The need for standards and certification for investigative genetic genealogy, and a notice of action.

As investigative genetic genealogy (IGG) becomes a more common tool for investigating agencies to resolve cold cases and provide names to unidentified human remains, there is an urgent need for standards and a certification process for IGG practitioners. There are four broad concerns that give rise to this need: data privacy, public trust, proficiency (and agency trust), and accountability. Yet, while the need is clear, the few discussions of standards and certification thus far have been plagued by misunderstandings of IGG and poor analogs for the profession. Thus, in addition to describing the need, this article analyzes three relevant analogs for IGG standards and certification and describes the strengths and weaknesses of each. Finally, this article announces the creation of a non-profit Board of Certification for Investigative Genetic Genealogy and a framework for standards and a certification process for IGG.

A multicenter study to evaluate automated platelet aggregometry on Sysmex CS-series coagulation analyzers-preliminary findings.

BACKGROUND AND OBJECTIVES: Investigations of platelet function by light transmission aggregometry (LTA) using a dedicated aggregometer is time consuming and labor intensive. This multicenter study evaluated an automated LTA method using a coagulation analyzer to establish reference ranges and ideal testing regimen. METHODS: Sysmex CS-2x00 series analyzers were used to measure aggregation using a range of agonists and concentrations: ADP (1-20 µM); arachidonic acid (0.5-1.5 mM); collagen (1.25-5 µg/mL); ristocetin (0.5-1.5 g/L); epinephrine (5-10 µM); TRAP (1-20 µM); U46619 (1 µM); and saline. Maximum and final aggregation, disaggregation, slope, and acquisition time were compared for each. RESULTS: For 42 normal subjects there was no significant difference in aggregation parameters for: 10 µM and 20 µm ADP; 2 and 2.5 µM ADP; 1 and 1.5 mM arachidonic acid; 2.5 and 5 µg/mL collagen; 1 and 1.25 µg/mL collagen; 1.25 and 1.5 g/L ristocetin; 5 and 10 µM epinephrine; 5 and 10 µM or 20 µM TRAP. Maximum aggregation was reached by 300 seconds with 20 and 10 µM ADP, 1 µM U46619, 1 and 1.25 µg/mL collagen, 1.5 g/L ristocetin and 5, 10, and 20 µM TRAP: all others agonists required 600s. CONCLUSIONS: A standard panel of agonists can be used on the Sysmex CS-2x00 series analyzers: ADP (10, 5, 2.5, and 1.25 µM); 1 mM arachidonic acid; 1 µM U46619; 2.5 and 1.25 µg/mL collagen; 1.25 and 0.5 g/L ristocetin; 5 µM epinephrine; 5 and 10 µM TRAP; and saline. Aggregation should be observed for 600 seconds for all agonists except TRAP and U46619, which require 300 seconds. If further studies confirm these concentrations detect platelet disorders then Sysmex CS-series analyzers could replace dedicated aggregometers, or perform LTA where it is currently not available.

Platelet function testing: from routine to specialist testing.

Platelets have many functions within the haemostatic system, and when these actions are diminished for whatever reason, a bleeding tendency can manifest. Unravelling the reason(s) for this bleeding can be complex due to the multiple roles platelets perform. This review seeks to explain each level of platelet testing moving from those performed at local hospital laboratories to those performed by specialist centres and university research departments. It will examine the testing available and discuss when to move on to additional testing.

Residual Stress Analysis Based on Acoustic and Optical Methods.

Co-application of acoustoelasticity and optical interferometry to residual stress analysis is discussed. The underlying idea is to combine the advantages of both methods. Acoustoelasticity is capable of evaluating a residual stress absolutely but it is a single point measurement. Optical interferometry is able to measure deformation yielding two-dimensional, full-field data, but it is not suitable for absolute evaluation of residual stresses. By theoretically relating the deformation data to residual stresses, and calibrating it with absolute residual stress evaluated at a reference point, it is possible to measure residual stresses quantitatively, nondestructively and two-dimensionally. The feasibility of the idea has been tested with a butt-jointed dissimilar plate specimen. A steel plate 18.5 mm wide, 50 mm long and 3.37 mm thick is braze-jointed to a cemented carbide plate of the same dimension along the 18.5 mm-side. Acoustoelasticity evaluates the elastic modulus at reference points via acoustic velocity measurement. A tensile load is applied to the specimen at a constant pulling rate in a stress range substantially lower than the yield stress. Optical interferometry measures the resulting acceleration field. Based on the theory of harmonic oscillation, the acceleration field is correlated to compressive and tensile residual stresses qualitatively. The acoustic and optical results show reasonable agreement in the compressive and tensile residual stresses, indicating the feasibility of the idea.

Von Willebrand factor, soluble P-selectin, and target organ damage in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

To investigate the relationship between soluble markers of platelet, endothelial and rheological function, and target organ damage and their response to intensified management in a population of middle-age hypertensive patients at high risk of cardiovascular complications, we studied 382 consecutive patients (308 men; mean age, 63 years, SD 8) along with 60 normotensive controls free of cardiovascular disease. Patients were divided into those with target organ damage (TOD; n=107) and those free of end-organ damage. Plasma levels of soluble P-selectin (sP-sel), a marker of platelet activation, and von Willebrand factor (vWF), an index of endothelial damage/dysfunction (both enzyme-linked immunosorbent assay), and the rheological indices fibrinogen, plasma viscosity, hematocrit, platelet, and white cell count were measured. In 53 patients, variables were further measured after 6 months of intensified cardiovascular risk management. Patients with TOD had significantly higher vWF, 137 (SD 33) versus 125 (SD 33) IU/dL (P=0.002,) and a greater proportion of smokers, 31% versus 16% (P=0.002). There were no statistically significant differences in plasma viscosity, fibrinogen, hematocrit, white blood cell count, platelet count, or sP-sel between the 2 subgroups. In multivariate analysis, vWF was a significant independent predictor for TOD. After 6 months of intensified management in 53 patients who entered the trial, there were significant reductions in systolic blood pressure, total cholesterol, hematocrit, plasma viscosity, sP-sel, and vWF (all P<0.01) but no significant change in fibrinogen. In conclusion, there is a relationship between TOD and endothelial damage/dysfunction in hypertension. Intensified management results in improvements in hemorheology, endothelial and platelet function.

A reliable plasma marker of platelet activation: does it exist?

Despite the clear importance of the platelet in various conditions and diseases, there are few opportunities to assess the physiological and pathological functions of this cell. Those without access to a flow cytometer or platelet aggregometer rely on secreted or release products of the platelet. Principle among these molecules are alpha granule components beta thromboglobulin and platelet factor four, and membrane constituents such as P selectin, gpV and glycocalicin. However, notwithstanding the ease of measurement of these markers (i.e., by ELISA) each one has its own particular disadvantage, mostly of methodology and specificity. Nevertheless, if our goal is to improve our ability to recognize and treat subjects with thrombotic disorders, then additional studies on these molecules may prove to be a sound investment.

Platelet P-selectin levels in relation to plasma soluble P-selectin and beta-thromboglobulin levels in atrial fibrillation.

BACKGROUND AND PURPOSE: The increased risk of stroke and thromboembolism in atrial fibrillation (AF) may be related to a prothrombotic or hypercoagulable state, with abnormalities of hemostasis and platelet activation. To investigate the role of platelets in AF and the influence of antithrombotic therapy, we developed and then applied a new assay to detect the absolute amount of P-selectin per platelet (pP-selectin) based on cell lysis. Thus, pP-selectin in AF patients was compared with that of healthy controls and also with plasma soluble P-selectin (sP-selectin) and beta-thromboglobulin as established indices of platelet activation. METHODSMDSAH: We studied 122 patients (mean [SD] age, 71 [9] years; 65 men) with chronic AF of >6 weeks' duration: 34 were not on antithrombotic therapy, 30 were taking aspirin (75 to 300 mg/d), and 58 were fully anticoagulated with warfarin. pP-selectin was compared with sP-selectin and plasma beta-thromboglobulin levels (enzyme-linked immunosorbent assay). Results were compared with those of 23 healthy controls (mean [SD] age, 74 [9] years; 7 men) in sinus rhythm. RESULTS: pP-selectin was significantly lower in AF patients on no antithrombotic therapy (P=0.03) than in healthy controls, but sP-selectin and beta-thromboglobulin levels were not significantly different and did not differ in patients taking aspirin or warfarin. However, pP-selectin was lower in patients with AF on aspirin than in those on warfarin (P<0.05). pP-selectin/sP-selectin correlated significantly in healthy controls (r=0.47, P=0.03) but inversely (r=-0.43, P=0.03) in AF patients on no antithrombotic therapy. CONCLUSIONS: Lower levels of pP-selectin may represent a depletion of pP-selectin after platelet activation in AF. Aspirin further decreases pP-selectin levels compared with warfarin. On the basis of the principle of platelet lysis, we demonstrate that it is possible to determine the amount of P-selectin per platelet, which may be regulated in the megakaryocyte through a cyclooxygenase-dependent pathway.