Risk Assessment Guidelines Research Articles

Review of Functional Aspects of Nanocellulose-Based Pickering Emulsifier for Non-Toxic Application and Its Colloid Stabilization Mechanism.

In the past few years, the research on particle-stabilized emulsion (Pickering emulsion) has mainly focused on the usage of inorganic particles with well-defined shapes, narrow size distributions, and chemical tunability of the surfaces such as silica, alumina, and clay. However, the presence of incompatibility of some inorganic particles that are non-safe to humans and the ecosystem and their poor sustainability has led to a shift towards the development of materials of biological origin. For this reason, nano-dimensional cellulose (nanocellulose) derived from natural plants is suitable for use as a Pickering material for liquid interface stabilization for various non-toxic product formulations (e.g., the food and beverage, cosmetic, personal care, hygiene, pharmaceutical, and biomedical fields). However, the current understanding of nanocellulose-stabilized Pickering emulsion still lacks consistency in terms of the structural, self-assembly, and physio-chemical properties of nanocellulose towards the stabilization between liquid and oil interfaces. Thus, this review aims to provide a comprehensive study of the behavior of nanocellulose-based particles and their ability as a Pickering functionality to stabilize emulsion droplets. Extensive discussion on the characteristics of nanocelluloses, morphology, and preparation methods that can potentially be applied as Pickering emulsifiers in a different range of emulsions is provided. Nanocellulose's surface modification for the purpose of altering its characteristics and provoking multifunctional roles for high-grade non-toxic applications is discussed. Subsequently, the water-oil stabilization mechanism and the criteria for effective emulsion stabilization are summarized in this review. Lastly, we discuss the toxicity profile and risk assessment guidelines for the whole life cycle of nanocellulose from the fresh feedstock to the end-life of the product.

Comparison of guidelines for biological ancillary materials used for the manufacture of gene and cellular therapy products in Asia

Background aimsAlthough biologiocal ancillay materials (AMs) have specific risk associated with their derivations, it plays key role to manufature cell and gene therapy (CGT) products. It is important to understand the regulation relevant to AMs for developers. MethodsThe authors investigated the guidelines and pharmacopeia (hereinafter referred to as “guidelines”) for biological AMs used for the manufacture of CGT products in Asia (China, India, Japan, Korea and Taiwan). In addition, the authors benchmarked the relevant guidelines in the United States (US) and European Union (EU). Results and discussionsThe guidelines could be classified into two types based on whether specific AMs are scoped: (i) general guidelines for risk assessment of AMs and (ii) guidelines for specific AMs. The authors compared the risk categories for each type of AM provided in the general guidelines between the US and China and the specific requirements for bovine serum and trypsin in the guidelines of China, Japan, Taiwan, US and EU. The authors further compiled in-depth descriptions of the respective regulations in China, India, Japan, Korea and Taiwan. There is limited availability of some guidelines for specific AMs. Moreover, there are no common requirements established across the surveyed countries and regions. Therefore, the authors suggest a risk assessment approach for AMs with consideration of their biological origin and traceability, production steps applied and ability to control or remove AMs from the final medicinal product over the CGT manufacturing process.

Analytical Methods for Physicochemical Characterization and Toxicity Assessment of Atmospheric Particulate Matter: A Review

Particle-bound pollutants are a critical risk factor for human respiratory/cardiovascular conditions. A comprehensive analysis of the physicochemical characteristics of PM is often challenging since it requires combining different practical methods with a good understanding the of characterization outputs. The present review aims to (1) provide a comprehensive assessment of the underlying mechanisms of PM cytotoxicity and the related biological response; (2) evaluate the selected methods for PM characterization in terms of outputs, technical aspects, challenges, and sample preparation; (3) present effective means of studying PM physicochemical toxicity and composition; and (4) provide recommendations for enhancing the human health risk assessment. The cellular response to potentially toxic elements in PM is complex to understand as exposure includes systemic inflammation, increased ROS accumulation, and oxidative stress. A comprehensive toxicity assessment requires blending morphological features and chemical composition data. For the morphological/chemical characterization, we recommend first using SEM-EDS as a practical method for the single-particle analysis. Then, the bulk chemistry of PM can be further studied using either a dry analysis (e.g., XRF) or wet analysis techniques (e.g., ICP and IC). Finally, when used on a need basis, the reviewed complementary laboratory methods may further add valuable information to the characterization. The accuracy of the human health risk assessment may be improved using bioaccessible/soluble fractions of the contaminants instead of the total contaminant concentration. Having an integrated understanding of the covered analytical methods along with the health risk assessment guidelines would contribute to research on atmospheric chemistry, molecular biology, and public health while helping researchers better characterize human exposure to PM and the associated adverse health effects.

Cardiovascular screening prior to stem cell transplantation in the United Kingdom.

Cardiovascular screening prior to stem cell transplantation in the United Kingdom.

Concentrations and source identification of priority polycyclic aromatic hydrocarbons in sediment cores from south and northeast Thailand

In this study, the environmental fate of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in tropical lake sediments and their potential sources have been discussed. 15 PAHs (i.e. ΣPAH) have been investigated in two lakes, namely Songkhla Lake (SKL) and Nong Han Kumphawapi Lake (NHL), which are located at the southern and north-eastern parts of Thailand, respectively. Since these two lakes are registered as important wetlands under the Ramsar convention (United Nations Educational, Scientific and Cultural Organization: UNESCO), the quantitative identification of potential contributors of PAHs is an inevitable analytical tool for launching an evidence-based policy. The ΣPAH concentrations observed in SKL and NHL sediments (n = 135) were in the range of 19.4–1,218 ng g−1 and 94.5–1,112 ng g−1, respectively. While the exponential decline of ΣPAH contents were detected in SKL sediments, NHL showed a trend of enhancing PAH contents with depth. The averaged benzo [a]pyrene (B [a]P) contents of surface sediments in both lakes were much below the value stipulated by the United States Environmental Protection Agency (US-EPA) guidelines for carcinogen risk assessment. Based on numerous multivariate statistical techniques coupled with source apportionment analysis, “biomass burning” and “anthropogenic activities” are two potential contributors of the PAHs detected in the study areas. To achieve the long-term conservation of nature with related ecosystem services and cultural values, it is therefore important to promote decision-making based on ecotoxicological studies of carcinogenic substances.

Interaction of Polycyclic Aromatic Hydrocarbon compounds in fish primary hepatocytes: From molecular mechanisms to genotoxic effects

Polycyclic Aromatic Hydrocarbons (PAHs) are persistent pollutants normally found in the environment as complex mixtures. Although several individual PAHs are classified as mutagenic and carcinogenic pollutants, the interaction effects between compounds in a mixture may trigger different toxicological mechanisms and, consequently, yield different effects to organisms which are not accounted for in risk assessment guidelines. Given the ubiquity of PAHs, understanding the mechanistic features of their mixtures is a pressing research need. Therefore, the present work aimed to disclose the interaction effects of three PAHs with different carcinogenic potential and chemical structure, in primary hepatocyte cells of gilt-headed seabreams (Sparus aurata). Hepatocytes were exposed to Phenanthrene (Phe), Benzo[a]pyrene (B[a]P) and Benzo[b]fluoranthene (B[b]F) and their mixtures at different proportions and several cellular responses were analyzed: cellular viability, CYP1A1 activity (EROD assay) and protein expression level (Western blot); transcript (mRNA) levels of CYP1A1, EPXH1 and GST-3 (qRT-PCR); genotoxic effects (DNA strand breakage) by the Comet assay. Results show that B[a]P induced CYP1A1 gene and protein expression increasing its activity and, therefore, increasing the production of metabolites that trigger genotoxic DNA damage (%). Most importantly, mixtures containing Phe and B[a]P increased even further CYP1A1 mRNA levels and DNA damage (up to 70 %) which suggests that, although Phe is considered a non-carcinogenic PAH, it potentiates CYP1A1 synthesis induced by B[a]P, increasing its genotoxicity. These findings indicate that the upregulation of CYP1A1 by carcinogenic PAHs will not weaken even when in mixtures with non-carcinogenic PAHs. On contrary, non-carcinogenic PAHs may potentiate the genotoxic effect of carcinogenic PAH and therefore mixture composition should be taken in account when assessing PAH toxicity. In fact, our results point to the need of redefining Environmental Risk Assessment protocols for mixtures of carcinogenic pollutants.

A scoping review of evaluations of and recommendations for default uncertainty factors in human health risk assessment.

Uncertainty factors (UFs) are used to account for uncertainties and variability when setting exposure limits or guidance values. Starting from a proposal of a single UF of 100 to extrapolate from an animal NOAEL to a human acceptable exposure, the aspects of uncertainty and number of UFs have diversified and today there are several risk assessment guidelines that contain schemes of default UFs of varying complexity. In the present work, we scoped the scientific literature on default UFs to map developments regarding recommendations and evaluations of these. We identified 91 publications making recommendations for one or several UFs and 55 publications evaluating UFs without making explicit recommendations about numerical values; these were published between 1954 and 2021. The 2000s was the decade with the largest number of publications, interspecies differences and intraspecies variability being the most frequent topics. The academic sector has been the most active (76 out of 146 publications). Authors from the private sector more often presented UF recommendations, but differences between sectors regarding size of recommendations were not statistically significant. The empirical underpinning of the reviewed recommendations ranges from four to 462 chemicals, that is, relatively low numbers compared with the range of chemicals these default UFs are expected to cover. The recommended UFs have remained remarkably constant, with merely a slight decrease over time. Although chemical specific UFs are preferable, the widespread use of default UFs warrants further attention regarding their empirical and normative basis.

The Study of Artificial Intelligent in Risk-Based Inspection Assessment and Screening: A Study Case of Inline Inspection

Abstract The work reports the systematic approach to the study of artificial intelligence (AI) in addressing the complexity of inline inspection (ILI) data management to forecast the risk in natural gas pipelines. A recent conventional standard may not be sufficient to address the variation data of corrosion defects and inherent human subjectivity. Such methodology undermines the accuracy assessment confidence and is ineffective in reducing inspection costs. In this work, a combination of unsupervised and supervised machine learning and deep learning has profoundly accelerated the probability of failure (PoF) assessment and analysis. K-means clustering and Gaussian mixture models show direct relevance between the corrosion depth and corrosion rate, while the overlapping PoF value is scattered in three clusters. Logistic regression, support vector machine, k-nearest neighbors, and ensemble classifiers of AdaBoost, random forest, and gradient boosting are constructed using particular features, labels, and hyperparameters. The algorithm correctly predicted the score of PoF from 4790 instances and confirmed the 25% metal loss at a location of 13.399 m. The artificial neural network (ANN) is designed with various layers (input, hidden, and output) architecture. It is optimized using an activation function to predict that 74% of the pipeline's anomalies that classified at low-medium and medium-high risk. Furthermore, it provides a quick and precise prediction about the external defects at 13.1 m and requires the personnel to conduct wrapping composite. This work can be used as a standard guideline for risk assessment based on ILI and applies to industry and academia.

Evaluation of existing guidelines for their adequacy for the food and feed risk assessment of microorganisms obtained through synthetic biology.

EFSA was asked by the European Commission to evaluate synthetic biology (SynBio) developments for agri‐food use in the near future and to determine whether or not they are expected to constitute potential new hazards/risks. Moreover, EFSA was requested to evaluate the adequacy of existing guidelines for risk assessment of SynBio and if updated guidance is needed. The scope of this Opinion covers food and feed risk assessment, the variety of microorganisms that can be used in the food/feed chain and the whole spectrum of techniques used in SynBio. This Opinion complements a previously adopted Opinion with the evaluation of existing guidelines for the microbial characterisation and environmental risk assessment of microorganisms obtained through SynBio. The present Opinion confirms that microbial SynBio applications for food and feed use, with the exception of xenobionts, could be ready in the European Union in the next decade. New hazards were identified related to the use or production of unusual and/or new‐to‐nature components. Fifteen cases were selected for evaluating the adequacy of existing guidelines. These were generally adequate for assessing the product, the production process, nutritional and toxicological safety, allergenicity, exposure and post‐market monitoring. The comparative approach and a safety assessment per se could be applied depending on the degree of familiarity of the SynBio organism/product with the non‐genetically modified counterparts. Updated guidance is recommended for: (i) bacteriophages, protists/microalgae, (ii) exposure to plant protection products and biostimulants, (iii) xenobionts and (iv) feed additives for insects as target species. Development of risk assessment tools is recommended for assessing nutritional value of biomasses, influence of microorganisms on the gut microbiome and the gut function, allergenic potential of new‐to‐nature proteins, impact of horizontal gene transfer and potential risks of living cell intake. A further development towards a strain‐driven risk assessment approach is recommended.

Knowledge and Behavior toward Venous Thromboembolism Event Prophylaxis and Treatment Protocols among Medical Interns in Riyadh.

Objective This study was aimed at evaluating the knowledge and behavior toward venous thromboembolism (VTE) prophylaxis among medical interns. Methods This is a questionnaire-based cross-sectional observational cohort study of medical interns that used a validated questionnaire. The questionnaire comprised of items that assessed behavior, knowledge, and self-assessment of VTE risk factors, diagnosis, and prophylaxis. The study was conducted in Riyadh, Saudi Arabia, from October 2020 till September 2021. Results The respondents were 246 medical interns. The overall rate of correct responses to behavior items was 41.82%. The overall rate of correct responses to knowledge items was 47.35%. A total of 61.8% responded negatively to the use of VTE risk assessment guidelines (p < 0.0001). For the self-assessment of knowledge of VTE, more than 70% believed they did not have appropriate knowledge, were not prepared to establish the risk of VTE, and were not prepared to provide adequate prophylaxis for VTE (p < 0.0001). A high proportion of medical interns (83.3%, p < 0.0001) believed they needed further training on this topic. Conclusion Participants in this study showed poor knowledge and negative behavior regarding the assessment of risk factors, diagnosis, and prophylaxis of VTE. The majority of participants reported they needed training on this topic. These findings underscore the need for educational programs during undergraduate training and orientation of medical interns for VTE risk assessment, diagnosis, and prophylaxis at the beginning of their internship.

Prediction of rupture and perforation limits of pressurised X80 pipelines using BP neural networks and generalised additive models

Impact resistance of in-service pressurised X80 pipelines is one of the top safety priorities in the petrochemical industry. Based on impact limits, including the rupture and perforation limits, the failure threshold can be identified and the impact resistance of target structures can be assessed. In this study, backpropagation neural networks (BPNNs) and generalised additive models (GAMs) were developed to predict the rupture and perforation limits of pressurised X80 pipelines. First, an explicit dynamic model was established to provide comprehensive training datasets considering the effects of various dominant parameters. Interdependencies between the impact limits and various dominant parameters were analysed using the Pearson correlation coefficient. Then, BPNN models optimised by the backpropagation algorithm and neuron numbers were trained to predict the impact limits. Based on the optimal smooth functions and smoothing coefficients, the GAMs then provided two integrated regression functions for impact limits. Finally, the predictive stabilities of the BPNN and GAM on impact limits were discussed using a random dataset. The BPNNs and GAMs were in a strong agreement with the expectations, and the predictive accuracy of the BPNNs was approximately three times that of GAMs. The findings of this study can be used as guidelines for protection design and risk assessment of pressurised X80 pipelines.

Evaluation of existing guidelines for their adequacy for the food and feed risk assessment of genetically modified plants obtained through synthetic biology.

Synthetic biology (SynBio) is an interdisciplinary field at the interface of molecular engineering and biology aiming to develop new biological systems and impart new functions to living cells, tissues and organisms. EFSA has been asked by the European Commission to evaluate SynBio developments in agri‐food with the aim of identifying the adequacy and sufficiency of existing guidelines for risk assessment and determine if updated guidance is needed. In this context, the GMO Panel has previously adopted an Opinion evaluating the SynBio developments in agri‐food/feed and the adequacy and sufficiency of existing guidelines for the molecular characterisation and environmental risk assessment of genetically modified plants (GMPs) obtained through SynBio and reaching the market in the next decade. Complementing the above, in this Opinion, the GMO Panel evaluated the adequacy and sufficiency of existing guidelines for the food and feed risk assessment of GMPs obtained through SynBio. Using selected hypothetical case studies, the GMO Panel did not identify novel potential hazards and risks that could be posed by food and feed from GMPs obtained through current and near future SynBio approaches; considers that the existing guidelines are adequate and sufficient in some Synbio applications; in other cases, existing guidelines may be just adequate and hence need updating; areas needing updating include those related to the safety assessment of new proteins and the comparative analysis. The GMO Panel recommends that future guidance documents provide indications on how to integrate the knowledge available from the SynBio design and modelling in the food and feed risk assessment and encourages due consideration to be given to food and feed safety aspects throughout the SynBio design process as a way to facilitate the risk assessment of SynBio GMPs and reduce the amount of data required.

Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies.

This scoping review aims to summarise the current understanding of selection for antifungal resistance (AFR) and to compare and contrast this with selection for antibacterial resistance, which has received more research attention. AFR is an emerging global threat to human health, associated with high mortality rates, absence of effective surveillance systems and with few alternative treatment options available. Clinical AFR is well documented, with additional settings increasingly being recognised to play a role in the evolution and spread of AFR. The environment, for example, harbours diverse fungal communities that are regularly exposed to antifungal micropollutants, potentially increasing AFR selection risk. The direct application of effect concentrations of azole fungicides to agricultural crops and the incomplete removal of pharmaceutical antifungals in wastewater treatment systems are of particular concern. Currently, environmental risk assessment (ERA) guidelines do not require assessment of antifungal agents in terms of their ability to drive AFR development, and there are no established experimental tools to determine antifungal selective concentrations. Without data to interpret the selective risk of antifungals, our ability to effectively inform safe environmental thresholds is severely limited. In this review, potential methods to generate antifungal selective concentration data are proposed, informed by approaches used to determine antibacterial minimal selective concentrations. Such data can be considered in the development of regulatory guidelines that aim to reduce selection for AFR.

The Role of Informatics in Implementing Guidelines for Chronic Opioid Therapy Risk Assessment in Primary Care: A Narrative Review Informed by the Socio-Technical Model.

Approximately 2 million Americans live with opioid use disorder (OUD), most of whom also have chronic pain. The economic burden of chronic pain and prescription opioid misuse runs into billions of dollars. Patients on prescription opioids for chronic non-cancer pain (CNCP) are at increased risk for OUD and overdose. By adhering to the Center for Disease Control and Prevention (CDC) opioid prescribing guidelines, primary care providers (PCPs) have the potential to improve patient outcomes. But numerous provider, patient, and practice-specific factors challenge adherence to guidelines in primary care. Many of the barriers may be mediated by informatics interventions, but gaps in knowledge and unmet needs exist. This narrative review examines the risk assessment and harm reduction process in a socio-technical context to highlight the gaps in knowledge and unmet needs that can be mediated through informatics intervention.

Method development and application to sediments for multi-residue analysis of organic contaminants using gas chromatography-tandem mass spectrometry.

A method for the determination of four classes of potentially toxic substances (PTSs) was developed and applied in marine sediments, including (i) polycyclic aromatic hydrocarbons (PAHs), (ii) polychlorinated biphenyls (PCBs), (iii) polybrominated diphenyl ethers (PBDEs), and (iv) organochlorinated pesticides (OCPs). The method is based on ultrasonic extraction with a mixture of dichloromethane:methanol (9:1 v/v) and gas chromatography coupled with tandem mass spectrometry analysis (GC-MS/MS) in multiple reaction monitoring (MRM) mode. A total of 89 compounds were identified using two precursor-product ion standards for each analyte. The method detection limit (MDL; 0.001-0.055ngg-1 dw) and method quantification limit (MQL; 0.002-0.184ngg-1 dw) are below the usual thresholds of pollution adopted by international sediment quality guidelines. The method proved to be selective, sensitive, accurate, and linear, with the advantage of reducing sample handling time and consumable expenses (solvent, adsorbents). The developed method was successfully applied to surface sediments of Sepetiba Bay, Rio de Janeiro State, Brazil. Total concentrations of PAH (29.20-209.5ngg-1 dw), PCB (0.06-2.16ngg-1 dw), OCP (0.03-0.33ngg-1 dw), and PBDE (0.06-0.21ngg-1 dw) represent a baseline for these compounds and revealed mild to low levels of contamination in comparison to other coastal bays in SE Brazil. By using the proposed method, we expect this preliminary dataset can be expanded and include other similar coastal systems from developing countries marked by scarcity of information about levels, risk assessment, and specific sediment quality guidelines encompassing multiple classes of regulated and emerging organic contaminants.

Joint effects of general population polygenic risk scores (PRS) and radiation treatment on subsequent neoplasm risk among childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

10008 Background: We examined whether PRS from general population studies are associated with risk of subsequent neoplasms (SNs) in childhood cancer survivors and evaluated joint associations between PRS and radiation treatment (RT), an established SN risk factor. Methods: Common genetic variants associated with risk of basal cell carcinoma (BCC), breast cancer, thyroid cancer, squamous cell carcinoma (SCC) or melanoma in general population studies were used to calculate cancer specific PRS among 5,911 5 year cancer survivors diagnosed &lt; 21 years of age and between 1970-1986 in the CCSS. We examined associations between each PRS and SN risk using conditional logistic regression in nested case control studies, with incidence density sampling and matching on childhood cancer type, age at diagnosis, sex, RT dose to the SN site, and chemotherapy exposure. Further analyses matching only on non-treatment factors assessed joint associations considering potential combinations of PRS and RT exposure. We calculated the relative excess risk due to interaction (RERI) to determine whether joint associations were consistent with additivity of the individual risk factors (RERI &gt; 0 indicates a more-than-additive joint association). Results: Among survivors (median age at follow-up 40 years, range 3-67; 62% exposed to RT), cancer specific PRS were associated with risk of subsequent BCC (N = 626; quartile 4 versus 1, OR [95% CI] = 1.9 [1.5-2.4]), breast cancer (N = 277; 4.5 [2.8-7.1]), thyroid cancer (N = 149; 1.9 [1.2-3.1]), and melanoma (N = 76; 2.7 [1.3-5.6]). Both PRS and RT were independently associated with SN risk, but joint analyses using a common reference group (PRS &lt; median, RT &lt; 1 Gy) found that both risk factors together resulted in more-than-additive increases in risk of BCC (RERI [95% CI] = 6.9 [2.0-11.8], breast cancer (6.6 [2.2-10.1], and thyroid cancer (4.8 [0.5-9.2]). Specifically, BCC risk was increased 28.8-fold for both PRS ≥ median and RT ≥ 1 Gy together, but only 3.3-fold for PRS ≥ median alone and 19.7-fold for RT ≥ 1 Gy alone. Similarly, breast cancer risk was increased 14.1-fold for both risk factors together, 2.5-fold for PRS ≥ median alone, and 6.5-fold for RT ≥ 1 Gy alone, and thyroid cancer risk was increased 12.3-fold for both risk factors together, 2.4-fold for PRS ≥ median alone, and 6.0-fold for RT ≥ 1 Gy alone. In joint analyses using more detailed RT categories, we found more-than-additive joint associations at both low and high RT doses. Conclusions: General population PRS were associated with SN risks after childhood cancer. More-than-additive increased risks with the combination of PRS and RT suggest that established markers of genetic susceptibility remain important in the context of treatment-related risks and may be useful in further refining risk assessment and follow-up guidelines for survivors.

Honey bee counter evaluation – Introducing a novel protocol for measuring daily loss accuracy

Automated bee counters advanced over the last hundred years and became increasingly diverse. However, to date, there is no method for standardized validation of counting accuracy and thus no reliable data on daily bee losses, or background mortality in colonies. However, such data are in urgent need by regulators to establish future guidelines for pesticide risk assessment. In this work, existing approaches were combined to form a novel protocol for validating bee counters. In a case study, we demonstrated that the protocol is sufficiently feasible to determine the measurement accuracy of a commercial counting system. Measurement accuracy was modeled by the difficulty of specific measurement conditions. Daily loss, i.e., the difference between incoming and outgoing bees, can be used to assess colony health, environmental impacts, and infer the effect of pesticides on bee colonies. The developed protocol makes innovations in this field measurable and creates a foundation for the benchmarking of different types of bee counting systems. We discuss how it can be utilized in an effort to move the sector forward in the future.

Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment

BRCA1/2 are tumor suppressor genes involved in DNA double-strand break repair. They are the most penetrant genes for hereditary breast and ovarian cancers, but pathogenic variants in these two genes can be identified only in a fraction of hereditary cases. Following the diffusion of BRCA molecular testing and the availability of specific therapeutic strategies for the management of pathogenic variant carriers, the demand for the analysis of additional predisposing genetic factors has increased. Indeed, there is accumulating evidence regarding the role of other genes, including CHEK2 and PALB2. Both of them are involved in the same molecular pathway as BRCA genes, with CHEK2 being responsible for cell cycle stopping to allow the repair of DNA double-strand breaks and PALB2 being able to interact with BRCA1 and activate BRCA2. Thus, their role as additional hereditary cancer predisposing factors is intriguing. Accordingly, guidelines for hereditary cancer risk assessment have been updated to include the criteria for additional genes testing. In this context, we validated a commercially available kit allowing for the simultaneous analysis of BRCA1, BRCA2, CHEK2 and PALB2. Forty-eight patients, already tested for BRCA mutational status, were re-analyzed in the present study. Results comparison showed that the tested method was able to correctly identify all the variants previously detected in the same patients. In particular, all single-nucleotide variants and small indels were correctly identified. Moreover, two copy number variants, included to assess the software’s performance in detecting this kind of gene alteration, were also detected. Even if copy number variant estimation still requires confirmation by a molecular technique to avoid false positive results, it is able to reduce the number of patients requiring multiplex ligation probe amplification analysis, positively impacting the test’s turnaround time. Finally, since the time and costs of the analysis are similar to those required just for BRCA genes, this strategy may be affordable for providing a more comprehensive test for hereditary cancer risk assessment.

Human Performance and Injury Prevention in Cold Weather Environments.

This article serves as a primer for those practitioners who serve as subject matter experts in cold weather medicine, whether it be medical planning for an outdoor event, making the determination "it is too cold to exercise," or investigating why an athlete is struggling to compete in a frigid environment. Cold weather exercise physiology is reviewed, and medical conditions that may impact performance at cold temperatures are briefly examined. Guidelines for cold weather risk assessment, injury prevention, and performance optimization also are discussed.

RAPEX 위해성 평가 가이드라인을 활용한 사고 신고 제품의 위해성 평가 연구

Purpose: This study mainly identifies the level of potential defects in products that can possibly cause accidents using a risk assessment process. Moreover, strategies for preventing future accidents are suggested.<BR>Methods: A risk assessment model was devised using the Rapid Exchange of Information System (RAPEX) Risk Assessment Guideline and based on accident report data. Risk assessment was conducted for each accident report, and items with high potential risks were classified.<BR>Results: The risk assessment confirmed that among the 136 accident reports, 20 accidents were identified to have been caused by products whose level of defect could be classified as “serious risk.”<BR>Conclusion: Accident information (except sensitive information) regarding products with a level of defect classified as “serious risk” must be available as public data. Manufacturing companies are expected to provide this information to the public as part of safety management.