Specific Risk Assessment Research Articles

A Cybersecurity Risk Framework for Unmanned Aircraft Systems under Specific Category

Nowadays, safety and cybersecurity are some of the most important issues involving the development of Unmanned Aircraft System (UAS) operations. For safety, the lawmakers and aviation authorities have a lot of efforts to establish an adequate safety level for UAS operations within the current airspace system. One of them is the Specific Operation Risk Assessment (SORA) methodology developed by Joint Authorities for Rulemaking on Unmanned Aircraft System (JARUS). This methodology provides a guide to conduct risk assessments for UAS operations under the Specific Category. However, the methodology supports only some problems related to safety. In this paper, we introduce our approach to extend the SORA methodology toward cybersecurity. We illustrate this approach by extending the methodology to cover the privacy problem - an aspect related to cybersecurity. Besides that, we also introduce our supporting tool in the form of a web application that helps users conduct automatic risk assessments.

Multicomponent material property characterization of atherosclerotic human carotid arteries through a Bayesian Optimization based inverse finite element approach

ObjectivePlaque rupture in atherosclerotic carotid arteries is a main cause of ischemic stroke and it is correlated with high plaque stresses. Hence, analyzing stress patterns is essential for plaque specific rupture risk assessment. However, the critical information of the multicomponent material properties of atherosclerotic carotid arteries is still lacking greatly. This work aims to characterize component-wise material properties of atherosclerotic human carotid arteries under (almost) physiological loading conditions. MethodsAn inverse finite element modeling (iFEM) framework was developed to characterize fibrous intima and vessel wall material properties of 13 cross sections from five carotids. The novel pipeline comprised ex-vivo inflation testing, pre-clinical high frequency ultrasound for deriving plaque deformations, pre-clinical high-magnetic field magnetic resonance imaging, finite element modeling, and a sample efficient machine learning based Bayesian Optimization. ResultsThe nonlinear Yeoh constants for the fibrous intima and wall layers were successfully obtained. The optimization scheme of the iFEM reached the global minimum with a mean error of 3.8% in 133 iterations on average. The uniqueness of the results were confirmed with the inverted Gaussian Process (GP) model trained during the iFEM protocol. ConclusionThe developed iFEM approach combined with the inverted GP model successfully predicted component-wise material properties of intact atherosclerotic human carotids ex-vivo under physiological-like loading conditions. SignificanceWe developed a novel iFEM framework for the nonlinear, component-wise material characterization of atherosclerotic arteries and utilized it to obtain human atherosclerotic carotid material properties. The developed iFEM framework has great potential to be advanced for patient-specific in-vivo application.

SORA Methodology for Multi-UAS Airframe Inspections in an Airport

Deploying Unmanned Aircraft Systems (UAS) in safety- and business-critical operations requires demonstrating compliance with applicable regulations and a comprehensive understanding of the residual risk associated with the UAS operation. To support these activities and enable the safe deployment of UAS into civil airspace, the European Union Aviation Safety Agency (EASA) has established a UAS regulatory framework that mandates the execution of safety risk assessment for UAS operations in order to gain authorization to carry out certain types of operations. Driven by this framework, the Joint Authorities for Rulemaking on Unmanned Systems (JARUS) released the Specific Operation Risk Assessment (SORA) methodology that guides the systematic risk assessment for UAS operations. However, existing work on SORA and its applications focuses mainly on single UAS operations, offering limited support for assuring operations conducted with multiple UAS and with autonomous features. Therefore, the work presented in this paper analyzes the application of SORA for a Multi-UAS airframe inspection (AFI) operation, that involves deploying multiple UAS with autonomous features inside an airport. We present the decision-making process of each SORA step and its application to a multiple UAS scenario. The results shows that the procedures and safety features included in the Multi-AFI operation such as workspace segmentation, the independent multi-UAS AFI crew proposed, and the mitigation actions provide confidence that the operation can be conducted safely and can receive a positive evaluation from the competent authorities. We also present our key findings from the application of SORA and discuss how it can be extended to better support multi-UAS operations.

Perioperative Pulmonary Atelectasis: Part II. Clinical Implications.

The development of pulmonary atelectasis is common in the surgical patient. Pulmonary atelectasis can cause various degrees of gas exchange and respiratory mechanics impairment during and after surgery. In its most serious presentations, lung collapse could contribute to postoperative respiratory insufficiency, pneumonia, and worse overall clinical outcomes. A specific risk assessment is critical to allow clinicians to optimally choose the anesthetic technique, prepare appropriate monitoring, adapt the perioperative plan, and ensure the patient's safety. Bedside diagnosis and management have benefited from recent imaging advancements such as lung ultrasound and electrical impedance tomography, and monitoring such as esophageal manometry. Therapeutic management includes a broad range of interventions aimed at promoting lung recruitment. During general anesthesia, these strategies have consistently demonstrated their effectiveness in improving intraoperative oxygenation and respiratory compliance. Yet these same intraoperative strategies may fail to affect additional postoperative pulmonary outcomes. Specific attention to the postoperative period may be key for such outcome impact of lung expansion. Interventions such as noninvasive positive pressure ventilatory support may be beneficial in specific patients at high risk for pulmonary atelectasis (e.g., obese) or those with clinical presentations consistent with lung collapse (e.g., postoperative hypoxemia after abdominal and cardiothoracic surgeries). Preoperative interventions may open new opportunities to minimize perioperative lung collapse and prevent pulmonary complications. Knowledge of pathophysiologic mechanisms of atelectasis and their consequences in the healthy and diseased lung should provide the basis for current practice and help to stratify and match the intensity of selected interventions to clinical conditions.

Workers with Cardiac AIMD Exposed to EMF: Methods and Case Studies for Risk Analysis in the Framework of the European Regulations.

Workers with cardiac active implantable medical devices (AIMD), such as a pacemaker (PM) or an implantable defibrillator (ICD), are considered by the occupational health and safety regulation framework as a particularly sensitive risk group that must be protected against the dangers caused by the interference of electromagnetic field (EMF). In this paper, we first describe the general methodology that shall be followed for the risk assessment of employees with a cardiac AIMD exposed to EMF, according to the EU regulation, and in particular to the EN 50527-2-1:2016 and 50527-2-2:2018 standards. Then, three case studies related to specific EMF sources are presented, to better describe how the initial analysis of the risk assessment can be performed in practice, and to understand if a further specific risk assessment analysis is required or not.

A Critical Analysis of the Specific Pharmacist Interventions and Risk Assessments During the 12-Month TRANSAFE Rx Randomized Controlled Trial.

Medication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss. To describe the frequency and types of interventions made during a pharmacist-led, mobile health-based intervention in KTX recipients and the impact on patient risk levels. This was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels. A total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients. A pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.

Intraoperative and postoperative complications in colorectal procedures: the role of continuous updating in medicine.

Accepting surgical complications, especially those related to the learning curve, as unavoidable events in colorectal procedures, is like accepting to fly onboard an aircraft with a 10% to 20% chance of not arriving at final destination. Under this condition, it is very likely that the aviation industry and the concurrent reshaping of the world and of our lives would have not been possible in the absence of high reliability and reproducibility of safe flights. It is hard to imagine surgery without any intraoperative and/or postoperative complications. Nevertheless, there is a plenty of room for improvement by simply adopting what has been explicitly and scientifically demonstrated; training outside of the operating room (OR), usage of modern information technologies and application of evidence-based perioperative care protocols. Additionally, the possibility to objectively measure and monitor the technical and even non-technical skills and competencies of individual surgeons and even of OR teams through the application of structured and validated assessment tools can finally put an end to the self-referential, purely hierarchical, and indeed extremely unreliable process of being authorized or not to perform operations on patients. Last but not least, a wide range of new technologies spanning from augmented imaging modalities, virtual reality for intraoperative guidance, improved robotic manipulators, artificial intelligence to assist in preoperative patient specific risk assessment, and intraoperative decision-making has the potential to tackle several hidden roots of surgical complications.

Leveraging Clinical Decision Support and Integrated Medical-Dental Electronic Health Records to Implementing Precision in Oral Cancer Risk Assessment and Preventive Intervention.

Introduction: Precision medicine is focused on serving the unique needs of individuals. Oral and oropharyngeal cancer risk assessment identifies individual risk factors while providing support to reduce risk. The objective is to examine potential current and future strategies to broadly implement evidence-based oral and oropharyngeal cancer risk assessment and screening in dental practices throughout the United States. Methods: Feasible and effective oral cancer risk assessment and risk reduction strategies, ripe for implementation in dental practice, were identified in the published literature. Results: The Screening, Brief Intervention, Referral for Treatment (SBIRT) model is a feasible approach to assessing individual oral cancer risk and providing risk reducing interventions in the dental setting. HPV is a more recently identified risk factor that dentistry is well positioned to address. Evidence supporting the utilization of specific risk assessment tools and risk reduction strategies is summarized and future opportunities discussed. Discussion: Current knowledge of risk factors for oral and oropharyngeal cancers support the recommendation for dental providers to routinely assess all patients for risk factors, educate them about their personal level of cancer risk, and recommend actions to reduce relevant risk factors. Individuals ages 9–26 should be asked about their HPV vaccination status, educated about HPV and oropharyngeal cancer and receive a recommendation to get the HPV vaccination.

Nano-Enable Materials Promoting Sustainability and Resilience in Modern Agriculture.

Intensive conventional agriculture and climate change have induced severe ecological damages and threatened global food security, claiming a reorientation of agricultural management and public policies towards a more sustainable development model. In this context, nanomaterials promise to support this transition by promoting mitigation, enhancing productivity, and reducing contamination. This review gathers recent research innovations on smart nanoformulations and delivery systems improving crop protection and plant nutrition, nanoremediation strategies for contaminated soils, nanosensors for plant health and food quality and safety monitoring, and nanomaterials as smart food-packaging. It also highlights the impact of engineered nanomaterials on soil microbial communities, and potential environmental risks, along with future research directions. Although large-scale production and in-field testing of nano-agrochemicals are still ongoing, the collected information indicates improvements in uptake, use efficiency, targeted delivery of the active ingredients, and reduction of leaching and pollution. Nanoremediation seems to have a low negative impact on microbial communities while promoting biodiversity. Nanosensors enable high-resolution crop monitoring and sustainable management of the resources, while nano-packaging confers catalytic, antimicrobial, and barrier properties, preserving food safety and preventing food waste. Though, the application of nanomaterials to the agri-food sector requires a specific risk assessment supporting proper regulations and public acceptance.

Incidence, risk factors and clinical outcome of venous thromboembolism in non-small cell lung cancer patients receiving immune checkpoint inhibition

BackgroundBesides the cancer itself, venous thromboembolism (VTE) is the leading cause of death in cancer patients receiving outpatient chemotherapy (CT). Data on VTE development and impact on treatment course and outcome in real-life NSCLC patients receiving immune check-point inhibitors (ICI) is currently sparse. More knowledge within this area is warranted due to the emerging use of ICI in clinical practice. ObjectivesTo quantify risk of VTE and recurrent VTE in NSCLC patients receiving ICI. Explore the clinical impact of VTE on ICI course and survival and explore potential risk factors for VTE. Patients/methodsPatients with advanced/metastatic NSCLC treated with an immune checkpoint inhibitor (ICI) at the University Hospital of Odense, Denmark during 2015–2018 were identified and data gathered retrospectively from electronic medical records (n = 118). All patients had finished ICI at the time of data-cut off. Baseline Khorana Score (KRS) was calculated within one week prior to ICI initiation. Based on follow-up data cumulative incidence of VTE and its impact on outcome and survival was performed using Kaplan Meier and cox-regression hazard estimation. ResultsRisk of VTE was 8% during ICI and 15% at any time point after ICI initiation. Cumulative incidence rates of VTE at 1, 3, 6 and 18 months after first ICI was 1.7%, 5.2%, 6.9% and 13.8% respectively. Median time to VTE during ICI was 2.3 months [IQR 0.6–5.4]. Having VTE during ICI lead to discontinuation of ICI in 78% of cases, most due to fatal PE. History of VTE before onset of ICI was a significant risk factor for recurrent VTE during ICI (24% within this subgroup) despite use of anticoagulant therapy. ConclusionsThe incidence and impact of VTE during ICI for real-life NSCLC patients is not negligible with almost 10% developing VTE leading to termination of further ICI in the majority of cases - many due to fatal PE. The risk of recurrent anticoagulant resistant VTE in patients with known VTE during ICI is also considerable, which calls for better management and prevention of VTE including development of treatment specific VTE risk assessment models.

Unmanned Aircraft Systems Risk Assessment Based on SORA for First Responders and Disaster Management

Worldwide, there is a significant increase in the use of unmanned aerial vehicles (UAVs) by emergency services. They offer a lot of possibilities during rescue operations. Such a wide application for various purposes and environments causes many threats related to their use. To minimize the risks associated with conducting air operations with UAVs, the application of the SORA (Specific Operations Risk Assessment) methodology will be important. Due to its level of detail, it is a methodology adapted to civilian use. In this article, the authors’ team will try to develop guidelines and directions for adapting SORA to the requirements of the operational work of emergency services. Thus, the following article aims to present the most important risks related to conducting operations with the use of UAVs by first responders (FRs), and to show the sample risk analysis performed for this type of operation on the example of the ASSISTANCE project. The paper describes, on the one hand, possibilities offered by UAVs in crisis or disaster management and step-by-step Specific Operations Risk Assessment (SORA), and on the other hand, presents possible threats, consequences and methods of their mitigation during FR missions.

Development of the Prevent for Work questionnaire (P4Wq) for assessment of musculoskeletal risk in the workplace: part 1—literature review and domains selection

ObjectiveThis study aims to define appropriate domains and items for the development of a self-administered questionnaire to assess the risk of developing work-related musculoskeletal disorder (WMSD) and the risk of...

Update and practical advice for travel vaccinations and consultations in primary care

Update and practical advice for travel vaccinations and consultations in primary care Abstract. Health issues during travels are common. Infections are amongst the most frequent problem besides accidents and cardiovascular events. Prevention is based on avoiding risks, drug prophylaxis and vaccinations. This article focuses on travel vaccinations and aims to provide a general update and practical advice for travel consultations in primary care. Vaccine-preventable infections are systematically summarized, including a specific risk assessment for children, general vaccination indication, vaccination schedule, and information particularities of specific vaccines. Updating the vaccination status is often neglected in regular GP consultations for adult patients. Appointments for travel advice are therefore an ideal and important means of checking and completing the recommended basic and booster immunizations. Travel immunizations typically aim at providing an individual protection from infection. In contrast, basic vaccinations also consider altruistic aspects such as herd immunity. Since ambivalence or skepticism about vaccination is widespread, this discrepancy may result in discussions. Travel consultations may therefore generate opportunities to clarify general ambivalences towards vaccinations. Based on the concept of "Motivational Interviewing", we show communicative possibilities to reduce ambivalence and resistance and ideally to promote the willingness to vaccinate through shared decision-making.

A Quickly Deployed and UAS-Based Logistics Network for Delivery of Critical Medical Goods during Healthcare System Stress Periods: A Real Use Case in Valencia (Spain)

On the one hand, Unmanned Aircraft Systems (UASs) have experienced great applicability surge in the recent years, arising as a promising technology with a wide field of use. On the other hand, healthcare, a critical system in modern society, is subject to a heavy and unexpected pressure in the case of situations such as the COVID-19 pandemic. This article aims to leverage the flexibility of UASs as complementary support for healthcare logistic systems when under high-stress conditions, via quick deployment of an air delivery network. We have defined a logistics network model and created three scenarios based on the model and current needs in Valencia (Spain). Flight tests have been performed in these scenarios, which include urban areas and controlled airspace. Operations complied with requirements derived from the application of Specific Operations Risk Assessment (SORA) methodology, recently adopted by the European Aviation Safety Agency (EASA). Flights were successful, being able to swiftly deliver medical goods without requiring any dedicated infrastructure. However, a moderate number of contingencies took place during the tests, mainly related to control link quality and Air Traffic Management (ATM) integration, forcing the use of dedicated procedures to cope with them. Although additional development is required to ensure the safety of large-scale automated operations, the use of UASs as part of logistic networks is a feasible means to support existing structures, especially in situations in dire need.

Theoretical and Practical Considerations Regarding the Use of Conditional Probability Assessment Algorithm in Early Warning Tasks Aimed to Prevent Acts of Terrorism and Violent Extremism

Over the last decade, the diversified spectrum of hybrid threats forced security agencies around the world to refine the tools used by intelligence analysts in early warning tasks. Thus, in order to anticipate and prevent violent acts, law enforcement analysts from the departments responsible for prevention and countering terrorism, violent extremism, and radicalization that lead to terrorism are constantly striving to identify tools and methods that are capable to measure the psychosocial–behavioral characteristics of individuals in terms of mathematical probabilities. Therefore, risk assessment tools targeting terrorists and violent extremists are a major topic of interest for international security experts and law enforcement professionals. In such context, the present study proposes a tool to assess conditional probabilities, built on the Bayes’ rule, which is based on a subjective way of defining probability. Bayes’ rule allows analysts to correctly quantify their estimates, which are often qualitative, subjective, and based on a limited number of indices and observations. The risk assessment tools developed for common violent crimes and for members of the organized crime groups should not be used for assessing terrorists, violent extremists, or individuals suspected of engaging in ideologically motivated violent actions, nor vice versa. Specific risk assessments with relevant indicators should be used separately for regular violent offenders and for terrorists and extremists.

Sensitivity of freshwater organisms to cadmium and copper at tropical temperature exposures: Derivation of tropical freshwater ecotoxicity thresholds using species sensitivity distribution analysis

Tropical freshwater ecosystems are increasingly influenced by chemical stressors including heavy metals posing threats to biodiversity. Adequate ecotoxicity data are not available for native tropical freshwater species for deriving water quality guidelines and for conducting ecological risk assessments. Objectives of this study were (i) to generate freshwater ecotoxicity data for cadmium (Cd) and copper (Cu) for tropical temperature exposures using standard laboratory bioassays with selected freshwater species and (ii) to derive ecotoxicity thresholds (protection concentrations, PC) for tropical freshwater life based on ‘tropical temperature-specific exposure’ ecotoxicity data. Estimated final chronic toxicity values of the six species tested in the study indicate that the most sensitive species was the crustacean, Moina macrocopa for both metals while the algae Chlorella vulgaris and the plant Lemna perpusilla showed highest tolerance to Cd and Cu respectively. Tropical temperature-specific exposure (25–30 °C) was used as the decision criterion for deriving ecotoxicity thresholds of Cd and Cu for protection of tropical freshwater life based on species sensitivity distribution analysis of the final chronic toxicity data sets which included published toxicity data of selected species in addition to the six species tested in this study. The derived PC99, PC95, PC90 and PC80 values for protection of tropical freshwater life under chronic exposure are 0.5, 1.2, 1.9 and 3.5 μg/L for Cd and 0.34, 0.84, 1.4 and 2.6 μg/L for Cu respectively. These derived threshold chronic values (PC99 and PC95) indicate that the established freshwater quality guidelines based on temperate species for Cu may not provide sufficient protection of the freshwater species in the tropics while the available freshwater guidelines for Cd would provide adequate protection for the tropical freshwater species. The tropical freshwater ecotoxicity thresholds derived in this study may be used with some caution as reference points for site specific ecological risk assessments in the tropics.

Drinking Water Consumption Patterns among Private Well Users in Ontario: Implications for Exposure Assessment of Waterborne Infection.

Understanding the water consumption patterns within a specific population informs development of increasingly accurate, spatially specific exposure and/or risk assessment of waterborne infection. The current study examined the consumption patterns of private well users in Ontario while considering potentially influential underlying sociodemographics, household characteristics, and experiential factors. A province-wide online survey was circulated between May and August 2018 (n = 1,162). Overall, 81.5% of respondents reported daily well water consumption (i.e., tap water). Results indicate a mean daily well water consumption rate of 1,132 mL/day (SD = 649 mL/day) among well water consumers. Gender was significantly associated with well water consumption, with higher consumption rates found among female respondents. The experience of acute gastrointestinal illness (AGI) symptoms or diagnosis in the past 12 months did not impact the volume of water consumed, suggesting that experiencing previous AGI does not decrease consumption volumes, and therefore exposure over time. Significantly higher rates of well water consumption were found among respondents who reported previous testing or ongoing water treatment. Approximately 45.5% of survey respondents who stated that they do not consume well water selected bottled water as their primary household drinking water supply. Bottled water consumption was also not associated with previous AGI experiences. Findings will inform future quantitative microbial risk assessments associated with private well water use by providing spatially and demographically specific estimates of well water consumption.

Exposure of Workers to Occupational Noxae

The discomfort caused by exposure in the work process to occupational hazards generates. In this regard, this paper examines how the nuisances generated by technological processes influence the activity of workers and the legislative framework for jobs in which these occupational hazards exceed the allowed limits. In order to monitor the exposure to occupational hazards, the team of the Toxicology Laboratory performed determinations for the main occupational hazards existing in the work environment to the beneficiaries, the method of determining exposure to toxins being the direct method with measuring devices with numerical display, in time respectively, taking samples and analyzing them in the laboratory. The methods of analysis are in accordance with the legal provisions in force, using devices (metrological verified) and certified methods of analysis. Following the determination of noxious substances, specific risk assessments, in accordance with the legislation in force applicable to the jobs, in order to assess their impact on the health status of the staff, respectively the employment in special / special / normal working conditions, s -drew the following conclusions: periodic determinations of occupational toxins must be widely used to confirm or refute their existence in the workplace, permanent medical monitoring performed by occupational medicine practices, in conjunction with determinations of toxins, to establish traceability of occupational diseases with exposure to the susceptibility to its occurrence.

Validation of the APRI+ALBI smart phone application for preoperative risk assessment after liver resection in a routine clinical setting

Presenter: David Pereyra MD | Mayo Clinic, Rochester Background: Liver surgery obtains the risk of development of postoperative liver dysfunction (LD) and associated increased morbidity and mortality. In order to mitigate the individual risk for adverse postoperative outcome, predictive markers and scores have been developed. In this context, APRI and ALBI, both based on routine laboratory parameters, and their summative conjunction were previously established as predictive markers for postoperative LD in patients undergoing liver resection after neoadjuvant chemotherapy, as well as in a set of more than 12,000 patients in the NSQUIP database. Here, we aimed to validate APRI+ALBI and our Smart phone application system in a routine clinical set of patients undergoing liver surgery. Methods: We identified 160 patients with available data on preoperative albumin, bilirubin, aspartate aminotransferase and platelet count and postoperative outcome. APRI and ALBI were calculated and prognostic value for postoperative outcome was evaluated. Results: Using receiver operating curve analysis, APRI+ALBI was found to be superior to APRI alone or ALBI alone in prediction of postoperative LD (area under the curve [AUC]=0.717, AUC=0.669, AUC=0.691, respectively). Further, APRI+ALBI was superior to parameters of indocyanine green clearance (plasma disappearance rate: AUC=0.628, retention rate at 15 minutes: AUC=0.669). A preoperative cut-off at -2.46 was able to stratify patients at risk for postoperative LD (6.1% vs 18.0%, p=0.017), morbidity (32.7% vs 63.9%, p<0.001), severe morbidity (11.2% vs 34.4%, p<0.001), and mortality within 90 postoperative days (1.0% vs 8.5%, p=0.028). Utilizing our previously established smart phones application, we were able to validate appropriate classification patients in individual risk groups according to their preoperative APRI/ALBI score. Conclusion: Here, we validate APRI+ALBI as a predictive marker for postoperative adverse outcome in a clinical routine set of patients undergoing liver resection. The detection of multiple with pathophysiological processes , such as for example chemotherapy associated liver injury but also alcoholic liver disease, by the APRI/ALBI score, allowed prediction of outcome after liver resection in an routine clinical setting. Applying this twice validated marker based on routine laboratory parameters allows estimation of individual patient risk prior to liver resection and might ultimately reduce occurrence of postoperative complications. A specific and gradual risk assessment seems to be possible using the APRI/ALBI smart phone application in a routine clinical setting. Until more specific markers are available, this application represents a valuable tool to assess individualized patients risk for postoperative outcome based on routine laboratory parameters.

Development and Validation of a Single Quadrupole LC/MS Method for the Trace Analysis of Six Nitrosamine Impurities in Valsartan

The findings that nitrosamine impurities, mutagenic carcinogens, have been detected in several classes of medicines, including valsartan, have raised safety concerns; regulatory authorities responded by strengthening surveillance, creating specific guidance and risk assessment strategies. At the core of these responses are a number of highly sensitive analytical methodologies to detect and quantitate trace amounts of nitrosamines in pharmaceutical products. However, many of the issued methods rely on high resolution or other advanced mass spectrometers which may not be readily available or ideally suited for routine analysis of large sample sets for risk assessment. Here we describe our efforts to develop an alternative approach based on a LC method coupled with a single quadrupole mass spectrometer. Six nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodiisopropylamine (NDIPA), N-nitrosoethylisopropylamine (NEIPA), N-nitrosodibutylamine (NDBA), and N-nitrosomethylaminobutyric acid (NMBA) were investigated and a LC/MS method was developed for the detection and quantitation of the six nitrosamine impurities in valsartan. Two commonly used techniques, large-volume injection (LVI) and matrix precipitation for sample preparation, were incorporated to enhance sensitivity. The developed single quadrupole LC/MS method has the capacity for detection and quantitation of the six nitrosamines listed with a LOQ of 0.05 ppm relative to valsartan. Furthermore, the method was validated within a wide dynamic range (0.05 – 3.6 ppm) and applied to commercial valsartan samples.