionable genomic alterations as well as the diverse range of cancer types potentially implicated. To address this emerging challenge, multi-histology, genomically selected, basket studies have been developed. These studies represent a potentially transformative approach to genomically targeted drug development. In basket studies, patients with tumors known to harbor a qualifying genomic alteration are enrolled irrespective of tumor histology. Tumor types most likely to harbor the genomic biomarker are enrolled to their own cohort. Notably, in these tumor types that enroll to sufficient quantities, efficacy assessments are independently undertaken, therefore accounting for the possibility that tumor lineage may influence drug sensitivity. While the first generation of basket studies were designed mainly to detect early signals of activity across multiple tumor types simultaneously, newer basket studies are now being designed to collect the data required to seek health authority approval. Here we review the current landscape of precision medicine basket studies, with a focus on how to maximize their potential for advancing the standard of care. Citation Format: David Hyman. Basket studies: Lessons learned and future directions. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr PL04-03.

On the Improvement of China’s Legal System of Foreign Direct Investment

China has not enacted unified foreign direct investment code, and the legal system of foreign direct investment is composed of separate laws and numerous regulations and rules at both national and local level. The establishment of all foreign investment enterprises in China is subject to examination and approval of relevant authorities, only after which enterprises can be registered. The operation duration of equity joint ventures, contractual joint ventures and solely foreign-founded enterprises shall comply with relevant provisions of Chinese laws. The operation duration and disillusion of foreign-invested stock joint limited companies are subject to Chinese Company Law. The 2-track legislation model, under which foreign investment enterprises and domestic enterprises are governed by different laws and regulations, caused conflicts among different laws and difficulties in application of laws. To overcome the defaults China must enact unified law on foreign direct investment.

The use of 'Omics technology to rationally improve industrial mammalian cell line performance.

Biologics represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 being in this class. Furthermore, health authority approval of biologics in the immuno-oncology space is expected to transform treatment of patients with debilitating and deadly diseases. The growing importance of biologics in the healthcare field has also resulted in the recent approvals of several biosimilars. These recent developments, combined with pressure to provide treatments at lower costs to payers, are resulting in increasing need for the industry to quickly and efficiently develop high yielding, robust processes for the manufacture of biologics with the ability to control quality attributes within narrow distributions. Achieving this level of manufacturing efficiency and the ability to design processes capable of regulating growth, death and other cellular pathways through manipulation of media, feeding strategies, and other process parameters will undoubtedly be facilitated through systems biology tools generated in academic and public research communities. Here we discuss the intersection of systems biology, 'Omics technologies, and mammalian bioprocess sciences. Specifically, we address how these methods in conjunction with traditional monitoring techniques represent a unique opportunity to better characterize and understand host cell culture state, shift from an empirical to rational approach to process development and optimization of bioreactor cultivation processes. We summarize the following six key areas: (i) research applied to parental, non-recombinant cell lines; (ii) systems level datasets generated with recombinant cell lines; (iii) datasets linking phenotypic traits to relevant biomarkers; (iv) data depositories and bioinformatics tools; (v) in silico model development, and (vi) examples where these approaches have been used to rationally improve cellular processes. We critically assess relevant and state of the art research being conducted in academic, government and industrial laboratories. Furthermore, we apply our expertise in bioprocess to define a potential model for integration of these systems biology approaches into biologics development.

Therapeutic equivalence of antipsychotics and antidepressants - A systematic review.

The number of newly approved generic psychotropic drugs increases every year and, in many countries, their sales exceed the sales of brand-name counterparts. In order for any generic drug to receive an approval of regulatory authorities, its bioequivalence with the corresponding reference product must be demonstrated. Moreover, generic drugs must meet the same quality standards as reference drugs. However, many psychiatrists express concerns about use of generic drugs. We carried out a systematic analysis of the relevant literature indexed in PubMed and Cochrane databases. The MeSH term "generic" was combined with terms describing antipsychotic and antidepressive drugs, including their pharmaceutical names and relevant mental disorders. All 26 articles including either clinical studies or case reports have been qualified for a detailed analysis. No cases describing switches between two generics were found. Therapeutic equivalence studies evaluating antipsychotics included clozapine, olanzapine, and risperidone. The clinical status was judged to have worsened in 15.7% patients treated with clozapine. The number of relapses before and after the switch was not significantly different in patients treated with olanzapine. Two case reports showed clinical state deterioration after switch to generic risperidone. The clinical outcome after conversion to a generic antidepressant was evaluated only in one retrospective study. That study analyzed the outcomes of treatment with citalopram and revealed mental state deterioration in 11.6% of patients. Only single reports describe cases of impaired efficacy or adverse events after the switch to a generic antidepressant, including fluoxetine, mirtazapine, and venlafaxine. No cases of suicidal attempt after the switch were reported. Although the overall number of described cases is rather modest, health professionals should be aware of possible changes in the therapeutic effectiveness after changing to a generic medicine.

Safety risk modeling and major accidents analysis of hydrogen and natural gas releases: A comprehensive risk analysis framework

The potential safety risk of hydrogen production is often the most important element to achieve authority approval and public acceptance. Safe application of hydrogen, especially in a large scale, will require adopting adequate risk control, which requires investment on reliable risk analysis methodology. In the present study, first of all, a reliable and comprehensive safety risk analysis methodology was developed for a hydrogen production plant in an oil refinery, that consists of two qualitative methods: Hazard and Operability (HAZOP) and Preliminary Risk Analysis (PRA), a hybrid method: Event Tree Analysis (ETA) and a quantitative method: Quantitative Risk Assessment (QRA) along with a risk and consequence simulator. A HAZOP study along with the PRA technique was used for determining main hazardous sources and carrying out a qualitative risk analysis. The incident outcomes of the identified high risk scenarios were modeled using the PHAST 6.7 simulator and the frequencies of the initial events and incident outcomes were calculated using risk assessment data directory of International Association Oil & Gas Producers (OGP) and ETA, respectively. Finally, the vulnerability areas of the incident outcomes were determined and the societal risk of hydrogen plant was shown using a ‘Frequency vs. Number of fatality’ graph, known as ‘F–N’ curves. The findings show that the maximum vulnerability distance is caused by the vapor cloud explosion (280 m, at 0.01 bar) and the jet fire (275 m, at 4 kW/m2), respectively. The societal risk of the plant fell in the As Low As Reasonable Practical (ALARP) and intolerable regions according to the F–N curve of UK HSE (Health, Safety Executive) The reformer were the highest and the heat exchanger was the lowest contributor to the total risk. Therefore, the ALARP principle should be applied to indicate the appropriate ways to reduce risks and, for the intolerable risks, the system must be modified structurally, functionally, or organizationally.

Risky Treatments: A Jewish Medical Ethics Perspective.

The Jewish principle concerning a decision with regard to a dangerous treatment is as following: A patient who is estimated to die within 12 months because of a fatal illness is permitted to undergo a treatment that on the one hand may extend his life beyond 12 months, but on the other hand may hasten his death. There are, however, several limitations to this ruling related to the chances of success with the proposed treatment, the nature of the treatment, whether it is intended to be curative or merely to postpone the danger and death, whether the treatment is absolutely necessary, and others. One is not obligated to undergo a dangerous treatment, but one is permitted to do so. The permissibility to forfeit a short life expectancy in order to achieve more prolonged life applies only with the patient’s consent. That consent is valid and is not considered a form of attempted suicide. Neither is a refusal to submit to treatment considered an act of suicide; the patient has the right to refuse a dangerous procedure. In all situations where a permissive ruling is granted for a patient to endanger his short life expectancy, the ruling should be arrived at after careful reflection and with the approval of the rabbinic authorities acting on the recommendation of the most expert physicians.

National Differences in Requirements for Ethical and Competent Authority Approval for a Multinational Vaccine Trial under the EU Directive 2001/20/EC.

Obtaining approval for a multinational vaccine trial from an ethics committee and the national competent authority of different Member States of the European Union (EU) is challenging under clinical trial Directive 2001/20/EC because of the differences in the implementation of the directive in national laws of Member States. In this review the national differences in requirements for ethical and competent authority approval are illustrated. The national ethical and competent authority review procedures in Finland, Hungary, The Netherlands, Norway and Slovenia are described under the EU trial directive after discussing the provisions of the trial directive related to both review procedures. The review illustrates the differences between the countries in the documents that have to be submitted for the review procedures, the submission procedures and the language requirements of the documents, the organization of the ethics committees and the role of the competent authority in the approval procedure.

Knowledge and perceptions of physicians from private medical centres towards generic medicines: a nationwide survey from Malaysia.

ObjectivesGeneric medicine prescribing has become a common practice in public hospitals. However, the trend in private medical centres seems to be different. The objective of this study was to investigate knowledge, perceptions and behavior of physicians from private medical centres in Malaysia regarding generic medicines.MethodsThis study was a cross-sectional nationwide survey targeting physicians from private medical centres in Malaysia. The survey was conducted using questionnaire having (i) background and demographic data of the physicians, volume of prescription in a day, stock of generic medicines in their hospital pharmacy etc. (ii) their knowledge about bioequivalence (iii) prescribing behavior (iv) physicians’ knowledge of quality, safety and efficacy of generic medicines, and their cost (v) perceptions of physicians towards issues pertaining to generic medicines utilization.ResultsA total of 263 questionnaires out of 735 were received, giving a response rate of 35.8%. Of the respondents, 214 (81.4%) were male and 49 (18.6%) were females. The majority of the participants were in the age range of 41–50 years and comprised 49.0% of the respondents. Only 2.3% of physicians were aware of the regulatory limits of bioequivalence standards in Malaysia. Of the respondents, 23.2% agreed that they ‘always’ write their prescriptions using originator product name whereas 50.2% do it ‘usually’. A number of significant associations were found between their knowledge, perceptions about generic medicines and their demographic characteristics.ConclusionsThe majority of the physicians from private medical centres in Malaysia had negative perceptions about safety, quality and the efficacy of generic medicines. These negative perceptions could be the cause of the limited use of generic medicines in the private medical centres. Therefore, in order to facilitate their use, it is recommended that the physicians need to be reassured and educated about the drug regulatory authority approval system of generic medicines with regard to their bioequivalence, quality, efficacy and safety. Apart from the policy on generic substitution, it would also be recommended to have a national medicine pricing policy, which controls drug prices, in both the public and private sector. These efforts are worthwhile to reduce the drug expenditure and improve the medicine affordability in Malaysia.

Myocardial perfusion echocardiography and coronary microvascular dysfunction.

Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking.

Perspectives of Cardiac Care Unit Nursing Staff about Developing Hospice Services in Iran for Terminally ill Cardiovascular Patients: A Qualitative Study.

Introduction:The present study was conducted aiming to determine the points of view of cardiac care units’ nursing staff about designing and providing Hospice services in Iran for cardiovascular patients in the final stages of life.Materials and Methods:In this qualitative study, the perspectives of 16 Cardiac Care Unit (CCU) nurses selected purposefully among hospitals of Tabriz-Iran University of Medical Sciences were investigated using semi-structured interviews and were analyzed in content analysis method.Results:33 themes were finally extracted. Some nurses were for and some were against designing and providing Hospice services in Iran. The main reasons identified for supporting this plan included: Possibility of designing and providing these services consistent with high ethical values of Iranian society; approval of authorities due to increasing the load of chronic diseases and aged population; need of families due to the problems in taking care of patients and life concerns; better pain relief and respectful death; decrease of costs as a result of lower usage of diagnostic-therapeutic services, less use of expensive facilities and drugs, and better usage of hospital beds.Conclusion:Growing load of chronic diseases has made the need for Hospice as a necessary issue in Iran. In order to provide these services, studying the viewpoints of health service providers is inevitable. Therefore using and applying the results of this study in planning and policy making about designing and providing these services in Iran for cardiovascular patients in their final stages of lives could be helpful.

دور المجني عليه في انقضاء الدعوى الجزائية عن طريق الصلح

The research problem is summarized in recognizing victim rights during peace, which is regarded as victim fundamental right, but there are some important terms and conditions must be taken in consideration during peace including : crime non effect upon society security and stabilization, legal peace terms and conditions for both criminal and victim and fair compensation, thus the victim must not ask for expensive compensation taking the chance of criminal need for peace. The study importance is released from discussing Iraqi law and punishment laws situation from peace. Thus, the certification of some laws and regulations to participate in criminal case and asking for public right in the private criminal suit and the asking for judgment authority approval as a term for peace in simple crime non affecting society. obstacle peace procedures and threaten victim right in motivating or terminating criminal suit. The researcher used the analytical methodology in the theoretical frame to analyze victim rights during peace from all aspects in order to discover terms and conditions required to approve peace and the resulting effects. In addition to using content analysis methodology.