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The ongoing COVID‐19 pandemic originated in Wuhan, Hubei Province, China, in December 2019. The etiologic agent is a novel coronavirus of presumed zoonotic origin with structural similarity to the viruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Like SARS and MERS, COVID‐19 infection manifests most frequently with lower respiratory symptoms. A minority of patients progress to acute respiratory distress syndrome/ diffuse alveolar damage. In addition to its central role in the diagnosis of COVID‐19 infection, the clinical laboratory provides critical information to clinicians regarding prognosis, disease course, and response to therapy. The purpose of this review is to (a) provide background context about the origins and course of the pandemic, (b) discuss the laboratory's role in the diagnosis of COVID‐19 infection, (c) summarize the current state of biomarker analysis in COVID‐19 infection, with an emphasis on markers derived from the hematology laboratory, (d) comment on the impact of COVID‐19 on hematology laboratory safety, and (e) describe the impact the pandemic has had on organized national and international educational activities worldwide. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Delayed platelet engraftment in group O patients after autologous progenitor cell transplantation" that was published in a previous issue.

Introduction: Implementing artificial intelligence‐based instruments in hematology laboratories requires evidence of efficiency in classifying pathological cells. In two‐Universities, we assessed the performance of the Mindray® MC‐80 for hematology patients with frequent leukemic and dysplastic cells. Methods: The Mindray MC‐80® locates and pre‐classifies cells in blood films. In a two‐university study, four films were prepared from 591 samples, two each for the analyser MC‐80 and the microscope reference method, using reagents from two different manufacturers. We used Microsoft Excel® statistics for imprecision and distributional inaccuracy and a matrix table model (H20‐A2 CLSI standard) for sensitivity, specificity and predictive value for atypical cells. Results: The results indicate minimal within‐run imprecision (ICSH method) and good intra‐method consistency even on duplicate analysis of 413 samples with a high incidence of hematological abnormalities (r = 0.942 or more, except for basophils, r = 0.841, and reactive lymphocytes, r = 0.847). Distributional inaccuracy was also very low compared to the microscope reference, with a pass rate higher than 80% for pathological cells (except 75.1% for reactive lymphocytes). The primary causes of discrepancy were bizarre shapes of dysplastic neutrophils and inconsistent nomenclature for lymphoma cells. Sensitivity for critical samples containing cells typically absent in circulating blood (immature or malignant) was 98.8% for immature granulocytes, 83.8% for all types of neoplastic cells, 93.6% for reactive lymphocytes and 97.5% for nucleated red blood cells. The negative predictive values of MC‐80 were 98.8% for immature granulocytes, 88.4% for the different types of neoplastic cells, 97.8% for reactive lymphocytes, and 96.9% for nucleated red blood cells. Conclusion: Our study highlights the outstanding diagnostic performance of this artificial intelligence–based blood film analyzer for hematology patients with circulating abnormal cells. We appreciated the morphological harmonization of cells observed on the screen and those seen in the microscope. [ABSTRACT FROM AUTHOR]

This article focuses on the relation between new public management (NPM) reforms and changing patterns of industrial relations (IRs) and social dialogue in the Italian education system. Drawing on data from the research project 'Social dialogue and industrial relations in education: The challenges of multi-level governance and privatisation in Europe' (IR-EDUREFORM), it uses cultural political economy to explore the effects of autonomy, evaluation, and management as policy technologies on teacher unions' collective bargaining, workplace representation and industrial action. Through the Italian case, the study analyses how NPM reforms operated three distinctive transformations: decentralisation of bargaining to school level, juridification and individualisation of industrial action and a shift from collective to professional unions. Beyond critically exploring the implications of NPM reforms and the processes of decollectivation and individualisation of IRs and social dialogue in education, the study also highlights some potential for the emergence of novel sites for collective representation. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are conflicting opinions regarding the effect of positive direct antiglobulin test (DAT) on hemoglobin (Hb) levels in human immunodeficiency virus–infected (HIV+) patients. STUDY DESIGN AND METHODS: A total of 166 samples from HIV+ outpatients were studied. The DAT was performed with the tube test and column agglutination technology (CAT). RESULTS: The DAT was positive in 18.67 percent with the tube method and 33.73 percent with the CAT. Patients with DAT-positive results showed lower Hb levels than DAT-negative patients, 12.3 g per dL versus 14.3 g per dL (p = 0.0002). The univariate logistic regression enabled us to study the phenomenon better and fit the probability of having a DAT-positive result on the basis of the Hb levels. The relationship between the CAT and the tube test when washing the red blood cells (RBC) at 4°C was stronger than when washing these at room temperature (φ = 0.8156; p = 0.000). The Hb levels were significantly lower in the positive DATs of Stage C (acquired immune deficiency syndrome [AIDS]) and Stage B (symptomatic non-AIDS patients), which showed decreasing Hb values for increasing agglutination strengths (p = 0.000). Anemia was related with the DAT results (odds ratio [OR], 8.005; p = 0.000) but not to the AIDS condition (OR, 1.741; p = 0.221). DISCUSSION: Our study indicates that the DAT-positive results may be specifically related to lower Hb levels in HIV+ patients. The immunologic RBC clearance could be part of the anemic multifactorial condition in HIV+ patients. [ABSTRACT FROM AUTHOR]

Microplate agglutination methods (MAMs) and column agglutination technology are widely employed for red cell typing and can be automated. Some tests, however, such as detection of weak D, require manual testing. The possibility of detecting weak D by a solid-phase RBC adherence (SPRCA) test was studied in a fully automated system. The results of 2609 blood samples, characterized as being D– or with a incomplete agglutination reaction, were analyzed for the presence of the weak D phenotype. The 2609 samples were tested by a weak D tube test (antiglobulin method) and a weak D-test with the new SPRCA method. When weak D was detected, which D epitope was involved and whether it was associated with a partial D phenotype were determined. Weak D was detected in 60 (2.3%) of the 2609 samples. The 60 samples that were weak D by the tube test were also weak D+ with the new automated SPRCA test. The sensitivity and specificity for the new weak D typing method were 100 percent, when compared with the standard weak D manual test. These results support the possibility of performing weak D detection with a SPRCA fully automated system. These preliminary results are encouraging, showing good sensitivity and specificity of the test. Detection of weak D will permit full automation of blood typing. [ABSTRACT FROM AUTHOR]

Introduction: The athlete biological passport monitors blood variables over time to uncover blood doping. With the phasing in of a new series of blood analyzers, the Sysmex XN series, it was necessary to examine the comparability of results with the previously employed XT/XE series. A previous comparison between XN and XT/XE series suggested a small but significant bias between the two instruments in the measurements of RET%. Here, we examined the comparability of RET% on the XN and XT/XE platform using data collected over the first year since the transition. Methods: The comparability of results obtained from XN and XT/XE instruments was assessed using three datasets: (i) 767 blood samples measured on both instrument series in 22 WADA‐accredited laboratories, (ii) 27 323 samples measured on either instrument across 31 laboratories, and (iii) 119 clinical samples and 110 anti‐doping samples measured on both instruments in a single laboratory. Results: Analysis of the three datasets confirms the previous observation of a bias toward higher RET% values for samples measured on Sysmex XN instruments compared with the XT/XE series. Using data across a larger number of XN instruments and a larger athlete population, the current work suggests that the bias is proportional and slightly higher than previously observed across most of the range RET% values. Conclusion: A model is proposed for the comparison of data across XN and XT/XE technologies whereby the instrument bias increases proportionally with RET% measured on Sysmex XN Series, but where the rate of increase is negatively related to IRF%. [ABSTRACT FROM AUTHOR]

The seasquirt Ciona robusta and its co-generic Ciona savignyi , are two long-divergent species, sharing the same habitat and competing for the same spaces and resources. Their very similar morphology has been responsible for the misidentification of the two organisms, and, consequently, for the underestimation of their geographic distributions and new areas of co-occurrence. In spite of the large amount of knowledge built up by developmental biologists, few data are available regarding the morpho-physiology of the two sea squirts. The comparison of morphological and physiological features carried out in the present study (i.e. length-body weight correlation, tunic/organ ratio, tissue-specific retained water and metabolic rate), highlighted slight, but significant, differences strongly supporting the hypothesis of different ecological strategies for the two species. More precisely, C. savignyi invests more energy in growing faster and taller, likely to improve the quality and concentration of the filtered food, and sustains a faster metabolic/growth rate. Conversely, C. robusta invests more into tunic thickness, reducing the risk of predation, even if this likely means a slower metabolic/growth rate. In addition it was noted that in both species, the tunic absorbs more water than the other tissues, a peculiarity that may allow them to better counteract sudden fluctuations in environmental salinity. [ABSTRACT FROM AUTHOR]

This paper describes the methodology used to develop a consensual glossary for haematopoietic cells within Diagnostics-WP10 of European-LeukemiaNet EU-project. This highly interactive work was made possible through the use of the net, requiring only a single two-day meeting of actual confrontation and debate. It resulted in the production of a freely accessible tool that could be useful for training as well as harmonization of morphological reports in onco-haematology especially, without geographic limitation, not limited to European countries. Moreover, this collective work resulted in the production of a consensus statement, taking into account individual practices, collegial agreement and literature data. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anti-D monoclonal antibody (MoAb) reagents have improved D typing in routine tests. However, they exhibit a wide range of reactivity with the weak D phenotype depending on the characteristics of the different MoAbs used. We analyzed the reactivity of immunoglobulin (IgM) anti-D by cluster analysis to characterize MoAb that have similar reactivities with the weak D phenotype. STUDY DESIGN AND METHODS: We used 36 consecutive samples with weak D phenotype in routine testing and determined their reactivity with different IgM and IgG anti-D MoAbs. The samples were characterized as belonging to a weak D type or category using commercial molecular biology kits. RESULTS: The various anti-D MoAbs showed a wide grade of reactivity with the weak D samples. Similarities and dissimilarities in the behavior of the anti-D MoAbs with the weak D phenotype samples were detected with cluster analysis and the multidimensional scaling analysis. These analyses indicated different families of MoAbs characterized as having a high degree of homogeneity in their reactivity with the weak D phenotype. Between these MoAb families, the most effective at reacting with the weak D phenotype were RUM-1 and 175-2. CONCLUSIONS: The results show that it is possible to classify the anti-D MoAbs on the basis of their reactivity with the weak D phenotype. This provides information about different MoAbs' properties on the basis of their belonging to a given of anti-D family. [ABSTRACT FROM AUTHOR]

Background: Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. In unstable angina, activated leukocytes may be found in peripheral and coronary-sinus blood, but it is unclear whether they are selectively activated in the vascular bed of the culprit stenosis. Methods: We measured the content neutrophil myeloperoxidase content in the cardiac and femoral circulations in five groups of patients: two groups with unstable angina and stenosis in either the left anterior descending coronary artery (24 patients) or the right coronary artery (9 patients); 13 with chronic stable angina; 13 with variant angina and recurrent ischemia; and 6 controls. Blood samples were taken from the aorta, the femoral vein, and the great cardiac vein, which selectively drains blood from the left but not the right coronary artery. Results: The neutrophil myeloperoxidase content of aortic blood was similar in both groups of patients with unstable angina (–3.9 and –5.5, with negative values representing depletion of the enzyme due to neutrophil activation) and significantly lower than in the other three groups (P<0.05). Independently of the site of the stenosis, the neutrophil myeloperoxidase content in blood from the great cardiac vein was significantly decreased in both groups of patients with unstable angina (–6.4 in those with a left coronary lesion and –6.6 in those with a right coronary lesion), but not in patients with stable angina and multiple stenoses, patients with variant angina and recurrent ischemia, or controls. There was also a significant transcoronary reduction in myeloperoxidase content in both groups with unstable angina. Conclusions: The widespread activation of neutrophils across the coronary vascular bed in patients with unstable angina, regardless of the location of the culprit stenosis, challenges the concept of a single vulnerable plaque in unstable coronary syndromes. (N Engl J Med 2002;347:5-12.) [ABSTRACT FROM AUTHOR]

Numerous studies have shown peculiar morphological anomalies in COVID-19 patients' smears. We searched all the peer-reviewed scientific publications that explicitly reference the cytomorphological alterations on peripheral blood smears of patients with COVID-19. We extracted data from sixty-five publications (case reports, patient group studies, reviews, and erythrocyte morphology studies). The results show that frequent alterations concern the morphology of lymphocytes (large lymphocytes with weakly basophilic cytoplasm, plasmacytoid lymphocytes, large granular lymphocytes). Neutrophils display abnormal nuclei and cytoplasm in a distinctive cytomorphological picture. Besides a left shift in maturation, granulations can be increased (toxic type) or decreased with areas of basophilia. Nuclei are often hyposegmented (pseudo-Pelger-Huёt anomaly). Apoptotic or pycnotic cells are not uncommon. Monocytes typically have a large cytoplasm loaded with heterogeneous and coalescing vacuoles. Platelets show large and giant shapes. The presence of erythrocyte fragments and schistocytes is especially evident in the forms of COVID-19 that are associated with thrombotic microangiopathies. Such atypia of blood cells reflects the generalized activation in severe COVID-19, which has been demonstrated with immunophenotypic, molecular, genetic, and functional methods. Neutrophils, in particular, are involved in the pathophysiology of hyperinflammation with cytokine storm, which characterizes the most unfavorable evolution., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

In 2012, the International Council for Standardization in Hematology (ICSH) published recommendations for the identification, quantitation, and diagnostic value of schistocytes. In the present review, the impact of these recommendations is evaluated. This work is based on citations in peer-reviewed papers published since 2012. The first 2012 ICSH Recommendations have also been revised to incorporate newly published data in the literature and current best laboratory practice. Recommended reference ranges have been proposed for healthy adults and full-term neonates of 1% or less schistocytes. More than 1% of morphologically identified schistocytes on the blood film are considered suspicious for thrombotic microangiopathy. For preterm infants, a normal level of 5% or less is recommended. The fragment red cell count (FRC) generated by some automated hematological analyzers provides a valuable screening tool for the presence of schistocytes. Specifically, the absence of FRCs can be used as a valuable parameter to exclude the presence of schistocytes on the blood film. The validity and usefulness of microscope schistocytes and automated FRCs, respectively, are discussed in the context of the laboratory diagnostic tests used for thrombotic microangiopathies., (© 2021 John Wiley & Sons Ltd.)

The extraordinary advances in clinical hematology, biology, and oncology in the last decades would not have been possible without discovering how to identify and count the cells circulating in the blood. For centuries, scientists have used slides, counting chambers (hemocytometers), and diluting and staining solutions for this task. Then, automated hemocytometry began. This science, now linked to the daily routine of laboratory hematology, has completed an overwhelming path over a few decades. Our laboratories today operate with versatile multiparameter systems, ranging from complex single-channel instruments to bulky continuous flow machines. In terms of clinical information obtained from a simple routine blood test, the full exploitation of their potential depends on the operators' imagination and courage. A comprehensive review of the scientific publications that have accompanied the development of hemocytometry from the 1950s to today would require entire volumes. More than seven hundred contributions that authors worldwide have published in Clinical and Laboratory Haematology until 2007 and then the International Journal of Laboratory Hematology are summarized. Such journals have represented and hopefully will continue to represent the privileged place of welcome for future scientific research in hemocytometry. Improved technologies, attention to quality, new reagents and electronics, information technology, and scientist talent ensure a more profound and deeper knowledge of cell properties: current laboratory devices measure and count even minor immature or pathological cell subpopulations. Full-field hemocytometry includes the analysis of nonhematic fluids, digital adds to the microscope, and the development of effective point-of-care devices., (© 2021 John Wiley & Sons Ltd.)

The value of Shannon's mutual information is commonly used to describe the total amount of information that the neural code transfers between the ensemble of stimuli and the ensemble of neural responses. In addition, it is often desirable to know which features of the stimulus or response are most informative. The literature offers several different decompositions of the mutual information into its stimulus or response-specific components, such as the specific surprise or the uncertainty reduction, but the number of mutually distinct measures is in fact infinite. We resolve this ambiguity by requiring the specific information measures to be invariant under invertible coordinate transformations of the stimulus and the response ensembles. We prove that the Kullback-Leibler divergence is then the only suitable measure of the specific information. On a more general level, we discuss the necessity and the fundamental aspects of the coordinate invariance as a selection principle. We believe that our results will encourage further research into invariant statistical methods for the analysis of neural coding.

Cytomorphological examination of aspirate smears remains the basic method to diagnose hematologic disorders and to evaluate treatment-related changes. Last-generation hematological analyzers can count, besides cells normally circulating in peripheral blood, some types of immature and abnormal cells, such as erythroblasts and immature granulocytes. The complex nature of bone marrow fluid, however, has prevented until now the routine utilization of blood cell counters in this area. Recent studies have shown the possibility of using bone marrow fluid as a substitute for peripheral blood for clinical tests in particular situations and for repetitive cytologic examinations in specific clinical and research fields., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: At present five evolutionary hypotheses have been proposed to explain the great variability of the genomic GC content among and within genomes: the mutational bias, the biased gene conversion, the DNA breakpoints distribution, the thermal stability and the metabolic rate. Several studies carried out on bacteria and teleostean fish pointed towards the critical role played by the environment on the metabolic rate in shaping the base composition of genomes. In mammals the debate is still open, and evidences have been produced in favor of each evolutionary hypothesis. Human genes were assigned to three large functional categories (as well as to the corresponding functional classes) according to the KOG database: (i) information storage and processing, (ii) cellular processes and signaling, and (iii) metabolism. The classification was extended to the organisms so far analyzed performing a reciprocal Blastp and selecting the best reciprocal hit. The base composition was calculated for each sequence of the whole CDS dataset., Results: The GC3 level of the above functional categories was increasing from (i) to (iii). This specific compositional pattern was found, as footprint, in all mammalian genomes, but not in frog and lizard ones. Comparative analysis of human versus both frog and lizard functional categories showed that genes involved in the metabolic processes underwent the highest GC3 increment. Analyzing the KOG functional classes of genes, again a well defined intra-genomic pattern was found in all mammals. Not only genes of metabolic pathways, but also genes involved in chromatin structure and dynamics, transcription, signal transduction mechanisms and cytoskeleton, showed an average GC3 level higher than that of the whole genome. In the case of the human genome, the genes of the aforementioned functional categories showed a high probability to be associated with the chromosomal bands., Conclusions: In the light of different evolutionary hypotheses proposed so far, and contributing with different potential to the genome compositional heterogeneity of mammalian genomes, the one based on the metabolic rate seems to play not a minor role. Keeping in mind similar results reported in bacteria and in teleosts, the specific compositional patterns observed in mammals highlight metabolic rate as unifying factor that fits over a wide range of living organisms.

We analyze the patterns and rates of amino acid evolution in tunicates with special interest on the extremely fast evolving Oikopleura dioica. We show that this species, on average, is twice as fast as the already fast evolving Ciona intestinalis. The acceleration in both species seems to be affected by similar evolutionary forces yet to different extent, since a substantial proportion of the most and less accelerated genes are orthologous between the two species. Among the possible causes that underlie the genome wide acceleration in Oikopleura, relaxation of functional constraints appears to be an important one, since all amino acids exhibit surprisingly homogenous levels of divergence. Such homogeneity, however, is not observed in Ciona. Apart from the genome wide acceleration, detailed analysis of functional groups of genes revealed that genes associated with regulatory functions (transcription regulators, chromatin remodeling proteins and metabolic regulators), have been subjected to an even more extreme process of acceleration, suggesting that adaptive evolution is the most probable cause of their unusual exacerbated rates. Another remarkable observation is that cysteine is among the less conserved amino acids, contrary to what is commonly observed in other species. The possible causes of this particular behavior are discussed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Full blood counts are now used as evidence that athletes have used banned blood doping. This has led to legal scrutiny of the efficacy of preanalytical procedures such as specimen homogenisation., Aims: To characterise the impact of different mixing strategies on whole-blood homogeneity., Methods: Manual inversion, mechanical mixing and automatic mixing performed by the Sysmex XT-2000i were evaluated., Results: Automated mixing by the instrument, or 1 min of mechanical mixing, thoroughly homogenised specimens even for tubes that had been refrigerated and left undisturbed for 36 h. Manual inversions were almost as effective, provided that specimens were first allowed to equilibrate to ambient temperatures., Conclusions: Current sport guidelines that mandate at least 15 min of mechanical mixing are excessive. Except where specimens are presented to the instrument manually, mechanical mixing is redundant in the context of full blood counts.

Aims: To assess changes in reticulocyte impedance volume, conductivity and light scatter (reticulocyte population data or RPD) obtained with the volume, conductivity and laser light scatter (VCS) technology in healthy subjects and in different erythropoietic states., Methods: Blood samples were analysed with the Beckman-Coulter LH750 system, using the VCS method, from a group of 40 healthy subjects and three groups of patients with different types of untreated or treated anaemia: 24 cases of iron deficiency at the time of diagnosis, 16 patients with iron deficiency anaemia during intravenous iron administration, and 57 patients with chronic kidney disease undergoing dialysis and administration of rHu-erythropoietin and intravenous iron., Results: RPD data were reproducible. Average mean channels for volume were 50.9 for controls and 49.2, 55.7 and 64.0 for the three patient groups, respectively. Average mean channels for conductivity were 52.0 for controls and 59.8, 55.7 and 56.1 for the three patient groups. Average mean channels for light scatter were 108.4 for controls and 113.3, 117.3 and 128.2 for the three patient groups. SD data indicated increased dispersion in the patient groups., Conclusion: When values in the patient groups are compared with reference values obtained in healthy controls, the main differences are found in impedance volume and light scatter, which were both increased in patients with stimulated erythropoiesis. These data indicate the opportunity to further evaluate the clinical usefulness of RPD in haematological diseases.

Teleosts are a highly diverse group of animals occupying all kind of aquatic environment. Data on routine mass specific metabolic rate were re-examined correcting them for the Boltzmann's factor. Teleostean fish were grouped in five broad groups, corresponding to major environmental classifications: polar, temperate, sub-tropical, tropical and deep-water. The specific routine metabolic rate, temperature-corrected using the Boltzmann's factor (MR), and the average base composition of genomes (GC%) were calculated in each group. Fish of the polar habitat showed the highest MR. Temperate fish displayed a significantly higher MR than tropical fish, which had the lowest average value. These results were apparently in agreement with the cold adaptation hypothesis. In contrast with this hypothesis, however, the MR of fish living in deep-water environment turned out to be not significantly different from that of fish living in tropical habitats. Most probably, the amount of oxygen dissolved in the water directly affects MR adaptation. Regarding the different habitats, the genomic GC levels showed a decreasing trend similar to that of MR. Indeed, both polar and temperate fish showed a GC level significantly higher than that of both sub-tropical and tropical fish. Plotting the genomic GC levels versus the MR a significant positive correlation was found, supporting the hypothesis that metabolic rate can explain not only the compositional transition mode (e.g. amphibian/mammals), but also the compositional shifting mode (e.g. fish/fish) of evolution observed for vertebrate genomes., (Copyright © 2010 Elsevier B.V. All rights reserved.)

As all methods for in-vivo dosimetry require special efforts many physicists are often discouraged in verifying the middle dose in a patient along the beam central axis. This work reports a practical method for the determination of the middle dose value, D(m), on the central beam axis, using a signal S(t), obtained by a small thimble ion-chamber positioned at the center of the electronic portal imaging device, and irradiated by the X-ray beam transmitted through the patient. The use of a stable ion-chamber reduces many of the disadvantages associated to the use of diodes as their periodic recalibration and time consuming positioning. The method makes use of a set of correlation functions obtained by the S(t) and D(m) ratios, determined by irradiating a water-equivalent phantom with 6 MV, 10 MV and 5 MV X-ray beams. Several tests were carried out in phantoms with asymmetric inhomogeneities. The method here proposed is based on the determination of the water-equivalent thickness of the patient, along the beam central axis, by the treatment planning system that makes use of the electron densities obtained by a computer tomography scanner, that works with calibrated Hounsfield numbers. This way, it is therefore possible to compare the dose, D(m, TPS), obtained by a treatment planning system, with the in-vivo dose D(m) value, both defined at density middle point (identified along the beam central axis, where the thick material, in terms of g cm(-2), above and below, is the same). The method has been applied for the in-vivo dosimetry of 30 patients, treated with conformed beams for pelvic tumor, checking: anterior-posterior or posterior-anterior irradiations and lateral-lateral irradiations. For every checked field at least five measurements were carried out. Applying a correct quality assurance program based on the tests of the patient set-up, machine settings and calculations, results showed that the method is able to verify agreements between the dose D(m,TPS) and the in-vivo dose value D(m), within 4% for 95% of the 240 measurements carried out in-vivo.

Background: In the last 30 years, the automatization of the hematology laboratory has led to a high increase in the number of full blood counts (FBC) performed daily as well as a very high degree in the quality assessment in terms of accuracy and precision. Moreover, the produced data are so many that their full interpretation needs an expert; often these new parameters are not exploited. The new challenge of the hematology laboratory consists in the translation of numerical data and new parameters into clinical meaningful information also offering, when possible, a pre-diagnostic guideline, maintaining similar high quality level also in these new aspects., Methods: Since the first development of automated cytochemistry for leukocyte differential count, a new efficient pre-microscopic approach to leukemia diagnosis and classification, was made possible at the time of the automated blood cell count. This original method, used by the Bayer hematological H* series and ADVIA120 analyzers, is based on a light assessment of basic cell properties: volume and peroxidase activity (P) in the Perox channel, which is used to differentiate the main leukocyte types according to the different enzyme content and Nuclear density (ND) in the basophil channel, which is used to count basophils and blast cells according the chromatin pattern and to flag the presence of abnormal or immature cells. The simple observation of P and ND two-dimensional cytograms can be used to include any single case in a separate and distinct diagnostic category correlated to FAB and WHO classifications of hematological malignancies. Moreover, on the RBC map, it is possible to obtain some information about the pathological cluster. The simultaneous observation of these three cytograms and the introduction of a simple and quick score provide objective informations on blast lineage, level of myeloid differentiation, chronic versus acute leukemias. Using a simple visual score system, we have reached in a previous study a pre-diagnostic efficiency in 91% of the analyzed samples. ADVIA120 provides cytogram cell distribution at the end of the analytical processes that include the evaluation of 492 signals, the so-called raw data. The working hypothesis is to create a knowledge-based system, an Artificial Neural Network able to directly handle these raw-data for producing classes of diagnostic probability with a high level of efficiency. The Bayer R&D team in Tarrytown has created an ANN software for connecting a set of input data to output through weighted "hidden layers" (i) assessing the 84 ADVIA120 parameter sets to be used, (ii) defining the interim analysis tool for fitting to standard "normal archetypes", (iii) finding a discriminant function normal vs. pathological. We have collected from 22 Italian hematological centers data from peripheral blood of 1000 patients having mainly hematopoietic disorders at diagnosis., Results and Conclusions: The ANN has been trained with labeled samples. Same analysis has been performed for constructing the "pathological archetypes". Finally, we have tested the ANN model with a small selected set of the collected pathological samples. The preliminary encouraging results show the high capability of this ANN of clustering signals according to the pre-defined normal as well as pathological archetypes. The next big step is to create an application for discriminating different types of anemia, simply using data from patient's peripheral blood.