Valores de referencia del antígeno prostático específico

En el presente estudio se determinaron los valores de referencia del PAS (antígeno prostático específico) en individuos en estado de salud para patologías prostáticas, teniendo en cuenta la falta de información en individuos en estas condiciones. Se incluyeron en el estudio, 618 individuos del sexo masculino, con edades comprendidas entre 40 y 69 años, que concurrieron al laboratorio “Medical Center” entre 1999 y 2001, procedentes de consultorios urológicos, con solicitudes de estudios laboratoriales. Para la selección de los individuos se siguieron las recomendaciones del Panel de Expertos en Teoría de los Valores de Referencia de la IFCC (Federación Internacional de Química Clínica). Individuos sin patología prostática, clínicamente sin dificultad en la micción y examen dígito rectal normal, con resultados negativos alos auxiliares de diagnóstico citoscopía y ecografía. Se realizó la medición con el método inmunoensayo de partículas (MEIA), IMX Abbott, USA. En primer término se analizó el tipo de distribución de los valores de concentración de PAS de todos los individuos, empleando el test deKolmogorov – Smirnov. Los valores de referencia de PAS obtenidos, entre los percentiles 2,5% y 97,5% mostraron diferencias de valores por grupo etário, con aumento progresivo (Kruskall-Wallis, p<0,0001). Los valores de referencia del PAS en ng/mL, fueron: de 40 a 49 años de 0,25 a 2; de50 a 59 años de 0,64 a 3,24; de 60 a 69 años de 0,54 a 3,7. Los valores obtenidos servirán de guía para aplicar criterios de medicina preventiva que ayudaran al profesional de la salud en el diagnóstico precoz de patología prostática

Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach

Under a Creative Commons license.-- et al.Melphalan 200 mg/m2 (MEL200) is the standard conditioning regimen administered to newly diagnosed patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). Few alternatives have been explored in order to improve the antimyeloma activity of this conditioning. We compare i.v. busulfan (BU) 9.6 mg/kg and MEL 140 mg/m2 (MEL140) versus MEL200 mg/m2 as a conditioning regimen before ASCT for newly diagnosed patients with MM. For this purpose, 51 patients receiving i.v. BU plus MEL were compared to 102 patients receiving MEL200 mg/m2 in a 1:2 matched control analysis. Matching criteria included age, clinical stage at diagnosis, and response to induction therapy. No differences in the overall and complete response (CR) rates were observed after ASCT between both groups. After a median follow-up of 63 and 50 months in control and BU plus MEL groups, progression-free survival (PFS) was 24 and 33 months, respectively (P = .10). Most frequent toxicities included mucositis and febrile neutropenia in both groups. No case of sinusoidal obstruction syndrome was observed. Transplant-related mortality was 4% and 2% in BU plus MEL and control groups, respectively. ASCT conditioned with i.v. BU plus MEL may be considered an effective and well-tolerated alternative to a MEL-only approach as a conditioning regimen for patients with MM who are candidates for ASCT. (Clinicaltrials.gov identifier: NCT00560053 and NCT00804947.).This study was supported in part by research funding from grants “Red Temática de Investigación Cooperativa en Cancer”RD06/0020/0031 and RD06/0020/0005 and “Red de Biobancos Hospitalarios”RD09/0076/00021, research project PS09/01882 from the “Instituto de Salud Carlos III”, research grant CA08/00141, CM10/00321 and CM09/00038 from the “Instituto de Salud Carlos III”, and “Ministerio de Ciencia e Innovación” grant BES2008-008053.Peer Reviewe

Opening the 21st Century Technologies to Industries: On the Special Issue Machine Learning for Society

Machine learning techniques, more commonly known today as artificial intelligence, are playing an increasingly important role in all aspects of our lives. Their applications extend to all areas of society where similar techniques can be accommodated to provide efficient and interesting solutions to a wide range of problems. In this Special Issue entitled Machine Learning for Society [1], we present some examples of the applications of this type of technique. From the valuation of unlisted companies to the characterization of clients, through the detection of financial crises or the prediction of the behavior of the exchange rate, this group of works presented here has in common the search for efficient solutions based on a set of historical data, and the application of artificial intelligence techniques. The techniques and datasets used, as well as the relevant findings developed in the different articles of this Special Issue, are summarized below

Quimioterapia a altas dosis y trasplante autólogo de progenitores hematopoyéticos en pacientes con mieloma múltiple. Evaluación de busulfán intravenoso y melfalán como régimen de acondicionamiento

El trasplante autólogo de progenitores hematopoyéticos (TAPH) ha supuesto uno de los avances más importante en el manejo de los paciente jóvenes con mieloma múltiple (02) pero, a pesar de los logros alcanzados con el TAPH en primera línea, no se trata de un procedimiento curativo. Con la intención de mejorar los resultados del TAPH, y tras los datos disponibles con la combinación de busulfán (BU) oral y melfalán (MEL), nos planteamos la utilización de un esquema alternativo al estándar de melfalán (dosis 200 mg/m2) como agente único (MEL200). Este esquema combinaba melfalán y busulfán administrado por vía intravenosa (BU(iv)MEL) lo que permitiría reducir la toxicidad asociada al BU oral. En esta Tesis se analizan los resultados de un estudio fase II en el que se utilizó BU(iv) (dosis única de 3,2 mg/kg/día desde el día −5 al −3) y MEL (140 mg/m2 el día −2) como esquema de acondicionamiento previo al TAPH en pacientes con 02. En el primer artículo se incluyeron 55 pacientes en primera línea o en recaída que recibieron como primera línea de inducción quimioterapia convencional. Tras demostrar con este trabajo la factibilidad del régimen, en el segundo estudio comparamos 51 pacientes con 02 de nuevo diagnóstico tratados con BU(iv)MEL frente a 102 controles que recibieron MEL200. La selección del grupo control se hizo teniendo en cuenta la edad, estadio clínico al diagnóstico y respuesta al tratamiento de inducción. También en este estudio todos los pacientes recibieron inducción con quimioterapia convencional. Tras comprobar que el perfil de toxicidad del régimen BU(iv)MEL era similar al observado con MEL200 y su eficacia anti mieloma no era inferior, se extendió el estudio y se realizó un tercer trabajo en el que se evaluó el impacto de BU(iv)MEL en 47 pacientes con 02 de nuevo diagnóstico tratados con esquemas de inducción basados en bortezomib. La recuperación hematopoyética tuvo lugar en todos los pacientes. La mucositis y la neutropenia febril fueron las toxicidades más frecuentemente observadas con BU(iv)MEL. En el estudio de comparación de BU(iv)MEL y MEL200, la incidencia de mucositis fue mayor con BU(iv)MEL. La incidencia de toxicidad hepática también fue mayor con BU(iv)MEL que con MEL200 pero de grado I-II y reversible sin necesidad de tratamiento específico en todos los casos. No se observó ningún caso de enfermedad venooclusiva hepática. La mortalidad relacionada con el tratamiento (MRT) fue del 3,6% y 4% en el primer y segundo estudio, respectivamente y sin diferencias significativas con respecto a MEL200. Sólo hubo dos pacientes que fallecieron por MRT siendo la infección la causa de muerte en ambos casos. BU(iv)MEL incrementó las tasas de muy buena respuesta parcial o mejor entre un 29% y 38,5% en los diferentes estudios. La tasa de tiempo hasta la progresión al año en el primer estudio fue del 87%. En el estudio de casos y controles con una mediana de seguimiento de 50 y 63 meses, la mediana de supervivencia libre de progresión (SLP) fue de 33 y 24 meses, respectivamente. Finalmente, en el tercer estudio con una mediana de seguimiento de 24,5 meses la mediana de SLP no se había alcanzado. Como esquema de acondicionamiento anti mieloma, BU(iv)MEL es un régimen bien tolerado y con una elevada actividad anti tumoral lo que apoya el desarrollo de estudios aleatorizados que confirmen si los beneficios observados en esta Tesis se reproducen en el contexto actual del tratamiento de los pacientes jóvenes con 02.Autologous stem cell transplant (ASCT) has been one of the most important advances in the treatment of young patients with multiple myeloma (MM) but, in spite of the achievements reached with ASCT as first-line of treatment, it is not a curative procedure. With the aim of improving the results of ASCT, and after the available data with the combination of oral busulfan (BU) and melphalan (MEL), we proposed the use of an alternative preparative regimen to standard single agent melphalan (dose 200 mg/m2) (MEL200). This regimen combined melphalan and busulfan administered intravenously (BU(iv)MEL), which may reduce toxicity associated with oral BU. In this thesis the results of a phase II study are analyzed, in which BU(iv) (a single dose 3.2 mg/kg/day from day −5 to −3) and MEL (140 mg/m2 on day −2) was used as conditioning regimen before ASCT in patients with MM. In the first article, 55 patients in first-line or relapsed were included, who received conventional chemotherapy as first-line induction. After demonstrating with this study the feasibility of the regimen, in the second study we compared 51 patients with newly diagnosed MM treated with BU(iv)MEL with 102 controls who received MEL200. The matching of control group was performed according to age, clinical stage at diagnosis and response to induction treatment. In this study all patients also received conventional chemotherapy as induction. After checking that the toxicity profile of BU(iv)MEL was similar to that observed with MEL200 and that its anti-myeloma efficacy was not inferior, the study was extended to a third study in which the impact of BU(iv)MEL in 47 patients with newly diagnosed MM treated with bortezomib-based combinations as induction therapy were evaluated. Hematopoietic reconstitution was observed in every patient. Mucositis and febrile neutropenia were the most frequently toxicities observed with BU(iv)MEL. In the comparison study BU(iv)MEL and MEL200, the incidence of mucositis was higher with BU(iv)MEL. The incidence of hepatic toxicity was also higher with BU(iv)MEL than with MEL200 but it was grade I-II and reversible without the need for specific treatment in all cases. No cases of hepatic sinusoidal occlusive syndrome were observed. Transplant-related mortality was 3.6% and 4% in the first and second study, respectively and with no significant differences regarding MEL200. There were only two treatment-related deaths, the infection was the cause of death in both cases. BU(iv)MEL increased the very good partial response rate or better by between 29% and 38.5% in the different studies. The time to progression rate per year in the first study was 87%. In the case-control study with a median follow-up of 50 and 63 months, median progression-free survival (PFS) was of 33 and 24 months, respectively. Finally, in the third study with a median follow-up of 24.5 months the median SLP was not been reached. As anti-myeloma conditioning regimen, BU(iv)MEL is a well-tolerated and with high antitumor activity, this supports the development of randomized trials to confirm that the benefits observed in this thesis are reproduced in the current context of treatment of young patients with MM

On the Differential Analysis of Enterprise Valuation Methods as a Guideline for Unlisted Companies Assessment (II): Applying Machine-Learning Techniques for Unbiased Enterprise Value Assessment

The search for an unbiased company valuation method to reduce uncertainty, whether or not it is automatic, has been a relevant topic in social sciences and business development for decades. Many methods have been described in the literature, but consensus has not been reached. In the companion paper we aimed to review the assessment capabilities of traditional company valuation model, based on company’s intrinsic value using the Discounted Cash Flow (DCF). In this paper, we capitalized on the potential of exogenous information combined with Machine Learning (ML) techniques. To do so, we performed an extensive analysis to evaluate the predictive capabilities with up to 18 different ML techniques. Endogenous variables (features) related to value creation (DCF) were proved to be crucial elements for the models, while the incorporation of exogenous, industry/country specific ones, incrementally improves the ML performance. Bagging Trees, Supported Vector Machine Regression, Gaussian Process Regression methods consistently provided the best results. We concluded that an unbiased model can be created based on endogenous and exogenous information to build a reference framework, to price and benchmark Enterprise Value for valuation and credit risk assessment

Sentiment Analysis of Political Tweets From the 2019 Spanish Elections

The use of sentiment analysis methods has increased in recent years across a wide range of disciplines. Despite the potential impact of the development of opinions during political elections, few studies have focused on the analysis of sentiment dynamics and their characterization from statistical and mathematical perspectives. In this paper, we apply a set of basic methods to analyze the statistical and temporal dynamics of sentiment analysis on political campaigns and assess their scope and limitations. To this end, we gathered thousands of Twitter messages mentioning political parties and their leaders posted several weeks before and after the 2019 Spanish presidential election. We then followed a twofold analysis strategy: (1) statistical characterization using indices derived from well-known temporal and information metrics and methods –including entropy, mutual information, and the Compounded Aggregated Positivity Index– allowing the estimation of changes in the density function of sentiment data; and (2) feature extraction from nonlinear intrinsic patterns in terms of manifold learning using autoencoders and stochastic embeddings. The results show that both the indices and the manifold features provide an informative characterization of the sentiment dynamics throughout the election period. We found measurable variations in sentiment behavior and polarity across the political parties and their leaders and observed different dynamics depending on the parties’ positions on the political spectrum, their presence at the regional or national levels, and their nationalist or globalist aspirations

On the Statistical and Temporal Dynamics of Sentiment Analysis

Despite the broad interest and use of sentiment analysis nowadays, most of the conclusions in current literature are driven by simple statistical representations of sentiment scores. On that basis, the generated sentiment evaluation consists nowadays of encoding and aggregating emotional information from a number of individuals and their populational trends. We hypothesized that the stochastic processes aimed to be measured by sentiment analysis systems will exhibit nontrivial statistical and temporal properties. We established an experimental setup consisting of analyzing the short text messages (tweets) of 6 user groups with different nature (universities, politics, musicians, communication media, technological companies, and financial companies), including in each group ten high-intensity users in their regular generation of traffic on social networks. Statistical descriptors were checked to converge at about 2000 messages for each user, for which messages from the last two weeks were compiled using a custom-made tool. The messages were subsequently processed for sentiment scoring in terms of different lexicons currently available and widely used. Not only the temporal dynamics of the resulting score time series per user was scrutinized, but also its statistical description as given by the score histogram, the temporal autocorrelation, the entropy, and the mutual information. Our results showed that the actual dynamic range of lexicons is in general moderate, and hence not much resolution is given within their end-of-scales. We found that seasonal patterns were more present in the time evolution of the number of tweets, but to a much lesser extent in the sentiment intensity. Additionally, we found that the presence of retweets added negligible effects over standard statistical modes, while it hindered informational and temporal patterns. The innovative Compounded Aggregated Positivity Index developed in this work proved to be characteristic for industries and at ..

Intravenous Busulfan and Melphalan as a Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Matched Comparison to a Melphalan-Only Approach

AbstractMelphalan 200 mg/m2 (MEL200) is the standard conditioning regimen administered to newly diagnosed patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). Few alternatives have been explored in order to improve the antimyeloma activity of this conditioning. We compare i.v. busulfan (BU) 9.6 mg/kg and MEL 140 mg/m2 (MEL140) versus MEL200 mg/m2 as a conditioning regimen before ASCT for newly diagnosed patients with MM. For this purpose, 51 patients receiving i.v. BU plus MEL were compared to 102 patients receiving MEL200 mg/m2 in a 1:2 matched control analysis. Matching criteria included age, clinical stage at diagnosis, and response to induction therapy. No differences in the overall and complete response (CR) rates were observed after ASCT between both groups. After a median follow-up of 63 and 50 months in control and BU plus MEL groups, progression-free survival (PFS) was 24 and 33 months, respectively (P = .10). Most frequent toxicities included mucositis and febrile neutropenia in both groups. No case of sinusoidal obstruction syndrome was observed. Transplant-related mortality was 4% and 2% in BU plus MEL and control groups, respectively. ASCT conditioned with i.v. BU plus MEL may be considered an effective and well-tolerated alternative to a MEL-only approach as a conditioning regimen for patients with MM who are candidates for ASCT. (Clinicaltrials.gov identifier: NCT00560053 and NCT00804947.

Clinico‐biological features and outcome of patients with splenic marginal zone lymphoma with histological transformation

We describe 36 patients with splenic marginal zone lymphoma (SMZL) with transformation (SMZL-T), including 15 from a series of 84 patients with SMZL diagnosed at the Hospital Clinic of Barcelona (HCB) and 21 diagnosed with SMZL-T in other centres. In the HCB cohort, the cumulative incidence of transformation at 5 years was 15%. Predictors for transformation were cytopenias, hypoalbuminaemia, complex karyotype (CK) and both the Intergruppo Italiano Linfomi (ILL) and simplified Haemoglobin, Platelet count, lactate dehydrogenase (LDH) and extrahilar Lymphadenopathy (HPLL)/ABC scores (P < 0·05). The only independent predictor for transformation in multivariate analysis was CK [hazard ratio (HR) 4·025, P = 0·05]. Patients with SMZL-T had a significantly higher risk of death than the remainder (HR 3·89, P < 0·001). Of the 36 patients with SMZL-T, one developed Hodgkin lymphoma and 35 a diffuse large B-cell lymphoma, 71% with a non-germinal centre phenotype. The main features were B symptoms, lymphadenopathy, and high serum LDH. CK was observed in 12/22 (55%) SMZL-T and fluorescence in situ hybridisation detected abnormalities of MYC proto-oncogene, basic helix-loop-helix transcription factor (MYC), B-cell leukaemia/lymphoma 2 (BCL2) and/or BCL6 in six of 14 (43%). In all, 21 patients received immunochemotherapy, six chemotherapy, one radiotherapy and three splenectomy. The complete response (CR) rate was 61% and the median survival from transformation was 4·92 years. Predictors for a worse survival in multivariate analysis were high-risk International Prognostic Index (HR 5·294, P = 0·016) and lack of CR (HR 2·67, P < 0·001)

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation