Unexpected Risk Research Articles

Idiosyncratic Volatility and the Cross-Section of Stock Returns of NEEQ Select

This paper investigates the empirical relationship between idiosyncratic volatility and the cross-section of stock returns of NEEQ Select. It finds that idiosyncratic volatility is positively related to expected stock returns, with no presence of idiosyncratic volatility anomalies. Idiosyncratic volatility serves as an important asset pricing factor of NEEQ Select, which better represents investors’ psychological expectation of idiosyncratic risk premium. Both expected and unexpected idiosyncratic volatility display a positive and robust relationship to stock returns, but unexpected idiosyncratic risk, which controls for unexpected returns, may exert relatively greater marginal effects. Based on the above conclusions, some suggestions are put forward to actively achieve the diversification management efficiency of NEEQ Select portfolios.

Relation of Brain Perfusion Patterns to Sudden Unexpected Death Risk Stratification: A Study in Drug Resistant Focal Epilepsy.

To explore the role of the interictal and ictal SPECT to identity functional neuroimaging biomarkers for SUDEP risk stratification in patients with drug-resistant focal epilepsy (DRFE). Twenty-nine interictal-ictal Single photon emission computed tomography (SPECT) scans were obtained from nine DRFE patients. A methodology for the relative quantification of cerebral blood flow of 74 cortical and sub-cortical structures was employed. The optimal number of clusters (K) was estimated using a modified v-fold cross-validation for the use of K means algorithm. The two regions of interest (ROIs) that represent the hypoperfused and hyperperfused areas were identified. To select the structures related to the SUDEP-7 inventory score, a data mining method that computes an automatic feature selection was used. During the interictal and ictal state, the hyperperfused ROIs in the largest part of patients were the bilateral rectus gyrus, putamen as well as globus pallidus ipsilateral to the seizure onset zone. The hypoperfused ROIs included the red nucleus, substantia nigra, medulla, and entorhinal area. The findings indicated that the nearly invariability in the perfusion pattern during the interictal to ictal transition observed in the ipsi-lateral putamen F = 12.60, p = 0.03, entorhinal area F = 25.80, p = 0.01, and temporal middle gyrus F = 12.60, p = 0.03 is a potential biomarker of SUDEP risk. The results presented in this paper allowed identifying hypo- and hyperperfused brain regions during the ictal and interictal state potentially related to SUDEP risk stratification.

Abstract 615A: HuGEMM࣪ modelling toxicology of species-specific immune checkpoint inhibitors

Abstract Background: Immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 monoclonal antibodies, have led to impressive clinical outcomes in treating certain cancers. However, the overall success rate of immunotherapeutic drugs remains low, due to poor efficacy (cancer immunotherapeutic effect [CITE]) or unexpected safety risks such as immune-related adverse events (irAEs), underlining the importance of predictive preclinical animal models. Notably, most immunotherapies cannot be modeled in xenograft tumor models, due to their immunodeficient phenotype, or syngeneic models, as most biologics are usually species-specific. Given these limitations, genetically engineered humanized mouse models (HuGEMM࣪) and syngeneic cell lines (HuCELL࣪), where human drug target gene(s) replace the original mouse ortholog(s), have been broadly used to assess species-restricted biologics for CITE. Since most irAEs in biologics are on-target toxicities, it is potentially possible to model the irAEs of biologics using non-tumor bearing HuGEMMs. In this study, the PD-1/CTLA-4 double knock-in (dKI) HuGEMM is used as an example to provide more insights into irAE evaluation in preclinical models. Methods: The PD-1 and CTLA-4 HuGEMM in BALB/c backgrounds were developed by substituting the mouse extracellular domains with their human counterparts, followed by crossbreeding to create dKI mice for both targets. The juvenile dKI mice (age 4-5 weeks) were treated with the vehicle control, anti-human PD-1, and a combination therapy of anti-human PD-1/anti-human CTLA-4. The models were monitored for toxicity parameters, including general welfare, body weight, mortality, gross pathology (arthritis, skin inflammation, and colitis scoring), and histopathology of different organs at study termination. Results: No body weight loss was observed throughout the study in all treatment groups. No mortality was observed in models treated with a monotherapy, while in the combination group (anti-human PD-1/anti-human CTLA-4), five mice displayed lethargy and tachypnea symptoms, and four mice experienced severe adverse effects. Per gross pathology analysis, combination treatment caused significant arthritis in the feet of the mice at study end. Histopathology analysis of the combination treatment group samples demonstrated colon epithelia damage and heart lymphocyte infiltration at termination. These observations for toxicity or irAE profiles are in line with those observed in patients undergoing the same treatment regimen. Conclusions: HuGEMM engineered to express human targets could be used in preclinical studies to test for assessing irAE of biologics. Citation Format: Daniel XF He. HuGEMM࣪ modelling toxicology of species-specific immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 615A.

Concurrent 5. Presentation for: Uncertainty analysis on environmental impacts of hydraulic fracturing

Presented on Tuesday 17 May: Session 5 Uncertainty is an undeniable aspect of underground operations, such as wellbore stimulation treatments, where combined rock and fluid interaction add a layer of complexity to the uncertainty. There are social and environmental concerns about the probable outcome of operations like hydraulic fracturing. Hydraulic fracturing treatments may affect the integrity of sub-surface geological strata or might initiate unexpected potential risks to the environment when the created fracture extends beyond its engineered design. Therefore, it is necessary to investigate a range of possible scenarios by which the fracture may experience a deviation from its planned behaviour. In this study, we model the uncertainty associated with hydraulic fracturing using fracture growth simulation. The uncertainty of a range of treatment parameters, such as pumping flow rate, injection duration and mechanical properties of the underground geological layer, is investigated. Monte Carlo simulation is used to examine different probable fracturing scenarios and numerous fracturing simulations with numerical and analytical models. The probability analysis is performed in a case study to identify the cumulative distribution functions (CDFs) of fracture growth. The emerging least, median and most likely situations of fracture growth are analysed to evaluate the fracturing uncertainty. Our results indicate that the numerical modelling approach may predict a more extensive fracture growth in the vertical plane. The numerical model may suggest a more conservative way to address environmental concerns. The resulting cumulative distribution of probabilities suggests the CDFs of the analytical model as the lower band for fracture length, whereas the numerical CDFs presents the upper band. To access the presentation click the link on the right. To read the full paper click here

Hospital-Wide SARS-CoV-2 seroprevalence in health care workers in a Spanish teaching hospital

IntroductionHospital-wide SARS-CoV-2 seroprevalence is rarely explored and can identify areas of unexpected risk. We determined the seroprevalence against SARS-CoV-2 in all health care workers (HCW) at a hospital. MethodsCross-sectional study (14-27/04/2020). We determined SARS-CoV-2 IgG by ELISA in all HCW including external workers of a teaching hospital in Madrid. They were classified by professional category, working area, and risk for SARS-CoV-2 exposure. ResultsAmong 2919 HCW, 2590 (88,7%) were evaluated. The mean age was 43.8 years (SD 11.1), and 73.9% were females. Globally, 818 (31.6%) workers were IgG positive with no differences for age, sex or previous diseases. Of these, 48.5% did not report previous symptoms. Seropositivity was more frequent in high- (33.1%) and medium- (33.8%) than in low-risk areas (25.8%, p=0.007), but not for hospitalization areas attending COVID-19 and non-COVID-19 patients (35.5 vs 38.3% p>0.05). HWC with a previous SARS-CoV2 PCR-positive test were IgG seropositive in 90.8%. By multivariate logistic regression analysis seropositivity was significantly associated with being physicians (OR 2.37, CI95% 1.61–3.49), nurses (OR 1.67, CI95% 1.14–2.46), nurse assistants (OR 1.84, CI95% 1.24–2.73), HCW working at COVID-19 hospitalization areas (OR 1.71, CI95% 1.22–2.40), non-COVID-19 hospitalization areas (OR 1.88, CI95% 1.30–2.73), and at the Emergency Room (OR 1.51, CI95% 1.01–2.27). ConclusionsSeroprevalence uncovered a high rate of infection previously unnoticed among HCW. Patients not suspected of having COVID-19 as well as asymptomatic HCW may be a relevant source for nosocomial SARS-CoV-2 transmission.

Recognition and Health Impacts of Organic Pollutants with Significantly Different Proportions in the Gas Phase and Size-Fractionated Particulate Phase in Ambient Air.

The distributions of organic pollutants in the gas phase and size-fractionated particle phases can largely affect human health risks posed by them. Gas-particle partitioning and particle-size distributions of some known pollutants have been investigated. However, the pollutants which are more likely to enter the human body and cause strong adverse effects may be neglected. In this study, a nontargeted screening approach combining comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry and chemometrics was developed. Eighty-eight compounds with markedly different proportions in the gas phase and PM1, as well as 50 contaminants with significant differences in PM1 and particles with diameters of 1-2.5 μm, were identified. Of these compounds, 18 were found in the air for the first time. There were obvious discrepancies between the measured and predicted gas-particle partitioning coefficients for some pollutants, suggesting unexpected environmental fates and health risks. The human daily intakes through inhalation and dermal exposure to these pollutants were estimated with the International Commission on Radiological Protection deposition model and transdermal permeability model. A risk-based prioritization was performed. The results indicated that adverse effects posed by 9H-fluoren-9-one, 2-ethylhexyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate, p-cumenol, 2,4-diisocyanato-1-methyl-benzene, bis(2-ethylhexyl) phthalate, perylene, (E)-cinnamaldehyde, 4-methyl-2-nitro-phenol, benzoic acid, and bis(2-methylpropyl) ester hexanedioic acid in ambient air may be more severe than those posed by conventionally monitored pollutants. The findings would facilitate raising concerns about these pollutants before they cause further severe and widespread impacts.

Uncertainty analysis on environmental impacts of hydraulic fracturing

Uncertainty is an undeniable aspect of underground operations, such as wellbore stimulation treatments, where combined rock and fluid interaction add a layer of complexity to the uncertainty. There are social and environmental concerns about the probable outcome of operations like hydraulic fracturing. Hydraulic fracturing treatments may affect the integrity of sub-surface geological strata or might initiate unexpected potential risks to the environment when the created fracture extends beyond its engineered design. Therefore, it is necessary to investigate a range of possible scenarios by which the fracture may experience a deviation from its planned behaviour. In this study, we model the uncertainty associated with hydraulic fracturing using fracture growth simulation. The uncertainty of a range of treatment parameters, such as pumping flow rate, injection duration and mechanical properties of the underground geological layer, is investigated. Monte Carlo simulation is used to examine different probable fracturing scenarios and numerous fracturing simulations with numerical and analytical models. The probability analysis is performed in a case study to identify the cumulative distribution functions (CDFs) of fracture growth. The emerging least, median and most likely situations of fracture growth are analysed to evaluate the fracturing uncertainty. Our results indicate that the numerical modelling approach may predict a more extensive fracture growth in the vertical plane. The numerical model may suggest a more conservative way to address environmental concerns. The resulting cumulative distribution of probabilities suggests the CDFs of the analytical model as the lower band for fracture length, whereas the numerical CDFs presents the upper band.

Sexual politics in the field: gendered research spaces in tourism geographies

Sexual violence and harassment in field research is an uncomfortable and under-discussed phenomenon in the social sciences. Tourism geographies, being cross-cultural, often require solo fieldwork that exposes one’s gender in geographically remote locations. There is a pressing need to normalise the discussion of sexual politics in the field, specifically concerning occurrences of gender-associated risks in fieldwork and report on the unexpected physical and mental health risks for women researchers. This study takes a feminist theoretical lens to unpack the hidden dimensions of women engaged in ‘voluntary’ risk taking by conducting field research in male-dominated research environments. Taking an exploratory approach within an interpretivist paradigm, this study is based on the fieldwork experiences of 13 women from diverse cultural and academic backgrounds with the participants sharing their subjective realities of researching in tourism geographies. A thematic analysis revealed the two key themes of risk/perceived vulnerabilities and wellbeing/care in the field as paramount for field research spaces for women, along with 11 subthemes. Findings reaffirmed the political nature of tourism geographies fieldwork and the need to challenge sexual politics and patriarchal domination, including for LGBTQ researchers. Further, the results highlighted the intersectionality of race and gender of women’s experiences of sexual violence and other risks in the field. Thus, the findings suggest an urgent need to provide an imperative for fieldworker safety, wellbeing considerations, and alternative ways of researching.

Fungal insecticidal activity elevated by non-risky markerless overexpression of an endogenous cysteine-free protein gene in Beauveria bassiana.

Fungal insecticides are notorious for slow kill action, an intrinsic trait that can be improved by the genetic engineering of an exogenous or endogenous virulence factor. However, transgenic insecticides expressing exogenous toxin and herbicide-resistant marker genes may cause unexpected ecological risks and are hardly permitted for field release due to strict regulatory hurdles. It is necessary to improve biotechnology that can speed up fungal insect-killing action and exclude ecological risk source. A markerless transformation system of Beauveria bassiana, a main source of wide-spectrum fungal insecticides, was reconstructed based on the fungal uridine auxotrophy (Δura3). The system was applied for overexpression of the small cysteine-free protein (120 amino acids) gene cfp previously characterized as a regulator of the fungal virulence and gene expression. Three cfp-overexpressed strains showed much faster kill action to Galleria mellonella larvae than the parental wild-type via normal cuticle infection but no change in vegetative growth and aerial condition. The faster kill action was achieved due to not only significant increases in conidial adherence to insect cuticle and total activity of secreted cuticle-degrading Pr1 proteases and of antioxidant enzymes crucial for collapse of insect immune defense but acceleration of hemocoel localization, proliferation in vivo and host death from mummification. The markerless system is free of any foreign DNA fragment as a source of ecologic risk and provides a novel biotechnological approach to enhancing fungal insecticidal activity with non-risky endogenous genes and striding over the regulatory hurdles. © 2022 Society of Chemical Industry.

Occupational Mortality Matrix: A Tool for Epidemiological Assessment of Work-Related Risk Based on Current Data Sources.

Mortality from occupational diseases significantly afflicts society, in terms of both economic costs and human suffering. The International Labour Organization (ILO) estimated that 2.4 million workers die from work-related diseases every year. In Europe, around 80,000 workers die from cancer attributed to occupational exposure to carcinogens. This study developed the Occupational Mortality Matrix (OMM) aimed to identify significant associations between causes of death and occupational sectors through an individual record linkage between mortality data and the administrative archive of occupational histories. The study population consisted of 6,433,492 deceased subjects in Italy (in the period 2005–2015), of which 2,723,152 records of work histories were retrieved (42%). The proportional mortality ratio (PMR) was estimated to investigate the excess of mortality for specific causes associated with occupational sectors. Higher PMRs were reported for traditionally risky occupations such as shipbuilding for mesothelioma cases (PMR: 8.15; 95% CI: 7.28–9.13) and leather production for sino-nasal cancer (PMR: 5.04; 95% CI: 3.54–7.19), as well as for unexpected risks such as male breast cancer in the pharmaceutical industry (PMR: 2.56; 95% CI: 1.33–4.93) and brain cancer in railways (PMR: 1.43; 95% CI: 1.24–1.66). The OMM proved to be a valid tool for research studies to generate hypotheses about the occupational etiology of diseases, and to monitor and support priority actions for risk reduction in workplaces.

Progress in urban resilience research and hotspot analysis: a global scientometric visualization analysis using CiteSpace.

Increasing global climate change has led to increasingly sudden, abnormal, and complex natural disasters. Global disaster governance is facing complex and severe challenges. Urban resilience research (URR) can help cities withstand disasters and quickly recover from adversities through the rational allocation of resources. Consequently, URR has attracted considerable attention from urban ecology researchers. Over the past decade, despite an increasing number of articles reported on URR, there has been no systematic theoretical framework, no comprehensive review of the research, and no clarity on how different perspectives have evolved. This research selects 1647 articles related to global urban resilience from the Web of Science Core Collection and performs a global scientometric visualization analysis using CiteSpace and ArcGIS software. In this study, we visually display the most productive institutions, authors, and sources in URR. Additionally, we explain how research topics have changed over time and analyze research frontiers. The results show that (1) URR has accelerated globally in the last decade; (2) research hotspots are mainly concentrated in environmental science and ecology, science and technology, and water resources; and (3) URR is gradually becoming a multidisciplinary research field. Our research reveals the status and future trends of URR through quantitative visualization methods, helping to address some emerging and unexpected risks and vulnerabilities.Supporting informationThe online version of this article (10.1007/s11356-022-20138-9)

Planning for Climate Change in Small Island Developing States: Can Dominica’s Climate Resilience and Recovery Plan Be a Model for Transformation in the Caribbean?

In response to a series of historical and contemporary extreme weather events, Dominica, a small island developing state (SIDS) in the Caribbean, is pursuing an objective of climate resilience by 2030. In 2018, the Government developed the Climate Resilience and Recovery Plan 2020–2030 (CRRP) in the context of its National Resilience Development Strategy. These policy responses have been hailed as transformational. In this paper, we focus on the CRRP and investigate its quality. To achieve this, we conduct a desk-based qualitative assessment of the CRRP’s (1) information base; (2) vision, goals and objectives; (3) priorities and options; (4) actions and implementation; and (5) monitoring and evaluation. We find that the CRRP is strongest on (1) and (3), which is not uncommon for similar policies. We also discuss whether it can be a model for transformation in the Caribbean, given the region’s long history with trying to recover from and build resilience to disasters. We conclude that, in order for it to be used as a model, there are three key factors that other jurisdictions would need to consider. The first consideration is developing mechanisms for equitably sharing any benefits derived from the blue economy. The second consideration is centering Indigenous perspectives in environmental policy- and decision-making. The third consideration is adequately accounting for exogenous, unexpected risks. Given these three considerations, we see this study as contributing to discussions about what constitutes good policy in a SIDS context, which is an underexplored area in the existing academic literature.

Motor torque estimation and security control for electric vehicles based on parameters feature extraction

Motor as well as its controller plays an important role in driving electric vehicle. As sole power device, it is closely related with actual torque accuracy to make sure security during EV driving. Due to complex controlling system for motor, there are some random failures of hardware and software which can bring a series of unexpected risks for EV acceleration or deceleration. A novel method based on motor parameters feature is proposed to estimate motor torque based on parameters feature extraction for three-phase of volts and currents. Additionally, Quality Factor ([Formula: see text]) and confidence coefficient are also adopted to judge whether motor estimation torque is reasonable or not and motor failure torque is limited to be output by setting fault flag in controller software. Finally, test bench is built to analyze torque accuracy compared with actual test value and verify security control strategy at failure modes, test results show that estimation torque accuracy is within ±5 Nm which is compared with actual test torque and motor system can effectively come into security state from failure state by security control strategy which is proposed in this paper.

Hydroxychloroquine non-availability during COVID-19 pandemic and its relation to anxiety level and disease activity in rheumatoid arthritis and lupus patients: a cross-sectional study

BackgroundDuring COVID-19 disease era, there is an accelerated demand for hydroxychloroquine since it was suggested by some centers as potential therapy for COVID-19 which has led to diminished supplies for patients with rheumatic disease and which carried unexpected risk for disease flare particularly in patients with systemic lupus erythematosus and rheumatoid arthritis. The purpose of the work is to detect the effect of HCQ shortage in patients with RA and SLE on anxiety and disease activity.ResultsA total of 320 patients were divided into two groups: group 1—216RA patients with mean age 45.5 ± 9.59 years, disease duration 43.4 ± 25.6 months with female predominance (62.5%). Group 2—104 SLE patients with mean33.4 ± 7.9 age years, disease duration 52.1 ± 34.6 months with female predominance (85.6%). HCQ shortage occurred in 174 RA patients (80.5%) and 76 lupus patients (73.1%). Despite HCQ shortage, there were no significant change in disease activity of RA (using CDAI) and SLE (using SELENA) p = 0.063 and 0.064 respectively before and after HCQ shortage. Anxiety level was higher in patients who were exposed to HCQ shortage in both groups (SLE p 0.0058 and RA p 0.0044) when we compared them to those without HCQ shortage.ConclusionIn most patients with RA and SLE, the COVID-19 pandemic resulted in a HCQ scarcity, with no effect on disease activity. Anxiety was found to be associated with HCQ shortage in both diseases.

Inhibition of base editors with anti-deaminases derived from viruses

Cytosine base editors (CBEs), combining cytidine deaminases with the Cas9 nickase (nCas9), enable targeted C-to-T conversions in genomic DNA and are powerful genome-editing tools used in biotechnology and medicine. However, the overexpression of cytidine deaminases in vivo leads to unexpected potential safety risks, such as Cas9-independent off-target effects. This risk makes the development of deaminase off switches for modulating CBE activity an urgent need. Here, we report the repurpose of four virus-derived anti-deaminases (Ades) that efficiently inhibit APOBEC3 deaminase-CBEs. We demonstrate that they antagonize CBEs by inhibiting the APOBEC3 catalytic domain, relocating the deaminases to the extranuclear region or degrading the whole CBE complex. By rationally engineering the deaminase domain, other frequently used base editors, such as CGBE, A&CBE, A&CGBE, rA1-CBE and ABE8e, can be moderately inhibited by Ades, expanding the scope of their applications. As a proof of concept, the Ades in this study dramatically decrease both Cas9-dependent and Cas9-independent off-target effects of CBEs better than traditional anti-CRISPRs (Acrs). Finally, we report the creation of a cell type-specific CBE-ON switch based on a microRNA-responsive Ade vector, showing its practicality. In summary, these natural deaminase-specific Ades are tools that can be used to regulate the genome-engineering functions of BEs.

Proton pump inhibitor therapy and risk of knee replacement surgery: a general population-based cohort study

Proton pump inhibitors (PPIs) are among the most commonly used medications for patients with osteoarthritis (OA). Various types of PPIs have different impacts on lowering serum magnesium level that may affect knee OA progression. We aimed to compare the risk of clinically relevant endpoint of knee replacement (KR) among initiators of five different PPIs with that among histamine-2 receptor antagonist (H2RA) initiators. Among patients with knee OA (≥50 years) in The Health Improvement Network database in the UK we conducted five sequential propensity-score matched cohort studies to compare the risk of KR over 5-year among patients who initiated omeprazole (n=2,672), pantoprazole (n=664), lansoprazole (n=3,747), rabeprazole (n=751), or esomeprazole (n=827) with those who initiated H2RA. The prevalence of PPI prescriptions among participants with knee OA increased from 12.7% in 2000-44.0% in 2017. Two-hundred-and-seventy-four KRs (30.8/1,000 person-years) occurred in omeprazole initiators and 230 KRs (25.4/1,000 person-years) in H2RA initiators. Compared with H2RA initiators, the risk of KR was 21% higher in omeprazole initiators (hazard ratio [HR]=1.21,95% confidence interval [CI]:1.01-1.44). Similar results were observed when pantoprazole use was compared with H2RA use (HR=1.38,95%CI:1.00-1.90). No such an increased risk of KR was observed among lansoprazole (HR=1.06,95%CI:0.92-1.23), rabeprazole (HR=0.97,95%CI:0.73-1.30), or esomeprazole (HR=0.83,95%CI:0.60-1.15) initiators compared with that among H2RA initiators. In this population-based cohort study, initiation of omeprazole or pantoprazole use was associated with a higher risk of KR than initiation of H2RA use. This study raises concern regarding an unexpected risk of omeprazole and pantoprazole on accelerating OA progression.

Somatic Mutations in Cardiovascular Disease.

Advances in population-scale genomic sequencing have greatly expanded the understanding of the inherited basis of cardiovascular disease (CVD). Reanalysis of these genomic datasets identified an unexpected risk factor for CVD, somatically acquired DNA mutations. In this review, we provide an overview of somatic mutations and their contributions to CVD. We focus on the most common and well-described manifestation, clonal hematopoiesis of indeterminate potential. We also review the currently available data regarding how somatic mutations lead to tissue mosaicism in various forms of CVD, including atrial fibrillation and aortic aneurism associated with Marfan Syndrome. Finally, we highlight future research directions given current knowledge gaps and consider how technological advances will enhance the discovery of somatic mutations in CVD and management of patients with somatic mutations.

Implementation of Ex-Gratia Claim Payment in Insurance Agreement

This study aims to explain descriptively about the implementation of ex-gratia claims on life insurance agreements, how to pay and settle ex-gratia claims and ex-gratia claim terms. In the Life Insurance agreement, the insured party when experiencing an unexpected risk of obtaining its rights in the settlement of claims. The occurrence of rejection of claims on life insurance, becomes the cause of a lack of understanding of the actual articles and regulations must be understood before deciding to use insurance. In fact, not all losses suffered by the insured in the insurance agreement can be paid according to the agreement. It is caused by several factors that are considered to violate the principles of insurance and regulations that have been determined in the insurance agreement, resulting in the cancellation of the insurer pays its obligations to the insured or commonly called rejected claims. But customers sometimes still demand that the company pay, therefore the insurance company takes the initiative to pay claims rejected through Ex-gratia. But many people do not know about the ex-gratia claim. Some insurers take the initiative to pay ex-gratia rejected claims. Implementation of ex gratia claims can be done by negotiation, good faith from the insurer to the insured.
 
 Received: 15 October 2021 / Accepted: 30 November 2021 / Published: 5 January 2022

АКТУАЛЬНІ ПИТАННЯ УПРАВЛІННЯ ДІЯЛЬНІСТЮ ВІТЧИЗНЯНИХ ПІДПРИЄМСТВ В СУЧАСНИХ УМОВАХ ГОСПОДАРЮВАННЯ

The author updates the problems of general uncertainty and riskiness of the economic activity of enterprises with the major crises of recent years: the Covid-19 pandemic and the military invasion of Russia, which caused additional specific risks for which most enterprises were not prepared. Having shown flexibility and adaptability, studying the experience of other countries, most enterprises overcame the crisis of the Covid-19 pandemic, managed to cope with unexpected risks in their activities, and found ways to overcome and eliminate them. However, the military threat from Russia posed new challenges. Threats provoked by Russian military aggression and the introduction of martial law in Ukraine made significant adjustments to the management system of enterprises, increasing the factor of unpredictability of events and the unpredictability of the development of the situation, the appearance of additional specific risks that are not inherent in normal activities in peacetime. In such conditions, there is not enough flexibility and ability to adapt to external conditions in enterprise management, special attention is paid to the introduction of risk-oriented management and the reorientation of its mechanisms in accordance with the special conditions of the military state. The author analyzed the analytics and characterized the risks of wartime. Attention is focused on the possibility of finding enterprises in a state of immediate hostilities and in a state of remote location. The risks associated with threats to people's lives, accidents, destruction of property, as a result of military operations, which make the production process impossible, are analyzed. Risks of complicating logistic support of material and technical support, risks of shortage of certain raw materials, materials, experienced employees, spare parts, etc. For all outlined risks that threaten enterprises during military operations, ways of overcoming or minimizing them were developed. Special emphasis was placed on the reorientation of export activities of enterprises to EU markets. The war brought great threats to the country and specific risks for the economic activity of enterprises. In order to minimize problems and not turn them into global ones that lead to the shutdown of the enterprise, management needs to see these risks in advance, establish backup processes, develop a preventive action plan and train personnel to face the challenges of wartime.

Will the EU Medical Device Regulation help to improve the safety and performance of medical AI devices?

Concerns have been raised over the quality of evidence on the performance of medical artificial intelligence devices, including devices that are already on the market in the USA and Europe. Recently, the Medical Device Regulation, which aims to set high standards of safety and quality, has become applicable in the European Union. The aim of this article is to discuss whether, and how, the Medical Device Regulation will help improve the safety and performance of medical artificial intelligence devices entering the market. The Medical Device Regulation introduces new rules for risk classification of the devices, which will result in more devices subjected to a higher degree of scrutiny before entering the market; more stringent requirements on clinical evaluation, including the requirement for appraisal of clinical data; new requirements for post-market surveillance, which may help spot early on any new, unexpected side effects and risks of the devices; and requirements for notified bodies, including for expertise of the personnel and consideration of relevant best practice documents. The guidance of the Medical Device Coordination Group on clinical evaluation of medical device software and the MEDDEV2.7 guideline on clinical evaluation also attend to some of the problems identified in studies on medical artificial intelligence devices. The Medical Device Regulation will likely help improve the safety and performance of the medical artificial intelligence devices on the European market. The impact of the Regulation, however, is also dependent on its adequate enforcement by the European Union member states.