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3D printed cardiovascular models for surgical planning in complex congenital heart diseases

(2015) Valverde, Israel; Gomez, Gorka; Suarez-Mejias, Cristina; Hosseinpour, Amir-Reza; Hazekamp, Mark; Roest, Arno; Vazquez-Jimenez, Jaime F; El-Rassi, Issam; Uribe Arancibia, Sergio A.; Gomez-Cia, Tomas

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3D quantification of hemodynamics parameters of pulmonary artery and aorta using finite-element interpolations in 4D flow MR data

(2015) Sotelo Parraguez, Julio Andrés; Urbina, Jesus.; Valverde, Israel.; Tejos Núñez, Cristián Andrés; Irarrázaval Mena, Pablo; Hurtado Sepúlveda, Daniel; Uribe Arancibia, Sergio A.

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3D quantification of wall shear stress using finite-element interpolations from 4D flow MR data in the Thoracic Aorta

(2014) Sotelo Parraguez, Julio Andrés; Urbina, Jesus.; Tejos Núñez, Cristián Andrés; Valverde, Israel.; Hurtado Sepúlveda, Daniel; Uribe Arancibia, Sergio A.

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3D whole-heart phase sensitive inversion recovery CMR for simultaneous black-blood late gadolinium enhancement and bright-blood coronary CMR angiography

(2017) Ginami, Giulia; Neji, Radhouene; Rashid, Imran; Chiribiri, Amedeo; Ismail, Tevfik F; Botnar, René Michael; Prieto Vásquez, Claudia

Abstract Background Phase sensitive inversion recovery (PSIR) applied to late gadolinium enhancement (LGE) imaging is widely used in clinical practice. However, conventional 2D PSIR LGE sequences provide sub-optimal contrast between scar tissue and blood pool, rendering the detection of subendocardial infarcts and scar segmentation challenging. Furthermore, the acquisition of a low flip angle reference image doubles the acquisition time without providing any additional diagnostic information. The purpose of this study was to develop and test a novel 3D whole-heart PSIR-like framework, named BOOST, enabling simultaneous black-blood LGE assessment and bright-blood visualization of cardiac anatomy. Methods The proposed approach alternates the acquisition of a 3D volume preceded by a T2-prepared Inversion Recovery (T2Prep-IR) module (magnitude image) with the acquisition of a T2-prepared 3D volume (reference image). The two volumes (T2Prep-IR BOOST and bright-blood T2Prep BOOST) are combined in a PSIR-like reconstruction to obtain a complementary 3D black-blood volume for LGE assessment (PSIR BOOST). The black-blood PSIR BOOST and the bright-blood T2Prep BOOST datasets were compared to conventional clinical sequences for scar detection and coronary CMR angiography (CMRA) in 18 patients with a spectrum of cardiovascular disease (CVD). Results Datasets from 12 patients were quantitatively analysed. The black-blood PSIR BOOST dataset provided statistically improved contrast to noise ratio (CNR) between blood and scar when compared to a clinical 2D PSIR sequence (15.8 ± 3.3 and 4.1 ± 5.6, respectively). Overall agreement in LGE depiction was found between 3D black-blood PSIR BOOST and clinical 2D PSIR acquisitions, with 11/12 PSIR BOOST datasets considered diagnostic. The bright-blood T2Prep BOOST dataset provided high quality depiction of the proximal coronary segments, with improvement of visual score when compared to a clinical CMRA sequence. Acquisition time of BOOST (~10 min), providing information on both LGE uptake and heart anatomy, was comparable to that of a clinical single CMRA sequence. Conclusions The feasibility of BOOST for simultaneous black-blood LGE assessment and bright-blood coronary angiography was successfully tested in patients with cardiovascular disease. The framework enables free-breathing multi-contrast whole-heart acquisitions with 100% scan efficiency and predictable scan time. Complementary information on 3D LGE and heart anatomy are obtained reducing examination time.Abstract Background Phase sensitive inversion recovery (PSIR) applied to late gadolinium enhancement (LGE) imaging is widely used in clinical practice. However, conventional 2D PSIR LGE sequences provide sub-optimal contrast between scar tissue and blood pool, rendering the detection of subendocardial infarcts and scar segmentation challenging. Furthermore, the acquisition of a low flip angle reference image doubles the acquisition time without providing any additional diagnostic information. The purpose of this study was to develop and test a novel 3D whole-heart PSIR-like framework, named BOOST, enabling simultaneous black-blood LGE assessment and bright-blood visualization of cardiac anatomy. Methods The proposed approach alternates the acquisition of a 3D volume preceded by a T2-prepared Inversion Recovery (T2Prep-IR) module (magnitude image) with the acquisition of a T2-prepared 3D volume (reference image). The two volumes (T2Prep-IR BOOST and bright-blood T2Prep BOOST) are combined in a PSIR-like reconstruction to obtain a complementary 3D black-blood volume for LGE assessment (PSIR BOOST). The black-blood PSIR BOOST and the bright-blood T2Prep BOOST datasets were compared to conventional clinical sequences for scar detection and coronary CMR angiography (CMRA) in 18 patients with a spectrum of cardiovascular disease (CVD). Results Datasets from 12 patients were quantitatively analysed. The black-blood PSIR BOOST dataset provided statistically improved contrast to noise ratio (CNR) between blood and scar when compared to a clinical 2D PSIR sequence (15.8 ± 3.3 and 4.1 ± 5.6, respectively). Overall agreement in LGE depiction was found between 3D black-blood PSIR BOOST and clinical 2D PSIR acquisitions, with 11/12 PSIR BOOST datasets considered diagnostic. The bright-blood T2Prep BOOST dataset provided high quality depiction of the proximal coronary segments, with improvement of visual score when compared to a clinical CMRA sequence. Acquisition time of BOOST (~10 min), providing information on both LGE uptake and heart anatomy, was comparable to that of a clinical single CMRA sequence. Conclusions The feasibility of BOOST for simultaneous black-blood LGE assessment and bright-blood coronary angiography was successfully tested in patients with cardiovascular disease. The framework enables free-breathing multi-contrast whole-heart acquisitions with 100% scan efficiency and predictable scan time. Complementary information on 3D LGE and heart anatomy are obtained reducing examination time.Abstract Background Phase sensitive inversion recovery (PSIR) applied to late gadolinium enhancement (LGE) imaging is widely used in clinical practice. However, conventional 2D PSIR LGE sequences provide sub-optimal contrast between scar tissue and blood pool, rendering the detection of subendocardial infarcts and scar segmentation challenging. Furthermore, the acquisition of a low flip angle reference image doubles the acquisition time without providing any additional diagnostic information. The purpose of this study was to develop and test a novel 3D whole-heart PSIR-like framework, named BOOST, enabling simultaneous black-blood LGE assessment and bright-blood visualization of cardiac anatomy. Methods The proposed approach alternates the acquisition of a 3D volume preceded by a T2-prepared Inversion Recovery (T2Prep-IR) module (magnitude image) with the acquisition of a T2-prepared 3D volume (reference image). The two volumes (T2Prep-IR BOOST and bright-blood T2Prep BOOST) are combined in a PSIR-like reconstruction to obtain a complementary 3D black-blood volume for LGE assessment (PSIR BOOST). The black-blood PSIR BOOST and the bright-blood T2Prep BOOST datasets were compared to conventional clinical sequences for scar detection and coronary CMR angiography (CMRA) in 18 patients with a spectrum of cardiovascular disease (CVD). Results Datasets from 12 patients were quantitatively analysed. The black-blood PSIR BOOST dataset provided statistically improved contrast to noise ratio (CNR) between blood and scar when compared to a clinical 2D PSIR sequence (15.8 ± 3.3 and 4.1 ± 5.6, respectively). Overall agreement in LGE depiction was found between 3D black-blood PSIR BOOST and clinical 2D PSIR acquisitions, with 11/12 PSIR BOOST datasets considered diagnostic. The bright-blood T2Prep BOOST dataset provided high quality depiction of the proximal coronary segments, with improvement of visual score when compared to a clinical CMRA sequence. Acquisition time of BOOST (~10 min), providing information on both LGE uptake and heart anatomy, was comparable to that of a clinical single CMRA sequence. Conclusions The feasibility of BOOST for simultaneous black-blood LGE assessment and bright-blood coronary angiography was successfully tested in patients with cardiovascular disease. The framework enables free-breathing multi-contrast whole-heart acquisitions with 100% scan efficiency and predictable scan time. Complementary information on 3D LGE and heart anatomy are obtained reducing examination time.

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A comparative evaluation of PDQ-Evidence

(2018) Johansen, Marit; Rada G., Gabriel; Rosenbaum, Sarah; Paulsen, Elizabeth; Motaze, Nkengafac V.; Opiyo, Newton; Wiysonge, Charles S.; Ding, Yunpeng; Mukinda, Fidele K.; Oxman, Andrew D.

Abstract Background A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. Methods We recruited healthcare policy-makers, managers and health researchers in low-, middle- and high-income countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. Results A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. Conclusions PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people. Trial registration The trial was prospectively registered in the ISRCTN registry 17 April 2015. Registration number: ISRCTN12742235 .Abstract Background A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. Methods We recruited healthcare policy-makers, managers and health researchers in low-, middle- and high-income countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. Results A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. Conclusions PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people. Trial registration The trial was prospectively registered in the ISRCTN registry 17 April 2015. Registration number: ISRCTN12742235 .Abstract Background A strategy for minimising the time and obstacles to accessing systematic reviews of health system evidence is to collect them in a freely available database and make them easy to find through a simple ‘Google-style’ search interface. PDQ-Evidence was developed in this way. The objective of this study was to compare PDQ-Evidence to six other databases, namely Cochrane Library, EVIPNet VHL, Google Scholar, Health Systems Evidence, PubMed and Trip. Methods We recruited healthcare policy-makers, managers and health researchers in low-, middle- and high-income countries. Participants selected one of six pre-determined questions. They searched for a systematic review that addressed the chosen question and one question of their own in PDQ-Evidence and in two of the other six databases which they would normally have searched. We randomly allocated participants to search PDQ-Evidence first or to search the two other databases first. The primary outcomes were whether a systematic review was found and the time taken to find it. Secondary outcomes were perceived ease of use and perceived time spent searching. We asked open-ended questions about PDQ-Evidence, including likes, dislikes, challenges and suggestions for improvements. Results A total of 89 people from 21 countries completed the study; 83 were included in the primary analyses and 6 were excluded because of data errors that could not be corrected. Most participants chose PubMed and Cochrane Library as the other two databases. Participants were more likely to find a systematic review using PDQ-Evidence than using Cochrane Library or PubMed for the pre-defined questions. For their own questions, this difference was not found. Overall, it took slightly less time to find a systematic review using PDQ-Evidence. Participants perceived that it took less time, and most participants perceived PDQ-Evidence to be slightly easier to use than the two other databases. However, there were conflicting views about the design of PDQ-Evidence. Conclusions PDQ-Evidence is at least as efficient as other databases for finding health system evidence. However, using PDQ-Evidence is not intuitive for some people. Trial registration The trial was prospectively registered in the ISRCTN registry 17 April 2015. Registration number: ISRCTN12742235 .

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A comparison of visual and quantitative methods to identify interstitial lung abnormalities

(2015) Kliment, Corrine R.; Araki, Tetsuro; Doyle, Tracy J.; Gao, Wei; Dupuis, Josée; Latourelle, Jeanne C.; Zazueta, Oscar E.; Fernandez, Isis E.; Nishino, Mizuki; Díaz Fuenzalida, Alejandro

Abstract Background Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density metrics and compared these to visual assessments of ILA. Methods To provide a comparison between ILA detection methods based on visual assessment we generated measures of high attenuation areas (HAAs, defined by attenuation values between −600 and −250 Hounsfield Units) in >4500 participants from both the COPDGene and Framingham Heart studies (FHS). Linear and logistic regressions were used for analyses. Results Increased measures of HAAs (in ≥10 % of the lung) were significantly associated with ILA defined by visual inspection in both cohorts (P < 0.0001); however, the positive predictive values were not very high (19 % in COPDGene and 13 % in the FHS). In COPDGene, the association between HAAs and ILA defined by visual assessment were modified by the percentage of emphysema and body mass index. Although increased HAAs were associated with reductions in total lung capacity in both cohorts, there was no evidence for an association between measurement of HAAs and MUC5B promoter genotype in the FHS. Conclusion Our findings demonstrate that increased measures of lung density may be helpful in determining the severity of lung volume reduction, but alone, are not strongly predictive of ILA defined by visual assessment. Moreover, HAAs were not associated with MUC5B promoter genotype.Abstract Background Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density metrics and compared these to visual assessments of ILA. Methods To provide a comparison between ILA detection methods based on visual assessment we generated measures of high attenuation areas (HAAs, defined by attenuation values between −600 and −250 Hounsfield Units) in >4500 participants from both the COPDGene and Framingham Heart studies (FHS). Linear and logistic regressions were used for analyses. Results Increased measures of HAAs (in ≥10 % of the lung) were significantly associated with ILA defined by visual inspection in both cohorts (P < 0.0001); however, the positive predictive values were not very high (19 % in COPDGene and 13 % in the FHS). In COPDGene, the association between HAAs and ILA defined by visual assessment were modified by the percentage of emphysema and body mass index. Although increased HAAs were associated with reductions in total lung capacity in both cohorts, there was no evidence for an association between measurement of HAAs and MUC5B promoter genotype in the FHS. Conclusion Our findings demonstrate that increased measures of lung density may be helpful in determining the severity of lung volume reduction, but alone, are not strongly predictive of ILA defined by visual assessment. Moreover, HAAs were not associated with MUC5B promoter genotype.Abstract Background Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density metrics and compared these to visual assessments of ILA. Methods To provide a comparison between ILA detection methods based on visual assessment we generated measures of high attenuation areas (HAAs, defined by attenuation values between −600 and −250 Hounsfield Units) in >4500 participants from both the COPDGene and Framingham Heart studies (FHS). Linear and logistic regressions were used for analyses. Results Increased measures of HAAs (in ≥10 % of the lung) were significantly associated with ILA defined by visual inspection in both cohorts (P < 0.0001); however, the positive predictive values were not very high (19 % in COPDGene and 13 % in the FHS). In COPDGene, the association between HAAs and ILA defined by visual assessment were modified by the percentage of emphysema and body mass index. Although increased HAAs were associated with reductions in total lung capacity in both cohorts, there was no evidence for an association between measurement of HAAs and MUC5B promoter genotype in the FHS. Conclusion Our findings demonstrate that increased measures of lung density may be helpful in determining the severity of lung volume reduction, but alone, are not strongly predictive of ILA defined by visual assessment. Moreover, HAAs were not associated with MUC5B promoter genotype.

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A do it yourself (DIY) point-of-care wrist ultrasound phantom for joint access training

(2024) Cheng, Andrea; Zhou, Justin; Chan, Chun H. R.; Chen, Connie; Cheng, Charlotte; Storm, Kaitlyn; Zhou, Anson; Mao, Alan; Kuk, Won J.; Fong, Tiffany C.; Villagrán Gutiérrez, Ignacio Andrés; Miranda Mendoza, Constanza Sofia

Joint access is essential for arthrocentesis, or joint aspiration of fluids. Joint treatments that are not performed properly can result in avoidable patient issues such as damage to the muscles, tendons, and blood vessels surrounding the joint. The use of ultrasound has become the gold standard for this procedure and proven to be a support in the skill learning process. However, success with this equipment, particularly in small joints like the wrist, depends on a clinician's capacity to recognize the crucial landmarks that guide these procedures. Prior to executing on a real patient, task trainers have proven to be an effective way for doctors to practice and prepare for procedures. However, shortcomings of current solutions include high purchase costs, incompatibility with ultrasound imaging, and low reusability. In addition, since this is a procedure that is not performed frequently, there may not be space or resources available in healthcare facilities to accommodate one at the point of care. This study aimed to close the existing gap by developing a DIY ultrasound compatible task trainer for wrist joint access training. Results We developed a novel ultrasound compatible wrist joint model that can be made from sustainable materials and reusable parts, thus reducing the costs for acquisition and environmental impact. Our model, which was produced utilizing small-batch production methods, is made up of 3D-printed bones enclosed in an ultrasound-compatible gelatin mixture. It can be easily remade after each practice session, removing needle tracks that are visible under ultrasound for conventional phantoms. The ultrasonic properties of this model were tested through pixel brightness analysis and visual inspection of simulated anatomical structures. Conclusion Our results report the advantages and limitations of the proposed model regarding production, practice, and ultrasound compatibility. While future work entails the transfer to patients of the same skill, this reusable and replicable model has proven, when presented to experts, to be successful in representing the physical characteristics and ultrasound profile of significant anatomical structures. This novel DIY product could be an effective alternative to teach procedures in the context of resource-restrained clinical simulation centers.

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A hypoperfusion context may aid to interpret hyperlactatemia in sepsis-3 septic shock patients : a proof-of-concept study

(2017) Alegría, Leyla.; Vera, Magdalena.; Dreyse, Jorge; Castro, Ricardo; Carpio Cordero, David; Henríquez, Carolina.; Gajardo, Daniela.; Bravo-Grau, Sebastian.; Araneda, Felipe.; Hernández P., Glenn

Abstract Background Persistent hyperlactatemia is particularly difficult to interpret in septic shock. Besides hypoperfusion, adrenergic-driven lactate production and impaired lactate clearance are important contributors. However, clinical recognition of different sources of hyperlactatemia is unfortunately not a common practice and patients are treated with the same strategy despite the risk of over-resuscitation in some. Indeed, pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of fluid overload and vasoactive drugs. We hypothesized that two different clinical patterns can be recognized in septic shock patients through a multimodal perfusion monitoring. Hyperlactatemic patients with a hypoperfusion context probably represent a more severe acute circulatory dysfunction, and the absence of a hypoperfusion context is eventually associated with a good outcome. We performed a retrospective analysis of a database of septic shock patients with persistent hyperlactatemia after initial resuscitation. Results We defined hypoperfusion context by the presence of a ScvO2 < 70%, or a P(cv-a)CO2 ≥6 mmHg, or a CRT ≥4 s together with hyperlactatemia. Ninety patients were included, of whom seventy exhibited a hypoperfusion-related pattern and 20 did not. Although lactate values were comparable at baseline (4.8 ± 2.8 vs. 4.7 ± 3.7 mmol/L), patients with a hypoperfusion context exhibited a more severe circulatory dysfunction with higher vasopressor requirements, and a trend to longer mechanical ventilation days, ICU stay, and more rescue therapies. Only one of the 20 hyperlactatemic patients without a hypoperfusion context died (5%) compared to 11 of the 70 with hypoperfusion-related hyperlactatemia (16%). Conclusions Two different clinical patterns among hyperlactatemic septic shock patients may be identified according to hypoperfusion context. Patients with hyperlactatemia plus low ScvO2, or high P(cv-a)CO2, or high CRT values exhibited a more severe circulatory dysfunction. This provides a starting point to launch further prospective studies to confirm if this approach can lead to a more selective resuscitation strategy.

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A Latin American, Portuguese and Spanish consensus on a core communication curriculum for undergraduate medical education

(2016) García de Leonardo, Cristina; Ruiz-Moral, Roger; Caballero, Fernando; Cavaco, Afonso; Moore Clive, Philippa María; Dupuy, Lila P; Pithon-Cyrino, Antonio; Cortés, Mª T; Gorostegui, Marilen; Loureiro, Elizabete

Abstract Background To present learning outcomes in clinical communication for a Core Curriculum for medical undergraduate students in Latin America, Portugal and Spain (LAPS-CCC) and to establish an expert network to support a transnational implementation. Methods Through an iterative process, an international group of 15 experts developed an initial set of learning outcomes following a review and discussion of relevant international and local literature. A two-round Delphi survey involving 46 experts from 8 countries was performed. Quantative and qualitative analisis permited the definition of the final consensus. Results The initial proposal included 157 learning outcomes. The Delphi process generated 734 comments and involved the modification, deletion and addition of some outcomes. At the end of the process, a consensus was reached on 136 learning outcomes grouped under 6 competency domains with a high overall acceptance (95.1 %). Conclusions The learning outcomes of this proposal provide a guide to introduce, support and develop communication curriculae for undergraduate medical studies in the countries involved or in other Spanish- or Portuguese-speaking countries.Abstract Background To present learning outcomes in clinical communication for a Core Curriculum for medical undergraduate students in Latin America, Portugal and Spain (LAPS-CCC) and to establish an expert network to support a transnational implementation. Methods Through an iterative process, an international group of 15 experts developed an initial set of learning outcomes following a review and discussion of relevant international and local literature. A two-round Delphi survey involving 46 experts from 8 countries was performed. Quantative and qualitative analisis permited the definition of the final consensus. Results The initial proposal included 157 learning outcomes. The Delphi process generated 734 comments and involved the modification, deletion and addition of some outcomes. At the end of the process, a consensus was reached on 136 learning outcomes grouped under 6 competency domains with a high overall acceptance (95.1 %). Conclusions The learning outcomes of this proposal provide a guide to introduce, support and develop communication curriculae for undergraduate medical studies in the countries involved or in other Spanish- or Portuguese-speaking countries.Abstract Background To present learning outcomes in clinical communication for a Core Curriculum for medical undergraduate students in Latin America, Portugal and Spain (LAPS-CCC) and to establish an expert network to support a transnational implementation. Methods Through an iterative process, an international group of 15 experts developed an initial set of learning outcomes following a review and discussion of relevant international and local literature. A two-round Delphi survey involving 46 experts from 8 countries was performed. Quantative and qualitative analisis permited the definition of the final consensus. Results The initial proposal included 157 learning outcomes. The Delphi process generated 734 comments and involved the modification, deletion and addition of some outcomes. At the end of the process, a consensus was reached on 136 learning outcomes grouped under 6 competency domains with a high overall acceptance (95.1 %). Conclusions The learning outcomes of this proposal provide a guide to introduce, support and develop communication curriculae for undergraduate medical studies in the countries involved or in other Spanish- or Portuguese-speaking countries.

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A methodological survey of the analysis, reporting and interpretation of Absolute Risk ReductiOn in systematic revieWs (ARROW): a study protocol

(2013) Alonso-Coello, Pablo; Carrasco-Labra, Alonso; Brignardello-Petersen, Romina; Neumann Burotto, Gonzalo Ignacio; Akl, Elie A; Sun, Xin; Johnston, Bradley C; Briel, Matthias; Busse, Jason W; Glujovsky, Demián; Granados, Carlos E; Iorio, Alfonso; Irfan, Affan; García, Laura M; Mustafa, Reem A; Ramirez-Morera, Anggie; Solà, Iván; Tikkinen, Kari A O; Ebrahim, Shanil; Vandvik, Per O; Zhang, Yuqing; Selva, Anna; Sanabria, Andrea J; Zazueta, Oscar E; Vernooij, Robin W M; Schünemann, Holger J; Guyatt, Gordon H

Abstract Background Clinicians, providers and guideline panels use absolute effects to weigh the advantages and downsides of treatment alternatives. Relative measures have the potential to mislead readers. However, little is known about the reporting of absolute measures in systematic reviews. The objectives of our study are to determine the proportion of systematic reviews that report absolute measures of effect for the most important outcomes, and ascertain how they are analyzed, reported and interpreted. Methods/design We will conduct a methodological survey of systematic reviews published in 2010. We will conduct a 1:1 stratified random sampling of Cochrane vs. non-Cochrane systematic reviews. We will calculate the proportion of systematic reviews reporting at least one absolute estimate of effect for the most patient-important outcome for the comparison of interest. We will conduct multivariable logistic regression analyses with the reporting of an absolute estimate of effect as the dependent variable and pre-specified study characteristics as the independent variables. For systematic reviews reporting an absolute estimate of effect, we will document the methods used for the analysis, reporting and interpretation of the absolute estimate. Discussion Our methodological survey will inform current practices regarding reporting of absolute estimates in systematic reviews. Our findings may influence recommendations on reporting, conduct and interpretation of absolute estimates. Our results are likely to be of interest to systematic review authors, funding agencies, clinicians, guideline developers and journal editors.

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A new piece of the puzzle: slag and ore analysis to reconstruct the prehispanic smelting technology at the Atacama Desert, Chile

(SPRINGER, 2023) Plaza, Maria Teresa; Garrido, Francisco; Larreina-García, David

The Incas appropriated many local metallurgical technologies throughout the Andes, each of which had its unique peculiarities and was based on local ancestral knowledge. The widespread use of tin-bronze during the Inca expansion, the development of mining and smelting sites, as well as ethno-historical records evidence the Incas' interest in copper smelting, a key activity in the Andes since ca. 1400 BC. However, little is known about the technical parameters achieved by ancient metallurgists and the changes that occurred during the Inca expansion. In this paper, we address these changes through a case study of Copiapo valley, focusing on the Vina del Cerro site, one of the most famous Inca smelting centres of the southern Andes. Although this place was architectonically restructured by the Incas, its operations began long before the imperial expansion and used wind-powered furnaces. We analysed 19 slag and 11 copper ore samples using OM, SEM-EDS, WD-XRF, and XRD analyses. Results identified heterogeneous and viscous slags, rich in SiO2 (43 wt%) and poor in FeO (13 wt%). Copper retention was high (up to 60 wt%). Microstructural analyses indicate that slags were formed under unstable oxidising conditions, reaching temperatures that ranged between 1000 to 1100 & DEG;C. The copper produced was very pure. High-grade copper ores containing up to 69 wt% CuO were reduced at the site, combining carbonates (malachite, azurite), halides (buttgenbachite, clinoatacamite), and some sulphates (brochantite). We propose that even under the relatively unfavourable conditions for slag formation, the smelting conditions generated at Vina del Cerro were competent enough to extract metal, but not necessarily enough to form liquid slag. These conditions were facilitated by the local metallurgists' thorough knowledge of the wind flow and their ability to select the right ore. This new information contributes to understanding the efficiency of metallurgical technology and the knowledge, skills, and adaptability of the ancient metallurgists from Copiapo valley, a group that was integrated into the economic networks of the Inca Empire.

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A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients

(2017) Rello, Jordi; Krenn, Claus-Georg; Locker, Gottfried; Pilger, Ernst; Madl, Christian; Balica, Laura; Dugernier, Thierry; Laterre, Pierre-Francois; Andresen Hernández, Max; Ruiz Balart, Carolina

Abstract Background Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. Conclusion This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. Trial registration ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.Abstract Background Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. Conclusion This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. Trial registration ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.Abstract Background Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. Conclusion This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. Trial registration ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.Abstract Background Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. Conclusion This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. Trial registration ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.Abstract Background Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. Conclusion This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. Trial registration ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.Abstract Background Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. Methods We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 μg or 200 μg IC43 with adjuvant, or 100 μg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. Results Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 μg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1–10.6%) was observed in the IC43 groups. Conclusion This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 μg IC43 without adjuvant compared with 200 μg IC43 with adjuvant, the 100 μg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. Trial registration ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.

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A randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302)

(2024) Lara, Primo N.; Villanueva, Luis; Ibáñez Cáceres, Carolina; Erman, Mustafa; Lee, Jae L.; Heinrich, Daniel; Lipatov, Oleg N.; Gedye, Craig; Gokmen, Erhan; Acevedo, Alejandro; Semenov, Andrey; Park, Se H.; Gafanov, Rustem A.; Kose, Fatih; Jones, Mark; Du, Xiaoqi; Munteanu, Mihaela; Perini, Rodolfo; Choueiri, Toni K.; Motzer, Robert J.

Background: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC. Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1. Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2–14.3) and 10.3 months (2.7–13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2–44.1] and sunitinib/pazopanib (29.2% [18.6–41.8]). Grade 3–5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects. Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab.

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A realistic MR compatible aortic phantom to validate hemodynamic parameters from MRI data: aortic coarctation patients comparison using catheterization

(2015) Urbina, Jesus; Sotelo Parraguez, Julio Andrés; Tejos Núñez, Cristián Andrés; Irarrázaval Mena, Pablo; Andía Kohnenkampf, Marcelo Edgardo; Razavi, Reza; Valverde, Israel; Uribe Arancibia, Sergio A.

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A remarkable synergistic effect at the transcriptomic level in peach fruits doubly infected by prunus necrotic ringspot virus and peach latent mosaic viroid

(2013) Herranz, Mari C.; Niehl, Annette; Rosales V., Marlene; Fiore, Nicola; Zamorano, Alan; Granell, Antonio; Pallas, Vicente

Abstract Background Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Results Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Conclusions Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in infected peach fruits. These field studies can help to fully understand plant-pathogen interactions and to develop appropriate crop protection strategies.Abstract Background Microarray profiling is a powerful technique to investigate expression changes of large amounts of genes in response to specific environmental conditions. The majority of the studies investigating gene expression changes in virus-infected plants are limited to interactions between a virus and a model host plant, which usually is Arabidopsis thaliana or Nicotiana benthamiana. In the present work, we performed microarray profiling to explore changes in the expression profile of field-grown Prunus persica (peach) originating from Chile upon single and double infection with Prunus necrotic ringspot virus (PNRSV) and Peach latent mosaic viroid (PLMVd), worldwide natural pathogens of peach trees. Results Upon single PLMVd or PNRSV infection, the number of statistically significant gene expression changes was relatively low. By contrast, doubly-infected fruits presented a high number of differentially regulated genes. Among these, down-regulated genes were prevalent. Functional categorization of the gene expression changes upon double PLMVd and PNRSV infection revealed protein modification and degradation as the functional category with the highest percentage of repressed genes whereas induced genes encoded mainly proteins related to phosphate, C-compound and carbohydrate metabolism and also protein modification. Overrepresentation analysis upon double infection with PLMVd and PNRSV revealed specific functional categories over- and underrepresented among the repressed genes indicating active counter-defense mechanisms of the pathogens during infection. Conclusions Our results identify a novel synergistic effect of PLMVd and PNRSV on the transcriptome of peach fruits. We demonstrate that mixed infections, which occur frequently in field conditions, result in a more complex transcriptional response than that observed in single infections. Thus, our data demonstrate for the first time that the simultaneous infection of a viroid and a plant virus synergistically affect the host transcriptome in infected peach fruits. These field studies can help to fully understand plant-pathogen interactions and to develop appropriate crop protection strategies.

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A search for top-squark pair production, in final states containing a top quark, a charm quark and missing transverse momentum, using the 139 fb−1 of pp collision data collected by the ATLAS detector

(2024) Aad, G.; Abbott, B.; Abeling, K.; Abicht, N. J.; Abidi, S. H.; Aboulhorma, A.; Abramowicz, H.; Abreu, H.; Abulaiti, Y.; Acharya, B. S.; Bourdarios, A.; Adamczyk, L.; Addepalli, S. V.; Addison, M. J.; Adelman, J.; Adiguzel, A.; Adye, T.; Díaz, Marco A.; Garay Walls, Francisca; Urrejola Pereira, Pedro Salvador; ATLAS Collaboration

Abstract: This paper presents a search for top-squark pair production in fnal states with a top quark, a charm quark and missing transverse momentum. The data were collected with the ATLAS detector during LHC Run 2 and correspond to an integrated luminosity of 139 fb−1 of proton-proton collisions at a centre-of-mass energy of √s = 13 TeV. The analysis is motivated by an extended Minimal Supersymmetric Standard Model featuring a non-minimal favour violation in the second- and third-generation squark sector. The top squark in this model has two possible decay modes, either t˜1 → cχ˜01 or t˜1 → tχ˜01, where the χ˜01 is undetected. The analysis is optimised assuming that both of the decay modes are equally probable, leading to the most likely fnal state of tc + Emiss T. Good agreement is found between the Standard Model expectation and the data in the search regions. Exclusion limits at 95% CL are obtained in the m(t˜1) vs. m(χ˜01) plane and, in addition, limits on the branching ratio of the t˜1 → tχ˜0 1 decay as a function of m(t˜1) are also produced. Top-squark masses of up to 800 GeV are excluded for scenarios with light neutralinos, and top-squark masses up to 600 GeV are excluded in scenarios where the neutralino and the top squark are almost mass degenerate.

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A snapshot of cancer in Chile: analytical frameworks for developing a cancer policy

(2015) Jiménez de la Jara, Jorge; Bastías, Gabriel; Ferreccio Readi, Catterina; Moscoso, Cristián; Sagués, Sofía; Cid Pedraza, Camilo; Bronstein, Eduardo; Herrera Riquelme, Cristian Alberto; Nervi, Bruno; Corvalán R., Alejandro; Jiménez de la Jara, Jorge; Bastías, Gabriel; Ferreccio Readi, Catterina; Moscoso, Cristián; Sagués, Sofía; Cid Pedraza, Camilo; Bronstein, Eduardo; Herrera Riquelme, Cristian Alberto; Nervi, Bruno; Corvalán R., Alejandro

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Absence of convincing evidence of Coxiella burnetii infection in Chile: a cross-sectional serosurvey among healthy adults in four different regions

(2016) Weitzel, Thomas; López, Javier; Acosta-Jamett, Gerardo; Edouard, Sophie; Parola, Philippe; Abarca Villaseca, Katia

Abstract Background Coxiella burnetii is an important zoonotic pathogen of global distribution. Still, in most parts of South America including Chile, systematic epidemiological data are lacking. The presented study aims to determine the seroprevalence of Coxiella burnetii antibodies in healthy adults of four different regions in Chile. Methods A cross-sectional study was performed, which included healthy adults living in rural and urban areas of four cities located in different regions in northern, central, and southern Chile. In urban sectors, households were chosen by double stratified random sampling, while in rural areas convenience sampling was performed. Serum specimens were taken and screened for the presence of IgG antibodies against C. burnetii phase II antigen using a commercial ELISA kit. Positive and indeterminate results were confirmed by a reference laboratory using indirect immunofluorescence assay (IFA). Results A total of 1112 individuals were included. Of those, 8 were positive by ELISA, but only one sample was confirmed using IFA. Statistical analysis for population freedom from disease revealed a high probability that C. burnetii was absent in our study population. Conclusion Our work provides the first epidemiological data on human Q fever in Chile indicating either a very low endemicity or the absence of this pathogen in the studied areas.Abstract Background Coxiella burnetii is an important zoonotic pathogen of global distribution. Still, in most parts of South America including Chile, systematic epidemiological data are lacking. The presented study aims to determine the seroprevalence of Coxiella burnetii antibodies in healthy adults of four different regions in Chile. Methods A cross-sectional study was performed, which included healthy adults living in rural and urban areas of four cities located in different regions in northern, central, and southern Chile. In urban sectors, households were chosen by double stratified random sampling, while in rural areas convenience sampling was performed. Serum specimens were taken and screened for the presence of IgG antibodies against C. burnetii phase II antigen using a commercial ELISA kit. Positive and indeterminate results were confirmed by a reference laboratory using indirect immunofluorescence assay (IFA). Results A total of 1112 individuals were included. Of those, 8 were positive by ELISA, but only one sample was confirmed using IFA. Statistical analysis for population freedom from disease revealed a high probability that C. burnetii was absent in our study population. Conclusion Our work provides the first epidemiological data on human Q fever in Chile indicating either a very low endemicity or the absence of this pathogen in the studied areas.Abstract Background Coxiella burnetii is an important zoonotic pathogen of global distribution. Still, in most parts of South America including Chile, systematic epidemiological data are lacking. The presented study aims to determine the seroprevalence of Coxiella burnetii antibodies in healthy adults of four different regions in Chile. Methods A cross-sectional study was performed, which included healthy adults living in rural and urban areas of four cities located in different regions in northern, central, and southern Chile. In urban sectors, households were chosen by double stratified random sampling, while in rural areas convenience sampling was performed. Serum specimens were taken and screened for the presence of IgG antibodies against C. burnetii phase II antigen using a commercial ELISA kit. Positive and indeterminate results were confirmed by a reference laboratory using indirect immunofluorescence assay (IFA). Results A total of 1112 individuals were included. Of those, 8 were positive by ELISA, but only one sample was confirmed using IFA. Statistical analysis for population freedom from disease revealed a high probability that C. burnetii was absent in our study population. Conclusion Our work provides the first epidemiological data on human Q fever in Chile indicating either a very low endemicity or the absence of this pathogen in the studied areas.

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Accelerating the acquisition of the 3D Dual Cardiac Phase technique using RPE trajectories

(2014) Letelier Farías, Karis del Pilar; Andía Kohnenkampf, Marcelo Edgardo; Tejos Núñez, Cristián Andrés; Irarrázaval Mena, Pablo; Prieto Vásquez, Claudia; Uribe Arancibia, Sergio A.

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Acute lung injury by gastric fluid instillation: activation of myofibroblast apoptosis during injury resolution

(2018) Ayala, Pedro; Torres, Jorge; Vivar, Raúl; Meneses, Manuel; Olmos Coelho, Pablo Roberto; San Martín, Tamara; Borzone, Gisella

Abstract Background Gastric contents aspiration in humans has variable consequences depending on the volume of aspirate, ranging from subclinical pneumonitis to respiratory failure with up to 70% mortality. Several experimental approaches have been used to study this condition. In a model of single orotracheal instillation of gastric fluid we have shown that severe acute lung injury evolves from a pattern of diffuse alveolar damage to one of organizing pneumonia (OP), that later resolves leaving normal lung architecture. Little is known about mechanisms of injury resolution after a single aspiration that could be dysregulated with repetitive aspirations. We hypothesized that, in a similar way to cutaneous wound healing, apoptosis may participate in lung injury resolution by reducing the number of myofibroblasts and by affecting the balance between proteases and antiproteases. Our aim was to study activation of apoptosis as well as MMP-2/TIMP-2 balance in the sub-acute phase (4–14 days) of gastric fluid-induced lung injury. Methods Anesthesized Sprague-Dawley rats received a single orotracheal instillation of gastric fluid and were euthanized 4, 7 and 14 days later (n = 6/group). In lung tissue we studied caspase-3 activation and its location by double immunofluorescence for cleaved caspase-3 or TUNEL and alpha-SMA. MMP-2/TIMP-2 balance was studied by zymography and Western blot. BALF levels of TGF-β1 were measured by ELISA. Results An OP pattern with Masson bodies and granulomas was seen at days 4 and 7 that was no longer present at day 14. Cleaved caspase-3 increased at day 7 and was detected by immunofluorescence in Masson body-alpha-SMA-positive and –negative cells. TUNEL-positive cells at days 4 and 7 were located mainly in Masson bodies. Distribution of cleaved caspase-3 and TUNEL-positive cells at day 14 was similar to that in controls. At the peak of apoptosis (day 7), an imbalance between MMP-2 activity and TIMP-2 expression was produced by reduction in TIMP-2 expression. Conclusions Apoptosis is activated in Masson body-alpha-SMA–positive and –negative cells during the sub-acute phase of gastric fluid-induced lung injury. This mechanism likely contributes to OP resolution, by reducing myofibroblast number and new collagen production. In addition, pre-formed collagen degradation is favored by an associated MMP-2/TIMP-2 imbalance.

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