Predictive validity of the CriSTAL tool for short-term mortality in older people presenting at Emergency Departments: a prospective study

© 2018, The Author(s). Abstract: To determine the validity of the Australian clinical prediction tool Criteria for Screening and Triaging to Appropriate aLternative care (CRISTAL) based on objective clinical criteria to accurately identify risk of death within 3 months of admission among older patients. Methods: Prospective study of ≥ 65 year-olds presenting at emergency departments in five Australian (Aus) and four Danish (DK) hospitals. Logistic regression analysis was used to model factors for death prediction; Sensitivity, specificity, area under the ROC curve and calibration with bootstrapping techniques were used to describe predictive accuracy. Results: 2493 patients, with median age 78–80 years (DK–Aus). The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% CI 7.7–8.6 vs. 5.8 95% CI 5.6–5.9) and Danish mean 7.1 (95% CI 6.6–7.5 vs. 5.5 95% CI 5.4–5.6). The model with Fried Frailty score was optimal for the Australian cohort but prediction with the Clinical Frailty Scale (CFS) was also good (AUROC 0.825 and 0.81, respectively). Values for the Danish cohort were AUROC 0.764 with Fried and 0.794 using CFS. The most significant independent predictors of short-term death in both cohorts were advanced malignancy, frailty, male gender and advanced age. CriSTAL’s accuracy was only modest for in-hospital death prediction in either setting. Conclusions: The modified CriSTAL tool (with CFS instead of Fried’s frailty instrument) has good discriminant power to improve prognostic certainty of short-term mortality for ED physicians in both health systems. This shows promise in enhancing clinician’s confidence in initiating earlier end-of-life discussions

Generative Design in Minecraft (GDMC), Settlement Generation Competition

This paper introduces the settlement generation competition for Minecraft, the first part of the Generative Design in Minecraft challenge. The settlement generation competition is about creating Artificial Intelligence (AI) agents that can produce functional, aesthetically appealing and believable settlements adapted to a given Minecraft map - ideally at a level that can compete with human created designs. The aim of the competition is to advance procedural content generation for games, especially in overcoming the challenges of adaptive and holistic PCG. The paper introduces the technical details of the challenge, but mostly focuses on what challenges this competition provides and why they are scientifically relevant.Comment: 10 pages, 5 figures, Part of the Foundations of Digital Games 2018 proceedings, as part of the workshop on Procedural Content Generatio

Randomized controlled trials of remdesivir in hospitalized coronavirus disease 2019 patients: A meta-analysis

Background: The first cases of the coronavirus disease 2019 (COVID-19) were reported in Wuhan, China. No antiviral treatment options are currently available with proven clinical efficacy. However, preliminary findings from phase III trials suggest that remdesivir is an effective and safe treatment option for COVID-19 patients with both moderate and severe disease.Objective: The aim of the present meta-analysis was to investigate whether remdesivir was effective for treating COVID-19 including reduced in-hospital adverse events, oxygen support, and mortality rates.Methods: According to the PRISMA reporting guidelines, a review was conducted from January 1, 2020, until August 25, 2020, with MeSH terms including COVID-19, COVID, coronavirus, SARS-CoV-2, remdesivir, adenosine nucleoside triphosphate analog, and Veklury using MEDLINE, Scopus, and CINAHL Plus. A modified Delphi process was utilized to include the studies and ensure that the objectives were addressed. Using dichotomous data for select values, the unadjusted odds ratios (ORs) were calculated applying Mantel-Haenszel random-effects method in Review Manager 5.4.Results: Randomized controlled trials pooled in 3013 participants with 46.3% (n = 1395) in the remdesivir group and 53.7% (n = 1618) in the placebo group. The placebo group had a higher risk of mortality as compared to the intervention group with significant OR (0.61) (95% confidence interval of 0.45-0.82; P = 0.001). There was minimal heterogeneity among the studies (I 2 = 0%).Conclusions: Our findings suggest that remdesivir extends clinical benefits by reducing mortality, adverse events, and oxygen support in moderate to severely ill COVID-19 patients. Concerted efforts and further randomized placebo-controlled trials are warranted to examine the potency of antiviral drugs and immunopathological host responses contributing to the severity of COVID-19

U-Pb LA-ICP-MS GEOCHRONOLOGY AND REGIONAL CORRELATION OF MIDDLE JURASSIC INTRUSIVE ROCKS FROM THE GARZON MASSIF, UPPER MAGDALENA VALLEY AND CENTRAL CORDILLERA, SOUTHERN COLOMBIA

Se presentan nuevas edades U-Pb en circones de cuatro unidades graníticas muestreadas a lo largo de una transecta SE-NW entre el Macizo de Garzón y la Serranía de las Minas (Cordillera Central), las cuales registran una actividad magmática en el Jurásico Medio en dos dominios espaciales y temporales diferentes: 189 Ma y 180 a 173 Ma. Estos cuatro granitoides tiene características mineralógicas y geoquímicas afines con un ambiente de arcomagmático continental. Los nuevos resultados sugieren que la margen continental al sur de Colombia incluye remanentes de elementos tectono-magmáticos formados por la subducción de la placa Farallón bajo la margen continental suramericana. Este magmatismo de arco del Jurásico medio es parte de la provincia de arco que se presenta a lo largo de los Andes, y es importante para el entendimiento de la dinámica tectónica y la paleogeografía que caracterizó el Mesozoico de los Andes del Norte. Palabras clave: Geocronología U-Pb, Colombia, Jurásico, Rocas intrusivas, Macizo de Garzón, CordilleraCentral.    New U-Pb zircon geochronology from four granitic units sampled along a southeast-northwest transect between the Garzón Massif and the Serranía de las Minas (Central Cordillera), records a Middle Jurassic magmatic activity with two different spatio-temporal domains at ca. 189 Ma and 180-173 Ma. Reconnaissance data suggest that the four granitoids are characterized by mineralogical and geochemical characteristics akin to acontinental magmatic arc setting. The new results suggest that the southern Colombian continental margin includes remnants of tectonomagmatic elements formed by the subduction of the Farallon plate under the South American continental margin. This Middle Jurassic arc magmatism is part of the broader Andean scale arc province, and is significant for understanding the tectonic and paleogeographic scenario that characterized the Mesozoic tectonic evolution of the Northern Andes. Key words: U-Pb geochronology, Colombia, Jurassic, Intrusive rocks, Garzón Massif, Central Cordillera. &nbsp

U-Pb LA-ICP-MS GEOCHRONOLOGY AND REGIONAL CORRELATION OF MIDDLE JURASSIC INTRUSIVE ROCKS FROM THE GARZON MASSIF, UPPER MAGDALENA VALLEY AND CENTRAL CORDILLERA, SOUTHERN COLOMBIA

Se presentan nuevas edades U-Pb en circones de cuatro unidades graníticas muestreadas a lo largo de una transecta SE-NW entre el Macizo de Garzón y la Serranía de las Minas (Cordillera Central), las cuales registran una actividad magmática en el Jurásico Medio en dos dominios espaciales y temporales diferentes: 189 Ma y 180 a 173 Ma. Estos cuatro granitoides tiene características mineralógicas y geoquímicas afines con un ambiente de arcomagmático continental. Los nuevos resultados sugieren que la margen continental al sur de Colombia incluye remanentes de elementos tectono-magmáticos formados por la subducción de la placa Farallón bajo la margen continental suramericana. Este magmatismo de arco del Jurásico medio es parte de la provincia de arco que se presenta a lo largo de los Andes, y es importante para el entendimiento de la dinámica tectónica y la paleogeografía que caracterizó el Mesozoico de los Andes del Norte. Palabras clave: Geocronología U-Pb, Colombia, Jurásico, Rocas intrusivas, Macizo de Garzón, CordilleraCentral.    New U-Pb zircon geochronology from four granitic units sampled along a southeast-northwest transect between the Garzón Massif and the Serranía de las Minas (Central Cordillera), records a Middle Jurassic magmatic activity with two different spatio-temporal domains at ca. 189 Ma and 180-173 Ma. Reconnaissance data suggest that the four granitoids are characterized by mineralogical and geochemical characteristics akin to acontinental magmatic arc setting. The new results suggest that the southern Colombian continental margin includes remnants of tectonomagmatic elements formed by the subduction of the Farallon plate under the South American continental margin. This Middle Jurassic arc magmatism is part of the broader Andean scale arc province, and is significant for understanding the tectonic and paleogeographic scenario that characterized the Mesozoic tectonic evolution of the Northern Andes. Key words: U-Pb geochronology, Colombia, Jurassic, Intrusive rocks, Garzón Massif, Central Cordillera. &nbsp

The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8â institution study from the US Neuroendocrine Tumor Study Group

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147162/1/jso25306_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147162/2/jso25306.pd

Time-Dependent Effects of CX3CR1 in a Mouse Model of Mild Traumatic Brain Injury

BACKGROUND: Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases. METHODS: In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated the effects of genetic deletion of CX3CR1 on histopathology, cell death/survival, microglia activation, and cognitive function for 30 days post-injury. RESULTS: During the acute post-injury period (24 h-15 days), motor deficits, cell death, and neuronal cell loss were more profound in injured wild-type than in CX3CR1-/- mice. In contrast, during the chronic period of 30 days post-TBI, injured CX3CR1-/- mice exhibited greater cognitive dysfunction and increased neuronal death than wild-type mice. The protective and deleterious effects of CX3CR1 were associated with changes in microglia phenotypes; during the acute phase CX3CR1-/- mice showed a predominant anti-inflammatory M2 microglial response, with increased expression of Ym1, CD206, and TGFβ. In contrast, increased M1 phenotypic microglia markers, Marco, and CD68 were predominant at 30 days post-TBI. CONCLUSION: Collectively, these novel data demonstrate a time-dependent role for CX3CL1/CX3CR1 signaling after TBI and suggest that the acute and chronic responses to mild TBI are modulated in part by distinct microglia phenotypes

Comparative genomics of ST5 and ST30 methicillin-resistant Staphylococcus aureus sequential isolates recovered from paediatric patients with cystic fibrosis

Staphylococcus aureus chronic airway infection in patients with cystic fibrosis (CF) allows this pathogen to adapt over time in response to different selection pressures. We have previously shown that the main sequence types related to community-acquired methicillin-resistant S. aureus (MRSA) infections in Argentina - ST5 and ST30 - are also frequently isolated from the sputum of patients with CF, but in these patients they usually display multi-drug antimicrobial resistance. In this study, we sequenced the genomes of MRSA from four paediatric CF patients with the goal of identifying mutations among sequential isolates, especially those possibly related to antimicrobial resistance and virulence, which might contribute to the adaptation of the pathogen in the airways of patients with CF. Our results revealed genetic differences in sequential MRSA strains isolated from patients with CF in both their core and accessory genomes. Although the genetic adaptation of S. aureus was distinct in different hosts, we detected independent mutations in thyA, htrA, rpsJ and gyrA - which are known to have crucial roles in S. aureus virulence and antimicrobial resistance - in isolates recovered from multiple patients. Moreover, we identified allelic variants that were detected in all of the isolates recovered after a certain time point; these non-synonymous mutations were in genes associated with antimicrobial resistance, virulence, iron scavenging and oxidative stress resistance. In conclusion, our results provide evidence of genetic variability among sequential MRSA isolates that could be implicated in the adaptation of these strains during chronic CF airway infection.Fil: Haim, Maria Sol. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Zaheer, Rahat. No especifíca;Fil: Bharat, Amrita. No especifíca;Fil: Di Gregorio, Sabrina Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Di Conza, José Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Galanternik, Laura Irene. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Departamento de Medicina; ArgentinaFil: Lubovich, Silvina Laura. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Departamento de Medicina; ArgentinaFil: Golding, George R.. No especifíca;Fil: Graham, Morag R.. No especifíca;Fil: Van Domselaar, Gary. No especifíca;Fil: Cardona, Silvia T.. University of Manitoba; CanadáFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Molecular Detection and Characterization of Blastocystis sp. and Enterocytozoon bieneusi in Cattle in Northern Spain

Some enteric parasites causing zoonotic diseases in livestock have been poorly studied or even neglected. This is the case in stramenopile Blastocystis sp. and the microsporidia Enterocytozoon bieneusi in Spain. This transversal molecular epidemiological survey aims to estimate the prevalence and molecular diversity of Blastocystis sp. and E. bieneusi in cattle faecal samples (n = 336) in the province of Álava, Northern Spain. Initial detection of Blastocystis and E. bieneusi was carried out by polymerase chain reaction (PCR) and Sanger sequencing of the small subunit (ssu) rRNA gene and internal transcribed spacer (ITS) region, respectively. Intra-host Blastocystis subtype diversity was further investigated by next generation amplicon sequencing (NGS) of the ssu rRNA gene in those samples that tested positive by conventional PCR. Amplicons compatible with Blastocystis sp. and E. bieneusi were observed in 32.1% (108/336, 95% CI: 27.2-37.4%) and 0.6% (2/336, 95% CI: 0.0-1.4%) of the cattle faecal samples examined, respectively. Sanger sequencing produced ambiguous/unreadable sequence data for most of the Blastocystis isolates sequenced. NGS allowed the identification of 10 Blastocystis subtypes including ST1, ST3, ST5, ST10, ST14, ST21, ST23, ST24, ST25, and ST26. All Blastocystis-positive isolates involved mixed infections of 2-8 STs in a total of 31 different combinations. The two E. bieneusi sequences were confirmed as potentially zoonotic genotype BEB4. Our data demonstrate that Blastocystis mixed subtype infections are extremely frequent in cattle in the study area. NGS was particularly suited to discern underrepresented subtypes or mixed subtype infections that were undetectable or unreadable by Sanger sequencing. The presence of zoonotic Blastocystis ST1, ST3, and ST5, and E. bieneusi BEB4 suggest cross-species transmission and a potential risk of human infection/colonization.This research was funded by the Health Institute Carlos III (ISCIII), Ministry of Science, Innovation and Universities (Spain), grant numbers PI16CIII/00024 and USDA-ARS Project No: 8042–32000-112–00-D.S

Capability Driven Development: An Approach to Designing Digital Enterprises

The need for organizations to operate in changing environments is addressed by proposing an approach that integrates organizational development with information system (IS) development taking into account changes in the application context of the solution. This is referred to as Capability Driven Development (CDD). A meta-model representing business and IS designs consisting of goals, key performance indicators, capabilities, context and capability delivery patterns, is being proposed. The use of the meta-model is validated in three industrial case studies as part of an ongoing collaboration project, whereas one case is presented in the paper. Issues related to the use of the CDD approach, namely, CDD methodology and tool support are also discussed