Artificial Intelligence Applied to Forced Spirometry in Primary Care.

Introduction: This study aims to create an artificial intelligence (AI) based machine learning (ML) model capable of predicting a spirometric obstructive pattern using variables with the highest predictive power derived from an active case-finding program for COPD in primary care. Material and methods: A total of 1190 smokers, aged 30-80 years old with no prior history of respiratory disease, underwent spirometry with bronchodilation. The sample was analyzed using AI tools. Based on an exploratory data analysis (EDA), independent variables (according to mutual information analysis) were trained using a gradient boosting algorithm (GBT) and validated through cross-validation. Results: With an area under the curve close to unity, the model predicted a spirometric obstructive pattern using variables with the highest predictive power: FEV1_theoretical_pre values. Sensitivity: 93%. Positive predictive value: 94%. Specificity: 97%. Negative predictive value: 96%. Accuracy: 95%. Precision: 94%. Conclusion: An ML model can predict the presence of an obstructive pattern in spirometry in a primary care smoking population with no prior diagnosis of respiratory disease using the FEV1_theoretical_pre values with an accuracy and precision exceeding 90%. Further studies including clinical data and strategies for integrating AI into clinical workflow are needed.

Introducción: Este estudio tiene como objetivo crear un modelo de aprendizaje automático (ML) basado en inteligencia artificial (IA) capaz de predecir un patrón obstructivo espirométrico utilizando variables con el mayor poder predictivo derivado de un programa activo de búsqueda de casos de enfermedad pulmonar obstructiva crónica (EPOC) en Atención Primaria. Materiales y métodos: Un total de 1.190 fumadores, de entre 30 y 80 años, sin antecedentes de enfermedad respiratoria, fueron sometidos a espirometría con IA artificial. Sobre la base de un análisis de datos exploratorio (EDA), las variables independientes (según el análisis de información mutua) se entrenaron utilizando un algoritmo de gradiente de aumento (GBT) y se validaron mediante validación cruzada. Resultados: Con un área bajo la curva cercana a la unidad, el modelo predijo un patrón obstructivo espirométrico utilizando los valores del FEV1 prebroncodilatador. Sensibilidad: 93%. Valor predictivo positivo: 94%. Especificidad: 97%. Valor predictivo negativo: 96%. Precisión: 95%. Precisión: 94%. Conclusión: Un modelo ML puede predecir la presencia de un patrón obstructivo en la espirometría en una población fumadora de atención primaria sin diagnóstico previo de enfermedad respiratoria utilizando los valores FEV1 prebroncodilatadores con una exactitud y precisión superiores al 90%. Se necesitan más estudios que incluyan datos clínicos y estrategias para integrar la IA en el flujo de trabajo clínico.

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant / Impacto de las puntaciones del riesgo en los resultados de los pacientes con neoplasias mieloides tras el trasplante alogénico de células madre

Background:The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity.Methods:Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed.Results:175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p=0.041.Conclusions:In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS. (AU)

Antecedentes:Las principales causas de fallo del trasplante alogénico de células madre hematopoyéticas (alotrasplante) en pacientes con leucemia mieloide aguda (LMA) y síndromes mielodisplásicos (SMD) son las recaídas y la mortalidad debida al trasplante. Se han diseñado diferentes puntuaciones para predecir el pronóstico de dichos pacientes. El objetivo de este estudio fue evaluar qué puntuación o combinación tiene la mejor capacidad predictiva del resultado.Métodos:Análisis retrospectivo de pacientes con LMA y SMD que recibieron un primer alotrasplante de sangre periférica en un único centro, entre diciembre de 2001 y octubre de 2019. Se calcularon las puntuaciones del Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), del European Group for Blood and Marrow Transplantation (EBMT) y del Disease Risk Index (DRI). Para cada puntuación y para las combinaciones HCT-CI/DRI y HCT-CI/EBMT se analizaron la supervivencia global (SG), la incidencia acumulada de recaídas (CIR), la mortalidad no relativa a las recaídas (NRM) y la supervivencia libre de recaídas y libre de enfermedad de injerto versus huésped (GRFS).Resultados:Se evaluaron 175 pacientes. Con un seguimiento medio (rango) de 3,96 (0,32-17,22) años, las probabilidades a 5años (IC95%) de SG, CIR, NRM y GRFS fueron del 36% (28-44), del 28% (21-35), del 38% (30-46) y del 24% (17-31), respectivamente. Para la SG, solo la puntuación DRI seleccionó dos grupos con diferencias estadísticamente significativas (DRI 0-1: 41% vs. DRI≥2: 24%; p=0,011). La combinación de DRI 0-1 y HCT-CI 0-2 reflejó probabilidades de SG del 45% vs. 26% para los pacientes con DRI 0-1 y HCT-CI≥3 (p=0,041).Conclusiones:En los pacientes con LMA y SMD sometidos a alotrasplante la combinación de las puntuaciones HCT-CI y DRI proporcionó la mejor estratificación para la SG. (AU)

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant.

BACKGROUND: The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity. METHODS: Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed. RESULTS: 175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32-17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%-44%), 28% (21%-35%), 38% (30%-46%) and 24% (17%-31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0-1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0-1 and HCT-CI 0-2 showed OS probabilities of 45% vs. 26% for those with DRI 0-1 and HCT-CI ≥3; p=0.041. CONCLUSIONS: In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS.

Frequent DPH3 promoter mutations in skin cancers.

Recent reports suggested frequent occurrence of cancer associated somatic mutations within regulatory elements of the genome. Based on initial exome sequencing of 21 melanomas, we report frequent somatic mutations in skin cancers in a bidirectional promoter of diphthamide biosynthesis 3 (DPH3) and oxidoreductase NAD-binding domain containing 1 (OXNAD1) genes. The UV-signature mutations occurred at sites adjacent and within a binding motif for E-twenty six/ternary complex factors (Ets/TCF), at -8 and -9 bp from DPH3 transcription start site. Follow up screening of 586 different skin lesions showed that the DPH3 promoter mutations were present in melanocytic nevi (2/114; 2%), melanoma (30/304; 10%), basal cell carcinoma of skin (BCC; 57/137; 42%) and squamous cell carcinoma of skin (SCC; 12/31; 39%). Reporter assays carried out in one melanoma cell line for DPH3 and OXNAD1 orientations showed statistically significant increased promoter activity due to -8/-9CC > TT tandem mutations; although, no effect of the mutations on DPH3 and OXNAD1 transcription in tumors was observed. The results from this study show occurrence of frequent somatic non-coding mutations adjacent to a pre-existing binding site for Ets transcription factors within the directional promoter of DPH3 and OXNAD1 genes in three major skin cancers. The detected mutations displayed typical UV signature; however, the functionality of the mutations remains to be determined.

Anions in pre- and post-blast consumer fireworks by capillary electrophoresis.

Consumer fireworks are a heterogeneous group of pyrotechnic items widely used by citizens around the world. There are a wide number of forensic cases related to consumer fireworks that require knowing their chemical composition and variety of designs to conduct accurate and comprehensive analyses. In this research paper, a selection of six consumer firework types (firecracker, rocket, pyrotechnic fountain, pyrotechnic battery, sparkler, and smoke bomb) is physically described and their anionic compositions are determined. Preblast (fuses and charges) samples and postblast residues of the different consumer fireworks were analyzed by CE in order to determine their anionic composition. Different types of chemical compositions in fuses and pyrotechnic charges were determined, although they were not related to any type of item. Additionally, several discrepancies were found between the analytical results and the declared item compositions. Regarding postblast residues, a huge variety of anions were identified and attributed to some unconsumed starting materials and different chemical reactions occurring during combustion.

Study of the suitability of DUO plastic bags for the storage of dynamites.

A comparative study on the retentiveness of two plastic bags (DUO and Royal Pack) has been carried out by gas chromatography with mass spectrometry detection. Two types of dynamites were packed in both plastic bags. The bags were placed into glass jars and headspace analyses were performed over 11 weeks to detect whether the volatile constituents of the dynamites were released from the bags. DUO plastic bags showed much better retentiveness than Royal Pack plastic bags. Ethylene glycol dinitrate (EGDN) was quickly detected in the headspace of the glass jars containing Royal Pack plastic bags after 1 week of storage. On the contrary, only a weak signal of EGDN, which was not detectable in the total ion chromatogram, was detected after 11 weeks of storage. Moreover, DUO plastic bags have shown less background signals than the Royal Pack bags, being the former bags much more suitable for the storage of dynamites.

Dynamite analysis by Raman spectroscopy as a unique analytical tool.

Apart from powerful explosives, dynamites are complex samples with an intricate analysis. These mixtures of compounds of diverse chemical nature present a challenge to the analyst, and as a result, several analytical techniques need to be applied currently for their analysis. Taking into account that presently there are almost no methods for dynamite analysis in the literature, it is crucial to develop analytical methods that could be applied for the analysis of these samples. This study introduces the use of Raman spectroscopy to analyze dynamites. Two different dynamites made up of ethylene glycol dinitrate and ammonium nitrate, among other minor components, were analyzed by Raman spectroscopy. First, confocal Raman spectroscopy allowed the identification of different components easily distinguished by eye (ammonium nitrate, ethylene glycol dinitrate, and sawdust). Then, Raman mapping was used to show the distribution of the main components throughout the dynamite mass. Finally, several minor components were identified after flocculation (nitrocellulose) or precipitation (sawdust, CaCO3, and flour). The results obtained demonstrate the huge potential of this technique for the analysis of such a complex and tricky sample.

Comparative analysis of smokeless gunpowders by Fourier transform infrared and Raman spectroscopy.

Fourier Transform Infrared (FTIR) and Raman spectroscopic techniques were used to perform a comparative study of the spectral profiles of single-base, double-base and triple-base smokeless gunpowders. Preliminary results based on visual comparison of the spectra point out that spectra obtained by both vibrational techniques were useful for a rapid identification of gunpowders containing dinitrotoluene as one of the major components and triple-base gunpowders. Additionally, the Raman spectra of gunpowders with diphenylamine in its primary composition showed a characteristic band, assigned to 2-nitro-diphenylamine, allowing the identification of this type of gunpowders. Further differentiation among the spectra of different types of smokeless gunpowders obtained by both vibrational spectroscopic techniques was investigated by discriminant analysis. Different analyses were applied to spectral data considering the different composition of gunpowders. The presence or absence of different compounds (such as dinitrotoluene, diphenylamine or dibutyl phthalate) or the type of gunpowder according to the number of active components (single-base or double-base gunpowder) has been taken into account. FTIR and Raman spectroscopy in combination with discriminant analyses were successful tools of forensic interest for the classification of gunpowders and the possible identification of unknown samples of gunpowders.

Why is methenamine detected in Goma-2 dynamites originally methenamine free? An interpretation of relevant forensic results.

After the train bombing in Madrid (Spain) on 11 March 2004, methenamine was detected in some of the specimens of Goma-2 ECO dynamite submitted to the forensic laboratories when analyzed by gas chromatography coupled with mass spectrometry detection (GC-MS). Methenamine is synthesized from formaldehyde and ammonia through a condensation reaction. However, neither methenamine nor any of these compounds were used to manufacture Goma-2 ECO dynamite. Four different experiments were designed in order to explain the presence of methenamine detected in the dynamite samples analyzed. In the first one, GC-MS was used to analyze the individual components of Goma-2 ECO provided by the manufacturer and the components mixed in a raw paste. Methenamine was detected in the manufacturer's ammonium nitrate and in the raw paste. The other experiments were designed to find the precursors sources for methenamine generation in Goma-2 ECO. Results revealed that these sources could be ammonium nitrate for ammonia and sawdust for formaldehyde. Under heating conditions, dynamite could produce these precursors, which could condense in the injection port of the GC-MS system and generate methenamine. However, methenamine was not always detected in these dynamites. This was explained by the existence of two opposite effects: (a) dynamite stability makes difficult that ammonium nitrate releases ammonia and (b) there is a gradual loss of formaldehyde in sawdust along the time. Both effects can prevent the formation of an amount of methenamine large enough to be detected.

Physical fitness in rural and urban children and adolescents from Spain.

OBJECTIVE: We aimed to examine the differences in fitness components between rural and urban Spanish children and adolescents. DESIGN/METHOD: A sample of 2569 school children (1068) and adolescents (1501) from urban and rural areas from the region of Aragón (Spain). Physical fitness was assessed by 7 tests: 20 m shuttle run, speed shuttle run, sit and reach, standing long jump, handgrip strength, bent arm hang and sit-ups in 30s (s). Differences (in fitness and anthropometry) by place of residence were examined by one-way analysis of covariance. RESULTS: Rural young people had higher cardiorespiratory fitness, but lower speed-agility and flexibility than urban young people (all p<0.001; mean differences=1.5 mL/kg per min, 0.4s and 0.9 cm respectively). Regarding muscular fitness, rural young people had a better performance in handgrip strength (mean difference=0.8 kg), bent arm hang (mean difference=2.3s), and a lower performance in sit-ups in 30s (mean difference=0.9s) (all p<0.001), compared to their urban peers. Rural young people had a lower body mass, body mass index (BMI) and sum of skinfolds (all p<0.05; mean differences=1.1 kg, 0.3 kg/m(2) and 4.9 mm respectively) than their urban peers. Effect size was small-medium (Cohen's d=0.1-0.3). CONCLUSION: Rural Spanish children and adolescents had overall a healthier profile than their urban peers in terms of cardiorespiratory fitness, upper- and lower-limb muscular fitness and adiposity, while they performed worse in speed-agility and flexibility. The place of residence should be taken into account when implementing effective interventions to promote physical activity and health.

Study of losses of volatile compounds from dynamites. Investigation of cross-contamination between dynamites stored in polyethylene bags.

The purpose of this work was to study the appropriateness of polyethylene bags for the preservation of explosive specimens. To this end, specimens of two types of dynamites, Goma-2 EC, containing nitroglycol (EGDN) and dinitrotoluene (DNT), and Goma-2 ECO, containing only EGDN, were placed individually inside bags and introduced into hermetically sealed glass jars, which were stored for a period of time. Losses of volatile compounds were studied by headspace analysis using gas chromatography coupled to mass spectrometry (GC-MS). The cross-contamination between dynamites was studied by using high performance liquid chromatography with mass spectrometry (HPLC-MS) to analyse the extracts obtained after a sequential solvent extraction of these specimens. Polyethylene bags permit the loss of volatile compounds since EGDN and DNT were detected in the headspaces of the jars. Moreover, cross-contamination between dynamites was also demonstrated since DNT content decreased in the dynamite containing this compound and increased in the dynamite that had not contained it.

Radiocirugía con acelerador lineal en el tratamiento del schwannoma vestibular / Linear accelerator radiosurgery for the treatment of vestibular schwannoma

Introducción y objetivo. Entre las opciones terapéuticas para pacientes con schwannoma vestibular se encuentra la radiocirugía. Presentamos así nuestra experiencia en el tratamiento de esta patología con esta técnica. Pacientes y métodos. Estudio retrospectivo de 20 pacientes (11 mujeres y 9 varones; edad media: 55,15 años) con diagnóstico de schwannoma vestibular, que recibieron tratamiento con radiocirugía con acelerador lineal desde abril del 2005 hasta diciembre del 2008. El tiempo de seguimiento fue de 12-42 meses, tanto clínico, con valoración de los pares craneales VII (escala de House-Brackmann) y VIII (escala de Gardner-Robertson), como radiológico (con medición del volumen tumoral). Se emplearon el test exacto de Fisher y la prueba de regresión logística para el análisis estadístico. Resultados. El 25% presentó algún empeoramiento de la audición. Cinco pacientes presentaron tumores grandes en el momento del tratamiento (iguales o mayores que 3,5 cm3), de los cuales cuatro empeoraron de cefalea, inestabilidad, mareos/vértigo, parestesias faciales y acúfenos, con una asociación estadísticamente significativa (p < 0,05) en las pruebas aplicadas. A partir del primer año del tratamiento, se observó una tendencia a la disminución del volumen tumoral, sin observarse ningún crecimiento de la lesión a medio-largo plazo, con control local del 100%. Conclusiones. La radiocirugía se ofrece como una alternativa de tratamiento para pacientes con schwannoma vestibular de tamaño adecuado, con alta seguridad terapéutica, que emplea dosis relativamente bajas de radiación, índice bajo de complicaciones y buen control del crecimiento tumoral a medio plazo (AU)

Introduction and aim. Radiosurgery is among the treatment options for patients with vestibular schwannoma. We present the experience in our institution in the treatment of this disease with this technique. Patients and methods. A retrospective study was made including 20 patients (11 women and 9 men; median age: 55.15 years-old) with vestibular schwannoma who received linear accelerator radiosurgery treatment since April 2005 until December 2008. Follow-up period was between 12 and 42 months, considering clinical examination of cranial nerves VII (House-Brackmann scale) and VIII (Gardner-Robertson scale) as well as radiological findings (considering tumor volume). For statistical analysis, the Fisher’s exact test and logistic regression test were used. Results. Certain worsening of hearing function was present in 25% of the patients. Five patients had large tumors at the moment of the treatment (equal or larger than 3.5 cm3), from which four deteriorated from headache, unsteady gait, dizziness/vertigo, facial numbness and tinnitus, with statistical significance (p < 0.05). From the first year of treatment on, there was a tumor volume decrease tendency, with no tumor growth in the medium/long term follow-up, achieving a local control rate of 100%. Conclusions. Radiosurgery has become an alternative in the treatment of patients with vestibular schwannoma of appropriate size, with high safety level, using low radiation doses, low rate of complications and good tumor control rate in the medium term follow-up (AU)

Mujer de 21 años con fiebre, artralgias y leucocitosis / Mujer de 21 años con fiebre, artralgias y leucocitosis

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New protocol for the isolation of nitrocellulose from gunpowders: utility in their identification.

In this work, a new approach for the isolation of nitrocellulose from smokeless gunpowders has been developed. A multistep solvent extraction method was needed to purify nitrocellulose contained in gunpowders. For single-base or double-base gunpowders six consecutive solvent extractions were selected: three extractions with methanol (to remove nitroglycerin, 2,4-dinitrotoluene, ethyl-centralite, diphenylamine, and diphenylamine derivatives); one extraction with dichloromethane (to remove colorants and plasticizers of organic nature); one extraction with methanol (to facilitate a final polar extraction); and one extraction with water (to remove ionic components) were necessary at 35 degrees C. For the triple-base gunpowder studied, eight solvent extractions were needed due to a high concentration of the water-soluble nitroguanidine was present. In addition to the same five initial phases used for the single-base and double-base gunpowders, three water extraction phases at a higher temperature (75 degrees C instead of 35 degrees C) were also needed. A final step to solubilize nitrocellulose in methyl ethyl ketone was used to remove inert components (mainly graphite). Nitrocellulose isolated from these propellants was characterized by Fourier-Transformed Infrared Spectroscopy (FTIR spectroscopy). The same FTIR spectra were observed for nitrocelluloses isolated from different types of gunpowders. A comparison of FTIR spectra of nitrocellulose samples of different nitration degree evidenced that the bands regions most affected by this factor were: 3600-3400cm(-1), corresponding to the stretching vibrations of residual hydroxyl groups; 1200-1000cm(-1), attributed to the valence vibrations nuCO of the glucopyranose cycle; and 750-690cm(-1), assigned to vibrations of the nitrate group. In both cases, the bands appearing in these regions were more pronounced in the spectra of nitrocellulose samples of low nitration degree.

Leucemia promielocítica aguda en un paciente con carcinoma de colon tratado con fluorouracilo / Acute promyelocytic leukemia in a patient with colon adenocarcinoma treated with fluorouracil

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