Lung cancer risk associated with occupations in women: a pooling study.

BACKGROUND: Occupation is an important risk factor for lung cancer. This knowledge is mainly based on studies conducted on men, with the results being generalized to women. AIMS: We aimed to identify the relationship between different occupations and lung cancer in women. METHODS: Pooling study in which data were pooled from six case-control studies conducted at 13 Spanish hospitals and 1 hospital in Portugal. Each woman's longest held job was coded as per the ISCO-08. Results were adjusted for age, smoking, and exposure to residential radon. RESULTS: The study population comprised 1262 women: 618 cases and 644 controls. The reference group were white-collar workers. The adjusted multivariate analysis showed a higher risk of developing lung cancer among teaching professionals (odds ratio [OR]: 4.36; 95% confidence interval [CI] 1.73-11.02), cooks (OR: 3.59; 95% CI 1.52-8.48), domestic cleaners and helpers (OR: 2.98; 95% CI 1.54-5.78), homemakers (OR: 2.30; 95% CI 1.26-4.21) and crop farmers, livestock farmers and gardeners (OR: 2.06, 95% CI: 1.11-3.81). For adenocarcinoma, the highest risk was observed in teaching professionals, and for small-cell carcinoma, the highest risk was observed in cooks. Higher risks were observed for small-cell carcinoma compared to other histological types. CONCLUSIONS: Some occupations may be associated with an increased risk of lung cancer in women and this risk could vary by histologic subtype; however, further research is needed to confirm these associations. In any case, protection measures must be implemented in the workplace aimed at reducing the risk of lung cancer among women workers, and more studies exclusively focused on women are warranted.

Self-perceived body weight and weight status: analysis of concordance by age group and sex.

OBJECTIVES: Previous studies suggest that there is discordance between actual weight status and body-weight perception. This fact has implications when it comes to designing public health interventions. The aim of this study was to estimate the prevalence of the different categories of weight status and body-weight perception and to analyse their concordance in a representative Spanish population sample. STUDY DESIGN: Cross-sectional study. METHODS: Data were sourced from the 2018 Galician Risk Behaviour Data System, with the target population being all persons aged 16 years and above. We collected data on self-perceived body weight and assessed weight status on the basis of body mass index (BMI). BMI was estimated using self-reported measures of weight and height. To estimate concordance, Cohen's kappa coefficient, both unweighted and weighted with Cicchetti weights, was calculated. RESULTS: Data were obtained for 7853 individuals aged 16 years and above, whereas the overall unweighted concordance was 0.393 (95%CI: 0.377-0.409), with an agreement percentage of 61.6%, weighted concordance was 0.503 (0.490-0.517), with an agreement percentage of 86.6%. The highest concordance between self-perceived body weight and weight status was observed in women. By age group, the highest concordance was observed in the youngest group (16-24 years) for the BMI categories of underweight and overweight, and in the 45-64 age group for the category of obesity. CONCLUSIONS: The results highlight the existence of differences between self-perceived body weight and weight status, according to sex and age.

Smoking-attributable mortality by sex in the 27 Brazilian federal units: 2019.

OBJECTIVES: The aim of this study was to estimate smoking-attributable mortality (SAM) in the population aged 35 years and over in Brazil's 27 federal units by sex, in 2019. STUDY DESIGN: This is an attributable mortality analysis. METHODS: We applied a method dependent on the prevalence of smoking, based on the population attributable fractions. Data on mortality due to causes causally related to smoking were derived from Brazil's Death Registry, data on prevalence of smoking from a survey conducted in Brazil in 2019, and data on relative risks from five US cohorts. Crude and age-adjusted SAM rates were calculated by sex. Estimates of SAM were calculated by specific causes of death and major mortality groups for each federal unit by sex. RESULTS: In 2019, smoking caused 480 deaths per day in Brazil. Although the SAM varied among the federal units, the pattern is not clear, with the greatest difference being between Rio Grande do Sul (crude rate: 248.8/100,000 inhabitants) and Amazonas (106.0/100,000). When the rates were adjusted by age, the greatest differences were observed between Acre (271.1/100,000) and Distrito Federal (131.1/100,000). SAM was higher in males; however, while the main specific cause of SAM in men was ischemic heart disease, in women it was chronic obstructive pulmonary disease. The major mortality group having the greatest impact on SAM across all federal units was the cardiometabolic diseases. CONCLUSIONS: The variability in the burden of SAM in the different regions of Brazil reaffirms the need for SAM data disaggregated at the geographic level.

Hospitalizaciones por y con enfermedad pulmonar obstructiva crónica en Galicia: 20 años de evolución / Hospitalizations due to and with chronic obstructive pulmonary disease in Galicia: 20 years of evolution

Objetivo Analizar la evolución de las hospitalizaciones relacionadas con enfermedad pulmonar obstructiva crónica (EPOC) en Galicia en el período 1996-2018, tanto como causa principal del ingreso (POR EPOC) como si se codificaba en cualquier posición diagnóstica (CON EPOC), estudiando la influencia de la edad, el sexo, la estacionalidad u otras causas principales del ingreso. Metodología Se realizó un análisis del conjunto mínimo básico de datos (CMBD) de Galicia sobre el primer ingreso por EPOC entre 1996 y 2018. Se calcularon tasas brutas, específicas y estandarizadas tanto globales como por sexo y por grupos de edad. Resultados En el período 1996-2018 se produjeron en Galicia 310.883 primeros ingresos CON EPOC, de los que el 29,6% fueron POR EPOC. Las tasas de ingresos tanto CON EPOC como POR EPOC aumentaron, fundamentalmente en varones. Existe una clara estacionalidad de los ingresos, especialmente relevante POR EPOC. La razón de masculinidad media es aproximadamente 4 en ambos escenarios, si bien es inferior en los grupos etarios extremos, sin cambios a lo largo del tiempo. La edad media al ingreso ha aumentado tres años en este período en los varones; en las mujeres no hubo variaciones. Las causas principales del ingreso cuando no es POR EPOC son insuficiencia cardíaca y neumonía. Conclusión La evaluación combinada de los registros de ingresos hospitalarios CON y POR EPOC aporta información complementaria para un mejor conocimiento de las tendencias de esta enfermedad y establecer hipótesis que expliquen los resultados descritos, aportando información para una mejor planificación sanitaria (AU)

Objective This work aims to analyze the evolution of COPD-related hospitalizations in Galicia from 1996 to 2018 both as main cause of admission (DUE TO COPD) or when coded in any diagnostic order (WITH COPD), assessing the influence of age, sex, seasonality, and other main causes of the hospitalization. Methods An analysis was conducted of administrative healthcare database (CMBD) data on index COPD-related hospitalizations in Galicia from 1996 to 2018. Crude, specific, and standardized rates were calculated for the entire sample and according to age and sex groups. Results In the period from 1996 to 2018, there were 310,883 index admissions WITH COPD in Galicia, of which 29.6% were DUE TO COPD. Both WITH COPD and DUE TO COPD admission rates increased, mainly in men. There was a clear seasonality that was especially relevant in the DUE TO COPD group. The mean male-to-female ratio was approximately 4:1 in both groups, although it was lower in the extreme age groups, with no change over time. The mean age at admission increased three years in men during this period; there were no changes among women. The main causes of admission in those not hospitalized DUE TO COPD were heart failure and pneumonia. Conclusion The combined evaluation of records of hospital admissions WITH COPD and DUE TO COPD offers additional information for a better understanding of the trends of this disease and allows for establishing hypotheses that explain the results described, providing information for better healthcare planning (AU)

Hospitalizations due to and with chronic obstructive pulmonary disease in Galicia: 20 years of evolution.

OBJECTIVE: This work aims to analyze the evolution of COPD-related hospitalizations in Galicia from 1996 to 2018 both as main cause of admission (DUE TO COPD) or when coded in any diagnostic order (WITH COPD), assessing the influence of age, sex, seasonality, and other main causes of the hospitalization. METHODS: An analysis was conducted of administrative healthcare database (CMBD) data on index COPD-related hospitalizations in Galicia from 1996 to 2018. Crude, specific, and standardized rates were calculated for the entire sample and according to age and sex groups. RESULTS: In the period from 1996 to 2018, there were 310,883 index admissions WITH COPD in Galicia, of which 29.6% were DUE TO COPD. Both WITH COPD and DUE TO COPD admission rates increased, mainly in men. There was a clear seasonality that was especially relevant in the DUE TO COPD group. The mean male-to-female ratio was approximately 4:1 in both groups, although it was lower in the extreme age groups, with no change over time. The mean age at admission increased three years in men during this period; there were no changes among women. The main causes of admission in those not hospitalized DUE TO COPD were heart failure and pneumonia. CONCLUSION: The combined evaluation of records of hospital admissions WITH COPD and DUE TO COPD offers additional information for a better understanding of the trends of this disease and allows for establishing hypotheses that explain the results described, providing information for better healthcare planning.

Mantenimiento del consumo de pescado rico en metilmercurio durante el embarazo: prevalencia, consejo profesional y características maternas asociadas / Maintaining methylmercury-rich fish consumption during pregnancy: prevalence, professional advice and associated maternal characteristics

Introducción: los objetivos de este estudio fueron estimar la prevalencia del consumo de pescado rico en metilmercurio (MeHg) durante el embarazo, la proporción de mujeres que recibieron recomendaciones sanitarias para evitar su consumo e identificar los factores asociados al mantenimiento del consumo. Material y métodos: en 2016 se realizó un estudio transversal siendo la población objetivo mujeres que habían dado a luz entre septiembre de 2015 y agosto de 2016 en Galicia (España). La información sobre el estado de la mujer seis meses antes del embarazo, durante el embarazo, en el momento del parto y en el momento de la encuesta se obtuvo con una entrevista telefónica estructurada. La prevalencia de consumo de pescados ricos en MeHg se estimó antes y durante la gestación y se ajustó un modelo de regresión logística para conocer las variables asociadas con el mantenimiento. Resultados: el consumo de pescado rico en MeHg fue del 30% durante los seis meses previos a la gestación y disminuyó a 7% durante esta. El mantenimiento del consumo se asoció con no vivir en entorno urbano, multiparidad, consumir más de una porción de pescado rico en MeHg/semana antes de la gestación y con no haber recibido recomendaciones profesionales para evitar el consumo; 5 de cada 10 mujeres recibieron estas recomendaciones durante los controles prenatales. Conclusiones: algunos factores asociados con continuar consumiendo pescados ricos en MeHg durante el embarazo son modificables y deben ser considerados en la elaboración de mensajes de salud pública destinados a promover una alimentación adecuada durante el embarazo (AU)

Introduction: Our aims were to estimate the prevalence of MeHg-rich fish consumption, the proportion of women who received healthcare recommendations to avoid their consumption and to identify the factors associated with the maintenance of consumption during pregnancy.Material and methods: In 2016, a cross-sectional study based on a random sampling of all the women who had given birth between September 2015 and August 2016 was conducted in Galicia, Spain. Information was collected through a structured telephone interview regarding the mother’s status 6 months before pregnancy, during pregnancy, at the time of delivery, and at the time of the survey. The prevalence of MeHg-rich fish consumption, was estimated before and during pregnancy and a logistic regression model was adjusted to ascertain variables associated with maintaining consumption during pregnancy.Results: The consumption of swordfish or bluefin, was 30% during the 6 months prior to pregnancy and decreased to 7% during pregnancy. Maintenance of MeHg-rich fish consumption during pregnancy was associated with not living in an urban environment, multiparity, consumption of over 1 portion of MeHg-rich fish per week prior pregnancy, and with not having received professional recommendations in order to avoid consumption; 5 out of 10 women received these recommendations during the prenatal check-ups.Conclusions: Some of the factors associated with continuing the consumption during pregnancy are modifiable and should be considered in the development of public health messages intended to promote an adequate diet during pregnancy. (AU)

A decision-tree approach for the differential diagnosis of chronic lymphoid leukemias and peripheral B-cell lymphomas.

BACKGROUND AND OBJECTIVE: Here we propose a decision-tree approach for the differential diagnosis of distinct WHO categories B-cell chronic lymphoproliferative disorders using flow cytometry data. Flow cytometry is the preferred method for the immunophenotypic characterization of leukemia and lymphoma, being able to process and register multiparametric data about tens of thousands of cells per second. METHODS: The proposed decision-tree is composed by logistic function nodes that branch throughout the tree into sets of (possible) distinct leukemia/lymphoma diagnoses. To avoid overfitting, regularization via the Lasso algorithm was used. The code can be run online at https://codeocean.com/2018/03/08/a-decision-tree-approach-for-the-differential-diagnosis-of-chronic-lymphoid-leukemias-and-peripheral-b-cell-lymphomas/ or downloaded from https://github.com/lauramoraes/bioinformatics-sourcecode to be executed in Matlab. RESULTS: The proposed approach was validated in diagnostic peripheral blood and bone marrow samples from 283 mature lymphoid leukemias/lymphomas patients. The proposed approach achieved 95% correctness in the cross-validation test phase (100% in-sample), 61% giving a single diagnosis and 34% (possible) multiple disease diagnoses. Similar results were obtained in an out-of-sample validation dataset. The generated tree reached the final diagnoses after up to seven decision nodes. CONCLUSIONS: Here we propose a decision-tree approach for the differential diagnosis of mature lymphoid leukemias/lymphomas which proved to be accurate during out-of-sample validation. The full process is accomplished through seven binary transparent decision nodes.

From big flow cytometry datasets to smart diagnostic strategies: The EuroFlow approach.

The rise in the analytical speed of mutiparameter flow cytometers made possible by the introduction of digital instruments, has brought up the possibility to manage progressively higher number of parameters simultaneously on significantly greater numbers of individual cells. This has led to an exponential increase in the complexity and volume of flow cytometry data generated about cells present in individual samples evaluated in a single measurement. This increase demands for new developments in flow cytometry data analysis, graphical representation, and visualization and interpretation tools to address the new big data challenges, i.e. processing data files of ≥10-25 parameters per cell in samples with >5-10 million cells (= up to 250 million data points per cell sample) obtained in a few minutes. Here, we present a comprehensive review of some of the tools developed by the EuroFlow consortium for processing flow cytometric big data files in diagnostic laboratories, particularly focused on automated EuroFlow approaches for: i) identification of all cell populations coexisting in a sample (automated gating); ii) smart classification of aberrant cell populations in routine diagnostics; iii) automated reporting; together with iv) new tools developed to visualize n-dimensional data in 2-dimensional plots to support expert-guided automated data analysis. The concept of using reference data bases implemented into software programs, in combination with multivariate statistical analysis pioneered by EuroFlow, provides an innovative, highly efficient and fast approach for diagnostic screening, classification and monitoring of patients with distinct hematological and immune disorders, as well as other diseases.

Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia.

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.

Impact of maternal education level on risk of low Apgar score.

OBJECTIVE: To investigate the association between 5-min Apgar score and socio-economic characteristics of pregnant women, particularly education level. STUDY DESIGN: Population-based cross-sectional study. METHODS: This study used hospital records of live term singleton births in Brazil from 2004 to 2009, obtained from the Ministry of Health National Information System. Crude and adjusted odds ratios (ORs) were used to estimate the risk of a low 5-min Apgar score (≤6) associated with maternal education level, maternal age, marital status, primiparity, number of prenatal visits and mode of delivery (vaginal/caesarean section). RESULTS: Nearly 12 million records were analysed. Births from mothers with 0, 1-3, 4-7 and 8-11 years of education resulted in crude ORs for low 5-min Apgar score of 3.1, 2.2, 1.8 and 1.3, respectively (reference: ≥12 years of education). The crude OR for mothers aged ≥41 years (reference 21-34 years) was 1.4, but no risk was detected for those with ≥12 years of education and those who gave birth by caesarean section (OR 1.0 [95% confidence interval 0.9-1.2]). Generally, the risk of a low 5-min Apgar score was found to increase as maternal age moved away from 21 to 34 years (OR 1.1-1.7), and for mothers with the same characteristics, the risk of a low 5-min Apgar score was found to decrease markedly as education level increased (adjusted OR decreased from 2.6 to 1.2). CONCLUSION: Maternal education level is clearly associated with the risk of a low 5-min Apgar score.

Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings.

Scalp EEG recordings and the classification of interictal epileptiform discharges (IED) in patients with epilepsy provide valuable information about the epileptogenic network, particularly by defining the boundaries of the "irritative zone" (IZ), and hence are helpful during pre-surgical evaluation of patients with severe refractory epilepsies. The current detection and classification of epileptiform signals essentially rely on expert observers. This is a very time-consuming procedure, which also leads to inter-observer variability. Here, we propose a novel approach to automatically classify epileptic activity and show how this method provides critical and reliable information related to the IZ localization beyond the one provided by previous approaches. We applied Wave_clus, an automatic spike sorting algorithm, for the classification of IED visually identified from pre-surgical simultaneous Electroencephalogram-functional Magnetic Resonance Imagining (EEG-fMRI) recordings in 8 patients affected by refractory partial epilepsy candidate for surgery. For each patient, two fMRI analyses were performed: one based on the visual classification and one based on the algorithmic sorting. This novel approach successfully identified a total of 29 IED classes (compared to 26 for visual identification). The general concordance between methods was good, providing a full match of EEG patterns in 2 cases, additional EEG information in 2 other cases and, in general, covering EEG patterns of the same areas as expert classification in 7 of the 8 cases. Most notably, evaluation of the method with EEG-fMRI data analysis showed hemodynamic maps related to the majority of IED classes representing improved performance than the visual IED classification-based analysis (72% versus 50%). Furthermore, the IED-related BOLD changes revealed by using the algorithm were localized within the presumed IZ for a larger number of IED classes (9) in a greater number of patients than the expert classification (7 and 5, respectively). In contrast, in only one case presented the new algorithm resulted in fewer classes and activation areas. We propose that the use of automated spike sorting algorithms to classify IED provides an efficient tool for mapping IED-related fMRI changes and increases the EEG-fMRI clinical value for the pre-surgical assessment of patients with severe epilepsy.

Green leaf allowance and dairy ewe performance grazing on tropical pasture.

The objective of this study was to explain the influence of green leaf allowance levels on the performance of dairy ewes grazing a tropical grass. Seventy-two lactating ewes grazed Aruana guineagrass (Panicum maximum Jacq. cv. Aruana) for 80 d. The treatments were 4 daily levels of green leaf allowance (GLA) on a DM basis corresponding to 4, 7, 10, and 13 kg DM/100 kg BW, which were named low, medium-low, medium-high, and high level, respectively. The experimental design was completely randomized with 3 replications. During the experimental period, 4 grazing cycles were evaluated in a rotational stocking grazing method (4 d of grazing and 16 d of rest). There was a linear effect of GLA on forage mass, and increasing GLA resulted in increased total leaf mass, reaching an asymptotic plateau around the medium-high GLA level. The stem mass increased with increased GLA, and a pronounced increase was observed between medium-high and high GLAs. Increasing GLA increased both forage disappearance rate and postgrazing forage mass. Leaf proportion increased with GLA, peaking at the medium-high level, and the opposite occurred for stem proportions, which reduced until medium-high GLA level, followed by an increase on high GLA. Forage CP decreased linearly with GLA, and increasing GLA from low to high reduced CP content by 31%. On the other hand, NDF increased 14% and ADF increased 26%, both linearly in response to greater GLA levels. Total digestible nutrients decreased linearly by 8% when GLA increased from low to high level. Milk yield increased, peaking at medium-high GLA (1.75 kg ewe(-1) d(-1)) and decreased at high GLA level (1.40 kg ewe(-1) d(-1)). Milk composition was not affected by the GLA levels. There was a reduction in stocking rate from 72 to 43 ewes/ha when GLA increased from low to high level. Productivity (milk yield kg ha(-1) d(-1)) increased as GLA increased, peaking at medium-low level (115 kg ha(-1) d(-1)). Although this tropical grass showed the same pattern in responses to GLA levels as reported in the literature with temperate pastures, the magnitude of the process changed and the maximum response in milk yield from lactating dairy ewes grazing a tropical pasture would be achieved with higher forage allowances than in temperate pastures. Overall, Aruana guineagrass grazed by lactating dairy ewes should be managed to provide 7 to 10 GLA in kg DM/100 kg BW according to the production goals.

Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping.

Immunophenotypic characterization of B-cell chronic lymphoproliferative disorders (B-CLPD) is becoming increasingly complex due to usage of progressively larger panels of reagents and a high number of World Health Organization (WHO) entities. Typically, data analysis is performed separately for each stained aliquot of a sample; subsequently, an expert interprets the overall immunophenotypic profile (IP) of neoplastic B-cells and assigns it to specific diagnostic categories. We constructed a principal component analysis (PCA)-based tool to guide immunophenotypic classification of B-CLPD. Three reference groups of immunophenotypic data files-B-cell chronic lymphocytic leukemias (B-CLL; n = 10), mantle cell (MCL; n = 10) and follicular lymphomas (FL; n = 10)--were built. Subsequently, each of the 175 cases studied was evaluated and assigned to either one of the three reference groups or to none of them (other B-CLPD). Most cases (89%) were correctly assigned to their corresponding WHO diagnostic group with overall positive and negative predictive values of 89 and 96%, respectively. The efficiency of the PCA-based approach was particularly high among typical B-CLL, MCL and FL vs other B-CLPD cases. In summary, PCA-guided immunophenotypic classification of B-CLPD is a promising tool for standardized interpretation of tumor IP, their classification into well-defined entities and comprehensive evaluation of antibody panels.

A new local-global approach for classification.

In this paper, we propose a new local-global pattern classification scheme that combines supervised and unsupervised approaches, taking advantage of both, local and global environments. We understand as global methods the ones concerned with the aim of constructing a model for the whole problem space using the totality of the available observations. Local methods focus into sub regions of the space, possibly using an appropriately selected subset of the sample. In the proposed method, the sample is first divided in local cells by using a Vector Quantization unsupervised algorithm, the LBG (Linde-Buzo-Gray). In a second stage, the generated assemblage of much easier problems is locally solved with a scheme inspired by Bayes' rule. Four classification methods were implemented for comparison purposes with the proposed scheme: Learning Vector Quantization (LVQ); Feedforward Neural Networks; Support Vector Machine (SVM) and k-Nearest Neighbors. These four methods and the proposed scheme were implemented in eleven datasets, two controlled experiments, plus nine public available datasets from the UCI repository. The proposed method has shown a quite competitive performance when compared to these classical and largely used classifiers. Our method is simple concerning understanding and implementation and is based on very intuitive concepts.

Generalized risk zone: selecting observations for classification.

In this paper, we extend the risk zone concept by creating the Generalized Risk Zone. The Generalized Risk Zone is a model-independent scheme to select key observations in a sample set. The observations belonging to the Generalized Risk Zone have shown comparable, in some experiments even better, classification performance when compared to the use of the whole sample. The main tool that allows this extension is the Cauchy-Schwartz divergence, used as a measure of dissimilarity between probability densities. To overcome the setback concerning pdf's estimation, we used the ideas provided by the Information Theoretic Learning, allowing the calculation to be performed on the available observations only. We used the proposed methodology with Learning Vector Quantization, feedforward Neural Networks, Support Vector Machines, and Nearest Neighbors.

A probabilistic approach for the evaluation of minimal residual disease by multiparameter flow cytometry in leukemic B-cell chronic lymphoproliferative disorders.

Multiparameter flow cytometry has become an essential tool for monitoring response to therapy in hematological malignancies, including B-cell chronic lymphoproliferative disorders (B-CLPD). However, depending on the expertise of the operator minimal residual disease (MRD) can be misidentified, given that data analysis is based on the definition of expert-based bidimensional plots, where an operator selects the subpopulations of interest. Here, we propose and evaluate a probabilistic approach based on pattern classification tools and the Bayes theorem, for automated analysis of flow cytometry data from a group of 50 B-CLPD versus normal peripheral blood B-cells under MRD conditions, with the aim of reducing operator-associated subjectivity. The proposed approach provided a tool for MRD detection in B-CLPD by flow cytometry with a sensitivity of < or =8 x 10(-5) (median of < or =2 x 10(-7)). Furthermore, in 86% of B-CLPD cases tested, no events corresponding to normal B-cells were wrongly identified as belonging to the neoplastic B-cell population at a level of < or =10(-7). Thus, this approach based on the search for minimal numbers of neoplastic B-cells similar to those detected at diagnosis could potentially be applied with both a high sensitivity and specificity to investigate for the presence of MRD in virtually all B-CLPD. Further studies evaluating its efficiency in larger series of patients, where reactive conditions and non-neoplastic disorders are also included, are required to confirm these results.

A new automated flow cytometry data analysis approach for the diagnostic screening of neoplastic B-cell disorders in peripheral blood samples with absolute lymphocytosis.

Currently, multiparameter flow cytometry immunophenotyping is the selected method for the differential diagnostic screening between reactive lymphocytosis and neoplastic B-cell chronic lymphoproliferative disorders (B-CLPD). Despite this, current multiparameter flow cytometry data analysis approaches still remain subjective due to the need of experienced personnel for both data analysis and interpretation of the results. In this study, we describe and validate a new automated method based on vector quantization algorithms to analyze multiparameter flow cytometry immunophenotyping data in a series of 307 peripheral blood (PB) samples. Our results show that the automated method of analysis proposed compares well with currently used manual approach and significantly improves semiautomated approaches and, that by using it, a highly efficient discrimination with 100% specificity and 100% sensitivity can be made between normal/reactive PB samples and cases with B-CLPD based on the total B-cell number and/or the sIgkappa+/sIglambda+ B-cell ratio. In addition, the method proved to be able to detect the presence of pathologic neoplastic B-cells even when these are present at low frequencies (<5% of all lymphocytes in the sample) and in poor-quality samples enriched in 'noise' events.

Health related quality of life and psychological outcome in patients treated for craniopharyngioma in childhood.

UNLABELLED: Patients with craniopharyngioma are at risk for many adverse effects related to the tumour's invasive behaviour and its proximity to many vital structures. Profound psychosocial problems, memory impairment, pituitary and hypothalamic dysfunction in addition to the physical handicap of visual loss are frequently recognized sequelae of craniopharyngioma treatment. OBJECTIVES: To examine health related quality of life (QoL) and psychological outcomes of patients treated for craniopharyngioma at the Royal Children's Hospital, Melbourne, between January 1980 and September 2003. PATIENTS: Seven (17.4%) of 46 (26 male) had died. Thirty-nine remained, of whom 30 were contactable. Eighteen of 30 (8 male), mean age 21.2 +/- 6.7 years, agreed to evaluation, of whom 16/18 (88.9%) had three or more pituitary hormone deficiencies, 11/18 had visual impairment and 9/18 obesity. MEASUREMENTS: The Adult GH-Deficient Assessment (AGHDA) and Psychological General Well-Being (PGWB) questionnaires were employed to assess quality of life in patients and age- and sex-matched healthy controls. Additional psychological assessment, including intellectual and academic skills, emotional function, and adaptive behaviour, had been undertaken in 12 patients at a previous time. RESULTS: High levels of physical morbidity and psychological disability were described. The General Health score of patients was significantly worse than for controls on PGWB (p = 0.025), anxiety was higher in those who had surgery alone (p = 0.008) and subjective QoL associated with GHD using AGHDA was lower (p = 0.006). Few craniopharyngioma survivors (18/30) were available for evaluation, demonstrating difficulties in attempts to assess this complex group. The discrepancy between results of objective and subjective measures of QoL is discussed in terms of adaptation to illness, disabilities and changed perception of life fulfilment. CONCLUSIONS: Craniopharyngioma and its treatment result in significant, complex medical, social, psychological and emotional difficulties. The degree of global disability is not reflected in subjective QoL reports for this group, highlighting the need for careful selection of assessment instruments.