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1. Quantification of nitromethane in mainstream smoke using gas chromatography and tandem mass spectrometry

Author

Juliana Giraldo Junco, Gala M. Chapman, Roberto Bravo Cardenas, Clifford H. Watson, and Liza Valentín-Blasini

Subjects
Nitromethane, Mainstream smoke, GC–MS/MS, Tobacco analysis, Toxicology. Poisons, RA1190-1270
Abstract

Nitromethane is a volatile organic compound categorized as a Group 2B carcinogen by the International Agency for Research on Cancer. It has been detected in mainstream cigarette smoke, but few reliable methods have been reported for accurate quantification. We developed, a sensitive, selective, fully validated method for the targeted determination of nitromethane in mainstream tobacco smoke in ten U.S. domestic brands and two quality control materials (3R4F and CM6). The vapor phase portion of machine-generated cigarette mainstream smoke, under modified ISO 3308:2000 regime (ISO) and modified intense regime (HCI), from single cigarettes was collected using airtight polyvinylfluoride sampling bags. The bags’ contents were extracted using methanol containing an isotopically labeled internal standard followed by gas chromatography-tandem mass spectrometry. This approach is sufficiently sensitive to measure nitromethane levels in the nanogram range, with a method limit of detection of 72.3 ng/cig. Within-product variability estimated from the replicate analysis of 10 products ranged from 4.6%–16.3% (n = 6) over the two different smoking regimes, and method reproducibility estimated from two products used as quality control materials (3R4F and CM6) yielded intermediate precision values ranging from 16.6 to 20.8% (n = 20). Under HCI, nitromethane yields in machine-generated cigarette smoke from ten different domestic cigarette products ranged from 3.2 to 12 μg/cig; under ISO yields ranged from 1.6 to 4.9 μg/cig under standardized smoking machine conditions.Nitromethane yields are related to both the smoke regime (blocking of vent holes, puff duration and puff volume) and the heterogeneity of tobacco mixtures. This method provides a selective and fully validated technique to accurately quantify nitromethane in mainstream cigarette smoke, with minimal waste generation. It is an improvement over previous methods with regards to specificity, throughput, and simplicity of the sample collection process.

Published
2021
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2. The impact of hydrostatic pressure, nonstoichiometry, and doping on trimeron lattice excitations in magnetite during axis switching

Author

Kołodziej, T., Piętosa, J., Puźniak, R., Wiśniewski, A., Król, G., Kąkol, Z., Biało, I., Tarnawski, Z., Ślęzak, M., Podgórska, K., Niewolski, J., Gala, M. A., Kozłowski, A., Honig, J. M., and Tabiś, W.

Subjects
Condensed Matter - Strongly Correlated Electrons, Condensed Matter - Materials Science
Abstract

Trimeron lattice excitations in single crystalline magnetite, in the form of the $c$ axis switching (i.e. the reorganization of the lattice caused by external magnetic field) at temperatures below the Verwey temperature $T_V$ are observed by magnetization experiments. These excitations exhibit strong sensitivity to doping (with Zn, Al, and Ti), nonstoichiometry and hydrostatic pressure ($p < 1.2$ GPa). The considered indicators of the axis switching (AS) are: the switching field $B_{sw}$, the energy density needed to switch the axis $E_{sw}$ and the activation energy $U$. Our results show that hydrostatic pressure $p$ weakens the low$-T$ magnetite structure (decreases $T_V$) and has roughly similar effects on AS in Zn-doped Fe$_3$O$_4$ and, in much less extent, in stoichiometric magnetite. We have, however, found that while doping/nonstoichiometry also lowers $T_V$, making it more prone to temperature chaos, it drastically increases the switching field, activation and switching energies suggesting that the trimeron order, subject to change while AS occurs, is more robust. Consequently, we conclude that the manipulation of trimerons in the process of axis switching and the mechanisms leading to the Verwey transition are distinct phenomena., Comment: Manuscript contains Supplemental Material

Published
2023
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5. Modelos mentales erróneos y persistentes en programación: cuestionario realizado y datos crudos anonimizados

Author

Universidad de Alicante. Departamento de Ciencia de la Computación e Inteligencia Artificial, Gallego-Durán, Francisco J., Compañ, Patricia, Villagrá-Arnedo, Carlos-José, García Sánchez, Gala M., Satorre Cuerda, Rosana, Universidad de Alicante. Departamento de Ciencia de la Computación e Inteligencia Artificial, Gallego-Durán, Francisco J., Compañ, Patricia, Villagrá-Arnedo, Carlos-José, García Sánchez, Gala M., and Satorre Cuerda, Rosana

Abstract

Estos son los datos crudos y análisis realizados del artículo "Modelos mentales erróneos y persistentes en programación", presentado al congreso JENUI 2023. Incluyen el cuestionario con todas las preguntas realizadas a los estudiantes, y las respuestas completas anonimizadas. El estudio aborda el proceso de aprendizaje a través de la creación de modelos mentales, representaciones análogas a lo aprendido que permiten realizar predicciones y tomar decisiones. Se sostiene que un aprendizaje efectivo puede ser representado por la refinación de estos modelos para acercarlos a la realidad. La programación, en particular, presenta un desafío adicional, ya que no solo requiere la refinación de modelos mentales, sino también la habilidad para navegar entre múltiples modelos precisos en ambas direcciones, a fin de crear un programa que produzca los efectos deseados. El estudio propone un método iterativo para identificar modelos mentales incorrectos en la programación, a partir de hipótesis basadas en la experiencia docente y la recopilación de evidencia empírica. Esta metodología, aplicada en un grupo de estudiantes de cuarto curso de Ingeniería, permite no solo la identificación de modelos erróneos potenciales, sino también la detección de otros no previstos que requieren más investigación. Estos hallazgos apuntan a la necesidad de mejorar los procesos de enseñanza para ayudar a los estudiantes a desarrollar modelos mentales más precisos y efectivos en el campo de la programación.

Published
2023

6. Modelos mentales erróneos y persistentes en programación

Author

Universidad de Alicante. Departamento de Ciencia de la Computación e Inteligencia Artificial, Gallego-Durán, Francisco J., Compañ, Patricia, Villagrá-Arnedo, Carlos-José, García Sánchez, Gala M., Satorre Cuerda, Rosana, Universidad de Alicante. Departamento de Ciencia de la Computación e Inteligencia Artificial, Gallego-Durán, Francisco J., Compañ, Patricia, Villagrá-Arnedo, Carlos-José, García Sánchez, Gala M., and Satorre Cuerda, Rosana

Abstract

El aprendizaje implica la creación de representaciones mentales análogas a lo aprendido, conocidas como modelos mentales. Estos modelos nos permiten realizar predicciones y tomar decisiones. Cuanto más cercanos sean a la realidad, mejores serán nuestras predicciones y decisiones, lo que indica que refinar estos modelos puede representar un aprendizaje efectivo. La programación, además, requiere realizar el proceso inverso: a partir de los efectos deseados, crear un programa que los produzca. Este proceso, más complejo que simplemente refinar un modelo mental, demanda múltiples modelos precisos y habilidad asociativa para navegar entre ellos en ambas direcciones. Los profesores enseñamos sobre modelos conceptuales, que son abstracciones claramente definidas. Adquirir estos modelos implica generalizar y extraer patrones de numerosos ejemplos específicos. A menudo, los modelos mentales iniciales se vinculan a detalles circunstanciales de los ejemplos, tanto al ruido como a la señal. Aunque estos modelos sean erróneos, pueden funcionar razonablemente bien en algunas situaciones específicas, ser suficientes para aprobar y persistir en el tiempo. Esto podría explicar dificultades futuras en la programación. Este estudio busca identificar modelos mentales incorrectos en la programación. Proponemos un método iterativo que parte de hipótesis basadas en la experiencia docente y llega hasta la evidencia empírica. Este enfoque también permite descubrir nuevos modelos y refinar nuestro conocimiento. Presentamos su aplicación con estudiantes de cuarto curso y conceptos de primer curso. Nuestros resultados destacan modelos erróneos potenciales y sugieren otros no previstos que requieren más investigación., Learning involves creating mental representations analogous to what is learned, known as mental models. These models allow us to make predictions and decisions. The closer they are to reality, the better our predictions and decisions will be, indicating that effective learning consists of refining these models. Programming, on the other hand, requires carrying out the reverse process: from the desired effects, create a program that produces them. This process, more complex than merely refining a mental model, demands multiple accurate models and associative skills to navigate between them in both directions. Teachers instruct on conceptual models, which are clearly defined abstractions. Acquiring these models involves generalizing and extracting patterns from numerous specific examples. Consequently, initial mental models often link to circumstantial details of the examples, both to the noise and the signal. Although these models may be erroneous, they can work reasonably well in some specific situations, be sufficient to pass, and persist over time. This could explain future difficulties in programming. This study seeks to identify incorrect mental models in programming. We propose an iterative method that starts from hypotheses based on teaching experience and reaches empirical evidence. This approach also allows discovering new models and refining our knowledge. We present its application with fourth-year students and first-year concepts. Our results highlight potential erroneous models and suggest other unforeseen ones that require further investigation.

Published
2023

7. New Perspectives in the Treatment of Inflammatory Myofibroblastic Tumor with ALK Translocation: Case Report

Author

Johana Benedetti Pedroza, Irene Carrasco García, Gala Martínez Bernal, and Isabel Miras Rodriguez

Subjects
head and neck, alk inhibitor, alectinib, inflammatory myofibroblastic tumor, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Inflammatory myofibroblastic tumor (IMT) is a rare entity, classified within soft tissue sarcomas. It is an intermediate malignancy tumor, which seldom presents as metastatic disease. The treatment of choice is surgery, except in cases where surgery is not possible due to localization or if it presents with metastatic disease. Approximately 50% of IMTs will exhibit ALK translocation, providing a therapeutic target for these patients. Case Presentation: A case is presented of a patient with metastatic IMT in complete response to treatment with alectinib, maintained for over 4 years. Conclusion: This case showed a long time complete response in patient with IMT treated with alectinib.

Published
2024
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8. Microsporidia infection in patients with autoimmune diseases

Author

Emad M. Eed, Yousry A. Hawash, Amany S. Khalifa, Ahmed M Khalifa, Osama Mahmoud Khalifa, Khadiga Ahmed Ismail, Saleh Alghamdi, Hatem K Althubiti, Taisir Saber, Khalaf F. Alsharif, and Gala M Alsofyani

Subjects
Diarrhea, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Immunology, lcsh:QR1-502, Polymerase Chain Reaction, Microbiology, Gastroenterology, lcsh:Microbiology, law.invention, Feces, 03 medical and health sciences, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), law, Immunity, Internal medicine, Microsporidiosis, medicine, Humans, Immunology and Allergy, In patient, autoimmune diseases, Prospective Studies, 030212 general & internal medicine, Polymerase chain reaction, General Immunology and Microbiology, biology, Tumor Necrosis Factor-alpha, business.industry, Intracellular parasite, biology.organism_classification, Microsporidium, Infectious Diseases, Case-Control Studies, Microsporidia, microsporidia, tumor necrosis factor alpha antagonists, Female, Tumor necrosis factor alpha, medicine.symptom, business
Abstract

Purpose: Microsporidium is a spore-forming intracellular parasite that affects a wide range of hosts including humans. The tumor necrosis factor alpha (TNF-α) plays a key role in the immunity to infection with microsporidia. Recently, the TNF-α antagonists have proven successful in treating variable autoimmune diseases. In the current study, we aimed to investigate the impact of using TNF-α antagonists as a therapeutic regimen in the prevalence of infections with microsporidia. Materials and Methods: Diarrheal patients with distinct autoimmune diseases (n = 100) were assigned to the study. Patients taking anti-TNF-α medications (n = 60) were allocated to Group 1A and those undergoing non-TNF-α inhibitor treatment (n = 40) to Group 1B. Furthermore, patients with diarrhea without autoimmune disorders (n = 20) were allocated as controls. Stool specimens, 3 per patient, were collected and microscopically examined for microsporidia spores. A microsporidia-specific stool polymerase chain reaction was used to confirm the microscopic findings. Results: Microsporidia infection was identified in 28.3% (17/60), 10% (4/40), and in 5% (1/20) of patients in Group 1A, Group 1B, and in the control group, respectively. Overall, infection was significantly high in cases compared to the controls and in patients receiving TNF-α antagonists compared to patients not given TNF-α inhibitors (P < 0.05). Finally, infection was significantly higher in cases treated with TNF-α antagonists for ≥2 months compared to cases treated for

Published
2020

9. Gas Chromatography-Tandem Mass Spectrometry Method for Selective Detection of 2-Nitropropane in Mainstream Cigarette Smoke

Author

Clifford H. Watson, Roberto Bravo Cardenas, Juliana Giraldo Junco, Liza Valentin-Blasini, and Gala M. Chapman

Subjects
volatile organic compound, Chromatography, Gas Chromatography/Tandem Mass Spectrometry, General interest, gas chromatography, 010401 analytical chemistry, 2-nitropropane, Plant culture, 010501 environmental sciences, tobacco, 01 natural sciences, Article, SB1-1110, 0104 chemical sciences, Cigarette smoke, mass spectrometry, 0105 earth and related environmental sciences
Abstract

Summary Although 2-nitropropane is a potentially harmful compound present in cigarette smoke, there are few fully-validated, modern methods to quantitate it in mainstream cigarette smoke. We developed an isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS) method for the detection of 2-nitropropane in mainstream cigarette smoke. The vapor fraction of mainstream cigarette smoke was collected in inert polyvinyl fluoride gas sampling bags and extracted with hexanes containing isotopically labeled internal standard, then purified and concentrated via solid-phase extraction using a normal phase silica adsorbent and a 100% dichloromethane eluant. This method is sensitive enough to measure vapor phase 2-nitro-propane concentrations in the nanogram range, with a 19 ng per cigarette method limit of detection. Product variability estimated from the analysis of 15 cigarette products yielded relative standard deviations ranging from 5.4% to 15.7%, and estimates of precision from two quality control products yielded relative standard deviations of 9.49% and 14.9%. Under the Health Canada Intense smoking regimen, 2-nitropropane in machine-generated mainstream smoke from 15 cigarette products ranged from 98.3 to 363 ng per cigarette.

Published
2019

13. Ustekinumab is effective for perianal fistulising Crohn's disease: a real-world experience and systematic review with meta-analysis

Author

Gala M Godoy Brewer, George Salem, Muhammad A Afzal, Berkeley N Limketkai, Zadid Haq, Maryam Tajamal, Joanna Melia, Mark Lazarev, Florin M Selaru, and Alyssa M. Parian

Subjects
Gastroenterology, gastrointestinal fistulae, Crohn Disease, inflammatory bowel disease, Crohn's colitis, Quality of Life, Humans, Rectal Fistula, Ustekinumab, Prospective Studies, anal, Retrospective Studies, Anorectal Disease
Abstract

BackgroundPerianal Crohn’s disease (pCD) is a debilitating complication affecting up to 30% of Crohn’s disease (CD) population, leading to increased morbidity, mortality and decreased quality of life. Despite the growing armamentarium of medications for luminal CD, their efficacy in pCD remains poorly studied.AimTo determine the efficacy of ustekinumab, a biologic approved for luminal CD, in pCD through a retrospective cohort study and systematic review.MethodsA retrospective cohort study on patients with CD with active perianal fistulae treated with ustekinumab from September 2013 to August 2019 was performed to determine perianal fistula response and remission at 6 and 12 months after ustekinumab induction. A systematic review was performed to further establish rates of fistula response and remission with ustekinumab.ResultsAt 6 months, 48.1% (13/27) patients achieved fistula response with none achieving fistula remission on provider exam, and 59.3% (16/27) achieved patient-reported symptomatic improvement with 3.7% (1/27) achieving symptomatic remission. At 1 year, on provider exam, 55.6% (5/9) had fistula response with none achieving fistula remission, and 100% (9/9) had symptomatic improvement with 22.2% (2/9) achieving symptomatic remission. There were no major safety signals during 1-year follow-up. The systematic review of 25 studies found 44% (92/209) of patients with active perianal fistulas had a clinical response within 6 months of follow-up, and 53.9% (85/152) of patients with 12 months of follow-up achieved clinical response.ConclusionUstekinumab presents a safe and effective therapy for treatment of pCD. Prospective, randomised trials are needed to further elucidate long-term efficacy of ustekinumab for pCD.

Published
2021

14. Genetic architectures of proximal and distal colorectal cancer are partly distinct

Author

Huyghe, JR, Harrison, TA, Bien, SA, Hampel, H, Figueiredo, JC, Schmit, SL, Conti, D, Chen, S, Qu, C, Lin, Y, Barfield, R, Baron, JA, Cross, AJ, Diergaarde, B, Duggan, D, Harlid, S, Imaz, L, Kang, HM, Levine, DM, Perduca, V, Perez-Cornago, A, Sakoda, LC, Schumacher, FR, Slattery, ML, Toland, AE, van Duijnhoven, FJB, Van Guelpen, B, Agudo, A, Albanes, D, Alonso, MH, Anderson, K, Arnau-Collell, C, Arndt, V, Banbury, BL, Bassik, MC, Berndt, S, Bezieau, S, Bishop, DT, Boehm, J, Boeing, H, Boutron-Ruault, M-C, Brenner, H, Brezina, S, Buch, S, Buchanan, DD, Burnett-Hartman, A, Caan, BJ, Campbell, PT, Carr, PR, Castells, A, Castellvi-Bel, S, Chan, AT, Chang-Claude, J, Chanock, SJ, Curtis, KR, de la Chapelle, A, Easton, DF, English, DR, Feskens, EJM, Gala, M, Gallinger, SJ, Gauderman, WJ, Giles, GG, Goodman, PJ, Grady, WM, Grove, JS, Gsur, A, Gunter, MJ, Haile, RW, Hampe, J, Hoffmeister, M, Hopper, JL, Hsu, W-L, Huang, W-Y, Hudson, TJ, Jenab, M, Jenkins, MA, Joshi, AD, Keku, TO, Kooperberg, C, Kuhn, T, Kury, S, Le Marchand, L, Lejbkowicz, F, Li, C, Li, L, Lieb, W, Lindblom, A, Lindor, NM, Mannisto, S, Markowitz, SD, Milne, RL, Moreno, L, Murphy, N, Nassir, R, Offit, K, Ogino, S, Panico, S, Parfrey, PS, Pearlman, R, Pharoah, PDP, Phipps, A, Platz, EA, Potter, JD, Prentice, RL, Qi, L, Raskin, L, Rennert, G, Rennert, HS, Riboli, E, Schafmayer, C, Schoen, RE, Seminara, D, Song, M, Su, Y-R, Tangen, CM, Thibodeau, SN, Thomas, DC, Trichopoulou, A, Ulrich, CM, Visvanathan, K, Vodicka, P, Vodickova, L, Vymetalkova, V, Weigl, K, Weinstein, SJ, White, E, Wolk, A, Woods, MO, Wu, AH, Abecasis, GR, Nickerson, DA, Scacheri, PC, Kundaje, A, Casey, G, Gruber, SB, Hsu, L, Moreno, V, Hayes, RB, Newcomb, PA, Peters, U, Huyghe, JR, Harrison, TA, Bien, SA, Hampel, H, Figueiredo, JC, Schmit, SL, Conti, D, Chen, S, Qu, C, Lin, Y, Barfield, R, Baron, JA, Cross, AJ, Diergaarde, B, Duggan, D, Harlid, S, Imaz, L, Kang, HM, Levine, DM, Perduca, V, Perez-Cornago, A, Sakoda, LC, Schumacher, FR, Slattery, ML, Toland, AE, van Duijnhoven, FJB, Van Guelpen, B, Agudo, A, Albanes, D, Alonso, MH, Anderson, K, Arnau-Collell, C, Arndt, V, Banbury, BL, Bassik, MC, Berndt, S, Bezieau, S, Bishop, DT, Boehm, J, Boeing, H, Boutron-Ruault, M-C, Brenner, H, Brezina, S, Buch, S, Buchanan, DD, Burnett-Hartman, A, Caan, BJ, Campbell, PT, Carr, PR, Castells, A, Castellvi-Bel, S, Chan, AT, Chang-Claude, J, Chanock, SJ, Curtis, KR, de la Chapelle, A, Easton, DF, English, DR, Feskens, EJM, Gala, M, Gallinger, SJ, Gauderman, WJ, Giles, GG, Goodman, PJ, Grady, WM, Grove, JS, Gsur, A, Gunter, MJ, Haile, RW, Hampe, J, Hoffmeister, M, Hopper, JL, Hsu, W-L, Huang, W-Y, Hudson, TJ, Jenab, M, Jenkins, MA, Joshi, AD, Keku, TO, Kooperberg, C, Kuhn, T, Kury, S, Le Marchand, L, Lejbkowicz, F, Li, C, Li, L, Lieb, W, Lindblom, A, Lindor, NM, Mannisto, S, Markowitz, SD, Milne, RL, Moreno, L, Murphy, N, Nassir, R, Offit, K, Ogino, S, Panico, S, Parfrey, PS, Pearlman, R, Pharoah, PDP, Phipps, A, Platz, EA, Potter, JD, Prentice, RL, Qi, L, Raskin, L, Rennert, G, Rennert, HS, Riboli, E, Schafmayer, C, Schoen, RE, Seminara, D, Song, M, Su, Y-R, Tangen, CM, Thibodeau, SN, Thomas, DC, Trichopoulou, A, Ulrich, CM, Visvanathan, K, Vodicka, P, Vodickova, L, Vymetalkova, V, Weigl, K, Weinstein, SJ, White, E, Wolk, A, Woods, MO, Wu, AH, Abecasis, GR, Nickerson, DA, Scacheri, PC, Kundaje, A, Casey, G, Gruber, SB, Hsu, L, Moreno, V, Hayes, RB, Newcomb, PA, and Peters, U

Abstract

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.

Published
2021

15. Quantification of nitromethane in mainstream smoke using gas chromatography and tandem mass spectrometry

Author

Roberto Bravo Cardenas, Gala M. Chapman, Clifford H. Watson, Juliana Giraldo Junco, and Liza Valentin-Blasini

Subjects
Health, Toxicology and Mutagenesis, Nitromethane, 010501 environmental sciences, Toxicology, Mass spectrometry, 01 natural sciences, Mainstream smoke, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, RA1190-1270, Volatile organic compound, Sidestream smoke, 0105 earth and related environmental sciences, ComputingMethodologies_COMPUTERGRAPHICS, chemistry.chemical_classification, Smoke, Detection limit, Chromatography, GC–MS/MS, Regular Article, Tobacco analysis, chemistry, Toxicology. Poisons, Sample collection, Gas chromatography, 030217 neurology & neurosurgery
Abstract

Graphical abstract, Highlights • A novel method was developed to detect nitromethane in cigarette smoke. • The method is sensitive, accurate, and fit for high-throughput applications. • The new method was used to quantify nitromethane in smoke from 10 cigarette brands. • Differences were observed depending on tobacco types used., Nitromethane is a volatile organic compound categorized as a Group 2B carcinogen by the International Agency for Research on Cancer. It has been detected in mainstream cigarette smoke, but few reliable methods have been reported for accurate quantification. We developed, a sensitive, selective, fully validated method for the targeted determination of nitromethane in mainstream tobacco smoke in ten U.S. domestic brands and two quality control materials (3R4F and CM6). The vapor phase portion of machine-generated cigarette mainstream smoke, under modified ISO 3308:2000 regime (ISO) and modified intense regime (HCI), from single cigarettes was collected using airtight polyvinylfluoride sampling bags. The bags’ contents were extracted using methanol containing an isotopically labeled internal standard followed by gas chromatography-tandem mass spectrometry. This approach is sufficiently sensitive to measure nitromethane levels in the nanogram range, with a method limit of detection of 72.3 ng/cig. Within-product variability estimated from the replicate analysis of 10 products ranged from 4.6%–16.3% (n = 6) over the two different smoking regimes, and method reproducibility estimated from two products used as quality control materials (3R4F and CM6) yielded intermediate precision values ranging from 16.6 to 20.8% (n = 20). Under HCI, nitromethane yields in machine-generated cigarette smoke from ten different domestic cigarette products ranged from 3.2 to 12 μg/cig; under ISO yields ranged from 1.6 to 4.9 μg/cig under standardized smoking machine conditions. Nitromethane yields are related to both the smoke regime (blocking of vent holes, puff duration and puff volume) and the heterogeneity of tobacco mixtures. This method provides a selective and fully validated technique to accurately quantify nitromethane in mainstream cigarette smoke, with minimal waste generation. It is an improvement over previous methods with regards to specificity, throughput, and simplicity of the sample collection process.

Published
2020

17. DNA repair and cancer in colon and rectum: Novel players in genetic susceptibility

Author

Pardini, B, Corrado, A, Paolicchi, E, Cugliari, G, Berndt, S, Bezieau, S, Bien, SA, Brenner, H, Caan, BJ, Campbell, PT, Casey, G, Chan, AT, Chang-Claude, J, Cotterchio, M, Gala, M, Gallinger, SJ, Haile, RW, Harrison, TA, Hayes, RB, Hoffmeister, M, Hopper, JL, Hsu, L, Huyghe, J, Jenkins, MA, Le Marchand, L, Lin, Y, Lindor, NM, Nan, H, Newcomb, PA, Ogino, S, Potter, JD, Schoen, RE, Slattery, ML, White, E, Vodickova, L, Vymetalkova, V, Vodicka, P, Gemignani, F, Peters, U, Naccarati, A, Landi, S, Pardini, B, Corrado, A, Paolicchi, E, Cugliari, G, Berndt, S, Bezieau, S, Bien, SA, Brenner, H, Caan, BJ, Campbell, PT, Casey, G, Chan, AT, Chang-Claude, J, Cotterchio, M, Gala, M, Gallinger, SJ, Haile, RW, Harrison, TA, Hayes, RB, Hoffmeister, M, Hopper, JL, Hsu, L, Huyghe, J, Jenkins, MA, Le Marchand, L, Lin, Y, Lindor, NM, Nan, H, Newcomb, PA, Ogino, S, Potter, JD, Schoen, RE, Slattery, ML, White, E, Vodickova, L, Vymetalkova, V, Vodicka, P, Gemignani, F, Peters, U, Naccarati, A, and Landi, S

Abstract

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.

Published
2020

18. Effect of low-dose and standard-dose aspirin on PGE2 biosynthesis among individuals with colorectal adenomas: A randomized clinical trial

Author

Drew, D. A., Schuck, M. M., Magicheva-Gupta, M. V., Stewart, K. O., Gilpin, K. K., Miller, P., Parziale, M. P., Pond, E. N., Takacsi-Nagy, O., Zerjav, D. C., Chin, S. M., Krems, J. M., Meixell, D., Joshi, A. D., Ma, W., Colizzo, F. P., Carolan, P. J., Nishioka, N. S., Staller, K., Richter, J. M., Khalili, H., Gala, M. K., Garber, J. J., Chung, D. C., Yarze, J. C., Zukerberg, L., Petrucci, Giovanna, Rocca, Bianca, Patrono, Carlo, Milne, G. L., Wang, M., Chan, A. T., Petrucci G. (ORCID:0000-0002-9280-3673), Rocca B. (ORCID:0000-0001-8304-6423), Patrono C., Drew, D. A., Schuck, M. M., Magicheva-Gupta, M. V., Stewart, K. O., Gilpin, K. K., Miller, P., Parziale, M. P., Pond, E. N., Takacsi-Nagy, O., Zerjav, D. C., Chin, S. M., Krems, J. M., Meixell, D., Joshi, A. D., Ma, W., Colizzo, F. P., Carolan, P. J., Nishioka, N. S., Staller, K., Richter, J. M., Khalili, H., Gala, M. K., Garber, J. J., Chung, D. C., Yarze, J. C., Zukerberg, L., Petrucci, Giovanna, Rocca, Bianca, Patrono, Carlo, Milne, G. L., Wang, M., Chan, A. T., Petrucci G. (ORCID:0000-0002-9280-3673), Rocca B. (ORCID:0000-0001-8304-6423), and Patrono C.

Abstract

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11a-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N 1⁄4 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8–12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 = 14.6 (mean = S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (=4.7 = 14.8) compared with no decrease (0.8 = 11.8) in the placebo group (P 1⁄4 0.015; mean duration of treatment 1⁄4 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P 1⁄4 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

Published
2020

19. Sensitive and selective gas chromatography-tandem mass spectrometry method for the detection of nitrobenzene in tobacco smoke

Author

Clifford H. Watson, Liza Valentin-Blasini, Roberto Bravo, Rayman D. Stanelle, and Gala M. Chapman

Subjects
Canada, 010501 environmental sciences, Isotope dilution, 01 natural sciences, Biochemistry, Article, Gas Chromatography-Mass Spectrometry, Tobacco smoke, Analytical Chemistry, Limit of Detection, Tandem Mass Spectrometry, Tobacco, Volatile organic compound, Sidestream smoke, Nitrobenzenes, 0105 earth and related environmental sciences, Ions, Detection limit, chemistry.chemical_classification, Chromatography, Gas Chromatography/Tandem Mass Spectrometry, Chemistry, 010401 analytical chemistry, Organic Chemistry, Reproducibility of Results, Tobacco Products, General Medicine, 0104 chemical sciences, Calibration, Particulate Matter, Tobacco Smoke Pollution, Gas chromatography, Gas chromatography–mass spectrometry
Abstract

Nitrobenzene, a potentially harmful compound found in tobacco smoke, has been largely excluded from prior analysis due to difficulties with quantification. Quantifying harmful compounds in cigarette smoke is useful to compare products, to examine the impact of design parameters on delivery, and to help estimate exposures. A sensitive high-throughput method has been developed for quantifying nitrobenzene in machine-generated mainstream cigarette smoke using isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS). This method has sufficient sensitivity to measure vapor phase nitrobenzene concentrations in the low nanogram range, with a 418 pg/cig method limit of detection. Precision estimates from two quality control cigarette products resulted in percent relative standard deviations of 11.5% and 14.9%; product variability estimates from 13 cigarette products resulted in percent relative standard deviations ranging from 2.8% to 16.9%. Nitrobenzene in the machine-generated, mainstream smoke from 15 cigarette products are reported and range from 18 to 38 ng/cig under the Health Canada Intense smoking regimen.

Published
2018

22. Bycatch mitigation from the sky: using helicopter communication for mobulid conservation in tropical tuna fisheries

Author

Jennifer L. Waldo, Ernesto Altamirano-Nieto, Donald A. Croll, Marta D. Palacios, Nerea Lezama-Ochoa, Jon Lopez, Gala Moreno, Stefany Rojas-Perea, and Melissa R. Cronin

Subjects
purse seine, management, eastern Pacific Ocean, stakeholder knowledge, elasmobranch, conservation technology, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

The incidental capture of non-target species (bycatch) in tuna fisheries impacts some marine vertebrates, particularly species with vulnerable life histories such as manta and devil rays (mobulids). There is broad interest in reducing mobulid bycatch in tuna purse seine fisheries, with existing efforts mainly focusing on reducing post-capture mortality rates. We explore a novel potential pre-capture mobulid bycatch avoidance strategy for the tuna purse seine fishery using communication between fishing vessels and associated spotter helicopters. We conducted a survey of tuna purse seine helicopter pilots, spotters, and fishers operating in the eastern Pacific Ocean (n = 33) to ascertain the ability of helicopter crew to detect mobulids prior to capture and communicate bycatch avoidance with vessel crew. Results indicate over half of the helicopter crew report being “always” or “sometimes” able to sight and identify mobulids and that helicopter crew regularly communicate mobulid sightings to the vessel already. Given that an average of 63% of class-6 vessel trips between 2017 to 2022 carried onboard helicopters, our results suggest that helicopter-vessel communication could be feasible and scalable for mobulid bycatch detection, enabling potential bycatch avoidance and early alerts for proper handling protocols. We also identify the potential use of helicopter detection to improve research efforts for mobulid conservation (e.g., data collection of population and habitat observations). This study is the first to investigate the utility of helicopter-vessel communication as a bycatch mitigation strategy for elasmobranchs and identifies research and management directions that could be further investigated to avoid bycatch of mobulids.

Published
2024
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23. AulaGinecología.com: una nueva herramienta formativa en ginecología y obstetricia

Author

Gala Melgar Hernández-Sampelayo, Juan Modesto Caballero, Txanton Martínez-Astorquiza Corral, and Carlos Santiago Piñel Pérez

Subjects
Aula Ginecología, Medical education, Educational resources, Residency training, Medical education learning tools, e-learning in medicine, Education (General), L7-991, Medicine (General), R5-920
Abstract

Resumen: AulaGinecologia.com es una herramienta docente de acceso online gratuito, que ofrece formación en la especialidad de obstetricia y ginecología. Fue creada para abordar las dificultades en la formación en esta especialidad, que incluyen la amplitud de los contenidos, el tiempo reducido de estudio debido a la sobrecarga de trabajo y la falta de acceso a recursos actualizados. AulaGinecologia.com ofrece formación mediante vídeos, podcasts, documentos PDF y preguntas de autoevaluación. La plataforma también cuenta con perfiles en redes sociales para difundir su contenido. Ha recibido una gran acogida por parte de los profesionales, con un alto número de suscriptores, opiniones y visualizaciones. La accesibilidad gratuita y la combinación de diferentes medios se consideran factores clave para el éxito de la herramienta. Los resultados cuantitativos y cualitativos indican una respuesta positiva por parte de los usuarios, aunque se plantean posibles mejoras y expansiones en el futuro. En conclusión, AulaGinecologia.com se presenta como una herramienta formativa amena, moderna y accesible que proporciona un contenido científico de calidad, actualizado y resumido contribuyendo a facilitar y mejorar la formación en obstetricia y ginecología. Abstract: AulaGinecologia.com is a free online educational tool aimed at providing education in the field of obstetrics and gynecology. The platform was created to address the challenges in training in this specialty, including the breadth of content, the reduced study time due to work overload and the lack of access to updated resources. AulaGinecologia.com offers training through videos, podcasts, PDF documents and self-assessment questions. The platform also has social media profiles to disseminate its content. To date, it has been well-received by professionals, with a high number of subscribers, opinions and material views. The free accessibility and combination of different media are considered key factors for the platform's success. Quantitative and qualitative results indicate a positive response from users, although potential improvements and expansions are being considered for the future. In conclusion, AulaGinecologia.com is presented as an entertaining, modern and accessible educational tool that provides updated and summarized scientific content, contributing to facilitate and improve training in obstetrics and gynecology.

Published
2024
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24. Microsporidia Infection in Patients with Autoimmune Diseases

Author

Ismail, Khadiga Ahmed, primary, Hawash, Yousry A., additional, Saber, Taisir, additional, Eed, Emad M., additional, Khalifa, Amany S., additional, Alsharif, Khalaf F., additional, Alghamdi, Saleh A., additional, Khalifa, Ahmed M., additional, Khalifa, Osama Mahmoud, additional, Althubiti, Hatem K., additional, and Alsofyani, Gala M., additional

Published
2020
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25. Discovery of common and rare genetic risk variants for colorectal cancer

Author

Huyghe, J.R. Bien, S.A. Harrison, T.A. Kang, H.M. Chen, S. Schmit, S.L. Conti, D.V. Qu, C. Jeon, J. Edlund, C.K. Greenside, P. Wainberg, M. Schumacher, F.R. Smith, J.D. Levine, D.M. Nelson, S.C. Sinnott-Armstrong, N.A. Albanes, D. Alonso, M.H. Anderson, K. Arnau-Collell, C. Arndt, V. Bamia, C. Banbury, B.L. Baron, J.A. Berndt, S.I. Bézieau, S. Bishop, D.T. Boehm, J. Boeing, H. Brenner, H. Brezina, S. Buch, S. Buchanan, D.D. Burnett-Hartman, A. Butterbach, K. Caan, B.J. Campbell, P.T. Carlson, C.S. Castellví-Bel, S. Chan, A.T. Chang-Claude, J. Chanock, S.J. Chirlaque, M.-D. Cho, S.H. Connolly, C.M. Cross, A.J. Cuk, K. Curtis, K.R. de la Chapelle, A. Doheny, K.F. Duggan, D. Easton, D.F. Elias, S.G. Elliott, F. English, D.R. Feskens, E.J.M. Figueiredo, J.C. Fischer, R. FitzGerald, L.M. Forman, D. Gala, M. Gallinger, S. Gauderman, W.J. Giles, G.G. Gillanders, E. Gong, J. Goodman, P.J. Grady, W.M. Grove, J.S. Gsur, A. Gunter, M.J. Haile, R.W. Hampe, J. Hampel, H. Harlid, S. Hayes, R.B. Hofer, P. Hoffmeister, M. Hopper, J.L. Hsu, W.-L. Huang, W.-Y. Hudson, T.J. Hunter, D.J. Ibañez-Sanz, G. Idos, G.E. Ingersoll, R. Jackson, R.D. Jacobs, E.J. Jenkins, M.A. Joshi, A.D. Joshu, C.E. Keku, T.O. Key, T.J. Kim, H.R. Kobayashi, E. Kolonel, L.N. Kooperberg, C. Kühn, T. Küry, S. Kweon, S.-S. Larsson, S.C. Laurie, C.A. Le Marchand, L. Leal, S.M. Lee, S.C. Lejbkowicz, F. Lemire, M. Li, C.I. Li, L. Lieb, W. Lin, Y. Lindblom, A. Lindor, N.M. Ling, H. Louie, T.L. Männistö, S. Markowitz, S.D. Martín, V. Masala, G. McNeil, C.E. Melas, M. Milne, R.L. Moreno, L. Murphy, N. Myte, R. Naccarati, A. Newcomb, P.A. Offit, K. Ogino, S. Onland-Moret, N.C. Pardini, B. Parfrey, P.S. Pearlman, R. Perduca, V. Pharoah, P.D.P. Pinchev, M. Platz, E.A. Prentice, R.L. Pugh, E. Raskin, L. Rennert, G. Rennert, H.S. Riboli, E. Rodríguez-Barranco, M. Romm, J. Sakoda, L.C. Schafmayer, C. Schoen, R.E. Seminara, D. Shah, M. Shelford, T. Shin, M.-H. Shulman, K. Sieri, S. Slattery, M.L. Southey, M.C. Stadler, Z.K. Stegmaier, C. Su, Y.-R. Tangen, C.M. Thibodeau, S.N. Thomas, D.C. Thomas, S.S. Toland, A.E. Trichopoulou, A. Ulrich, C.M. Van Den Berg, D.J. van Duijnhoven, F.J.B. Van Guelpen, B. van Kranen, H. Vijai, J. Visvanathan, K. Vodicka, P. Vodickova, L. Vymetalkova, V. Weigl, K. Weinstein, S.J. White, E. Win, A.K. Wolf, C.R. Wolk, A. Woods, M.O. Wu, A.H. Zaidi, S.H. Zanke, B.W. Zhang, Q. Zheng, W. Scacheri, P.C. Potter, J.D. Bassik, M.C. Kundaje, A. Casey, G. Moreno, V. Abecasis, G.R. Nickerson, D.A. Gruber, S.B. Hsu, L. Peters, U.

Abstract

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10 −8 , bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development. © 2018, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Published
2019

27. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author

Schmit, SL, Edlund, CK, Schumacher, FR, Gong, J, Harrison, TA, Huyghe, JR, Qu, C, Melas, M, Van den Berg, DJ, Wang, H, Tring, S, Plummer, SJ, Albanes, D, Alonso, MH, Amos, CI, Anton, K, Aragaki, AK, Arndt, V, Barry, EL, Berndt, SI, Bezieau, S, Bien, S, Bloomer, A, Boehm, J, Boutron-Ruault, M-C, Brenner, H, Brezina, S, Buchanan, DD, Butterbach, K, Caan, BJ, Campbell, PT, Carlson, CS, Castelao, JE, Chan, AT, Chang-Claude, J, Chanock, SJ, Cheng, I, Cheng, Y-W, Chin, LS, Church, JM, Church, T, Coetzee, GA, Cotterchio, M, Correa, MC, Curtis, KR, Duggan, D, Easton, DF, English, D, Feskens, EJM, Fischer, R, FitzGerald, LM, Fortini, BK, Fritsche, LG, Fuchs, CS, Gago-Dominguez, M, Gala, M, Gallinger, SJ, Gauderman, WJ, Giles, GG, Giovannucci, EL, Gogarten, SM, Gonzalez-Villalpando, C, Gonzalez-Villalpando, EM, Grady, WM, Greenson, JK, Gsur, A, Gunter, M, Haiman, CA, Hampe, J, Harlid, S, Harju, JF, Hayes, RB, Hofer, P, Hoffmeister, M, Hopper, JL, Huang, S-C, Huerta, JM, Hudson, TJ, Hunter, DJ, Idos, GE, Iwasaki, M, Jackson, RD, Jacobs, EJ, Jee, SH, Jenkins, MA, Jia, W-H, Jiao, S, Joshi, AD, Kolonel, LN, Kono, S, Kooperberg, C, Krogh, V, Kuehn, T, Kury, S, LaCroix, A, Laurie, CA, Lejbkowicz, F, Lemire, M, Lenz, H-J, Levine, D, Li, CI, Li, L, Lieb, W, Lin, Y, Lindor, NM, Liu, Y-R, Loupakis, F, Lu, Y, Luh, F, Ma, J, Mancao, C, Manion, FJ, Markowitz, SD, Martin, V, Matsuda, K, Matsuo, K, McDonnell, KJ, McNeil, CE, Milne, R, Molina, AJ, Mukherjee, B, Murphy, N, Newcomb, PA, Offit, K, Omichessan, H, Palli, D, Cotore, JPP, Perez-Mayoral, J, Pharoah, PD, Potter, JD, Raskin, L, Rennert, G, Rennert, HS, Riggs, BM, Schafmayer, C, Schoen, RE, Sellers, TA, Seminara, D, Severi, G, Shi, W, Shibata, D, Shu, X-O, Siegel, EM, Slattery, ML, Southey, M, Stadler, ZK, Stern, MC, Stintzing, S, Taverna, D, Thibodeau, SN, Thomas, DC, Trichopoulou, A, Tsugane, S, Ulrich, CM, van Duijnhoven, FJB, van Guelpan, B, Vijai, J, Virtamo, J, Weinstein, SJ, White, E, Win, AK, Wolk, A, Woods, M, Wu, AH, Wu, K, Xiang, Y-B, Yen, Y, Zanke, BW, Zeng, Y-X, Zhang, B, Zubair, N, Kweon, S-S, Figueiredo, JC, Zheng, W, Le Marchand, L, Lindblom, A, Moreno, V, Peters, U, Casey, G, Hsu, L, Conti, DV, Gruber, SB, Schmit, SL, Edlund, CK, Schumacher, FR, Gong, J, Harrison, TA, Huyghe, JR, Qu, C, Melas, M, Van den Berg, DJ, Wang, H, Tring, S, Plummer, SJ, Albanes, D, Alonso, MH, Amos, CI, Anton, K, Aragaki, AK, Arndt, V, Barry, EL, Berndt, SI, Bezieau, S, Bien, S, Bloomer, A, Boehm, J, Boutron-Ruault, M-C, Brenner, H, Brezina, S, Buchanan, DD, Butterbach, K, Caan, BJ, Campbell, PT, Carlson, CS, Castelao, JE, Chan, AT, Chang-Claude, J, Chanock, SJ, Cheng, I, Cheng, Y-W, Chin, LS, Church, JM, Church, T, Coetzee, GA, Cotterchio, M, Correa, MC, Curtis, KR, Duggan, D, Easton, DF, English, D, Feskens, EJM, Fischer, R, FitzGerald, LM, Fortini, BK, Fritsche, LG, Fuchs, CS, Gago-Dominguez, M, Gala, M, Gallinger, SJ, Gauderman, WJ, Giles, GG, Giovannucci, EL, Gogarten, SM, Gonzalez-Villalpando, C, Gonzalez-Villalpando, EM, Grady, WM, Greenson, JK, Gsur, A, Gunter, M, Haiman, CA, Hampe, J, Harlid, S, Harju, JF, Hayes, RB, Hofer, P, Hoffmeister, M, Hopper, JL, Huang, S-C, Huerta, JM, Hudson, TJ, Hunter, DJ, Idos, GE, Iwasaki, M, Jackson, RD, Jacobs, EJ, Jee, SH, Jenkins, MA, Jia, W-H, Jiao, S, Joshi, AD, Kolonel, LN, Kono, S, Kooperberg, C, Krogh, V, Kuehn, T, Kury, S, LaCroix, A, Laurie, CA, Lejbkowicz, F, Lemire, M, Lenz, H-J, Levine, D, Li, CI, Li, L, Lieb, W, Lin, Y, Lindor, NM, Liu, Y-R, Loupakis, F, Lu, Y, Luh, F, Ma, J, Mancao, C, Manion, FJ, Markowitz, SD, Martin, V, Matsuda, K, Matsuo, K, McDonnell, KJ, McNeil, CE, Milne, R, Molina, AJ, Mukherjee, B, Murphy, N, Newcomb, PA, Offit, K, Omichessan, H, Palli, D, Cotore, JPP, Perez-Mayoral, J, Pharoah, PD, Potter, JD, Raskin, L, Rennert, G, Rennert, HS, Riggs, BM, Schafmayer, C, Schoen, RE, Sellers, TA, Seminara, D, Severi, G, Shi, W, Shibata, D, Shu, X-O, Siegel, EM, Slattery, ML, Southey, M, Stadler, ZK, Stern, MC, Stintzing, S, Taverna, D, Thibodeau, SN, Thomas, DC, Trichopoulou, A, Tsugane, S, Ulrich, CM, van Duijnhoven, FJB, van Guelpan, B, Vijai, J, Virtamo, J, Weinstein, SJ, White, E, Win, AK, Wolk, A, Woods, M, Wu, AH, Wu, K, Xiang, Y-B, Yen, Y, Zanke, BW, Zeng, Y-X, Zhang, B, Zubair, N, Kweon, S-S, Figueiredo, JC, Zheng, W, Le Marchand, L, Lindblom, A, Moreno, V, Peters, U, Casey, G, Hsu, L, Conti, DV, and Gruber, SB

Abstract

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: T

Published
2019

28. Discovery of common and rare genetic risk variants for colorectal cancer

Author

Huyghe, JR, Bien, SA, Harrison, TA, Kang, HM, Chen, S, Schmit, SL, Conti, DV, Qu, C, Jeon, J, Edlund, CK, Greenside, P, Wainberg, M, Schumacher, FR, Smith, JD, Levine, DM, Nelson, SC, Sinnott-Armstrong, NA, Albanes, D, Alonso, MH, Anderson, K, Arnau-Collell, C, Arndt, V, Bamia, C, Banbury, BL, Baron, JA, Berndt, SI, Bezieau, S, Bishop, DT, Boehm, J, Boeing, H, Brenner, H, Brezina, S, Buch, S, Buchanan, DD, Burnett-Hartman, A, Butterbach, K, Caan, BJ, Campbell, PT, Carlson, CS, Castellvi-Bel, S, Chan, AT, Chang-Claude, J, Chanock, SJ, Chirlaque, M-D, Cho, SH, Connolly, CM, Cross, AJ, Cuk, K, Curtis, KR, de la Chapelle, A, Doheny, KF, Duggan, D, Easton, DF, Elias, SG, Elliott, F, English, DR, Feskens, EJM, Figueiredo, JC, Fischer, R, FitzGerald, LM, Forman, D, Gala, M, Gallinger, S, Gauderman, WJ, Giles, GG, Gillanders, E, Gong, J, Goodman, PJ, Grady, WM, Grove, JS, Gsur, A, Gunter, MJ, Haile, RW, Hampe, J, Hampel, H, Harlid, S, Hayes, RB, Hofer, P, Hoffmeister, M, Hopper, JL, Hsu, W-L, Huang, W-Y, Hudson, TJ, Hunter, DJ, Ibanez-Sanz, G, Idos, GE, Ingersoll, R, Jackson, RD, Jacobs, EJ, Jenkins, MA, Joshi, AD, Joshu, CE, Keku, TO, Key, TJ, Kim, HR, Kobayashi, E, Kolonel, LN, Kooperberg, C, Kuehn, T, Kury, S, Kweon, S-S, Larsson, SC, Laurie, CA, Le Marchand, L, Leal, SM, Lee, SC, Lejbkowicz, F, Lemire, M, Li, CI, Li, L, Lieb, W, Lin, Y, Lindblom, A, Lindor, NM, Ling, H, Louie, TL, Mannisto, S, Markowitz, SD, Martin, V, Masala, G, McNeil, CE, Melas, M, Milne, RL, Moreno, L, Murphy, N, Myte, R, Naccarati, A, Newcomb, PA, Offit, K, Ogino, S, Onland-Moret, NC, Pardini, B, Parfrey, PS, Pearlman, R, Perduca, V, Pharoah, PDP, Pinchev, M, Platz, EA, Prentice, RL, Pugh, E, Raskin, L, Rennert, G, Rennert, HS, Riboli, E, Rodriguez-Barranco, M, Romm, J, Sakoda, LC, Schafmayer, C, Schoen, RE, Seminara, D, Shah, M, Shelford, T, Shin, M-H, Shulman, K, Sieri, S, Slattery, ML, Southey, MC, Stadler, ZK, Stegmaier, C, Su, Y-R, Tangen, CM, Thibodeau, SN, Thomas, DC, Thomas, SS, Toland, AE, Trichopoulou, A, Ulrich, CM, Van den Berg, DJ, van Duijnhoven, FJB, Van Guelpen, B, van Kranen, H, Vijai, J, Visvanathan, K, Vodicka, P, Vodickova, L, Vymetalkova, V, Weigl, K, Weinstein, SJ, White, E, Win, AK, Wolf, CR, Wolk, A, Woods, MO, Wu, AH, Zaidi, SH, Zanke, BW, Zhang, Q, Zheng, W, Scacheri, PC, Potter, JD, Bassik, MC, Kundaje, A, Casey, G, Moreno, V, Abecasis, GR, Nickerson, DA, Gruber, SB, Hsu, L, Peters, U, Huyghe, JR, Bien, SA, Harrison, TA, Kang, HM, Chen, S, Schmit, SL, Conti, DV, Qu, C, Jeon, J, Edlund, CK, Greenside, P, Wainberg, M, Schumacher, FR, Smith, JD, Levine, DM, Nelson, SC, Sinnott-Armstrong, NA, Albanes, D, Alonso, MH, Anderson, K, Arnau-Collell, C, Arndt, V, Bamia, C, Banbury, BL, Baron, JA, Berndt, SI, Bezieau, S, Bishop, DT, Boehm, J, Boeing, H, Brenner, H, Brezina, S, Buch, S, Buchanan, DD, Burnett-Hartman, A, Butterbach, K, Caan, BJ, Campbell, PT, Carlson, CS, Castellvi-Bel, S, Chan, AT, Chang-Claude, J, Chanock, SJ, Chirlaque, M-D, Cho, SH, Connolly, CM, Cross, AJ, Cuk, K, Curtis, KR, de la Chapelle, A, Doheny, KF, Duggan, D, Easton, DF, Elias, SG, Elliott, F, English, DR, Feskens, EJM, Figueiredo, JC, Fischer, R, FitzGerald, LM, Forman, D, Gala, M, Gallinger, S, Gauderman, WJ, Giles, GG, Gillanders, E, Gong, J, Goodman, PJ, Grady, WM, Grove, JS, Gsur, A, Gunter, MJ, Haile, RW, Hampe, J, Hampel, H, Harlid, S, Hayes, RB, Hofer, P, Hoffmeister, M, Hopper, JL, Hsu, W-L, Huang, W-Y, Hudson, TJ, Hunter, DJ, Ibanez-Sanz, G, Idos, GE, Ingersoll, R, Jackson, RD, Jacobs, EJ, Jenkins, MA, Joshi, AD, Joshu, CE, Keku, TO, Key, TJ, Kim, HR, Kobayashi, E, Kolonel, LN, Kooperberg, C, Kuehn, T, Kury, S, Kweon, S-S, Larsson, SC, Laurie, CA, Le Marchand, L, Leal, SM, Lee, SC, Lejbkowicz, F, Lemire, M, Li, CI, Li, L, Lieb, W, Lin, Y, Lindblom, A, Lindor, NM, Ling, H, Louie, TL, Mannisto, S, Markowitz, SD, Martin, V, Masala, G, McNeil, CE, Melas, M, Milne, RL, Moreno, L, Murphy, N, Myte, R, Naccarati, A, Newcomb, PA, Offit, K, Ogino, S, Onland-Moret, NC, Pardini, B, Parfrey, PS, Pearlman, R, Perduca, V, Pharoah, PDP, Pinchev, M, Platz, EA, Prentice, RL, Pugh, E, Raskin, L, Rennert, G, Rennert, HS, Riboli, E, Rodriguez-Barranco, M, Romm, J, Sakoda, LC, Schafmayer, C, Schoen, RE, Seminara, D, Shah, M, Shelford, T, Shin, M-H, Shulman, K, Sieri, S, Slattery, ML, Southey, MC, Stadler, ZK, Stegmaier, C, Su, Y-R, Tangen, CM, Thibodeau, SN, Thomas, DC, Thomas, SS, Toland, AE, Trichopoulou, A, Ulrich, CM, Van den Berg, DJ, van Duijnhoven, FJB, Van Guelpen, B, van Kranen, H, Vijai, J, Visvanathan, K, Vodicka, P, Vodickova, L, Vymetalkova, V, Weigl, K, Weinstein, SJ, White, E, Win, AK, Wolf, CR, Wolk, A, Woods, MO, Wu, AH, Zaidi, SH, Zanke, BW, Zhang, Q, Zheng, W, Scacheri, PC, Potter, JD, Bassik, MC, Kundaje, A, Casey, G, Moreno, V, Abecasis, GR, Nickerson, DA, Gruber, SB, Hsu, L, and Peters, U

Abstract

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

Published
2019

29. New horizons in breast cancer: the promise of immunotherapy

Author

Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla. CTS151: Bioquímica médica., Cruz Merino, Luis de la, Palazón Carrión, N., Henao-Carrasco, F., Nogales-Fernández, E., Álamo de la Gala, M., Vallejo Benítez, A., Chiesa, M., Universidad de Sevilla. Departamento de Medicina, Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Universidad de Sevilla. CTS151: Bioquímica médica., Cruz Merino, Luis de la, Palazón Carrión, N., Henao-Carrasco, F., Nogales-Fernández, E., Álamo de la Gala, M., Vallejo Benítez, A., and Chiesa, M.

Abstract

Immunology and immunotherapy of cancer is an expanding feld in oncology, with recent great achievements obtained through the new successful approaches implemented to circumvent immune evasion, which is undoubtedly considered a novel hallmark of cancer. Translational research in this topic has revealed targets that can be modulated in the clinical setting with new compounds and strategies. Like most of the tumors, breast cancer is considered a complex and heterogeneous disease in which host immune responses have been also recently demonstrated of critical relevance. T infltrating lymphocyte measure ment is suggested as a powerful new tool necessary to predict early breast cancer evolution, especially for the her2-positive and triple-negative subtypes. Other biomarkers in tissue and peripheral blood are under intense scrutiny to ascertain their eventual role as prognostic and/or predictive factors. This background has fueled the interest in developing clinical research strategies to test activity of modern immunotherapy in breast cancer, which constitutes the main focus of this review.

Published
2019

30. Evolution of myeloid-derived suppressor cells and objective response rate in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) patients after receiving immunotherapy

Author

Cortegana, C Jiménez, primary, Carrión, N Palazón, additional, Fernández, E Nogales, additional, García, M A Nieto, additional, Margalet, V Sánchez, additional, de la Gala, M D C Álamo, additional, de Ilárduya, M Suengas Martínez, additional, Burgos, E Montilla, additional, Fernández, I Araújo, additional, Carrasco, F Henao, additional, García-Sancho, A Martín, additional, Carnicero, F., additional, Herranz, E Rios, additional, de la Cruz Vicente, F., additional, Fernández, R., additional, Dominguez, A Rueda, additional, and de la Cruz Merino, L., additional

Published
2019
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32. Sound, Smell, Objects, and the Discursive Space of Nagai Kafū’s 1920s Fiction

Author

Gala Maria Follaco

Subjects
Nagai Kafū, sound, smell, modernity, city in literature, Literature (General), PN1-6790
Abstract

Throughout his life, Nagai Kafū (1879–1959) tackled crucial issues of modernity, such as the urban experience and conflicting notions of selfhood. This article explores some aspects of his narrative practice that enrich our understanding of his literary output while suggesting new avenues for future research on space-time representation in twentieth-century literature. I focus on passive senses such as hearing and smell, and on material objects and physical sensations as narrative devices employed by the author in order to broaden comprehension and enrich the experience of objective reality. In particular, I examine Yukidoke (Melting Snow), a 1922 short story understudied thus far but that offers useful insights as regards the author’s intent to defy superimposed notions of affect and space.

Published
2023
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33. Harmonizing taxon names in biodiversity data: A review of tools, databases and best practices

Author

Matthias Grenié, Emilio Berti, Juan Carvajal‐Quintero, Gala Mona Louise Dädlow, Alban Sagouis, and Marten Winter

Subjects
R packages, taxonomic databases, taxonomic harmonization, taxonomic name matching, taxonomic tools, taxonomy, Ecology, QH540-549.5, Evolution, QH359-425
Abstract

Abstract The process of standardizing taxon names, taxonomic name harmonization, is necessary to properly merge data indexed by taxon names. The large variety of taxonomic databases and related tools are often not well described. It is often unclear which databases are actively maintained or what is the original source of taxonomic information. In addition, software to access these databases is developed following non‐compatible standards, which creates additional challenges for users. As a result, taxonomic harmonization has become a major obstacle in ecological studies that seek to combine multiple datasets. Here, we review and categorize a set of major taxonomic databases publicly available as well as a large collection of R packages to access them and to harmonize lists of taxon names. We categorized available taxonomic databases according to their taxonomic breadth (e.g. taxon specific vs. multi‐taxa) and spatial scope (e.g. regional vs. global), highlighting strengths and caveats of each type of database. We divided R packages according to their function, (e.g. syntax standardization tools, access to online databases, etc.) and highlighted overlaps among them. We present our findings (e.g. network of linkages, data and tool characteristics) in a ready‐to‐use Shiny web application (available at: https://mgrenie.shinyapps.io/taxharmonizexplorer/). We also provide general guidelines and best practice principles for taxonomic name harmonization. As an illustrative example, we harmonized taxon names of one of the largest databases of community time series currently available. We showed how different workflows can be used for different goals, highlighting their strengths and weaknesses and providing practical solutions to avoid common pitfalls. To our knowledge, our opinionated review represents the most exhaustive evaluation of links among and of taxonomic databases and related R tools. Finally, based on our new insights in the field, we make recommendations for users, database managers and package developers alike.

Published
2023
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35. Monitorización de pacientes con pulseras inteligentes

Author

García Sánchez, Gala M., Garcia-Rodriguez, Jose, and Universidad de Alicante. Departamento de Tecnología Informática y Computación

Subjects
Aplicación, eSalud, Monitorización, Daño cerebral adquirido, Arquitectura y Tecnología de Computadores, Pulseras inteligentes, Epilepsia
Abstract

El presente documento es la memoria del trabajo de fin de grado que lleva por nombre “Monitorización de pacientes con pulseras inteligentes”. Ha sido realizado por Gala M. García Sánchez, bajo la supervisión de su tutor José García Rodríguez durante el periodo 2015-2016. A día de hoy, el uso de las pulseras inteligentes para una monitorización continua de las constantes vitales del usuario está normalizado. En cambio, pese a la fiabilidad de los sensores gracias al avance tecnológico y a su abaratamiento, no es posible encontrar tan fácilmente aplicaciones destinadas a un control médico exhaustivo que contribuya a mejorar la calidad de vida de los pacientes. Con este objetivo, se ha realizado un profundo estudio orientado al desarrollo de una aplicación, capaz de detectar ataques epilépticos en personas dependientes con Daño Cerebral Adquirido. De esta forma, se pretende que los cuidadores tengan una mayor tranquilidad al poder recibir una alerta configurable cuando se esté produciendo un ataque epiléptico, logrando así mejorar su autonomía al no ser obligatoria una vigilancia presencial continua. El desarrollo de este proyecto puede dividirse en dos partes diferenciadas: teórica y práctica. En primer lugar, el apartado teórico se basa en las investigaciones realizadas previas a la programación de la aplicación. Se comenzó con el análisis de las enfermedades a las que se dirige este trabajo y de los dispositivos en las que se basaría su implementación. En consecuencia, se derivó a un estudio sobre el ámbito de la e-Salud, al que pertenece el producto final, y al Internet de las Cosas, principio esencial sobre el que se apoyan el surgimiento de la tecnología weareable y que explica la hiperconexión entre dispositivos. Por último, se realizó el estudio del mercado para la elección de la pulsera inteligente, que finalmente sería Angel Sensor, y en búsqueda de aplicaciones similares. Finalmente, el apartado práctico engloba todos los pasos seguidos para alcanzar el resultado final. Por tanto, comenzaría con la elección de la metodología empleada y estudio de la viabilidad, para continuar con el análisis de requerimientos, el diseño conceptual y terminar con su implementación.

Published
2016

36. Experiencias españolas en la promoción de la autonomía personal en las personas mayores

Author

Muñoz Mayorga I, Herrera Molina E, Cid Gala M, and Martin Galán

Subjects
business.industry, media_common.quotation_subject, Psychological intervention, Podiatry, Public Health, Environmental and Occupational Health, Social Welfare, Cognition, Subsidy, Public relations, Reading (process), Cognitive rehabilitation therapy, business, Independent living, media_common
Abstract

OBJECTIVES To identify studies analyzing the development of initiatives and the requisite characteristics of programs that promote personal autonomy, to identify the initiatives and policies developed in Spain to promote active aging and to determine whether the programs developed are consistent with the evidence in this field. METHOD We performed a literature review and analyzed the policies developed in each Spanish region. Programs to promote personal autonomy were identified and analyzed through a questionnaire sent to the autonomous regions. RESULTS Personal autonomy should be promoted through interventions to improve physical, cognitive, social and psycho-affective functions and by eliminating barriers that hamper independent living. Functional capacities are promoted through leisure activities (83%), reading and cognitive rehabilitation. Independent living is encouraged through podiatry services (38.9%) and food services at home (38.9%). Thirteen autonomous communities and the Biscay Regional Council have developed specific policies to promote personal autonomy. Personal autonomy activities are often conducted in senior or day centers. CONCLUSIONS There are differences in the provision of programs to promote active aging. The development and implementation of these programs depends on the competent authority (Institute for the Elderly and Social Services, town councils, subsidized private entities, etc.). More evidence and a framework that defines common standards and criteria for the development of effective programs are required.

Published
2011
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37. Establishment of a Regional Virtual Tumor Board Program to Improve the Process of Care for Patients With Hepatocellular Carcinoma

Author

Daniel A. Anaya, Gala M. Barden, Mina Hanna, Diana L. Castillo, Nancy J. Petersen, Aitua Salami, Jessica A. Davila, and Aanand D. Naik

Subjects
Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cohort Studies, Multidisciplinary approach, mental disorders, Medicine, Tumor board, Humans, Medical physics, Referral and Consultation, Simulation, Aged, Retrospective Studies, Oncology (nursing), business.industry, Health Policy, Remote Consultation, Liver Neoplasms, Retrospective cohort study, Process of care, Middle Aged, medicine.disease, digestive system diseases, United States, Health Care Delivery, Patient Care Management, United States Department of Veterans Affairs, Logistic Models, Oncology, Hepatocellular carcinoma, Videoconferencing, business
Abstract

Multidisciplinary evaluation (MDE) of hepatocellular cancer (HCC) is the current standard, often provided through a tumor board (TB) forum; this standard is limited by oncology workforce shortages and lack of a TB at every institution. Virtual TBs (VTBs) may help overcome these limitations. Our study aim was to assess the impact of a regional VTB on the MDE process for patients with HCC.A retrospective cohort study was conducted, including patients with HCC referred to a tertiary cancer center from regional facilities (2009 to 2013). Baseline characteristics and outcomes were compared based on the referral mechanism: VTB versus subspecialty consultation (non-VTB). The primary outcome was comprehensive MDE (all required specialists present and key topics discussed). Secondary outcomes included timeliness of MDE and travel burden to complete MDE. Univariable and multivariable logistic regressions were performed to examine the association of a VTB with comprehensive MDE.A total of 116 patients were included in the study; 48 (41.4%) were evaluated through the VTB. A higher proportion of VTB patients received comprehensive MDE (91.7% v 64.7%; P = .001); the VTB was independently associated with higher odds of accomplishing comprehensive MDE (odds ratio, 6.0; 95% CI, 1.2 to 29.9; P = .02). VTB patients completed MDE significantly faster (median, 23 v 39 days; P.001), with lower travel burden (median, 0 v 683 miles traveled; P.001).This VTB program positively affected the process of care for patients with HCC by improving the quality and timeliness of the MDE process, while avoiding the burden arising from travel needs. Future studies should focus on implementation of VTB programs on a wider scale.

Published
2014

38. Monitorización de pacientes con pulseras inteligentes

Author

Garcia-Rodriguez, Jose, Universidad de Alicante. Departamento de Tecnología Informática y Computación, García Sánchez, Gala M., Garcia-Rodriguez, Jose, Universidad de Alicante. Departamento de Tecnología Informática y Computación, and García Sánchez, Gala M.

Abstract

El presente documento es la memoria del trabajo de fin de grado que lleva por nombre “Monitorización de pacientes con pulseras inteligentes”. Ha sido realizado por Gala M. García Sánchez, bajo la supervisión de su tutor José García Rodríguez durante el periodo 2015-2016. A día de hoy, el uso de las pulseras inteligentes para una monitorización continua de las constantes vitales del usuario está normalizado. En cambio, pese a la fiabilidad de los sensores gracias al avance tecnológico y a su abaratamiento, no es posible encontrar tan fácilmente aplicaciones destinadas a un control médico exhaustivo que contribuya a mejorar la calidad de vida de los pacientes. Con este objetivo, se ha realizado un profundo estudio orientado al desarrollo de una aplicación, capaz de detectar ataques epilépticos en personas dependientes con Daño Cerebral Adquirido. De esta forma, se pretende que los cuidadores tengan una mayor tranquilidad al poder recibir una alerta configurable cuando se esté produciendo un ataque epiléptico, logrando así mejorar su autonomía al no ser obligatoria una vigilancia presencial continua. El desarrollo de este proyecto puede dividirse en dos partes diferenciadas: teórica y práctica. En primer lugar, el apartado teórico se basa en las investigaciones realizadas previas a la programación de la aplicación. Se comenzó con el análisis de las enfermedades a las que se dirige este trabajo y de los dispositivos en las que se basaría su implementación. En consecuencia, se derivó a un estudio sobre el ámbito de la e-Salud, al que pertenece el producto final, y al Internet de las Cosas, principio esencial sobre el que se apoyan el surgimiento de la tecnología weareable y que explica la hiperconexión entre dispositivos. Por último, se realizó el estudio del mercado para la elección de la pulsera inteligente, que finalmente sería Angel Sensor, y en búsqueda de aplicaciones similares. Finalmente, el apartado práctico engloba todos los pasos seguidos para alcanzar el resu

Published
2016

39. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants

Author

Wang, J, Du, M, Jiao, S, Bien, SA, Gala, M, Abecasis, G, Bezieau, S, Brenner, H, Butterbach, K, Caan, BJ, Carlson, CS, Casey, G, Chang-Claude, J, Conti, DV, Curtis, KR, Duggan, D, Gallinger, S, Haile, RW, Harrison, TA, Hayes, RB, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jenkins, MA, Kury, S, Le Marchand, L, Leal, SM, Newcomb, PA, Nickerson, DA, Potter, JD, Schoen, RE, Schumacher, FR, Seminara, D, Slattery, ML, Hsu, L, Chan, AT, White, E, Berndt, SI, Peters, U, Wang, J, Du, M, Jiao, S, Bien, SA, Gala, M, Abecasis, G, Bezieau, S, Brenner, H, Butterbach, K, Caan, BJ, Carlson, CS, Casey, G, Chang-Claude, J, Conti, DV, Curtis, KR, Duggan, D, Gallinger, S, Haile, RW, Harrison, TA, Hayes, RB, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jenkins, MA, Kury, S, Le Marchand, L, Leal, SM, Newcomb, PA, Nickerson, DA, Potter, JD, Schoen, RE, Schumacher, FR, Seminara, D, Slattery, ML, Hsu, L, Chan, AT, White, E, Berndt, SI, and Peters, U

Abstract

Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s).

Published
2016

40. 1267P - Evolution of myeloid-derived suppressor cells and objective response rate in relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) patients after receiving immunotherapy

Author

Cortegana, C Jiménez, Carrión, N Palazón, Fernández, E Nogales, García, M A Nieto, Margalet, V Sánchez, de la Gala, M D C Álamo, de Ilárduya, M Suengas Martínez, Burgos, E Montilla, Fernández, I Araújo, Carrasco, F Henao, García-Sancho, A Martín, Carnicero, F., Herranz, E Rios, de la Cruz Vicente, F., Fernández, R., Dominguez, A Rueda, and de la Cruz Merino, L.

Published
2019
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41. Improving sustainable practices in tuna purse seine fish aggregating device (FAD) fisheries worldwide through continued collaboration with fishers

Author

Jefferson Murua, Gala Moreno, Laurent Dagorn, David Itano, Martin Hall, Hilario Murua, and Victor Restrepo

Subjects
participatory approach, fishers ecological knowledge, tuna fisheries, bycatch mitigation, fish aggregated devices (FADs), co-management, Science, General. Including nature conservation, geographical distribution, QH1-199.5
Abstract

More than a decade of bottom-up collaborative workshops and research with fishers from the principal tropical tuna purse seine fleets to reduce ecological impacts associated with the use of fish aggregating devices (FADs) has yielded novel improved sustainable fishing practices in all oceans. This integrative effort is founded on participatory knowledge-exchange workshops organized by the International Seafood Sustainability Foundation (ISSF), referred to as “ISSF Skippers Workshops”, where scientists, fishers, and key stakeholders examine and develop together ways and tools to minimize fishery impacts. Workshops organized since 2010 have reached fleet members in 23 countries across Asia, Africa, the Americas, Europe, and Oceania, with over 4,000 attendances, mostly skippers and crew, operating in the Indian, Atlantic, and Pacific oceans. Structured and continued open transparent discussions on ocean-specific options to minimize FAD associated bycatch, ghost fishing and marine pollution have produced an array of novel co-constructed solutions and a better understanding of ecosystem and fishery dynamics. Dedicated at sea research cruises in commercial purse seiners have enabled testing some of the ideas proposed in workshops. Results obtained were then communicated back to fishers for a double loop learning system resulting in solution refinement and/or adoption. Furthermore, fishers’ increased trust and stewardship have stimulated unprecedented large-scale science-industry research projects across oceans, such as multi-fleet biodegradable FAD trials, the adoption and widespread use of non-entangling FADs, and the development and adoption of best practices for the safe handling and release of vulnerable bycatch. This model of collaborative research is broadly applicable to other natural resource conservation fields. Support for long-term inclusive programs enabling harvesters to proactively collaborate in impact mitigation research contributes to improved scientific advice, voluntary compliance, and adaptive management for lasting sustainability trajectories.

Published
2023
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42. The effect of a regional hepatopancreaticobiliary surgical program on clinical volume, quality of cancer care, and outcomes in the Veterans Affairs system

Author

Victoria Poppelaars, Aitua Salami, Kelsey S. Lau, Gala M. Barden, David H. Berger, Daniel A. Anaya, Avo Artinyan, Shumaila Khawja, Daniel Albo, Samir S. Awad, and Diana L. Castillo

Subjects
medicine.medical_specialty, Referral, Hospitals, Veterans, Digestive System Neoplasms, Medical Oncology, Cohort Studies, Surgical oncology, Internal medicine, Health care, Outcome Assessment, Health Care, Ambulatory Care, Medicine, Hepatectomy, Humans, Adverse effect, Veterans Affairs, Referral and Consultation, Quality of Health Care, Retrospective Studies, business.industry, Cancer, Retrospective cohort study, Odds ratio, Length of Stay, medicine.disease, Texas, United States, Surgery, United States Department of Veterans Affairs, Logistic Models, business, Program Evaluation
Abstract

Malignant neoplasms of the hepatopancreaticobiliary (HPB) system constitute a significant public health problem worldwide. Treatment coordination for these tumors is challenging and can result in substandard care. Referral centers for HPB disease have been used as a strategy to improve postoperative outcomes, but their effect on accomplishing regionalization of care and improving quality of cancer care is not well known.To evaluate the effect of implementing a multidisciplinary HPB surgical program (HPB-SP) on regionalization of care, the quality of cancer care, and surgical outcomes within an integrated health care system.We designed a retrospective cohort study in a tertiary referral Veterans Affairs (VA) medical center within an 8-state designated VA health care region from November 23, 2005, through December 31, 2013. We compared patients with HPB tumors undergoing evaluation by the surgical oncology service before and after implementation of the HPB-SP on November 1, 2008.Implementation of the HPB-SP to improve access to specialized, multidisciplinary cancer care for veterans across the region.Clinical and surgical volume, proportion of patients undergoing a comprehensive multidisciplinary evaluation, and postoperative adverse events included as a composite outcome defined by occurrence of postoperative mortality, severe complications, and/or reoperation.We identified 516 patients referred to the surgical oncology service. Establishment of the HPB-SP resulted in significant increases in regional referrals (17.3% vs 44.4%; P .001), median monthly clinic visits (5 vs 20; P .001), and median number of HPB surgical procedures (3 vs 9; P = .003) per quarter. Multidisciplinary assessment increased from 52.6% to 70.0% (P .001). When we compared patients with hepatocellular carcinoma before (n = 55) and after (n = 131) implementation, more patients received any treatment (35 [63.6%] vs 109 [83.2%]; P = .004) with increased use of liver resection (0 vs 20 [15.3%]; P = .002), percutaneous ablation (0 vs 15 [11.5%]; P = .009), and oncosurgical strategies (0 vs 16 [12.2%]; P = .007) after implementation. Among patients with colorectal liver metastases (29 before vs 76 after implementation), a significant shift occurred from use of ablations (5 [17.2%] vs 3 [3.9]%; P = .02) to resections (6 [20.7%] vs 40 [52.6%]; P = .003), and use of perioperative chemotherapy increased (5 of 11 [45.5%] vs 33 of 43 [76.7%]; P = .01). The HPB-SP was associated with lower odds of postoperative adverse events, even after adjusting for important covariates (odds ratio, 0.29 [95% CI, 0.12-0.68]; P = .005), and a high rate of margin-negative liver (94.6%) and pancreatic (90.0%) resections.The development of an HPB-SP led to regionalization of care and improved quality of cancer care and surgical outcomes. Establishment of regional programs within the VA system can help improve the quality of care for patients presenting with complex cancers requiring subspecialized care.

Published
2014

43. Le foglie morte. Il tema della vecchiaia nell’opera di Nagai Kafū a partire da due saggi del 1943-44

Author

Gala Maria Follaco

Subjects
Ageing, Modernity, Nagai Kafū, Language and Literature
Abstract

This contribution explores the meanings and literary influences behind the “fallen leaves” motif and the “old man” pose in the writings of Nagai Kafū (1879-1959). Starting from two short essays published in the first half of the 1940s, a number of fiction and non-fiction works written from 1908 through 1937 will be analysed in order to demonstrate that the theme of ageing has much deeper connotations than one could expect and that the author resorted to it with a view to criticising Japan’s path modern society.

Published
2022
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44. Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Author

Schumacher, FR, Schmit, SL, Jiao, S, Edlund, CK, Wang, H, Zhang, B, Hsu, L, Huang, S-C, Fischer, CP, Harju, JF, Idos, GE, Lejbkowicz, F, Manion, FJ, McDonnell, K, McNeil, CE, Melas, M, Rennert, HS, Shi, W, Thomas, DC, Van Den Berg, DJ, Hutter, CM, Aragaki, AK, Butterbach, K, Caan, BJ, Carlson, CS, Chanock, SJ, Curtis, KR, Fuchs, CS, Gala, M, Giocannucci, EL, Gogarten, SM, Hayes, RB, Henderson, B, Hunter, DJ, Jackson, RD, Kolonel, LN, Kooperberg, C, Kury, S, LaCroix, A, Laurie, CC, Laurie, CA, Lemire, M, Levine, D, Ma, J, Makar, KW, Qu, C, Taverna, D, Ulrich, CM, Wu, K, Kono, S, West, DW, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Chan, AT, Chang-Claude, J, Coetzee, GA, Conti, DV, Duggan, D, Figueiredo, JC, Fortini, BK, Gallinger, SJ, Gauderman, WJ, Giles, G, Green, R, Haile, R, Harrison, TA, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jacobs, E, Iwasaki, M, Jee, SH, Jenkins, M, Jia, W-H, Joshi, A, Li, L, Lindor, NM, Matsuo, K, Moreno, V, Mukherjee, B, Newcomb, PA, Potter, JD, Raskin, L, Rennert, G, Rosse, S, Severi, G, Schoen, RE, Seminara, D, Shu, X-O, Slattery, ML, Tsugane, S, White, E, Xiang, Y-B, Zanke, BW, Zheng, W, Le Marchand, L, Casey, G, Gruber, SB, Peters, U, Schumacher, FR, Schmit, SL, Jiao, S, Edlund, CK, Wang, H, Zhang, B, Hsu, L, Huang, S-C, Fischer, CP, Harju, JF, Idos, GE, Lejbkowicz, F, Manion, FJ, McDonnell, K, McNeil, CE, Melas, M, Rennert, HS, Shi, W, Thomas, DC, Van Den Berg, DJ, Hutter, CM, Aragaki, AK, Butterbach, K, Caan, BJ, Carlson, CS, Chanock, SJ, Curtis, KR, Fuchs, CS, Gala, M, Giocannucci, EL, Gogarten, SM, Hayes, RB, Henderson, B, Hunter, DJ, Jackson, RD, Kolonel, LN, Kooperberg, C, Kury, S, LaCroix, A, Laurie, CC, Laurie, CA, Lemire, M, Levine, D, Ma, J, Makar, KW, Qu, C, Taverna, D, Ulrich, CM, Wu, K, Kono, S, West, DW, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Chan, AT, Chang-Claude, J, Coetzee, GA, Conti, DV, Duggan, D, Figueiredo, JC, Fortini, BK, Gallinger, SJ, Gauderman, WJ, Giles, G, Green, R, Haile, R, Harrison, TA, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jacobs, E, Iwasaki, M, Jee, SH, Jenkins, M, Jia, W-H, Joshi, A, Li, L, Lindor, NM, Matsuo, K, Moreno, V, Mukherjee, B, Newcomb, PA, Potter, JD, Raskin, L, Rennert, G, Rosse, S, Severi, G, Schoen, RE, Seminara, D, Shu, X-O, Slattery, ML, Tsugane, S, White, E, Xiang, Y-B, Zanke, BW, Zheng, W, Le Marchand, L, Casey, G, Gruber, SB, and Peters, U

Abstract

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.

Published
2015

45. Genome-wide association study of colorectal cancer identifies six new susceptibility loci (vol 6, 7138, 2015)

Author

Schumacher, FR, Schmit, SL, Jiao, S, Edlund, CK, Wang, H, Zhang, B, Hsu, L, Huang, S-C, Fischer, CP, Harju, JF, Idos, GE, Lejbkowicz, F, Manion, FJ, McDonnell, K, McNeil, CE, Melas, M, Rennert, HS, Shi, W, Thomas, DC, Van den Berg, DJ, Hutter, CM, Aragaki, AK, Butterbach, K, Caan, BJ, Carlson, CS, Chanock, SJ, Curtis, KR, Fuchs, CS, Gala, M, Giovannucci, EL, Gogarten, SM, Hayes, RB, Henderson, B, Hunter, DJ, Jackson, RD, Kolonel, LN, Kooperberg, C, Kuery, S, LaCroix, A, Laurie, CC, Laurie, CA, Lemire, M, Levine, D, Ma, J, Makar, KW, Qu, C, Taverna, D, Ulrich, CM, Wu, K, Kono, S, West, DW, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Chan, AT, Chang-Claude, J, Coetzee, GA, Conti, DV, Duggan, D, Figueiredo, JC, Fortini, BK, Gallinger, SJ, Gauderman, WJ, Giles, G, Green, R, Haile, R, Harrison, TA, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jacobs, E, Iwasaki, M, Jee, SH, Jenkins, M, Jia, W-H, Joshi, A, Li, L, Lindor, NM, Matsuo, K, Moreno, V, Mukherjee, B, Newcomb, PA, Potter, JD, Raskin, L, Rennert, G, Rosse, S, Severi, G, Schoen, RE, Seminara, D, Shu, X-O, Slattery, ML, Tsugane, S, White, E, Xiang, Y-B, Zanke, BW, Zheng, W, Le Marchand, L, Casey, G, Gruber, SB, Peters, U, Schumacher, FR, Schmit, SL, Jiao, S, Edlund, CK, Wang, H, Zhang, B, Hsu, L, Huang, S-C, Fischer, CP, Harju, JF, Idos, GE, Lejbkowicz, F, Manion, FJ, McDonnell, K, McNeil, CE, Melas, M, Rennert, HS, Shi, W, Thomas, DC, Van den Berg, DJ, Hutter, CM, Aragaki, AK, Butterbach, K, Caan, BJ, Carlson, CS, Chanock, SJ, Curtis, KR, Fuchs, CS, Gala, M, Giovannucci, EL, Gogarten, SM, Hayes, RB, Henderson, B, Hunter, DJ, Jackson, RD, Kolonel, LN, Kooperberg, C, Kuery, S, LaCroix, A, Laurie, CC, Laurie, CA, Lemire, M, Levine, D, Ma, J, Makar, KW, Qu, C, Taverna, D, Ulrich, CM, Wu, K, Kono, S, West, DW, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Chan, AT, Chang-Claude, J, Coetzee, GA, Conti, DV, Duggan, D, Figueiredo, JC, Fortini, BK, Gallinger, SJ, Gauderman, WJ, Giles, G, Green, R, Haile, R, Harrison, TA, Hoffmeister, M, Hopper, JL, Hudson, TJ, Jacobs, E, Iwasaki, M, Jee, SH, Jenkins, M, Jia, W-H, Joshi, A, Li, L, Lindor, NM, Matsuo, K, Moreno, V, Mukherjee, B, Newcomb, PA, Potter, JD, Raskin, L, Rennert, G, Rosse, S, Severi, G, Schoen, RE, Seminara, D, Shu, X-O, Slattery, ML, Tsugane, S, White, E, Xiang, Y-B, Zanke, BW, Zheng, W, Le Marchand, L, Casey, G, Gruber, SB, and Peters, U

Published
2015

46. Depth and Dimension: Exploring the Problems and Potential of Photogrammetric Models for Ancient Coins

Author

Gala Morris, Joshua Emmitt, and Jeremy Armstrong

Subjects
photogrammetry, 3d modelling, ancient coins, numismatics, digitisation, Archaeology, CC1-960, Electronic computers. Computer science, QA75.5-76.95
Abstract

In numismatic collections, coins are typically documented and studied using 2D images of their obverse and reverse. While two photographs, under the correct lighting, provide adequate information for basic research, detailed numismatic study has generally required the physical handling of the items to capture the three-dimensional aspects of the coin. Recent advances in photogrammetry and digitisation provide new opportunities for numismatic research. Digitised, 3D models of ancient coins allow researchers and students to interact with these coins remotely, providing opportunities to study coins from collections that would otherwise be difficult to access. Ancient coins, however, can be challenging to digitise due to their small size, irregular shape, and reflectance. This study will explore and outline a methodology for creating 3D models of ancient coins that balances both expediency with quality. Three Roman Republican coins from the University of Auckland’s numismatic collection were digitised using photogrammetric methods to create 3D digital models for student use. Expedient capture relied primarily on the quality of the photogrammetry setup, as well as the use of macrophotography, to capture the detail of each coin effectively. While the digital models took longer to produce than traditional 2D images, it was possible to create high-quality digital 3D model coins in a relatively expedient manner. The balance between speed and increased data opens the door for a new era in numismatic cataloguing and qualitative research opportunities.

Published
2022
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48. Debate e interacción doctrinal en las artes epistolares castellanas de mediados del XVI

Author

Navarro Gala, M. Josefa

Subjects
Lengua española, Cartas, Debate, Gaspar de Texeda, Antonio de Torquemada, Secretarios, Epistolographic tendencies, Secretaries, Formularis, Tendencias epistolográficas, Literatura, Formularios, Letters, Juan de Yciar
Abstract

Gaspar de Texeda’s Primero Libro de cartas mensageras en estilo cortesano (1547-1553) is usually taken as a “not too serious” manual, and thus, it has a low place in the history of epistolography. This assessment does not come from a rigorous study of the work, but from the consolidation of prejudices defended by secretaries professionally and personally hostile to the author and to his writing style. The invectives exchanged between Texeda, Torquemada and Yciar in their respective manuals, illustrate well the different styles each one defended, as well as the debate taking place around the vernacular episolography. El Primero Libro de cartas mensageras en estilo cortesano (1547-1553) de Gaspar de Texeda es habitualmente considerado un manual ‘poco serio’, por lo que se le reserva un exiguo lugar en la historia de la epistolografía. Esta valoración no procede de un estudio riguroso de la obra sino de la consolidación de prejuicios extemporáneos defendidos por secretarios contrarios estilísticamente al autor y hostiles a éste profesional y personalmente. Las invectivas y réplicas contenidas en los tratados de Texeda, de Toquemada y de Yciar ilustran magníficamente las distintas corrientes epistolográficas de la época, así como el virulento debate que en esos momentos se estaba dirimiendo en torno a la práctica epistolar vernácula.

Published
2010

49. The unread critic. Higuchi Ichiyō’s diaries as bungei hyōron

Author

Gala Maria Follaco

Subjects
higuchi ichiyō, nikki, diary, autobiographic writing, criticism, bundan, shintaishi, kagawa kageki, Language and Literature, Japanese language and literature, PL501-889
Abstract

The diaries of Higuchi Ichiyō (1872–1896) are usually seen as examples of autobiographic writing, whereas her critical attitude is seldom considered. I argue that some parts of her nikki can be seen as criticism even if they do not resemble canonical forms of this kind of writing. As early as 1893, for instance, Ichiyō commented on shintai questioning the presumed ‘modernity’ of the most recent stylistic trends, and close reading of her notes reveals her deep knowledge of Japan's literature. These sections signal her literary consciousness at a very specific time: the years between 1893 and 1894, when, according to the dominant scholarship, her narrative production was still heavily dependent on previous models, thus not yet mature, a reading that my contribution will try to challenge. Further, her relationship with the contemporary bundan, as well as her acquaintance with Kagawa Kageki's thought will be considered, in order to assess her critical attitude against the backdrop of both her time and her literary education.

Published
2020
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