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BACKGROUND: Oral cancer has a high worldwide incidence and mortality rate showing an upward trend year by year, predominantly occurring in emerging countries. Oral squamous cell carcinoma (OSCC) is one of the main types of oral cancer, accounting for more than 90% of all cases in oral cancer. OBJECTIVE: To evaluate the diagnostic value of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-Prostaglandin F2alpha (8-iso-PGF2α) and tumor necrosis factor (TNF)-α as biomarkers in the early carcinogenesis of erosive oral lichen planus (EOLP) by measuring their levels in the blood of patients with EOLP and oral squamous cell carcinoma (OSCC). METHODS: A total of 69 patients were enrolled in this case-control study [including an OSCC group (n= 23), an EOLP group (n= 23), and an age- and gender-matched healthy control group (n= 23)]. Blood levels of 8-OHdG, 8-iso-PGF2α and TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). Statistical differences in these indicators among the three groups were analyzed. RESULTS: Plasma levels of 8-OHdG and 8-iso-PGF2α in the OSCC group were significantly higher than those in both the EOLP group and the control group (all P< 0.05); no significant statistical difference was found between the EOLP group and the control group. Serum levels of TNF-α in both the OSCC and EOLP groups were elevated compared with the control group, showing significant differences among all three groups (all P< 0.05). Receiver operating characteristic (ROC) curves revealed that plasma 8-OHdG and 8-iso-PGF2α levels and serum TNF-α levels had diagnostic effects on early carcinogenesis in EOLP patients. When these indicators were combined for diagnosis, the diagnostic effect was enhanced, with an area under the ROC curve (AUC) values of 0.819. CONCLUSION: 8-OHdG, 8-iso-PGF2α and TNF-α may serve as biological indicators for monitoring the early carcinogenesis of EOLP, and the diagnostic effect was augmented when these indicators were combined.
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Background: Pancreatic cancer and colon cancer pose significant challenges in treatment, with poor prognoses. Natural products have long been explored for their potential as anticancer agents. Iso-mukaadial acetate has shown promise in inducing apoptosis in breast and ovarian cancer cells. The objective of this study was to investigate the effect of Iso-mukaadial acetate on pancreatic (MIA-PACA2) and colon (HT29) cancer cell lines. Methods: Pancreatic (MIA-PACA2) cancer cells, colon (HT29) cancer cells, normal embryonic kidney cells (HEK 293), and normal lung cells (MRC5) were cultured and treated with Iso-mukaadial acetate (IMA) for 24 hours. The viability assays were conducted using Alamarblue reagent and a real-time cell viability monitoring system, xCELLigence. The IC50 values were determined, followed by assessments of ATP production, caspase 3/7 activation, mitochondrial function, morphological changes using a light microscope, and gene expression changes via RT-PCR. Results: This study indicates that Iso-mukaadial acetate exhibited concentration-dependent cytotoxic effects, slowing cellular proliferation in both cancer cell lines. Activation of the mitochondrial apoptotic pathway and caspase 3/7 suggests induction of apoptosis. Reduced ATP production and altered gene expression further support its anticancer properties. Morphological changes after treatment with Iso-mukaadial acetate showed apoptotic characteristics which may suggest that apoptosis was induced. Conclusions: According to the results obtained, Iso-mukaadial acetate shows potential as an anticancer agent, evidenced by its effects on cellular viability, mitochondrial function, ATP production, caspase activation, and gene expression in pancreatic and colon cancer cells. These findings highlight its promise for further investigation and potential in the development of therapeutic agents.
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The application of antimicrobial surfaces requires the proof of their effectivity by in vitro methods in laboratories. One of the most well-known test methods is ISO 22196:2011, which represents a simple and inexpensive protocol by applying the bacterial suspension with known volume and concentration covered under a polyethylene film on the surfaces. The incubation is then done under defined humidity conditions for 24 h. Another approach for testing of non-porous surfaces is the newly published ISO 7581:2023. A "dry test" is achieved through spreading and drying 1 µL of a bacterial suspension on the surface. In this study, low alloyed carbon steel, polyethylene terephthalate (PET), and glass specimens were tested uncoated (reference) and coated with zinc according to both ISOs to compare and to evaluate the advantages and disadvantages of each one of them. Although ISO 7581:2023 allows a more realistic test environment than ISO 22196:2011, the reproducibility of the results is not given due to the low application volume. In addition, not all bacterial strains are equally suitable for this testing type. Individual adaptations to the protocols, including incubation conditions (time, temperature, or relative humidity), testing strains and volume, seem necessary to generate conditions that simulate the final application. Nevertheless, both ISOs, if used correctly, provide a good basis for estimating the antimicrobial efficacy of non-porous surfaces.
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A new 2-quinolone alkaloid, iso-oligophyline (1), and two very unusual C34 terpenoids, proposed names ravespanol (2) and ravespanone (3), along with two known compounds, ß-sitosterol (4), and methyl linoleate (5), were isolated from the leaf extract of Ravenia spectabilis engl. Methyl linoleate constitutes the first report of isolation from this species. We have already reported the isolation of atanine (6), oligophyline (7), ravenoline (8), and arborinine (9) from the plant. Based on nuclear magnetic resonance (NMR) spectroscopy and mass spectrometric analysis, the structure of the isolated chemicals was determined. The crude fractions and four compounds (6,7,8 and 9) were evaluated for a cytotoxicity study on a panel of six human stomach cancer cell lines (SCL, SCL-6, SCL-37'6, SCL-9, K-3, N21) by MTT assay. Among the plant extracts and isolated compounds, petroleum ether fraction and compound 7 exhibited the highest cytotoxic activity against SCL and SCL-6 cells, where the IC50 values were 17.9 and 16.56 µM, respectively.
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PURPOSE: To investigate the effects of the elemental composition and the manufacturing process of cobalt chromium-molybdenum (CoCr-Mo), cobalt chromium-tungsten (CoCr-W), and CoCr-Mo-W alloys on metal-ceramic bond strength. MATERIALS AND METHODS: Six CoCr-based alloys were included in this study, a were classified into three different groups depending on their elemental composition (Ν = 10, for each group). The first group had molybdenum (Mo) as the third alloying element, the second group contained tungsten (W) (without Mo), and the third group included both alloying elements. The groups were further divided by the manufacturing process (casting or selective laser melting, SLM). Interfacial analysis was carried out using backscattered electron imaging (BEI) and energy-dispersive X-ray microanalysis (EDX) operating in line scan mode. The metal-ceramic bond strength was tested by a 3-point bending test according to the ISO 9693 requirements. The fracture mode of all specimens was examined under a stereomicroscope. The bond strength results were statistically analyzed by 2-way ANOVA and Tukey's multiple comparison post hoc test (a = 0.05). RESULTS: A continuous interface with the porcelain was found without pores, debonding areas, or other defects. Of the major elements found at the interface, Co showed the highest diffusion rate, while titanium (Ti) had the lowest diffusion rate. No statistically significant differences were identified in metal-ceramic bond strength either among materials or between manufacturing processes. The fracture mode was found to be cohesive for all specimens. CONCLUSIONS: The metal-ceramic bond strength is independent of the current CoCr alloy type and manufacturing process when comparing conventional casting and SLM. Interfacial analysis revealed no differences between the tested groups.
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This study introduces a novel in vitro methodology that employs the 3-D reconstructed tissue model, EpiOcular, to assess the irritation and phototoxicity potential of medical devices and drugs in contact with the eye. Our study evaluated diverse test materials, including medical devices, ophthalmological solutions and an experimental drug (cemtirestat), for their potential to cause eye irritation and phototoxicity. The protocols used in this study with the EpiOcular tissue model were akin to those used in the ultra-mildness testing of cosmetic formulations, which is challenging to predict with standard in vivo rabbit tests. To design these protocols, we leveraged experience gained from the validation project on the EpiDerm skin irritation test for medical devices (ISO 10993-23:2021) and the OECD TG 498 method for photo-irritation testing. The predictions were based on the tissue viability and inflammatory response, as determined by IL-1α release. By developing and evaluating these protocols for medical devices, we aimed to expand the applicability domain of the tests referred to in ISO 10993-23. This will contribute to the standardisation and cost-effective safety evaluation of ophthalmic products, while reducing reliance on animal testing in this field. The findings obtained from the EpiOcular model in the photo-irritation test could support its implementation in the testing strategies outlined in OECD TG 498.
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In our investigation, we investigated the role of macrophage migration inhibitory factor (MIF), a key cytokine, in chronic nonbacterial prostatitis (CNP), an underexplored pathology. Elevated MIF expression was observed in the serum of individuals with chronic prostatitis-like symptoms (CP-LS) as well as in serum and tissue samples from experimental autoimmune prostatitis (EAP) mouse model. Treatment with ISO-1, a specific MIF antagonist, effectively mitigated prostatic inflammation and macrophage infiltration, thereby emphasizing the critical role of MIF in orchestrating immune responses within the prostate microenvironment. Further analyses revealed that MIF stimulates the PI3K/AKT and NLRP3 inflammasome pathways, which are integral to inflammation and cellular immunity. Pharmacological inhibition of the PI3K/AKT pathway by LY294002 substantially reduced prostatic inflammation and macrophage infiltration, potentially by inhibiting NLRP3 inflammasome activation. These findings collectively suggest that MIF is a potential diagnostic marker for CNP and suggest that targeting MIF or its downstream signalling pathways, PI3K/AKT and NLRP3, might represent a novel therapeutic strategy for this condition.
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There are numerous unresolved research questions, along with ongoing debates regarding how to achieve circular economy and at what level. The forthcoming circular economy standard (ISO 59000 framework) as a result from the ISO/TC 323, from the International Organization for Standardization (ISO) aims to offer global implementation pathways using a unified technical language. The most challenging aspect of circularity, whether viewed scientifically, technically, and/or legislatively, is how to enhance prosperity while reducing reliance on primary materials and energy to achieve climate neutrality by 2050, thereby aiding the EU in achieving a successful and equitable transition towards a sustainable future. Strategies in the framework of waste management and circular economy are essential and needed to reduce the impact of several processes on the environment through product, processes, and corporate policies using green applicable sustainable resources and environmental management systems. In addition, "measuring something that is not there" is very complex and not fully comprehensible, not clear and not tangible from organizations, researchers, policy makers and citizens. The willingness and ability of individuals or organizations to take actions towards a low-carbon society involves grappling with various perspectives, such as social norms and economic viability. Circular economy is considered a tool in combating climate change and implementing climate mitigation (as well as adaptation) measures. Moreover, to date, there has been no common scientific or technical language for the application of the circular economy concept. This paper highlights the multitude of "Rs" beyond the well-known (3Rs) Reduce-Reuse-Recycle pattern, which can be applied in various contexts to assist SMEs and organizations (and even more citizens) in successfully adopting circular economy principles, while also shedding light on how these "Rs" can be utilized to measure intangible aspects (something that is not there). The results indicates that more than 55Rs exist which directly involved in the circular economy framework considering also waste management strategies. The findings of this study reveal the existence of over 82 "Rs" beyond the well-known principles of "reduce, reuse, recycle," each playing a distinct role in the development of strategies aimed at addressing waste management issues and advancing circularity towards a low-carbon society. Furthermore, the results could be useful for any policy makers, consultants, engineers, practitioners, urban planners, academics etc., in order to develop, apply, monitor and improve any strategy such as waste prevention, reuse, reduce, energy recovery etc., in the framework of circular economy principles, solid waste management and beyond.
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Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.
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Apoptosis , Autofagia , Boraginaceae , Miocitos Cardíacos , Terpenos , Apoptosis/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Autofagia/efectos de los fármacos , Boraginaceae/química , Ratas , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificación , Animales , Estructura Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Insuficiencia Cardíaca/tratamiento farmacológico , Cardiotónicos/farmacología , Cardiotónicos/química , Cardiotónicos/aislamiento & purificación , Línea CelularRESUMEN
With the growing importance of alternative test methods that implement the 3Rs principles (Reduction, Refinement and Replacement) and the global importance of biological safety assessment data for medical devices is increasing. We have developed and optimized the 'KeraSkin™ Skin Irritation Test (KeraSkin™ SIT) for medical device' for regulatory application in biological evaluation according to ISO 10993-23. We conducted a round robin study to optimize and evaluate the performance of KeraSkin™ SIT for medical devices using KeraSkin™ Reconstructed Human Epidermis (RhE), which is developed and manufactured in Korea. This round robin study was performed to assess the transferability, reproducibility (within and between laboratories) and predictive capacity in 1 lead laboratory and 3 participating laboratories based on OECD Guidance Document 34. The predictive capacity, the results showed 83.3 % of sensitivity, 100 % of specificity and 91.6 % of accuracy. In conclusion, the results demonstrate that 'KeraSkin™ SIT for medical device' provides a robust test method for detecting irritant activity of medical device extracts and can be utilized for identifying low levels of potent irritants in medical device extracts. Therefore, it fulfills the requirements to be included as a 'me-too' test method to EpiDerm™ and SkinEthic™ skin irritation test in ISO 10993-23.
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Administrable dose form can be obtained after (no-)transformation from pharmaceutical dose form. Building on the creation of a small ontology of 428 pharmaceutical dose forms from EDQM to support alignment with other dose form ontologies (SNOMED-CT, RxNorm), the present study is focused on a simple ontology of 308 administrable dose forms, 27 Intended Sites and an intermediary level of 65 dose form groupers. The ontology was created after 432 pharmaceutical dose forms, 65 combined pharmaceutical dose forms and 73 combined terms were linked by EDQM to administrable dose forms during the UNICOM project. The article describes these resources, the resulting ontology, the differences between its top-level concepts and the source's. It presents the protocol for a validation study through expert review, as a preparation for use case studies.
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Systematized Nomenclature of Medicine , Humanos , Preparaciones Farmacéuticas , Procesamiento de Lenguaje Natural , Vocabulario ControladoRESUMEN
The Valkyrie project aims to develop a demonstration Federated Electronic Health Record for the use of mental health practitioners in Norway. Information for the record is drawn from existing records in Source Systems operating across primary and secondary care. Recording of information in any such system, in response to a healthcare event, triggers the generation of an Encrypted Token, containing summary metadata about the event, clinical coding indicating its clinical context and a locator that can be used to retrieve the full record of the event from the original Source System. The Valkyrie architecture consists of a number of interlinked Security Domains, each with its own private and public keys, through which the Encrypted Tokens are passed. Each Security Domain performs a specific function on a set of Tokens and only has access to the information within each Token that is necessary to perform that function. This paper describes the structure of the Encrypted Token, the function of each Security Domain and the orchestration of the flow of Tokens through the Domains. Together this allows a user to run a Valkyrie Session, in which they can view the content of a patient record, where all content has been drawn in real-time from heterogenous Source Systems (ISO13606- and openEHR-based) and is destroyed when the session terminates.
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Cadena de Bloques , Seguridad Computacional , Registros Electrónicos de Salud , Noruega , Humanos , Registro Médico Coordinado/métodosRESUMEN
Sodium-ion batteries are increasingly recognized as ideal for large-scale energy storage applications. Alluaudite Na2+2 δFe2- δ(SO4)3 has become one of the focused cathode materials in this field. However, previous studies employing aqueous-solution synthesis often overlooked the formation mechanism of the impurity phase. In this study, the nonequilibrium evolution mechanism between Na2+2 δFe2- δ(SO4)3 and impurities by adjusting ratios of the Na2SO4/FeSO4·7H2O in the binary system is investigated. Then an optimal ratio of 0.765 with reduced impurity content is confirmed. Compared to the poor electrochemical performance of the Na2.6Fe1.7(SO4)3 (0.765) cathode, the optimized Na2.6Fe1.7(SO4)3@CNTs (0.765@CNTs) cathode, with improved electronic and ionic conductivity, demonstrates an impressive discharge specific capacity of 93.8 mAh g-1 at 0.1 C and a high-rate capacity of 67.84 mAh g-1 at 20 C, maintaining capacity retention of 71.1% after 3000 cycles at 10 C. The Na2.6Fe1.7(SO4)3@CNTs//HC full cell reaches an unprecedented working potential of 3.71 V at 0.1 C, and a remarkable mass-energy density exceeding 320 Wh kg-1. This work not only provides comprehensive guidance for synthesizing high-voltage Na2+2 δFe2- δ(SO4)3 cathode materials with controllable impurity content but also lays the groundwork of sodium-ion batteries for large-scale energy storage applications.
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Endoscopes are crucial for assisting in surgery and disease diagnosis, including the early detection of cancer. The effective use of endoscopes relies on their optical performance, which can be characterized with a series of metrics such as resolution, vital for revealing anatomical details. The modulation transfer function (MTF) is a key metric for evaluating endoscope resolution. However, the 2020 version of the ISO 8600-5 standard, while introducing an endoscope MTF measurement method, lacks empirical validation and excludes opto-electronic video endoscopes, the largest family of endoscopes. Measuring the MTF of video endoscopes requires tailored standards that address their unique characteristics. This paper aims to expand the scope of ISO 8600-5:2020 to include video endoscopes, by optimizing the MTF test method and addressing parameters affecting measurement accuracy. We studied the effects of intensity and uniformity of image luminance, chart modulation compensation, linearity of image digital values, auto gain control, image enhancement, image compression and the region of interest dimensions on images of slanted-edge test charts, and thus the MTF based on these images. By analyzing these effects, we provided recommendations for setting and controlling these factors to obtain accurate MTF curves. Our goal is to enhance the standard's relevance and effectiveness for measuring the MTF of a broader range of endoscopic devices, with potential applications in the MTF measurement of other digital imaging devices.
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The pyrochlore iridates,A2Ir2O7, show a wide variety of structural, electronic, and magnetic properties controlled by the interplay of different exchange interactions, which can be tuned by external pressure. In this work, we report pressure-induced iso-structural phase transitions at ambient temperature using synchrotron-based x-ray diffraction (up to â¼20 GPa) and Raman-scattering measurements (up to â¼25 GPa) of the pyrochlore series (Sm_{1-x}Bix)2Ir2O7(x= 0, 0.02, and 0.10). Our Raman and x-ray data suggest an iso-structural transition in Sm2Ir2O7atPcâ¼ 11.2 GPa, associated with the rearrangement of IrO6octahedra in the pyrochlore lattice. The transition pressure decreases to â¼10.2 and 9 GPa forx= 0.02 and 0.10, respectively. For all the samples, the linewidth of three phonons associated with Ir-O-Ir (A1gandEg) and Ir-O (T2g4) vibrations show anomalous decrease up toPc, due to decrease in electron-phonon interaction.
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PURPOSE: The aim of this study is to find optimal gantry, collimator, and couch angles for performing single isocenter, multiple target stereotactic radiosurgery (SIMT-SRS). Nineteen angle sets were tested across seven linear accelerators for radiation-isocenter coincidence and off-isocenter coincidence. The off-isocenter Winston-Lutz test was performed to evaluate the accuracy of isocenter alignment for each angle set, and optimal angle sets as well as maximum off-isocenter distance to target for each angle set was determined. The influence of simulated patient weight on off-iso Winston-Lutz test accuracy was also inspected. METHOD: The SNC MultiMet-WL phantom and MultiMet-WL QA Software v2.1 were used for the direct measurement and analysis of the off-iso Winston-Lutz test (also referred to as Winston-Lutz-Gao test). A two-step method was developed to ensure precise initial placement of the target. Nineteen beams were delivered at 6X energy and 2 × 2 cm field size to each of six targets on the MultiMet Cube with couch kicks at five cardinal angles (90°, 45°, 0°, 315°, and 270°). To reduce imaging uncertainty, only EPID was used in target alignment and test image acquisition. A total of 200 Ibs (90.7 kg) of weight was also used to mimic patient weight. All tests were performed on both the free table and the weighted table. RESULTS: For two new TrueBeam machines, the maximum offset was within the 1 mm tolerance when the off-iso distance is less than 7 cm. Two older VitalBeam machines exhibited unfavorable gantry, couch, and collimator (GCC) angle sets: Linac No. 3 at (0,90,0), (0,270,0) and Linac No. 4 at (0,45,45) and (0,90,0). The C-Series Linacs failed in the majority of GCC angle sets, with Linac No. 5 exhibiting a maximum offset of 1.53 mm. Four of seven machines show a clear trend that offset increases with off-isocenter distance. Additionally, the IGRT table was less susceptible to the addition of simulated patient weight than the ExactCouch. CONCLUSION: Among the seven linear accelerators addressed, newer model machines such as the Varian TrueBeam were more precise than older models, especially in comparison to the C-Series Linacs. The newer machines are more suitable for delivering SIMT-SRS procedures in all GCC angle sets, and the results indicate that newer TrueBeams are capable of performing SIMT-SRS procedures at all angle sets for targets of off-iso distances up to 7 cm. The trend that offset between the target center and radiation field center increases with off-iso distance, however, does not always hold true across machines. This may be comprised by the EPID's severe off-axis horn effect. Lastly, the IGRT couch was less susceptible to patient weight compared to ExactCouch in the off-isocenter Winston-Lutz test.
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BACKGROUND: Before a new test can be routinely used in your laboratory, its reliability must be established in the laboratory where it will be used. International standards demand validation and verification procedures for new tests. The International Organization for Standardization (ISO) 15189 was recently updated, and the European Commission's In Vitro Diagnostic Regulation (IVDR) came into effect. These events will likely increase the need for validation and verification procedures. OBJECTIVES: This paper aims to provide practical guidance in validating or verifying microbiology tests, including antimicrobial susceptibility tests in a clinical microbiology laboratory. SOURCES: It summarizes and interprets certain parts of standards such as ISO 15189:2022, and regulations, such as IVDR 2017/746 regarding validation or verification of a new test in a routine clinical microbiology laboratory. CONTENT: The reasons for choosing a new test and the outline of the validation and verification plan are discussed. Furthermore, the following topics are touched upon: the choice of reference standard, number of samples, testing procedures, how to solve the discrepancies between results from new test and reference standard, and acceptance criteria. Arguments for selecting certain parameters (such as reference standard and sample size) and examples are given. IMPLICATIONS: With the expected increase in validation and verification procedures because of the implementation of IVDR, this paper may aid in planning and executing these procedures.
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Objectives: The primary aim of this study was to determine quantitatively the extent of coverage of the Hong Kong Laboratory Accreditation Scheme (HOKLAS 015) requirements by guidance checklists (HOKLAS 016-02 and HOKLAS 021). Methods: The level of conformance requirement coverage of HOKLAS 015 by HOKLAS 016-02 and HOKLAS 021 was calculated by an evaluation checklist based on conformance requirements in HOKLAS 015. A distribution analysis of conformance requirements relating to the International Standard ISO 15189:2012 process-based quality management system model was also performed to elicit further coverage information. Results: HOKLAS 016-02 was found to provide coverage of 76% while HOKLAS 021 was found to provide coverage of 11%. HOKLAS 015 was also found to have a distribution coverage of 78% relating to the International Standard ISO 15189:2012 process-based quality management system model. Conclusion: The results of this analysis should be of value to medical laboratories wishing to maintain the internal auditability required by HOKLAS 015 by gaining an awareness of the extent of coverage provided by HOKLAS 016-02 and HOKLAS 021.