Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and ...hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.
This randomized trial assessed whether urate-lowering treatment with allopurinol could attenuate eGFR decline in at-risk patients with stage 3 or 4 chronic kidney disease. Allopurinol did not slow ...the decline in eGFR as compared with placebo.
Proficiency testing (PT), or external quality assessment (EQA), is intended to verify on a recurring basis that laboratory results conform to expectations for the quality required for patient care.
...Key factors for interpreting PT/EQA results are knowledge of the commutability of the samples used and the process used for target value assignment. A commutable PT/EQA sample demonstrates the same numeric relationship between different measurement procedures as that expected for patients' samples. Noncommutable PT/EQA samples frequently have a matrix-related bias of unknown magnitude that limits interpretation of results. PT/EQA results for commutable samples can be used to assess accuracy against a reference measurement procedure or a designated comparison method. In addition, the agreement of the results between different measurement procedures for commutable samples reflects that which would be seen for patients' samples. PT/EQA results for noncommutable samples must be compared to a peer group mean/median of results from participants who use measurement procedures that are expected to have the same or very similar matrix-related bias. Peer group evaluation is used to asses whether a laboratory is using a measurement procedure in conformance to the manufacturer's specifications and/or in conformance to other laboratories using the same technology. A noncommutable PT/EQA sample does not give meaningful information about the relationship of results for patients' samples between different measurement procedures.
PT/EQA provides substantial value to the practice of laboratory medicine by assessing the performance of individual laboratories and, when commutable samples are used, the status of standardization or harmonization among different measurement procedures.
The multispecies coalescent model provides a formal framework for the assignment of individual organisms to species, where the species are modeled as the branches of the sp tree. None of the ...available approaches so far have simultaneously co-estimated all the relevant parameters in the model, without restricting the parameter space by requiring a guide tree and/or prior assignment of individuals to clusters or species.
We present DISSECT, which explores the full space of possible clusterings of individuals and species tree topologies in a Bayesian framework. It uses an approximation to avoid the need for reversible-jump Markov Chain Monte Carlo, in the form of a prior that is a modification of the birth-death prior for the species tree. It incorporates a spike near zero in the density for node heights. The model has two extra parameters: one controls the degree of approximation and the second controls the prior distribution on the numbers of species. It is implemented as part of BEAST and requires only a few changes from a standard *BEAST analysis. The method is evaluated on simulated data and demonstrated on an empirical dataset. The method is shown to be insensitive to the degree of approximation, but quite sensitive to the second parameter, suggesting that large numbers of sequences are needed to draw firm conclusions.
http://tree.bio.ed.ac.uk/software/beast/, http://www.indriid.com/dissectinbeast.html.
Supplementary data are available at Bioinformatics online.
This article focuses on the problem of estimating a species tree from multilocus data in the presence of incomplete lineage sorting and migration. I develop a mathematical model similar to IMa2 (Hey ...2010) for the relevant evolutionary processes which allows both the population size parameters and the migration rates between pairs of species tree branches to be integrated out. I then describe a BEAST2 package DENIM (Divergence estimation notwithstanding ILS and migration) which is based on this model and which uses an approximation to sample from the posterior. The approximation is based on the assumption that migrations are rare, and it only samples from certain regions of the posterior which seem likely given this assumption. The method breaks down if there is a lot of migration. Using simulations, Leaché et al. (2014) showed that using the standard multispecies coalescent model to infer a species tree can result in poor accuracy if migration is present. I reanalyze this simulated data to explore DENIM’s performance and demonstrate substantial improvements in accuracy over *BEAST. I also reanalyze an empirical data set.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The role of an External Quality Assurance (EQA) program is generally seen as providing a service to routine laboratories that their analytical performance is satisfactory and stimulating corrective ...action in the event of poor results. It is recognised that an ideal EQA program uses materials that are commutable with patient samples and have values assigned by higher-order reference methods. Despite this, most routine EQA programs use materials without verified commutability and use consensus means (based on either peer group or all laboratories) as target values. We propose an ongoing role for EQA programs using non-commutable materials and consensus targets to support the measurement services of routine laboratories. This is provided the relevant comparators supplied by the laboratory, e.g. reference intervals and clinical decision points, are based on the same or equivalent measurement system as is used by the laboratory. Materials without verified commutability often have certain practical advantages, which may include the range of analyte concentrations, verified stability, replicate samples and, significantly, lower costs. Laboratories using such programs need to be aware of the limitations, especially comparing results from different measurement systems. However, we also recognise that as well as individual laboratories, data from EQA programs informs manufacturers, professional organisations, clinical guideline writers and other medical bodies For consideration beyond an individual laboratory, proper assessment of differences between measurement systems (results harmonization) and demonstration of correct implementation of metrological traceability (methods trueness) become vital, and for that purpose, commutability of EQA materials and traceability of target values are required.
Secrecy Jones, Graham M
Annual review of anthropology,
01/2014, Letnik:
43, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Although expansions of state secrecy and the countervailing leaks of classified documents imbue the anthropology of secrecy with urgent relevance, secrecy has a long-standing status as a ...paradigmatically anthropological topic. In the ethnographic record, initiatory secrets often stand for the quiddity of culture, and the revelation of concealed realities is an organizing trope in much ethnographic writing. While situating research on secrecy as a reflection of epistemological and ethical dimensions of cultural anthropology more broadly, this review simultaneously explores parallels between different anthropological traditions by focusing on descriptions of the media through which social relations involving secrecy are transacted. Attending to ethnographic accounts of the way secrets travel across different media and coexist simultaneously in various mediated states provides both a novel intellectual framework for surveying recent research and a basis for conceptualizing the anthropology of secrecy itself as a practice that involves intermedial and transmedial knowledge flows.
Biologics such as monoclonal antibodies are much more complex than small-molecule drugs, which raises challenging questions for the development and regulatory evaluation of follow-on versions of such ...biopharmaceutical products (also known as biosimilars) and their clinical use once patent protection for the pioneering biologic has expired. With the recent introduction of regulatory pathways for follow-on versions of complex biologics, the role of analytical technologies in comparing biosimilars with the corresponding reference product is attracting substantial interest in establishing the development requirements for biosimilars. Here, we discuss the current state of the art in analytical technologies to assess three characteristics of protein biopharmaceuticals that regulatory authorities have identified as being important in development strategies for biosimilars: post-translational modifications, three-dimensional structures and protein aggregation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The Joint Committee for Traceability in Laboratory Medicine (JCTLM) was formed to bring together the sciences of metrology, laboratory medicine and laboratory quality management. The aim of this ...collaboration is to support worldwide comparability and equivalence of measurement results in clinical laboratories for the purpose of improving healthcare. The JCTLM has its origins in the activities of international metrology treaty organizations, professional societies and federations devoted to improving measurement quality in physical, chemical and medical sciences. The three founding organizations, the International Committee for Weights and Measures (CIPM), the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the International Laboratory Accreditation Cooperation (ILAC) are the leaders of this activity. The main service of the JCTLM is a web-based database with a list of reference materials, reference methods and reference measurement services meeting appropriate international standards. This database allows manufacturers to select references for assay traceability and provides support for suppliers of these services. As of mid 2015 the database lists 295 reference materials for 162 analytes, 170 reference measurement procedures for 79 analytes and 130 reference measurement services for 39 analytes. There remains a need for the development and implementation of metrological traceability in many areas of laboratory medicine and the JCTLM will continue to promote these activities into the future.
•Metrological traceability is a vital mechanism to ensure comparability of results over time and place•The JCTLM provides a database of validated higher-order reference materials, measurement procedures and measurement services.
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