Plasma protein biomarkers for the detection of pancreatic neuroendocrine tumors and differentiation from small intestinal neuroendocrine tumors

There is an unmet need for novel biomarkers to diagnose and monitor patients with neuroendocrine neoplasms. The EXPLAIN study explores a multi-plasma protein and supervised machine learning strategy to improve the diagnosis of pancreatic neuroendocrine tumors (PanNET) and differentiate them from small intestinal neuroendocrine tumors (SI-NET). At time of diagnosis, blood samples were collected and analyzed from 39 patients with PanNET, 135 with SI-NET (World Health Organization Grade 1-2) and 144 controls. Exclusion criteria were other malignant diseases, chronic inflammatory diseases, reduced kidney or liver function. Prosed Oncology-II (i.e., OLink) was used to measure 92 cancer related plasma proteins. Chromogranin A was analyzed separately. Median age in all groups was 65-67 years and with a similar sex distribution (females: PanNET, 51%; SI-NET, 42%; controls, 42%). Tumor grade (G1/G2): PanNET, 39/61%; SI-NET, 46/54%. Patients with liver metastases: PanNET, 78%; SI-NET, 63%. The classification model of PanNET versus controls provided a sensitivity (SEN) of 0.84, specificity (SPE) 0.98, positive predictive value (PPV) of 0.92 and negative predictive value (NPV) of 0.95, and area under the receiver operating characteristic curve (AUROC) of 0.99; the model for the discrimination of PanNET versus SI-NET providing a SEN 0.61, SPE 0.96, PPV 0.83, NPV 0.90 and AUROC 0.98. These results suggest that a multi-plasma protein strategy can significantly improve diagnostic accuracy of PanNET and SI-NET.Peer reviewe

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

La administración electrónica como herramienta de inclusión digital

¿Puede ser la administración electrónica una herramienta de inclusión digital? ¿Qué puede aportar la administración electrónica para avanzar en la inclusión digital? ¿Qué podemos hacer, cada uno desde nuestra actividad, para favorecer la inclusión digital? Estas son algunas de las preguntas que se formulaban los participantes en las III Jornadas sobre Derecho y Tecnología así como al XI Encuentro de Gobierno Electrónico e Inclusión Digital, celebrados en Zaragoza los días 23 y 24 de mayo de 2011. Cada uno, desde su perspectiva, trató de aportar ideas en esa línea que marcamos en la convocatoria del evento: «La administración electrónica como herramienta de inclusión digital». Estas aportaciones están recogidas en este libro, agrupadas en tres bloques diferentes. En el primero, bajo el título Políticas de inclusión digital desde la perspectiva de la administración electrónica, tienen cabida aquellas reflexiones sobre qué hacer para favorecer la inclusión digital desde la administración electrónica, con enfoques concretos en Brasil o Iberoamérica, o de tipo general, aplicable en cualquier país. En el segundo, el título Casos reales de inclusión digital desde la perspectiva de la administración electrónica reúne experiencias concretas llevadas a cabo en España y Brasil. Por último, y no menos importante, el título Inclusión digital desde las aulas universitarias recoge propuestas para fomentar la inclusión digital desde las aulas universitarias

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Fertility, mastitis and longevity in dairy cattle analyzed using survival models

The aim of the thesis was to investigate whether survival analysis (SA) results in a better genetic evaluation of female fertility and mastitis traits and to study the effects of mastitis and pregnancy status as risk factors for culling. Sire breeding values for interval between calving and last insemination (CLI) and interval between first and last insemination (FLI) were predicted using SA and mixed linear models (LM). Correlations between simulated true breeding values for conception rate and breeding values for CLI and FLI predicted by SA were higher than corresponding correlations with LM. When pregnancy status was known, SA was better than LM for genetic evaluation of conception rate when using observations on CLI and FLI. If selection were carried out on these predicted breeding values, this would translate into 8 to 12% higher genetic progress for FLI and CLI, respectively. Clinical mastitis was analyzed with LM (binary trait), and time to first mastitis with SA. The higher accuracies for SA could be translated into a higher genetic response, approximately, 3% for first parity and 25 % for later parities. The effect of pregnancy status and mastitis on culling in Swedish dairy cattle was analyzed with SA. Mastitis affected culling decisions throughout the lactation, but its effect depended on pregnancy status and the stage during which the cow was treated. The risk of culling was low for pregnant cows, whether or not they had been treated for mastitis. Different patterns were observed for the risk of culling between open and pregnant cows. For both groups, the risk of being culled was higher for cows treated for mastitis than for untreated cows. For open cows, the risk was higher for cows treated in earlier stages, whereas for pregnant cows, the risk was similar across different stages of lactation. This thesis showed the potential of using SA for genetic evaluation of fertility traits and clinical mastitis in dairy cattle. SA was also found to be a useful method to analyze the effect of pregnancy status and clinical mastitis as risk factors for culling by treating them as time-dependent covariates

Cultural and Gender Differences in the Implications of Competition for Early Adolescent Friendship

Harry Stack Sullivan maintained that competition between friends in early adolescence would generally destroy their friendship. Working with early adolescent samples in Canada, Costa Rica, and Cuba, we found that hypercompetitiveness— a form of competition involving the need to prove one’s own superiority— was linked with conflict between friends, with termination of friendship, and, in general, with less closeness. However, simple enjoyment of competition with a friend was unrelated to friendship continuation. There were important gender and cultural differences in both the levels of competitive behavior and in the mediators between competition and friendship continuation. In general, girls were less competitive with their friends than were boys. Path analysis revealed that both closeness and conflict mediated the link between hypercompetitiveness and the continuation of friendship. Several dimensions of competition were associated with greater companionship in the friendships of boys, especially in the Canadian sample, but were negative correlates of companionship between female friends

Design of a testing strategy using non-animal based test methods: Lessons learnt from the ACuteTox project

In the framework of toxicology, a testing strategy can be viewed as a series of steps which are taken to come to a final prediction about a characteristic of a compound under study. The testing strategy is performed as a single-step proce dure, usually called a test battery, using simultaneously all information collected on different endpoints, or as tiered approach in which a decision tree is followed. Design of a testing strategy involves statistical considerations, such as the development of a statistical prediction model. During the EU FP6 ACuteTox project, several prediction models were proposed on the basis of statistical classification algorithms which we illustrate here. The final choice of testing strategies was not based on statistical considerations alone. However, without thorough statistical evaluations a testing strategy cannot be identified. We present here a number of observations made from the statistical viewpoint which relate to the development of testing strategies. The points we make were derived from problems we had to deal with during the evaluation of this large research project. A centr al issue during the development of a prediction model is the danger of overfitting. Procedures are presented to deal with this challenge.JRC.I.2-Public Health Policy Suppor

Impact of protective agents and drying methods on desiccation tolerance of Salix nigra L. seeds

Willow seeds are classified as orthodox, but they show some recalcitrant characteristics, as they lose viability in a few weeks at room temperature. The aim of this work was to improve the desiccation tolerance of willow seeds (Salix nigra L.), as a model of sensitive materials to dehydration, through imbibition in solutions and later vacuum (VD) or freeze-drying (FD). Imbibition was conducted with 45% w/v trehalose or polyethylene glycol 400 -PEG- or water prior to dehydration treatments. Water- and especially trehalose-imbibed seeds subjected to VD showed better germination capability with respect to the freeze-dried ones. Water crystallization was mainly responsible for the great loss of capability germination observed in water- or trehalose-imbibed seeds subjected to FD. PEG behavior was better when seeds were FD instead of VD. DSC thermograms of seeds allowed to identify two thermal transitions corresponding to lipids melting and to proteins denaturation. This last transition reveals information about proteins state/functionality. Dehydration of control and PEG- or water-imbibed seeds affected proteins functionality leading to lower germinability. In the case of trehalose-imbibed seeds subjected to VD, proteins maintained their native state along dehydration, and the seeds showed a great germination capacity for all the water content range. Germinated seeds showed higher luminosity (L*), greenness (a*) and yellowness (b*) values than not-germinated seeds independently of the employed agent. Present work reveals that the presence of adequate protective agents as well the dehydration method were the main critical factors involved in willow seed desiccation tolerance.Fil: Santagapita, Patricio Roman. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ott Schneider, Helena. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; ArgentinaFil: Agudelo Laverde, Lina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; ArgentinaFil: Buera, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias; Argentin