Guidance for laboratories performing molecular pathology for cancer patients

Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here

Estimation of the Optimal Statistical Quality Control Sampling Time Intervals Using a Residual Risk Measure

Background: An open problem in clinical chemistry is the estimation of the optimal sampling time intervals for the application of statistical quality control (QC) procedures that are based on the measurement of control materials. This is a probabilistic risk assessment problem that requires reliability analysis of the analytical system, and the estimation of the risk caused by the measurement error. Methodology/Principal Findings: Assuming that the states of the analytical system are the reliability state, the maintenance state, the critical-failure modes and their combinations, we can define risk functions based on the mean time of the states, their measurement error and the medically acceptable measurement error. Consequently, a residual risk measure rr can be defined for each sampling time interval. The rr depends on the state probability vectors of the analytical system, the state transition probability matrices before and after each application of the QC procedure and the state mean time matrices. As optimal sampling time intervals can be defined those minimizing a QC related cost measure while the rr is acceptable. I developed an algorithm that estimates the rr for any QC sampling time interval of a QC procedure applied to analytical systems with an arbitrary number of critical-failure modes, assuming any failure time and measurement error probability density function for each mode. Furthermore, given the acceptable rr, it can estimate the optimal QC sampling time intervals

Urinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the United States

BACKGROUND: Perchlorate is commonly found in the environment and known to inhibit thyroid function at high doses. Assessing the potential effect of low-level exposure to perchlorate on thyroid function is an area of ongoing research. OBJECTIVES: We evaluated the potential relationship between urinary levels of perchlorate and serum levels of thyroid stimulating hormone (TSH) and total thyroxine (T(4)) in 2,299 men and women, ≥ 12 years of age, participating in the National Health and Nutrition Examination Survey (NHANES) during 2001–2002. METHODS: We used multiple regression models of T(4) and TSH that included perchlorate and covariates known to be or likely to be associated with T(4) or TSH levels: age, race/ethnicity, body mass index, estrogen use, menopausal status, pregnancy status, premenarche status, serum C-reactive protein, serum albumin, serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and selected medication groups. RESULTS: Perchlorate was not a significant predictor of T(4) or TSH levels in men. For women overall, perchlorate was a significant predictor of both T(4) and TSH. For women with urinary iodine < 100 μg/L, perchlorate was a significant negative predictor of T(4) (p < 0.0001) and a positive predictor of TSH (p = 0.001). For women with urinary iodine ≥ 100 μg/L, perchlorate was a significant positive predictor of TSH (p = 0.025) but not T(4) (p = 0.550). CONCLUSIONS: These associations of perchlorate with T(4) and TSH are coherent in direction and independent of other variables known to affect thyroid function, but are present at perchlorate exposure levels that were unanticipated based on previous studies

Derivation and internal validation of an equation for albumin-adjusted calcium

YesFunding provided by the Open Access Authors Fund

Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting

<p>Abstract</p> <p>Background</p> <p>When a test for diagnosis of infectious diseases is introduced in a resource-limited setting, monitoring quality is a major concern. An optimized design of experiment and statistical models are required for this assessment.</p> <p>Methods</p> <p>Interferon-gamma release assay to detect tuberculosis (TB) infection from whole blood was tested in Hanoi, Viet Nam. Balanced incomplete block design (BIBD) was planned and fixed-effect models with heterogeneous error variance were used for analysis. In the first trial, the whole blood from 12 donors was incubated with nil, TB-specific antigens or mitogen. In 72 measurements, two laboratory members exchanged their roles in harvesting plasma and testing for interferon-gamma release using enzyme linked immunosorbent assay (ELISA) technique. After intervention including checkup of all steps and standard operation procedures, the second trial was implemented in a similar manner.</p> <p>Results</p> <p>The lack of precision in the first trial was clearly demonstrated. Large within-individual error was significantly affected by both harvester and ELISA operator, indicating that both of the steps had problems. After the intervention, overall within-individual error was significantly reduced (<it>P </it>< 0.0001) and error variance was no longer affected by laboratory personnel in charge, indicating that a marked improvement could be objectively observed.</p> <p>Conclusion</p> <p>BIBD and analysis of fixed-effect models with heterogeneous variance are suitable and useful for objective and individualized assessment of proficiency in a multistep diagnostic test for infectious diseases in a resource-constrained laboratory. The action plan based on our findings would be worth considering when monitoring for internal quality control is difficult on site.</p

Search for fast particles produced at large lab angles at NAL

An experiment is proposed to look for charged particles emitted at large lab angles that are normally forbidden kinematically. These particles if found would correspond to hitherto unobserved events such as the production of particles with imaginary mass values (''tachyons''). Also, they wish to look for fractionally-charged particles produced at these angles. These particles, if found, would correspond to strongly-bound quark-quark states formed in a dissociation of the target nucleon. The detection system will consist of wire-chambers, dE/dx and time-of-flight counters. The basic hardware is under construction and the final system will be ready for test runs at a lower-energy machine in six months. The detection telescope will view interactions of the primary proton beam from backward (in lab) directions and the first choice experimental site is the straight section B with a thin internal target. They would like to use the highest available beam at NAL and since the beam transport and intensity requirements are very minimal, they will be able to run parasitically during the tuning periods of the NAL machine in the next year. The machine time required for this experiment is about three months

Probabilistic change detection and visualization methods for the assessment of temporal stability in biomedical data quality

The final publication is available at Springer via http://dx.doi.org/DOI 10.1007/s10618-014-0378-6. Published online.Knowledge discovery on biomedical data can be based on on-line, data-stream analyses, or using retrospective, timestamped, off-line datasets. In both cases, changes in the processes that generate data or in their quality features through time may hinder either the knowledge discovery process or the generalization of past knowledge. These problems can be seen as a lack of data temporal stability. This work establishes the temporal stability as a data quality dimension and proposes new methods for its assessment based on a probabilistic framework. Concretely, methods are proposed for (1) monitoring changes, and (2) characterizing changes, trends and detecting temporal subgroups. First, a probabilistic change detection algorithm is proposed based on the Statistical Process Control of the posterior Beta distribution of the Jensen–Shannon distance, with a memoryless forgetting mechanism. This algorithm (PDF-SPC) classifies the degree of current change in three states: In-Control, Warning, and Out-of-Control. Second, a novel method is proposed to visualize and characterize the temporal changes of data based on the projection of a non-parametric information-geometric statistical manifold of time windows. This projection facilitates the exploration of temporal trends using the proposed IGT-plot and, by means of unsupervised learning methods, discovering conceptually-related temporal subgroups. Methods are evaluated using real and simulated data based on the National Hospital Discharge Survey (NHDS) dataset.The work by C Saez has been supported by an Erasmus Lifelong Learning Programme 2013 Grant. This work has been supported by own IBIME funds. 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Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine

BACKGROUND\ud \ud A pivotal phase III study of the RTS,S/AS01 malaria candidate vaccine is ongoing in several research centres across Africa. The development and establishment of quality systems was a requirement for trial conduct to meet international regulatory standards, as well as providing an important capacity strengthening opportunity for study centres.\ud \ud METHODS\ud \ud Standardized laboratory methods and quality assurance processes were implemented at each of the study centres, facilitated by funding partners.\ud \ud RESULTS\ud \ud A robust protocol for determination of parasite density based on actual blood cell counts was set up in accordance with World Health Organization recommendations. Automated equipment including haematology and biochemistry analyzers were put in place with standard methods for bedside testing of glycaemia, base excess and lactacidaemia. Facilities for X-rays and basic microbiology testing were also provided or upgraded alongside health care infrastructure in some centres. External quality assurance assessment of all major laboratory methods was established and method qualification by each laboratory demonstrated. The resulting capacity strengthening has ensured laboratory evaluations are conducted locally to the high standards required in clinical trials.\ud \ud CONCLUSION\ud \ud Major efforts by study centres, together with support from collaborating parties, have allowed standardized methods and robust quality assurance processes to be put in place for the phase III evaluation of the RTS, S/AS01 malaria candidate vaccine. Extensive training programmes, coupled with continuous commitment from research centre staff, have been the key elements behind the successful implementation of quality processes. It is expected these activities will culminate in healthcare benefits for the subjects and communities participating in these trials.\ud \ud TRIAL REGISTRATION\ud \ud Clinicaltrials.gov NCT00866619