Biological variation: back to basics

Biological variation: back to basics

Design-time Models for Resiliency

Resiliency in process-aware information systems is based on the availability of recovery flows and alternative data for coping with missing data. In this paper, we discuss an approach to process and information modeling to support the specification of recovery flows and alternative data. In particular, we focus on processes using sensor data from different sources. The proposed model can be adopted to specify resiliency levels of information systems, based on event-based and temporal constraints

An approach for estimating measurement uncertainty in medical laboratories using data from long-term quality control and external quality assessment schemes

The present study was prompted by the ISO 15189 requirements that medical laboratories should estimate measurement uncertainty (MU)

Diabetes Mellitus and Reprogrammed Glucose Metabolism in Pancreatic Cancer: Features for Clinical Translation

The reprogrammed metabolism of cancer cells underlies the shift of glucose energetics from the highly efficient oxidative phosphorylation to the less efficient aerobic glycolysis, the Warburg effect. This phenomenon, with the activation of the glutamine pathway, advantage survival and proliferation of pancreatic ductal adenocarcinoma (PDAC) cells, which live in an adverse hypoxic and nutrient restricted microenvironment. In PDAC, glucose metabolic alterations occur also at the whole organism, diabetes mellitus (DM) being diagnosed in approximately 60% to 80% of patients. The association beteen PDAC and DM is a dual face phenomenon, DM being both a risk factor for and a consequence of this tumor type. Data from epidemiology indicate that longstanding DM increases PDAC risk 1.5 to 2.0 fold, probably because of the pro-proliferative effects of hyperinsulinemia. By contrast early onset DM, i.e. diabetes diagnosed no more than two years prior to cancer diagnosis, is considered a consequence of PDAC. Secondary DM is due to complex interactions between tumor cells, tumor microenvironment and pancreatic endocrine cells. In this scenario the role of the inflammatory S100A8 calcium binding protein, matrix metalloproteinases, Vanin1 or amylin has been experimentally demonstrated. However, the efforts made to translate in the clinical practice any individual new poteantial biomarker failed, because none reached enough sensitivity and specificity to be considered a reliable biomarker to diagnose PDAC even in high risk subjects as those with new onset DM. Therefore the identification and clinical validation of new biomarkers remains a challenge for future studies

The 99th percentile of reference population for cTnI and cTnT assay: Methodology, pathophysiology and clinical implications

According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision â\u89¤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines

Verification of examination procedures in clinical laboratory for imprecision, trueness and diagnostic accuracy according to ISO 15189:2012: a pragmatic approach

Background The International Standard ISO 15189 is recognized as a valuable guide in ensuring high quality clinical laboratory services and promoting the harmonization of accreditation programmes in laboratory medicine. Examination procedures must be verified in order to guarantee that their performance characteristics are congruent with the intended scope of the test. The aim of the present study was to propose a practice model for implementing procedures employed for the verification of validated examination procedures already used for at least 2 years in our laboratory, in agreement with the ISO 15189 requirement at the Section 5.5.1.2. Methods In order to identify the operative procedure to be used, approved documents were identified, together with the definition of performance characteristics to be evaluated for the different methods; the examination procedures used in laboratory were analyzed and checked for performance specifications reported by manufacturers. Then, operative flow charts were identified to compare the laboratory performance characteristics with those declared by manufacturers. Results The choice of performance characteristics for verification was based on approved documents used as guidance, and the specific purpose tests undertaken, a consideration being made of: imprecision and trueness for quantitative methods; diagnostic accuracy for qualitative methods; imprecision together with diagnostic accuracy for semi-quantitative methods. Conclusions The described approach, balancing technological possibilities, risks and costs and assuring the compliance of the fundamental component of result accuracy, appears promising as an easily applicable and flexible procedure helping laboratories to comply with the ISO 15189 requirements

Impaired release of Vitamin D in dysfunctional adipose tissue: New cues on Vitamin D supplementation in obesity

Context: Vitamin D accumulates in adipose tissue (AT) and vitamin D deficiency is frequent in obesity. Objective: We hypothesize that trafficking of vitamin D is altered in dysfunctional AT. Design, Patients, Settings: 54 normal-weight and 67 obese males were recruited in a prospective study and randomly assigned to supplementation with 50 \ub5g/week 25-hydroxyvitamin-D3 (25(OH)D) or 150 \ub5g/week vitamin D3 for 1 year, raising dosage by 50% if vitamin D-sufficiency (serum 25(OH)D>50 nomol/l), was not achieved at 6 months; 97 subjects completed the study. Methods: Vitamin D3 (D3) and 25(OH)D were quantified by HPLC-MS in control and insulin-resistant (IR) 3T3-L1 cells and subcutaneous AT (SAT) from lean and obese subjects, incubated with or without adrenaline; expression of 25-hydroxylase (CYP27A1), 1\u3b1-hydroxylase (CYP27B1) and vitamin D receptor (VDR) were analysed by real-time PCR. Results: In IR adipocytes the uptake of D3 and 25(OH)D was higher, but after adrenaline stimulation, the decrement in D3 and 25(OH)D was stronger in control cells, which also showed increased expression of CYP27A1 and CYP27B1 and higher levels of 25(OH)D. In SAT from obese subjects, the adrenaline-induced release of D3 and 25(OH)D was blunted; in both IR cells and obese SAT, protein expression of \u3b22-adrenergic receptor was reduced. Supplementation with 25-hydroxyvitamin-D3 was more effective in achieving vitamin D sufficiency in obese, but not in normal weight subjects. Conclusion: Dysfunctional AT shows a reduced catecholamine-induced release of D3 and 25(OH)D, and altered activity of vitamin D-metabolizing enzymes, for these reasons supplementation with 25-hydroxyvitamin-D3 is more effective in obese individuals

A new sampling device for faecal immunochemical testing: haemoglobin stability is still an open issue

Abstract Background: The detection of faecal occult blood is a fundamental step in making an early diagnosis of colorectal cancer. The aim of the present study was to evaluate the stability of haemoglobin in faeces collected with two sampling devices specific for faecal immunochemical testing (FOB Gold Tube Screen and FOB Gold Tube NG) that contain different preservative buffers (buffer H, BH, and buffer N, BN, respectively). Methods: Fifteen true positive faecal samples were collected with both devices. A pool from each sample was made. Each pool was portioned and stored at +4\ub0C, +21\ub0C and +32\ub0C for 10 days. One aliquot of each pool stored at each of the respective temperatures was tested at five time intervals between sampling and analysis. The same procedure was followed for three synthetic haemoglobin solutions in both buffers. Results: The percentage of cumulative faecal haemoglobin decrease (HbCD%) was evaluated. No significant difference was found between BH and BN in HbCD% at +4\ub0C (p=0.106); at +21\ub0C and +32\ub0C, HbCD% was lower in BH than in BN samples (p=0.002 and