Risk In Terms Of Safety Research Articles

Safe Optimal Control of Dynamic Systems: Learning from Experts and Safely Exploring New Policies

Many real-life systems are usually controlled through policies replicating experts’ knowledge, typically favouring “safety” at the expense of optimality. Indeed, these control policies are usually aimed at avoiding a system’s disruptions or deviations from a target behaviour, leading to suboptimal performances. This paper proposes a statistical learning approach to exploit the historical safe experience—collected through the application of a safe control policy based on experts’ knowledge— to “safely explore” new and more efficient policies. The basic idea is that performances can be improved by facing a reasonable and quantifiable risk in terms of safety. The proposed approach relies on Gaussian Process regression to obtain a probabilistic model of both a system’s dynamics and performances, depending on the historical safe experience. The new policy consists of solving a constrained optimization problem, with two Gaussian Processes modelling, respectively, the safety constraints and the performance metric (i.e., objective function). As a probabilistic model, Gaussian Process regression provides an estimate of the target variable and the associated uncertainty; this property is crucial for dealing with uncertainty while new policies are safely explored. Another important benefit is that the proposed approach does not require any implementation of an expensive digital twin of the original system. Results on two real-life systems are presented, empirically proving the ability of the approach to improve performances with respect to the initial safe policy without significantly affecting safety.

Analysis of the Effect of Seismic Loads on Residential RC Buildings using the Change in Building Size and Return Period

Unlike a completed building, a building under construction may be at risk in terms of safety if a load exceeds the value considered in the design stage owing to various factors, such as a load action different from that in the design stage and insufficient concrete strength. In addition, if an earthquake occurs in a building under construction, greater damage may occur. Therefore, this study studied example models with various sizes of 5, 15, 25, and 60 floors for typical building types and analyzed the effects of seismic load on buildings under construction using construction-stage models according to frame completeness. Because the construction period of the building is much shorter than the period of use after completion, applying same earthquake loads as the design stage to buildings under construction may be excessive. Therefore, earthquakes with a return period of 50 to 2,400 years were applied to the construction stage model to review the seismic loads and analyze the structural performances of the members. Thus, we reviewed whether a load exceeding that of the design stage was applied and the return period level of the earthquake that could ensure structural safety. In addition, assuming the construction period of each example model, the earthquake return period according to the construction period was selected, and the design appropriateness with the selected return period was checked.

Construction of a Novel Doxorubicin Nanomedicine Using Bindarit as a Carrier: A Multiscale Computer Simulation-Assisted Design-Based Study

Nanomedicines typically use polymeric materials or liposomes as carriers. This provides targeting advantages but may lead to a series of defects, such as low drug loading, high risk in terms of safety, and high production costs. Herein, we report a computer simulation-assisted designing method for the construction of a novel doxorubicin (DOX) nanomedicine without any polymer carriers. We used a small molecular drug, bindarit (BIN), as a carrier of DOX to provide synergistic antitumor effects. First, the intermolecular forces between DOX and BIN were calculated for evaluating the interaction and potential conformation of the DOX/BIN complex. Then, the potential assembly ability of the DOX/BIN complex was predicated here by using dissipative particle dynamic stimulation. These computational simulation results suggested that BIN could form an amphiphilic complex with DOX through π–π stacking, hydrogen bonding, and electrostatic interaction and then self-assemble to nanoaggregates at the mesoscopic scale. Under the computational guidance, doxorubicin/bindarit nanoparticles (DOX/BIN NPs) in a spherical morphology were successfully prepared, and these NPs possess the original cytotoxic activity of DOX. Thus, this multiscale computer simulation-assisted design strategy can serve as an effective approach to develop nanomedicines using small molecules as a carrier.

Impact of Switching on Pharmacokinetics of Therapeutic Biologics and Interchangeability Assessment—A Simulation Study

The risk in terms of safety or diminished efficacy of switching between an originator biological product and a proposed interchangeable product is an important consideration for interchangeability evaluation in the regulatory framework. This simulation study evaluated the impact of several switching study design scenarios on the pharmacokinetic (PK) assessment between a virtual originator biological product and a virtual proposed interchangeable product. Our results show that (1) at least 3 switches are needed to optimize the detection of potential PK differences, (2) the initial incidence of antidrug antibodies after treatment with the reference product in the lead-in period is a significant covariate affecting the PK results, and (3) the area under the concentration-time curve is more sensitive than peak concentration in assessing the impact of switching on PK similarity. Our simulation work illustrates that a range of factors should be carefully considered when designing a switching study for the assessment of interchangeability between 2 biological products.

Where There’s Smoke: Validating a Nonproprietary Single-Item Burnout-Impacting-Safety Scale

This study aimed to assess the utility of a single survey item to predict the impact of burnout on safety and quality of healthcare providers as perceived by their colleagues. The primary objective is to determine if the item predicts the frequency of patient safety event reports within certain clinical departments. The secondary objective will be to determine if there is an acceptable cutoff score for the item which predicts low versus high numbers of safety events reported by healthcare providers in each clinical department. Participants were 424 healthcare providers in an academic medical center in the mid-Atlantic region of the United States. The item was designed to assess for the perception of the impact of burnout on work in terms of quality or safety using a 5-point Likert scale. Data from a patient safety event reporting system was accessed for the year of survey completion (2017). A negative binomial regression was used to assess the ability of the item to predict reported patient safety event reports. The item was found to significantly predict objective safety event data. Sensitivity and specificity, as well as receiver operating characteristic (ROC) curve analyses, were conducted to determine appropriateness of cutoff scores to identify low- and high-risk clinical departments. The item was found to demonstrate adequate sensitivity (82%) using a cutoff score of 4 on the survey item. However, the area under the curves (AUCs) which assess diagnostic accuracy fell in the poor range. These results suggest that healthcare administrators could deploy this single item as a brief pulse or screener of teams of individuals who are within a work unit and use a cutoff score of 4 as a means to assess for hot spots where healthcare provider burnout may be putting patients at high risk in terms of safety.

EMA approval procedures and assessment of innovation by AIFA: a cross sectional analysis.

Innovativeness of medicines is a much debated topic: the Italian Medicines Agency (AIFA) has established criteria according to which new medicines are classified as innovative, while European Medicine Agency (EMA) has established, for medicines of major interest for public health, accelerated assessment procedures to allow faster availability of drugs for patients. The aim of this study is to evaluate the association between the AIFA innovation requirement and the marketing authorization procedures by EMA. All the medicines for which AIFA has produced an innovation evaluation report were considered, for these same drugs were extracted, from the EMA website, data on: "accelerated assessment", "orphan medicines", "conditional marketing" and authorizations "under exceptional circumstances". AIFA produced and made available 57 innovativeness evaluation reports for 53 different drugs, expressing a judgment of full innovativeness in 19 cases, conditional innovativeness in 11 cases, non-innovativeness in 25 cases; EMA granted an accelerated assessment to 8 drugs with full innovativeness, 0 with conditional innovativeness and 2 non-innovative drugs respectively. EMA grants accelerated assessment less often than AIFA's judgment of innovation; these differences may be caused by the different moments of the evaluation, one before and the other after the marketing authorization, or by the similar but different objectives of EMA and AIFA. It is fundamental to recognize innovative medicines to give the patient an extra possibility of treatment in the shortest possible time, at the same time shorten the times of evaluation could represent a risk in terms of safety of use of the treatment. We need a balance, which AIFA is finding with the adoption of the GRADE method to assess the quality of scientific evidence and that the EMA is achieving through the PRIME, a new scheme for "PRIority Medicines".

Multi Criteria Analysis of Road Handling Type at Banda Aceh – Meulaboh National Road Segment Indonesia

The western and southern path of highway that connects Banda Aceh to Meulaboh City is national road. The distance between the two cities is 246 kilometers. On the connecting link between the two cities there are at least three locations in the mountainous area. Roads geometric in these locations have low capacity, uphill and downhill with high grade and also have a small curved radius. These conditions cause low levels of road services and the risk of traffic accidents is high. These three segment area are: Paro, Kulu and Geurutee mountain area. Traffic at these three road locations is often hampered and also has a high risk in terms of safety. Consider with current and future traffic condition, there is a discourse to increase the capacity of existing roads or plans for new road trace on the mountain with tunnels construction. In the feasibility study stage, there will generally be alternatives that must be selected for the best alternative. To choose the best alternative, it should be done by considering the many criteria. For this reason, this paper is the selection of the best route using the Multi Criteria Analysis (MCA) method.

Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States?

A biosimilar is a biologic drug that is “highly similar to a reference (originator) product, with no clinically meaningful differences between the two products in safety, purity, and potency”. Regulatory approval of a biosimilar is based on analytical, structural, and functional comparisons with the reference product, comparative nonclinical (in vivo) studies, clinical pharmacokinetics and/or pharmacodynamics, and immunogenicity. In addition, comparative clinical efficacy and safety assessments are usually conducted and, taken together, comprise the “totality of the evidence” supporting biosimilarity. For a biosimilar to meet the additional designation of interchangeability in the United States (US), the applicant must demonstrate that the biological drug can be expected to produce the “same clinical result as the reference product in any given patient” and “if the biological drug is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological drug and the reference product is no greater than the risk of using the reference product without such alternation or switch”. The challenges faced in conducting clinical studies to support a designation of interchangeability, as defined in the final interchangeability guidance from the US Food and Drug Administration, are considered. Potential alternative approaches to generating adequate and sufficient clinical data to support a designation of interchangeability are also presented.

Abstract 1152: Disulfiram targets both proliferating cancer cells and cancer stem-like population in ER-positive breast cancer

Abstract Drug repositioning can benefit from reduced development risk in terms of safety, toxicity and dosage, as it centers upon drugs that have already been tested in clinical trials. Disulfiram (DSF), a drug for the treatment of alcoholism, has potential anti-cancer activities in a copper (Cu)-dependent manner. In the present study, we investigated the effect of DSF on cell viability, apoptosis, breast cancer stem cells (BCSC)-like properties and p53 activation in ER-positive breast cancer MCF7 and T47D cells. DSF treatment caused a significant suppression of cell viability and marked induction of cell death in a Cu-dependent manner. This response was accompanied by caspase-3/-7 and p53 activation in ER-positive breast cancer cells. The latter phenomenon was associated with G1 phase arrest, coinciding with a significant increase in accumulation of nuclear p21 and downregulation of cyclin D1 and survivin. DSF treatment elicits a significant inhibitory effect on these BCSC-like properties including ALDH1 activity and CD44+/CD24- subpopulations. To examine the effect of DSF on mammosphere-forming ability, MCF7 and T47D cells were cultured in anchorage-independent serum-free culture conditions in the presence or absence of DSF and Cu. DSF considerably suppressed mammosphere formation, as evidenced by significant reduction in the number and volume of mammospheres. Our results demonstrate that DSF induces apoptosis and effectively targets cancer stem-like population, suggesting that disulfiram may be potentially effective for the treatment of ER-positive cancer. Citation Format: Seojin Jang, Eunhye Oh, Yoon-Jae Kim, Tae-Min Cho, Jung Min Park, Soeun Park, Minsu Park, Jae Hong Seo, Ji Young Kim. Disulfiram targets both proliferating cancer cells and cancer stem-like population in ER-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1152.

The Linkage of the Board of Directors and the Status of Aviation Industry Licensing Law

Aviation business is a capital intensive and high risk in terms of safety. Legislation in force in Indonesia requires enterprises should cost in the form of a limited liability company that is obliged to deposit the basic capital of 500 billion rupiah. The capital cannot be made in working capital which is useful for the collateral to a third party. The regulations for a limited liability company are to be established by at least 2 people. The purpose of this research is to analyze the linkage of the board directors and the status of aviation industry licensing law. The position of the legal status of business entities where shareholder is only one person is to be studied in this descriptive study. The result shows that the airlines company should provide the capital risk and high insurance of the third party. UUPT also has given the authority of the shareholders (who owns 20 % of the share) to be decision makers in the company. However, without independent surveillance, it is possible that the shareholders do some mistakes in making decisions. Some mistakes are related to the policy, the using of authorized capital, and others. Aviation business is a capital intensive and high risk in terms of safety. Legislation in force in Indonesia requires enterprises should cost in the form of a limited liability company that is obliged to deposit the basic capital of 500 billion rupiah. The capital cannot be made in working capital which is useful for the collateral to a third party. The regulations for a limited liability company are to be established by at least 2 people. The position of the legal status of business entities where shareholder is only one person is to be studied in this descriptive study.

Helping America's Most Vulnerable Children and Parents

This article examines the question of how governments should allocate resources designed to promote children’s wellbeing. Most government policies focus on three goals: protecting children’s basic physical safety and mental health, helping children acquire the academic skills needed for economic success in adulthood, and increasing equal opportunity for economic and social mobility. In trying to achieve these outcomes, policymakers must decide how to allocate resources among programs that focus primarily on the child, such as preschool and K-12 education; programs seeking to improve parenting, such as home visiting; and programs that provide economic resources, such as cash and subsidies, to families. Over the past 40 years, most investments have focused on enhancing the likelihood of economic success and closing the opportunity gap rather than on protecting children’s safety and mental health. To this end, most resources are invested in child-focused services, not parenting. Unfortunately, this strategy leaves at least 20% of children at substantial risk in terms of safety and mental health. New strategies and greater investments are needed to help children in families facing multiple adversities. The article identifies some of the issues that must be addressed in designing a system of services for strengthening parents facing multiple adversities and proposes several directions for change.

The Linkage of the Board of Directors and the Status of Aviation Industry Licensing Law

Aviation business is a capital intensive and high risk in terms of safety. Legislation in force in Indonesia requires enterprises should cost in the form of a limited liability company that is obliged to deposit the basic capital of 500 billion rupiah. The capital cannot be made in working capital which is useful for the collateral to a third party. The regulations for a limited liability company are to be established by at least 2 people. The purpose of this research is to analyze the linkage of the board directors and the status of aviation industry licensing law. The position of the legal status of business entities where shareholder is only one person is to be studied in this descriptive study. The result shows that the airlines company should provide the capital risk and high insurance of the third party. UUPT also has given the authority of the shareholders (who owns 20 % of the share) to be decision makers in the company. However, without independent surveillance, it is possible that the shareholders do some mistakes in making decisions. Some mistakes are related to the policy, the using of authorized capital, and others. Aviation business is a capital intensive and high risk in terms of safety. Legislation in force in Indonesia requires enterprises should cost in the form of a limited liability company that is obliged to deposit the basic capital of 500 billion rupiah. The capital cannot be made in working capital which is useful for the collateral to a third party. The regulations for a limited liability company are to be established by at least 2 people. The position of the legal status of business entities where shareholder is only one person is to be studied in this descriptive study.

Preparation of activated carbon with high surface area using crab shell and shochu waste and the development of methane storage technology

Methane gas is an energy alternative to petroleum. However, the two conventional methods of storing methane gas, as Liquefied Natural Gas (LNG) and Compressed Natural Gas (CNG), involve a high degree of risk in terms of safety. To develop a high-safety and low-cost method of storing methane gas, we examined its adsorption on activated carbon newly prepared from biomass waste (crab shell and shochu waste) by chemical activation with K2CO3. The activated carbons prepared from the mixture of crab shell and shochu waste exhibited a maximum specific surface area of 3212 m2/g as measured by nitrogen gas adsorption, which is more than double that of commercially available activated carbon. The adsorption isotherms of methane gas at 25 °C were measured using the new activated carbons and the results revealed that their adsorption capacities for methane gas were particularly influenced by their micropore volume. [TANSO 2014 (No. 262), 53–58.]

Risk Management in Construction Projects

Risk is involved in every business and construction industry is no exception. Risk in terms of safety, economy and timely completion are more crucial for a project to be a successful one. Indian construction industry is worth about $100 billion and this could grow considerably driven by major projects across the country. The demand for infrastructure is going to be in great volume in the coming future. Use of modern construction equipments and techniques has accelerated the growth. As the industry grows the associated risk also grows. Risk management in construction is one important area that needs attention for successful completion of the project. A risk free project is one that results in a zero dispute situation so that there is a reasonable profit for the parties involved in a project. A well-drafted, balanced contract with a proper administration can mitigate exposure to risk and keep the project on track. Construction Managers need to know how to balance the contingencies of risk with their specific contractual, financial and organizational requirements. In order to achieve this balance, proper Risk identification and Risk analysis is required. The objective of the paper is to study the aspects that are more vital for the success of the project and highlight those pitfalls that increase the risk of the project. It is also attempted to arrive at some suggestions by referring to various cases and their judgments delivered in the past.

カニ殻および焼酎カスを原料とした高比表面積活性炭の調製とメタン貯蔵技術の開発

Methane gas is an energy alternative to petroleum. However, the two conventional methods of storing methane gas, as Liquefied Natural Gas (LNG) and Compressed Natural Gas (CNG), involve a high degree of risk in terms of safety. To develop a high-safety and low-cost method of storing methane gas, we examined its adsorption on activated carbon newly prepared from biomass waste (crab shell and shochu waste) by chemical activation with K2CO3. The activated carbons prepared from the mixture of crab shell and shochu waste exhibited a maximum specific surface area of 3212 m2/g as measured by nitrogen gas adsorption, which is more than double that of commercially available activated carbon. The adsorption isotherms of methane gas at 25 °C were measured using the new activated carbons and the results revealed that their adsorption capacities for methane gas were particularly influenced by their micropore volume.

Drug safety evaluation profile of stavudine plus lamivudine for HIV-1/AIDS infection

Introduction: The lamivudine (3TC) + stavudine (d4T) combination is still widely used as part of first-line therapy for HIV-1-infected patients in low-resource countries. This review is intended to assess the benefits and risks in terms of safety of d4T + 3TC-based combination antiretroviral therapy (ART) for the treatment of HIV-1 infection.Areas covered: The most relevant papers related to the safety of d4T + 3TC-based ART were selected and summarized.Expert opinion: In industrialized countries, the 3TC + d4T combination is not recommended for initial therapy because of long-term metabolic toxicities associated with d4T. In developing countries, it may have a role in the treatment of HIV-infected patients if there is no other chance for starting antiretroviral therapy.

Statistical Designs for Assessing Interchangeability of Biosimilar Products

More and more biopharmaceutical and/or biotech companies begin to concern regulatory approval of biosimilar products, due to some innovator products will expire in decades. Once more biological products are going off patient, the problem whether approving biosimilar products used interchangeably and safely will be considered. Using a biological product of the reference product interchangeably, the United States Food and Drug Administration (FDA) requires that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological product and the reference product, is not greater than the risk of using the reference product without such alternation or switch. For this purpose, based on the concept of switching and/or alternation several useful designs for assessing drug interchangeability are proposed. In addition, by developed biosimilarity index, a uni?ed approach is discussed. The proposed method is robust against biosimilarity criteria and is applicable under a valid and appropriate study design.

The power of partnership to shape the future of nursing: the evolution of the clinical nurse leader

This article describes the evolution of the clinical nurse leader role and demonstrates the vital nature of partnerships between academia and practice in the design and implementation of this new role. The health care system as it exists in the United States may put patients at risk in terms of safety and quality of care. Nursing leadership from across the US recognized a need for nursing practice and academia to work in partnership to develop workable and effective solutions. The vision was of a nurse generalist who would be prepared to address the complexities that make the current systems dysfunctional. Review, share experiences and discuss the benefits of engaging stakeholders with broad and diverse viewpoints. Engaging a group of stakeholders with diverse backgrounds, varied world views and experiences for the purpose of developing common mutually beneficial goals, creates synergy and greater commitment to the goals, which results in success. The power of partnership in the development and implementation of the CNL is evident. Old ways of trying to 'go it alone' are no longer viable in a complex health care environment. With continued collaboration, practice and academia can continue to confront challenges and develop effective solutions.