| 1. |
- Carraminana, Albert, et al.
(författare)
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Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
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Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
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| 2. |
- Lara-Gonzalez, Samuel, et al.
(författare)
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Substrate-induced dimerization of engineered monomeric variants of triosephosphate isomerase from trichomonas vaginalis
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The dimeric nature of triosephosphate isomerases (TIMs) is maintained by an extensive surface area interface of more than 1600 Å2. TIMs from Trichomonas vaginalis (TvTIM) are held in their dimeric state by two mechanisms: A ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A) is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.
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| 3. |
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| 4. |
- Colins, Olivier F., et al.
(författare)
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The Prognostic Usefulness of Multiple Specifiers for Subtyping Conduct Problems in Early Childhood
- 2024
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 63:4, s. 443-453
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To better describe and treat children with conduct problems (CP), grandiose-manipulative and daring-impulsive traits are proposed for subtyping CP, instead of using only a callous-unemotional specifier. However, the acclaimed benefits of having multiple specifiers for CP remain largely untested and therefore highly speculative. To fill this gap, this study tested longitudinal relations between these 3 specifiers and developmental outcomes in childhood and adolescence, independent of early childhood CP.METHOD: Longitudinal data from 2 community studies were used. Teacher ratings were used to measure CP and the specifiers in 3- to 5-year-olds from Sweden (n = 2,064) and Spain (n = 2,055). Developmental outcomes were assessed by multiple informants (ie, teachers, parents, and children) 1 to 8 years later. RESULTS: Early childhood CP were predictive of all outcomes. Callous-unemotional traits predicted low levels of social competence and prosocial behavior, independent of CP (and age, gender, and socioeconomic status). Grandiose-manipulative and daring-impulsive traits were predictive of aggression and violent delinquency, respectively, independent of CP, but also of higher levels of prosocial behavior or social competence.CONCLUSION: The 3 specifiers are predictive of different outcomes, independent of CP, which is thought to form the basis for developing specifiers for CP. Findings tentatively challenge the centrality of callous-unemotional traits for subtyping CP, but it is premature to conclude that grandiose-manipulative and daring-impulsive specifiers are needed in future revisions of DSM and ICD. Efforts to systematically evaluate the utility of these specifiers should be welcomed to inform ongoing debates on this matter.
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| 5. |
- Colins, Olivier F., et al.
(författare)
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The Prognostic Usefulness of Multiple Specifiers for Subtyping Conduct Problems in Early Childhood
- 2023
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier. - 0890-8567 .- 1527-5418. ; 62:10S, s. S160-S161
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Better descriptions and treatment of children with conduct problems (CP) grandiose-manipulative (GM) and daring-impulsive (DI) traits are proposed for subtyping CP, instead of only using a callous-unemotional (CU) specifier. Unfortunately, the acclaimed benefits of having multiple specifiers for CP remain largely untested and, therefore, highly speculative. To fill this gap, we tested longitudinal relations between these 3 specifiers and developmental outcomes in childhood and adolescence, independent of early childhood CP.Methods: We relied on longitudinal data from 2 community studies. Teacher-ratings were used to measure CP and the specifiers in 3- to 5-year-olds from Sweden (N = 2064) and Spain (N = 2055). Developmental outcomes were assessed by multiple informants (ie, teachers, parents, and children) 1 to 8 years later.Results: Early childhood CP were predictive of all outcomes. CU traits predicted low levels of social competence and prosocial behavior, independent of CP (and age, gender, and socioeconomic status). GM and DI traits were predictive of aggression and violent delinquency, respectively, independent of CP, but also of higher levels of prosocial behavior or social competence.Conclusions: The 3 specifiers are predictive of different outcomes, independent of CP, which is thought to form the basis for developing specifiers for CP. Findings tentatively challenge the centrality of CU traits for subtyping CP, but it is premature to conclude that GM and DI specifiers are needed in future revisions of the DSM and ICD. Efforts to systematically evaluate the utility of these specifiers should be welcomed to inform ongoing debates on this matter.
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| 6. |
- Fanti, Kostas A., et al.
(författare)
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Fearlessness as an Underlying Mechanism Leading to Conduct Problems : Testing the INTERFEAR Model in a Community Sample in Spain
- 2024
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Ingår i: Children. - : MDPI. - 2227-9067. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Conduct problems (CP) in childhood and adolescence have a significant impact on the individual, family, and community. To improve treatment for CP, there is a need to improve the understanding of the developmental pathways leading to CP in boys and girls. Prior research has linked the child's fearlessness and callous-unemotional (CU) traits, as well as experiences of parental warmth and punitive parenting, to CP. However, few studies have tested the interplay of these factors in contributing to future CP development. The present study aimed to test the InterFear model, which suggests that fearlessness in early childhood leads to CP through an indirect pathway involving low positive parenting, high negative/punitive parenting, and callous-unemotional (CU) traits. The sample included 2467 Spanish children (48.1% girls; Mage = 4.25; SD = 0.91), followed up across a five-year period. Besides a direct association between fearlessness in early childhood and future CP, the results found an indirect pathway whereby fearlessness reduces positive parenting and increases punitive parenting, which contributes to the development of CU traits and sets the stage for CP in later childhood. The specific indirect effect from fearlessness to CP via CU traits accounted for most of the variance, suggesting the existence of a temperamental pathway independent of parental variables. Further, two additional indirect pathways, exclusive of fearlessness, were identified, which started with low parental warmth and positive parenting, leading to CP via CU traits. These findings support the InterFear model, demonstrating multiple pathways to CP with the involvement of fearlessness, parenting practices, and CU traits. This model might play a pivotal role in the development of targeted prevention and intervention strategies for CP.
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| 7. |
- Kodra, Yllka, et al.
(författare)
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Recommendations for Improving the Quality of Rare Disease Registries
- 2018
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 15:8
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Forskningsöversikt (refereegranskat)abstract
- Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality.
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| 8. |
- Laurie, Steven, et al.
(författare)
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The RD-Connect Genome-Phenome Analysis Platform : Accelerating diagnosis, research, and gene discovery for rare diseases
- 2022
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:6, s. 717-733
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Tidskriftsartikel (refereegranskat)abstract
- Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
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| 9. |
- Lopez-Romero, Laura, et al.
(författare)
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Conduct problems in childhood and adolescence : developmental trajectories, predictors and outcomes in a six-year follow up
- 2015
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Ingår i: Child Psychiatry and Human Development. - : Springer Science and Business Media LLC. - 0009-398X .- 1573-3327. ; 46:5, s. 762-773
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Tidskriftsartikel (refereegranskat)abstract
- Understanding youth conduct problems requires examination from a developmental perspective, analyzing distinctive pathways across childhood and adolescence, and identifying early predictors which will lead to specific adolescent outcomes. Bearing this in mind, developmental trajectories of conduct problems were identified from a person-oriented perspective, and using data collected from three waves over a six-year period, in a sample of Spanish children aged 6-11 at the onset of the study. Conduct problems showed five distinctive trajectories which were grouped into three major pathways in further analyses: Stable low, Stable high, and Decreasing. Associations with early personality and psychopathic traits, as well as with a wide range of adolescent behavioral and psychosocial outcomes were examined, revealing the Stable high group as exhibiting the highest risk profile. These results contribute to improving our knowledge about one of the most relevant problems in youth populations, and will help in refining interventions strategies by recognizing the developmental heterogeneity of the construct.
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| 10. |
- López-Romero, Laura, et al.
(författare)
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In Search of Conceptual Clarity About the Structure of Psychopathic Traits in Children : A Network-Based Proposal
- 2024
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Ingår i: Child Psychiatry and Human Development. - : Springer. - 0009-398X .- 1573-3327.
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Tidskriftsartikel (refereegranskat)abstract
- Psychopathic traits in childhood have been revealed as potential identifiers of risk, being predictive of later forms of behavioral maladjustment. Yet, it is still under debate how psychopathic traits in children should be best conceptualized and which are the core dimensions for construct definition and prediction. The present study aims to examine the structure of psychopathic traits in childhood, and its predictive value, by using a combination of traditional factor analysis and more recent network-based methods. Data on psychopathic traits, as measured by the Child Problematic Traits Inventory (CPTI), were collected in a large sample of children (n = 2454; 48.2% girls), aged 3 to 6 at the onset of the study (Mage = 4.26; SD = 0.91), who were followed-up one and two years later using parent- and teacher-reports. Results showed that psychopathic traits measured via CPTI are best conceptualized as five latent factors encompassing grandiosity, deceitfulness, callousness, impulsivity and need of stimulation, a result that converged across informants and time. Callousness and grandiosity emerged as central traits using network analysis of parent-reports, while deceitfulness was most central using teacher-reports. Finally, callousness, impulsivity and deceitfulness emerged as the best predictors of concurrent, prospective and stable conduct problems. These results provide a refined structure of psychopathic traits in children that better accounts for the core elements of the construct. Additional theoretical and practical implications will be discussed in terms of assessment, diagnostic classification and tailored prevention/intervention.
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