Analytical Specifications Research Articles

Antithrombin diagnostics by mass spectrometry: Development and analytical validation of a next-generation test

BackgroundAntithrombin deficiency is a rare but severe disorder leading to high risk of thrombosis. The current clinical care pathway relies on activity tests, which only provide overall functional information on the in vitro activity of antithrombin. However, antithrombin exists in many different forms, also known as proteoforms, with varying clinical phenotypes. Precision diagnostics, facilitated by mass spectrometry, provides a strategy to improve patient diagnostics by molecular characterization. ObjectivesTo develop and analytically validate a mass spectrometry–based test for molecular characterization of antithrombin. MethodsThe test was analytically validated based on predefined analytical performance specifications. The validation covered imprecision, carryover, linearity, stability, analytical specificity, a provisional reference interval, and an explorative method comparison. ResultsThe test passed the predefined analytical performance specifications with a mean within-laboratory imprecision of 5.9%, linearity between 0.08 and 2.58 μmol/L, and a provisional reference interval of 1.07 to 1.49 μmol/L. When measuring samples with a suspected quantitative deficiency, the test showed a good correlation with a commercial activity test (Pearson r = 0.88). ConclusionThe test passed the validation, and we now envision the use of the test for exploration of the clinical relevance of specific antithrombin proteoforms. Puzzling cases of antithrombin deficiency, for instance, due to ambiguous activity results or an atypical clinical presentation, can be investigated by the LC-MRM mass spectrometry test serving as an add-on to the activity test and providing a molecular diagnosis. Clinical studies are planned to investigate the potential of the test to improve antithrombin diagnostics. Furthermore, the molecular information gained using the test may aid in establishing better risk stratification and a basis for personalized medicine.

AUTHORITIES OF CIVIL SERVANT INVESTIGATES IN CONDUCTING INVESTIGATIONS ON ACTS OF CORPORATE MALADMINISTRATION IN TELECOMMUNICATIONS ACCORDING TO LAW NO. 36 OF 1999 CONCERNING TELECOMMUNICATIONS ADJUSTED TO THE PRINCIPLE OF LEGAL CERTAINTY

This research was conducted to find out how the laws and regulations regulate PPNS Authority in conducting investigations of corporate maladministration in the telecommunications sector, then regarding the Implementation of PPNS Authority in conducting investigations or corporate maladministration actions in the field of telecommunications, and find out how the PPNS authority mechanism to conduct maladministration investigations telecommunications sector corporations on the principle of legal certainty. This study uses a normative juridical approach, namely by examining theories, concepts, legal principles and laws and regulations and using the preparation of analytical descriptive research specifications, and the data used are primary, secondary, and tertiary. The results of this study are that PPNS is obliged to notify the investigation to Polri investigators. in the form of tactical assistance, technical assistance, coercive assistance and investigative consulting assistance. The case files must be submitted to the Prosecutor, in accordance with Article 110 paragraph (1) of the Criminal Procedure Code, the submission is carried out through Polri investigators in accordance with Article 107 paragraph (3) of the Criminal Procedure Code

Inclusion Complex of Clomiphene Citrate with Hydroxypropyl-β-Cyclodextrin for Intravenous Injection: Formulation and Stability Studies.

Clomiphene citrate is the first-line treatment for women with abnormal or failed ovulation. Currently, it is available as oral tablets, and the parenteral formulation does not exist. In this study, we prepared clomiphene citrate-hydroxypropyl-β-cyclodextrin inclusion complex for its use in intravenous injection. The inclusion complex was characterized in the liquid state (phase solubility) and solid state by differential scanning calorimetry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy analyses. The sterile intravenous injection containing 0.5% clomiphene citrate was prepared and characterized for its physical properties, assay, pH, and osmolality. A stability-indicating high-performance liquid chromatography (HPLC) method for the injection was developed. The HPLC method was validated for the assay, linearity, precision and repeatability, benchtop stability, and forced degradation to elute clomiphene isomers from the degradation products. The injection was packed in sterile 10-ml glass vials with butyl rubber stoppers and stored at 40°C, room temperature, and 4°C. The samples at 0, 0.5, 1, 2, 3, and 6months were analyzed for clarity, pH, osmolality, and drug assay. The HPLC method was linear (R2 = 0.9999), precise (0.86% relative standard deviation), and stability indicating. The stability data at the accelerated (40°C) storage condition for 6months showed satisfactory results: the drug assay in the injection was between 90 and 105%, the injection remained clear, pH was between 4.0 and 4.4, and osmolality was between 270 and 350mOsm. The stability data suggests that the product is stable and meets the given analytical specifications.

Clinical decision limits as criteria for setting analytical performance specifications for laboratory tests

BackgroundThe biological (CVI), preanalytical (CVPRE), and analytical variation (CVA) are inherent to clinical laboratory testing and consequently, interpretation of clinical test results. MethodsThe sum of the CVI, CVPRE, and CVA, called diagnostic variation (CVD), was used to derive clinically acceptable analytical performance specifications (CAAPS) for clinical chemistry measurands. The reference change concept was applied to clinically significant differences (CD) between two measurements, with the formula CD = z*√2* CVD. CD for six measurands were sought from international guidelines. The CAAPS were calculated by subtracting variances of CVI and CVPRE from CVD. Modified formulae were applied to consider statistical power (1-β) and repeated measurements. ResultsThe obtained CAAPS were 44.9% for urine albumin, 0.6% for plasma sodium, 22.9% for plasma pancreatic amylase, and 8.0% for plasma creatinine (z = 3, α = 2.5%, 1-β = 85%). For blood HbA1c and plasma low-density lipoprotein cholesterol, replicate measurements were necessary to reach CAAPS for patient monitoring. The derived CAAPS were compared with analytical performance specifications, APS, based on biological variation. ConclusionsThe CAAPS models pose a new tool for assessing APS in a clinical laboratory. Their usability depends on the relevance of CD limits, required statistical power and the feasibility of repeated measurements.

Development of an LC-MRM-MS-Based Candidate Reference Measurement Procedure for Standardization of Serum Apolipoprotein (a) Tests.

Medical results generated by European CE Marking for In Vitro Diagnostic or in-house tests should be traceable to higher order reference measurement systems (RMS), such as International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)-endorsed reference measurement procedures (RMPs) and reference materials. Currently, serum apolipoprotein (a) [apo(a)] is recognized as a novel risk factor for cardiovascular risk assessment and patient management. The former RMS for serum apo(a) is no longer available; consequently, an International System of Units (SI)-traceable, ideally multiplexed, and sustainable RMS for apo(a) is needed. A mass spectrometry (MS)-based candidate RMP (cRMP) for apo(a) was developed using quantitative bottom-up proteomics targeting 3 proteotypic peptides. The method was provisionally validated according to ISO 15193 using a single human serum based calibrator traceable to the former WHO-IFCC RMS. The quantitation of serum apo(a) was by design independent of its size polymorphism, was linear from 3.8 to 456 nmol/L, and had a lower limit of quantitation for apo(a) of 3.8 nmol/L using peptide LFLEPTQADIALLK. Interpeptide agreement showed Pearson Rs of 0.987 and 0.984 for peptides GISSTVTGR and TPENYPNAGLTR, and method comparison indicated good correspondence (slopes 0.977, 1.033, and 1.085 for LFLEPTQADIALLK, GISSTVTGR, and TPENYPNAGLTR). Average within-laboratory imprecision of the cRMP was 8.9%, 11.9%, and 12.8% for the 3 peptides. A robust, antibody-independent, MS-based cRMP was developed as higher order RMP and an essential part of the apo(a) traceability chain and future RMS. The cRMP fulfils predefined analytical performance specifications, making it a promising RMP candidate in an SI-traceable MS-based RMS for apo(a).

Worker aging, control, and well-being: A specification curve analysis

Among the many work (and life) characteristics of relevance to adult development and aging, various forms of control are some of the most extensively and diversely studied. Indeed, “control,” whether objectively held (i.e., “actual” control), perceived, or enacted through self-regulation, is a concept central to our understanding of person-environment interactions, development, and well-being within and across life domains. However, variability in conceptualization and analysis in the literature on control presents challenges to integration. To partially address these gaps, the present study sought to explore the effects of conceptual and analytical specification decisions (e.g., construct types, time, covariates) on observed control-well-being relationships in a large, age-diverse, longitudinal sample (Midlife in the United States I, II, and III datasets), providing a specification curve analysis (SCA) tutorial and guidance in the process. Results suggest that construct types and operationalizations, particularly predictor variables, have bearing on observed results, with certain types of control serving as better predictors of various forms of well-being than others. These findings and identified gaps are summarized to provide direction for theoretical clarification and reconciliation in the control and lifespan development literatures, construct selection and operationalization in future aging and work research, and inclusive, well-specified interventions to improve employee well-being.

Redesigning the surveillance of in vitro diagnostic medical devices and of medical laboratory performance by quality control in the traceability era.

IVD manufacturers have total responsibility in terms of the traceability of marketed in vitro diagnostic medical devices (IVD-MD). This includes the provision of a quality control (QC) material as a part of the measuring system, suitable for traceability verification and alignment surveillance by end-users in daily practice. This material [to be used for the internal QC (IQC) component I as described in this paper] should have unbiased target values and an acceptability range corresponding to analytical performance specifications (APS) for suitable (expanded) measurement uncertainty (MU) on clinical samples. On the other hand, medical laboratories (by the IQC component II as described in this paper) should improve the IQC process and its judging criteria to establish a direct link between their performance, estimated as MU of provided results, and APS defined according to recommended models to apply corrective actions if the performance is worsening with the risk to jeopardize the clinical validity of test results. The participation to external quality assessment (EQA) programs that meet specific metrological criteria is also central to the evaluation of performance of IVD-MDs and of medical laboratories in terms of harmonization and clinical suitability of their measurements. In addition to the use of commutable materials, in this type of EQA it is necessary to assign values to them with selected reference procedures and to define and apply maximum allowable APS to substantiate the suitability of laboratory measurements in the clinical setting.

Biological variation: recent development and future challenges.

Biological variation (BV) data have many applications in laboratory medicine. However, these depend on the availability of relevant and robust BV data fit for purpose. BV data can be obtained through different study designs, both by experimental studies and studies utilizing previously analysed routine results derived from laboratory databases. The different BV applications include using BVdata for setting analytical performance specifications, tocalculate reference change values, to define the index ofindividuality and to establish personalized reference intervals. In this review, major achievements in the area of BV from last decade will be presented and discussed. These range from new models and approaches to derive BV data, the delivery of high-quality BV data by the highly powered European Biological Variation Study (EuBIVAS), the Biological Variation Data Critical Appraisal Checklist (BIVAC) and other standards for deriving and reporting BV data, the EFLM Biological Variation Database and new applications of BV data including personalized reference intervals and measurement uncertainty.

IMPLEMENTASI PENDAFTARAN DOKUMEN ADMINISTRASI KEPENDUDUKAN DENGAN SISTEM ONLINE SEBAGAI UPAYA TERTIB ADMINISTRASI DI DINAS KEPENDUDUKAN DAN PENCATATAN SIPIL KABUPATEN DEMAK

<p><em>Registration of population administration documents as an effort to orderly administration is carried out by the government with an online system to provide convenience for the community, so this study seeks to examine the implementation of registration of the population administration documents with an online system as an effort to orderly administration at the Department of Population and Civil Registration of Demak Regency, obstacles and efforts overcome it. The research methods used are: type of sociological juridical research, analytical descriptive specifications. The data used is primary data supported by secondary data with qualitative data analysis. The results showed that the registration of family card population administration documents with an online system as an effort to orderly administration at the Demak Regency Population and Civil Registration Office in January 2017 - February 2021 was based on the Republic of Indonesia Law Number 24 of 2013 concerning Population Administration changes. on Law Number 23 of 2006 concerning Population Administration, and Regulation of the Minister of Home Affairs of the Republic of Indonesia Number 7 of 2019 concerning Online Population Administration Services with the mechanism starting with register, login, select menu, upload, send, finish. For the implementation of the registration, there were 5,472 documents. The orderliness of administrative documents after using the online system before using the online system shows that it is more orderly to use the online system, as indicated by the increasing number from year to year. The obstacles include 2 things, first, the public's lack of understanding to access online services, in this case it can be attempted by means of socialization, namely through brochures, websites, Instagram and Youtube; Second, the absence of a strong network/signal in some areas, in this case it can be attempted by serving reporters who wish to register documents directly.</em><em></em></p>

Criminal Acts of Gratification Between Doctors and Pharmaceutical Companies

The system of health services and medical services run by the medical profession, deals with medical ethics and the problems that arise in medical ethics. Normative juridical research method, with descriptive analytical specifications. Normative legal research is research that only uses secondary data sources, namely legislation and legal theories. The basic needs of human life are the main thing in the fulfillment of the right to public health. The government's responsibility in fulfilling the right to health is to regulate, foster, and supervise the implementation of health efforts that are equitable and affordable by the community and improve the health status of the community. This need for health is felt by the community, which ultimately makes doctors a much-needed profession. One of the services provided is the provision of health, where patients should receive drugs according to their needs. This is where the crime of gratification occurs. It should be noted that gratification is included in the criminal act of corruption. Efforts to overcome crime in criminal acts of gratification with penal and no-penal efforts. According to criminal policy, penal measures are efforts to eradicate criminal acts of gratification. When the case occurs, legal remedies will be carried out according to the provisions in the law through criminal justice. Meanwhile, efforts to tackle non-permanent crimes are preventive in nature. This prevention is important and considered effective to prevent such cases from happening

Sex Hormones and Adrenal Steroids: Biological Variation Estimated Using Direct and Indirect Methods.

Biological variation (BV) data may be used to develop analytical performance specifications (APS), reference change values (RCV), and support the applicability of population reference intervals. This study estimates within-subject BV (CVI) for several endocrine biomarkers using 3 different methodological approaches. For the direct method, 30 healthy volunteers were sampled weekly for 10 consecutive weeks. Samples were analyzed in duplicate for 17-hydroxyprogesterone (17-OHP), androstenedione, cortisol, cortisone, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), and testosterone. A CV-ANOVA with outlier removal and a Bayesian model were applied to derive the CVI. For estradiol, FSH and LH, only the male subgroup was included. In the indirect method, using the same analytes and groups, pairs of sequential results were extracted from the laboratory information system. The total result variation for individual pairs was determined by identifying a central gaussian distribution in the ratios of the result pairs. The CVI was then estimated by removing the effect of analytical variation. The estimated CVI from the Bayesian model (μCVP(i)) in the total cohort was: 17-OHP, 23%; androstenedione, 20%; cortisol, 18%; cortisone, 11%; SHBG, 7.4%; testosterone, 16%; and for the sex hormones in men: estradiol, 14%; FSH, 8%; and LH, 26%. CVI-heterogeneity was present for most endocrine markers. Similar CVI data were estimated using the CV-ANOVA and the indirect method. Similar CVI data were obtained using 2 different direct and one indirect method. The indirect approach is a low-cost alternative ensuring implementation of CVI data applicable for local conditions.

Evaluation of Laboratory Performance in Consideration with Pre analytical and Post analytical Quality Indicators.

Implementation of Quality indicators (QIs) plays an imperative role in improving the total testing process, as it provides a quantitative basis for evaluating the laboratory performance. Besides monitoring of analytical quality specifications, several lines of experimental and clinical evidence have alluded a pivotal role of extra-analytical phases in improving the quality of laboratory services and therefore a relevance of pre- and post-analytical steps have been speculated on the overall quality in the total testing process and consequently on clinical decision-making. This was a retrospective study designed to evaluate and review different extra-analytical quality indicators in NABL accredited clinical biochemistry laboratory at BJ Medical College and Civil Hospital, Ahmedabad, Gujarat in an endeavour to ameliorate the performance of the laboratory. All Clinical Chemistry Laboratory test requests with their respective samples from January 2018 to December 2021 were included in the study. A total of 1,439,011samples were processed, and were evaluated for seven QIs [(% of number of suitable samples not received; QI-8), (% of number of samples received in inappropriate container; QI-9), (% of number of samples hemolysed; QI-10), (% of number of samples with inadequate sample volume; QI 12) (% of number of samples received mismatched; QI 15), (% of number of samples reported after turnaround time; QI 21) and (% of number of samples with critical values informed; QI 22)] based on defined criteria of Quality Specification given by International Federation of Clinical Chemistry. Total number of preanalytical errors was 53,669 (3.72%). Among the preanalytical errors, inadequate sample volume (2.37% of total samples; 63.49% of total pre-analytical errors) was the most common anomaly followed by Not received samples (24.18%) hemolysis (8.26%) mismatched (3.91%) and 0.14% samples were received in Inappropriate container; manifesting that the error frequency was unacceptable for QI 21 and QI 8, acceptable for QI 10, minimally acceptable for QI 15 and optimum for QI QI 9. Furthermore, there was year-wise progressive decline in error rate of inadequate sample volume, hemolysed sample received and mismatched samples. Total number of post analytical errors were 19,002 (1.32%). TAT outlier and critical values communicated were the two QIs evaluated for this phase and results of both QI were within acceptable limits. Quality indicators serve as a tool to monitor process performance and consequently derived error rates warrant active intervention to improve the laboratory services and patient health care. Dissemination of certified documents, regular staff training and evaluation needs to be conducted.

Method evaluation in the clinical laboratory.

Method evaluation is one of the critical components of the quality system that ensures the ongoing quality of a clinical laboratory. As part of implementing new methods or reviewing best practices, the peer-reviewed published literature is often searched for guidance. From the outset, Clinical Chemistry and Laboratory Medicine (CCLM) has a rich history of publishing methods relevant to clinical laboratory medicine. An insight into submissions, from editors' and reviewers' experiences, shows that authors still struggle with method evaluation, particularly the appropriate requirements for validation in clinical laboratory medicine. Here, we consider through a series of discussion points an overview of the status, challenges, and needs of method evaluation from the perspective of clinical laboratory medicine. We identify six key high-level aspects of clinical laboratory method evaluation that potentially lead to inconsistency. 1.Standardisation of terminology, 2. Selection of analytical performance specifications, 3. Experimental design of method evaluation, 4. Sample requirements of method evaluation, 5. Statistical assessment and interpretation ofmethod evaluation data, and 6. Reporting of method evaluation data. Each of these areas requires considerable work to harmonise the practice of method evaluation inlaboratory medicine, including more empirical studies to be incorporated into guidance documents that are relevant to clinical laboratories and are freely and widely available. To further close the loop, educational activities and fostering professional collaborations are essential to promote and improve the practice of method evaluation procedures.

Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice.

Laboratories should estimate and validate [using analytical performance specifications (APS)] the measurement uncertainty (MU) of performed tests. It is therefore essential to appropriately define APS for MU, but also to provide a perspective on suitability of the practical application of these APS. In this study, 23 commonly ordered measurands were allocated to the models defined during the 2014 EFLM Strategic Conference to derive APS for MU. Then, we checked if the performance of commercial measuring systems used in our laboratory may achieve them. Most measurands (serum alkaline phosphatase, aspartate aminotransferase, creatine kinase, γ-glutamyltransferase, lactate dehydrogenase, pancreatic amylase, total proteins, immunoglobulin G, A, M, magnesium, urate, and prostate-specific antigen, plasma homocysteine, and blood red and white cells) were allocated to the biological variation (BV) model and desirable APS were defined accordingly (2.65%, 4.75%, 7.25%, 4.45%, 2.60%, 3.15%, 1.30%, 2.20%, 2.50%, 2.95%, 1.44%, 4.16%, 3.40%, 3.52%, 1.55%, and 5.65%, respectively). Desirable APS for serum total cholesterol (3.00%) and urine albumin (9.00%) were derived using outcome-based model. Lacking outcome-based information, serum albumin, high-density lipoprotein cholesterol, triglycerides, and blood platelets were temporarily reallocated to BV model, the corresponding desirable APS being 1.25%, 2.84%, 9.90%, and 4.85%, respectively. A mix between the two previous models was employed for serum digoxin, with a 6.00% desirable APS. In daily practice by using our laboratory systems, 16 tests fulfilled desirable and five minimum APS, while two (serum albumin and plasma homocysteine) exceeded goals, needing improvements.

Itsbat Nikah terhadap Perkawinan di Bawah Umur tanpa Dispensasi Kawin Ditinjau dari Undang-Undang Perkawinan dan Hukum Islam

The Marriage Law stipulates that marriages that occur must be recorded by an authorized official. If you have not registered your marriage, you can apply to the Religious Courts for Muslims. The Marriage Law stipulates the age requirement for marriage as one of the requirements for marriage. Underage marriages to be carried out must obtain dispensation permission from the Court. Marriages are often carried out under the hands without regard to the terms of the marriage. For example, the application for itsbat marriage against underage marriages without a marriage dispensation that occurs in the Religious Courts. The purpose of this study was to determine and analyze the validity and legal consequences of itsbat marriage on underage marriages without a marriage dispensation in terms of Marriage Law and Islamic Law. This study uses a normative juridical approach with analytical descriptive specifications. The data collection technique used is by conducting library research and field studies through interviews with related sources. The analytical method used is juridical qualitative. The absence of a marriage dispensation does not affect the validity of an underage marriage. Underage marriages without a marriage dispensation can be legalized in the Religious Courts by taking into account the conditions for itsbat marriage. Underage marriages without a marriage dispensation that have been legalized in the Religious Courts will have the same legal consequences as marriages in general. The marital status will have permanent legal force as evidenced by obtaining a Marriage Certificate Quotation

Conformity assessment of medicines containing antibiotics – A multivariate assessment

Pharmaceutical products must meet quality requirements to ensure the efficacy and safety of pharmacological treatment. Non-compliance of medicines can cause economic losses and compromise the patient's health. In this work, the risks of false compliance/non-compliance decisions for parenteral antibiotics (cephalothin, ciprofloxacin and metronidazole) were evaluated on the basis of analytical results, measurement uncertainties and specification limits. Physicochemical and biological quality assays were performed according to pharmacopeial procedures. Measurement uncertainties were determined using the bottom-up approach or the probability of false-positive/false-negative results. The risks of false compliance/non-compliance decisions were estimated using the frequentist approach and Monte Carlo simulations. Guard-bands were determined through a validated spreadsheet for calculating univariate and multivariate acceptance limits. All risk values (particular risks and total risk, consumer's or producer's risk) were below the maximum permissible risk value. The univariate and multivariate guard-bands defined more restrictive specification values, reducing the risks of false compliance/non-compliance decisions. One antibiotic presented unsatisfactory results regarding the drug content and was classified as out of specification product. The application of risk management tools in the pharmaceutical area contributes to improving the quality and safety of products and supports decision-making.

Pertimbangan Hakim Menjatuhkan Hukuman Pidana Bersyarat terhadap Pelaku Tindak Pidana Narkotika

Abstract One of the goals of criminal law is as a social institution that includes several things, namely as part of a social reaction when there is a violation of applicable norms. When the judge's decision by imposing a conditional criminal sentence on narcotics, it often invites debate and dissatisfaction from various parties. The problem of this journal is what is the basis for the judge's consideration of imposing a conditional criminal sentence and what are the inhibiting factors for the application of the judge's decision. This research is an empirical legal research that prioritizes field data using the analytical descriptive specification method. The results of the study that the judge's consideration of imposing a conditional sentence in a narcotics crime case at the Palembang Class IA District Court was based on juridical considerations (legal certainty), namely Article 14a to Article 14f of the Criminal Code, Article 127 paragraph (1) letter c of the Narcotics Law and sociological considerations and philosophical considerations. The inhibiting factors for applying conditional criminal penalties at the Class IA Palembang District Court are the law factor, law enforcement officers, infrastructure, and the cultural factor of the community itself.

Analytical performance verification protocols and performance specifications of platelet-dependent von Willebrand factor activity testing

Objective: To investigate the analytical performance verification protocols and performance specifications of platelet-dependent von Willebrand factor (VWF) activity testing (VWF:GPIbM) for clinical laboratories. Methods: According to Clinical Laboratory Standards Institute (CLSI) documents and National Health Standard of China, the performance verification of VWF:GPIbM was designed and implemented using Sysmex CS-5100 instrument and its corresponding reagents. (1) Precision verification: Two commercial quality control samples (with normal and low activity levels) and three plasma pools (with activity range from 5.0% to 150.0%) were prepared. Each sample was tested five times daily for five consecutive days. The coefficient of variation (CV) of intra-and inter-run precisions were calculated, and the precision evaluation criterion was set according to package inserts. (2) Trueness verification: The calibrator was diluted to five reference materials with activity values of 5.2%, 31.2%, 62.4%, 104.0% and 138.7%, and each reference material was tested five times daily for five consecutive days. The bias between the measured value and the reference value was calculated, and the trueness evaluation criterion was set according to the total allowable error. (3) Linearity verification: Ten pooled plasmas with theoretical value range from 3.6% to 160.4% were prepared for the linearity verification of two calibration curves set by the manufacturer (i.e. low range and normal range calibration curve). Each pooled plasma was tested three times in a single run. The slope and R2 of linear regression of mean of measured value and theoretical value, as well as bias, were calculated, and the linearity evaluation criterion was set according to National Health Standard of China and package inserts. (4) Limit of quantitation verification: The calibrator was diluted to two reference materials with activity values of 3.3% and 2.7%, and each material was tested twelve times. The limit of quantitation evaluation criterion was set according to CLSI document. Results: The CVs of intra-and inter-run were 1.0%-2.5% and 1.1%-2.6%, respectively. The biases of trueness verification were -0.4%, 1.0%, -2.6%, 0.3% and -2.7%, respectively. The linearity verification results of low range (3.6%-31.8%) and normal range (28.4%-160.4%) showed that the slopes of regression equation were 1.021 7 and 0.996 2, respectively, R2 were 0.993 5 and 0.993 9, respectively, and the biases with 0-1.8% and -10.1%-0 of plasmas met the criterion. The biases ranged from -0.4% to 0.3% of test results in the verification of limit of quantitation met the criterion. Conclusion: The verification results of VWF:GPIbM assay for precision, trueness, linearity and limit of quantification meet the performance requirements indicated in the package inserts and the criteria set in this study, which can be taken as a reference of performance verification for the clinical laboratories.

Ginkgo biloba leaf extract EGb 761® as a paragon of the product by process concept.

It is an often-neglected fact that extracts derived from the very same plant can differ significantly in their phytochemical composition, and thus also in their pharmacokinetic and pharmacodynamic properties which are the basis for their clinical efficacy and safety. The Ginkgo biloba L. [Ginkgoaceae] special extract EGb 761® is one of the best-studied plant extracts in the world. In the present review, using that extract as a paradigm, we describe insights how climate, the harvest region, processing of the plant material, the drying process, the extraction solvents, and the details of the subsequent process steps substantially impact the quality and uniformity of the final extract. We highlight the importance of regulating active constituent levels and consistent reduction of undesired substances in herbal extracts. This is accomplished by a controlled production process and corresponding analytical specifications. In conclusion, since extracts derived from the same plant can have very different phytochemical compositions, results from pharmacological, toxicological and clinical studies gained with one specific extract cannot be extrapolated to other extracts that were generated using different production processes. We propose that the heterogenous nature of extracts should be meticulously considered when evaluating the efficacy and safety of plant-derived remedies.

Kajian Hukum Hak Cipta Penggunaan Audio Populer dalam Pembuatan Vidio

This research aimz to knowing about copyright using a popular audio on making video. The research method used is sociological juridical, with descriptive analytical research specifications. The results of this study are violations of the use of popular audio in making videos using the dubsmash application in terms of the UUHC can be categorized as acts that include violations of economic rights in which the Creator or economic rights holders are taken away. The role of the Notary in legal protection of the creator in the case of the use of popular audio that makes videos using the Dubsmash application without permission from UUHC is as a consultant registered with the Directorate General. The obstacle is the binding of the creator of the Dubsmash application when uploading with the provisions of Mobile Motion and in the case of investigations carried out by PPNS based on an investigation warrant issued by officials who have competence in copyright.