Monitoring the growth of a microbubble generated photothermally onto an optical fiber by means Fabry–Perot interferometry

In the present paper, we show the experimental measurement of the growth of a microbubble created on the tip of a single mode optical fiber, in which zinc nanoparticles were photodeposited on its core by using a single laser source to carry out both the generation of the microbubble by photothermal effect and the monitoring of the microbubble diameter. The photodeposition technique, as well as the formation of the microbubble, was carried out by using a single-mode pigtailed laser diode with emission at a wavelength of 658 nm. The microbubble’s growth was analyzed in the time domain by the analysis of the Fabry–Perot cavity, whose diameter was calculated with the number of interference fringes visualized in an oscilloscope. The results obtained with this technique were compared with images obtained from a CCD camera, in order to verify the diameter of the microbubble. Therefore, by counting the interference fringes, it was possible to quantify the temporal evolution of the microbubble. As a practical demonstration, we proposed a vibrometer sensor using microbubbles with sizes of 83 and 175 m as a Fabry–Perot cavity; through the time period of a full oscillation cycle of an interferogram observed in the oscilloscope, it was possible to know the frequency vibration (500 and 1500 Hz) for a cuvette where the microbubble was created.CONACyT (FOINS) Grant No. 2319Fondo Sectorial de Investigación para la Educación Grant No. A1-S-28440

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857). Copyright © 2022 Llera, Abdelhay, Artagaveytia, Daneri-Navarro, Müller, Velazquez, Alcoba, Alonso, Alves da Quinta, Binato, Bravo, Camejo, Carraro, Castro, Castro-Cervantes, Cataldi, Cayota, Cerda, Colombo, Crocamo, Del Toro-Arreola, Delgadillo-Cisterna, Delgado, Dreyer-Breitenbach, Fejerman, Fernández, Fernández, Fernández, Franco-Topete, Gabay, Gaete, Garibay-Escobar, Gómez, Greif, Gross, Guerrero, Henderson, Lopez-Muñoz, Lopez-Vazquez, Maldonado, Morán-Mendoza, Nagai, Oceguera-Villanueva, Ortiz-Martínez, Quintero, Quintero-Ramos, Reis, Retamales, Rivera-Claisse, Rocha, Rodríguez, Rosales, Salas-González, Sanchotena, Segovia, Sendoya, Silva-García, Trinchero, Valenzuela, Vedham, Zagame, United States-Latin American Cancer Research Network (US-LACRN) and Podhajcer.Fil: Llera, Andrea Sabina. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; ArgentinaFil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Câncer. Bone Marrow Transplantation Unit; BrasilFil: Artagaveytia, Nora. Universidad de la República. Hospital de Clínicas Manuel Quintela; UruguayFil: Daneri-Navarro, Adrián. Universidad de Guadalajara; MéxicoFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa B. Hospital Municipal de Oncología María Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Alves da Quinta, Daniela B. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; ArgentinaFil: Alves da Quinta, Daniela B. Universidad Argentina de la Empresa (UADE). Instituto de Tecnología (INTEC); ArgentinaFil: Binato, Renata. Instituto Nacional de Câncer. Bone Marrow Transplantation Unit; BrasilFil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la República. Hospital de Clínicas Manuel Quintela; UruguayFil: Carraro, Dirce Maria. AC Camargo Cancer Center. Centro Internacional de Pesquisa (CIPE). Laboratory of Genomics and Molecular Biology; BrasilFil: Castro, Mónica. Instituto de Oncología Angel Roffo; ArgentinaFil: Castro-Cervantes, Juan M. Hospital de Especialidades CMNO-IMSS; MéxicoFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Institut Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile. Instituto de Neurociencias Biomédicas. Facultad de Medicina. Centro de Informática Médica y Telemedicina. Instituto de Ciencias Biomédicas (ICBM). Integrative Biology Program; ChileFil: Colombo, Alicia. Universidad de Chile. Facultad de Medicina y Hospital Clínico. Department of Pathology; ChileFil: Crocamo, Susanne. Instituto Nacional de Câncer. Oncology Department; BrasilFil: Del Toro-Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo-Cisterna, Raúl. Hospital de Especialidades CMNO-IMSS; MéxicoFil: Delgado, Lucía. Universidad de la República. Hospital de Clínicas Manuel Quintela; UruguayFil: Dreyer-Breitenbach, Marisa. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes; BrasilFil: Fejerman, Laura. University of California Davis. Department of Public Health Sciences and Comprehensive Cancer Center; Estados UnidosFil: Fernández, Elmer A. Universidad Católica de Córdoba. CONICET. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas [Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE); ArgentinaFil: Fernández, Elmer A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Fernández, Wanda. Hospital San Borja Arriarán; ChileFil: Franco-Topete, Ramón A. Universidad de Guadalajara. Hospital Civil de Guadalajara. Organismo Público Descentralizado (OPD); MéxicoFil: Gabay, Carolina. Instituto de Oncología Angel Roffo; ArgentinaFil: Gaete, Fancy. Hospital Luis Tisne; ChileFil: Garibay-Escobar, Adriana. Universidad de Sonora; MéxicoFil: Gómez, Jorge. Texas A&M University; Estados UnidosFil: Greif, Gonzalo. Institut Pasteur de Montevideo; UruguayFil: Gross, Thomas G. Center for Global Health, National Cancer Institute; Estados UnidosFil: Guerrero, Marisol. Hospital San José; ChileFil: Henderson, Marianne K. Center for Global Health, National Cancer Institute; Estados UnidosFil: Lopez-Muñoz, Miguel E. Universidad de Sonora; MéxicoFil: Lopez-Vazquez, Alejandra. Universidad de Sonora; MéxicoFil: Maldonado, Silvina. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Morán-Mendoza, Andrés J. Hospital de Gineco-Obstetricia CMNO-IMSS; MéxicoFil: Nagai, Maria Aparecida. Sao Paulo University Medical School. Cancer Institute of São Paulo (ICESP). Center for Translational Research in Oncology; BrasilFil: Oceguera-Villanueva, Antonio. Instituto Jalisciense de Cancerologia; MéxicoFil: Ortiz-Martínez, Miguel A. Hospital General Regional No. 1. IMSS; MéxicoFil: Quintero, Jael. Universidad de Sonora; MéxicoFil: Quintero-Ramos, Antonio. Universidad de Guadalajara; MéxicoFil: Reis, Rui M. Hospital de Câncer de Barretos. Molecular Oncology Research Center; BrasilFil: Retamales, Javier. Grupo Oncológico Cooperativo Chileno de Investigación; ChileFil: Rivera-Claisse, Ernesto. Centro Estatal de Oncologia; MéxicoFil: Rocha, Darío. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Rodríguez, Robinson. Hospital Central de las Fuerzas Armadas; UruguayFil: Rosales, Cristina. Hospital Municipal de Oncología María Curie; ArgentinaFil: Salas-González, Efrain. Hospital de Gineco-Obstetricia CMNO-IMSS; MéxicoFil: Sanchotena, Verónica. Hospital Municipal de Oncología María Curie; ArgentinaFil: Segovia, Laura. Hospital Barros Luco Trudeau; ChileFil: Sendoya, Juan Martín. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; ArgentinaFil: Silva-García, Aida A. Universidad de Guadalajara. Hospital Civil de Guadalajara. Organismo Público Descentralizado (OPD); MéxicoFil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Vedham, Vidya. National Cancer Institute. Center for Global Health; Estados Unido

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

PurposesMost molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches.Patients and methodsWe collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes.ResultsPAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors.ConclusionsThis is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America.Clinical trial registrationClinicalTrials.gov (Identifier: NCT02326857)

The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age

Abstract Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focus on the maternal genetic makeup of the Neolithic (~ 5500–3000 BCE), Chalcolithic (~ 3000–2200 BCE) and Early Bronze Age (~ 2200–1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research