To GP or not to GP: a natural experiment in children triaged to see a GP in a tertiary paediatric emergency department (ED)

Objective: To evaluate the impact of integrating a general practitioner (GP) into a tertiary paediatric emergency department (ED) on admissions, waiting times and antibiotic prescriptions. Design: Retrospective cohort study. Setting: Alder Hey Children’s NHS Foundation Trust, a tertiary paediatric hospital in Liverpool, UK. Participants: From October 2014, a GP was colocated within the ED, from 14:00 to 22:00 hours, 7 days a week. Children triaged green on the Manchester Triage System without any comorbidities were classed as ‘GP appropriate’. The natural experiment compared patients triaged as ‘GP appropriate’ and able to be seen by a GP between 14:00 and 22:00 hours (GP group) to patients triaged as ‘GP appropriate’ seen outside of the hours when a GP was available (ED group). Intention-to-treat (ITT) analysis was used to assess the main outcomes. Results: 5223 patients were designated as ‘GP appropriate’—18.2% of the total attendances to the ED over the study period. There were 2821 (54%) in the GP group and 2402 (46%) in the ED group. The median duration of stay in the ED was 94 min (IQR 63–141) for the GP group compared with 113 min (IQR 70–167) for the ED group (p<0.0005). Using the ITT analysis equivalent, we demonstrated that the GP group were less likely to: be admitted to hospital (2.2% vs 6.5%, OR 0.32, 95% CI 0.24 to 0.44), wait longer than 4 hours (2.3% vs 5.1%, OR 0.45, 95% CI 0.33 to 0.61) or leave before being seen (3.1% vs 5.7%, OR 0.53, 95% CI 0.41 to 0.70), but more likely to receive antibiotics (26.1% vs 20.5%, OR 1.37, 95% CI 1.10 to 1.56). Sensitivity analyses yielded similar results. Conclusions: Introducing a GP to a paediatric ED service can significantly reduce waiting times and admissions, but may lead to more antibiotic prescribing. This study demonstrates a novel, potentially more efficient ED care pathway in the current context of rising demand for children’s emergency services

Diagnosing Causes of Water Scarcity in Complex Water Resources Systems and Identifying Risk Management Actions

From the water management perspective, water scarcity is an unacceptable risk of facing water shortages to serve water demands in the near future. Water scarcity may be temporary and related to drought conditions or other accidental situation, or may be permanent and due to deeper causes such as excessive demand growth, lack of infrastructure for water storage or transport, or constraints in water management. Diagnosing the causes of water scarcity in complex water resources systems is a precondition to adopt effective drought risk management actions. In this paper we present four indices which have been developed to evaluate water scarcity. We propose a methodology for interpretation of index values that can lead to conclusions about the reliability and vulnerability of systems to water scarcity, as well as to diagnose their possible causes and to propose solutions. The described methodology was applied to the Ebro river basin, identifying existing and expected problems and possible solutions. System diagnostics, based exclusively on the analysis of index values, were compared with the known reality as perceived by system managers, validating the conclusions in all case

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

Sentimientos de adolescentes con Diabetes Mellitus delante del proceso de vivir con la enfermedad

Qualitative research conducted in a diabetes service in the countryside of the state of Ceará, Brazil, with 11 teenagers with diabetes mellitus. The study aimed to understand the experience of adolescents facing the process of living with diabetes. Data were collected in 2007 May and June, through semi-structured interviews. It was observed that the teenager faces difficulties since the moment of diagnosis, especially because their food habits and lifestyles need to change, triggering feelings like fear, insecurity and anger. Over time, they incorporate the necessary changes to treatment and care, and begin to see the disease as normal. One concludes that it is necessary to understand teenagers, their behaviors, fears and desires and support them in the different areas of this experience.Investigación cualitativa, llevada a cabo en un servicio de diabetes del interior del estado de Ceará, Brasil, con 11 adolescentes con diabetes mellitus. El objetivo fue comprender la experiencia del adolescente delante del proceso de vivir con diabetes. Los datos fueron recolectados entre mayo y junio de 2007 a través de entrevistas semi estructuradas. Se observó que el adolescente enfrenta dificultades desde el momento del diagnóstico, sobre todo en el plan alimentar y cambios en el estilo de vida, desencadenando sentimientos como miedo, inseguridad e ira. Con el tiempo, incorporan los cambios necesarios al tratamiento y atención, y llegan a ver la enfermedad como algo normal. En conclusión, que es necesario entender los adolescentes, sus comportamientos, miedos y deseos, y apoyarlos en las diferentes áreas de esta experiencia.Pesquisa de natureza qualitativa, realizada em um serviço de diabetes do interior do Ceará com 11 adolescentes portadores de diabetes mellitus. O estudo objetivou compreender a experiência do adolescente frente ao processo de viver com o diabetes. Os dados foram coletados nos meses de maio e junho de 2007 por meio de entrevista semiestruturada. Constatou-se que o adolescente enfrenta dificuldades desde o momento do diagnóstico, principalmente no plano alimentar e nas mudanças no estilo de vida, desencadeando sentimentos como medo, insegurança e revolta. Com o passar do tempo, incorporam as mudanças necessárias ao tratamento e cuidados; e passam a ver a doença de forma normal. Conclui-se que é necessário compreender os adolescentes, seus comportamentos, medos e anseios e apoiá-los nos diversos âmbitos dessa experiência.Secretaria Municipal de Saúde de Pio IX-PI Programa de Saúde da FamíliaUniversidade Federal do Ceará Faculdade de Farmácia Odontologia e Enfermagem Departamento de EnfermagemUniversidade Federal de São Paulo (UNIFESP) Programa de Pós-Graduação em Saúde ColetivaUNIFESP, Programa de Pós-Graduação em Saúde ColetivaSciEL

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Development of a biosensor for urea assay based on amidase inhibition, using an ion-selective electrode

A biosensor for urea has been developed based on the observation that urea is a powerful active-site inhibitor of amidase, which catalyzes the hydrolysis of amides such as acetamide to produce ammonia and the corresponding organic acid. Cell-free extract from Pseudomonas aeruginosa was the source of amidase (acylamide hydrolase, EC 3.5.1.4) which was immobilized on a polyethersulfone membrane in the presence of glutaraldehyde; anion-selective electrode for ammonium ions was used for biosensor development. Analysis of variance was used for optimization of the biosensorresponse and showed that 30 mu L of cell-free extract containing 7.47 mg protein mL(-1), 2 mu L of glutaraldehyde (5%, v/v) and 10 mu L of gelatin (15%, w/v) exhibited the highest response. Optimization of other parameters showed that pH 7.2 and 30 min incubation time were optimum for incubation ofmembranes in urea. The biosensor exhibited a linear response in the range of 4.0-10.0 mu M urea, a detection limit of 2.0 mu M for urea, a response timeof 20 s, a sensitivity of 58.245 % per mu M urea and a storage stability of over 4 months. It was successfully used for quantification of urea in samples such as wine and milk; recovery experiments were carried out which revealed an average substrate recovery of 94.9%. The urea analogs hydroxyurea, methylurea and thiourea inhibited amidase activity by about 90%, 10% and 0%, respectively, compared with urea inhibition

Forest Biomass Density across Large Climate Gradients in Northern South America is related to Water Availability but not with Temperature

Understanding and predicting the likely response of ecosystems to climate change are crucial challenges for ecology and for conservation biology. Nowhere is this challenge greater than in the tropics as these forests store more than half the total atmospheric carbon stock in their biomass. Biomass is determined by the balance between biomass inputs (i.e., growth) and outputs (mortality). We can expect therefore that conditions that favor high growth rates, such as abundant water supply, warmth, and nutrient-rich soils will tend to correlate with high biomass stocks. Our main objective is to describe the patterns of above ground biomass (AGB) stocks across major tropical forests across climatic gradients in Northwestern South America. We gathered data from 200 plots across the region, at elevations ranging between 0 to 3400 m. We estimated AGB based on allometric equations and values for stem density, basal area, and wood density weighted by basal area at the plot-level. We used two groups of climatic variables, namely mean annual temperature and actual evapotranspiration as surrogates of environmental energy, and annual precipitation, precipitation seasonality, and water availability as surrogates of water availability. We found that AGB is more closely related to water availability variables than to energy variables. In northwest South America, water availability influences carbon stocks principally by determining stand structure, i.e. basal area. When water deficits increase in tropical forests we can expect negative impact on biomass and hence carbon storage

Insulin-Stimulated Degradation of Apolipoprotein B100: Roles of Class II Phosphatidylinositol-3-Kinase and Autophagy

Both in humans and animal models, an acute increase in plasma insulin levels, typically following meals, leads to transient depression of hepatic secretion of very low density lipoproteins (VLDL). One contributing mechanism for the decrease in VLDL secretion is enhanced degradation of apolipoprotein B100 (apoB100), which is required for VLDL formation. Unlike the degradation of nascent apoB100, which occurs in the endoplasmic reticulum (ER), insulin-stimulated apoB100 degradation occurs post-ER and is inhibited by pan-phosphatidylinositol (PI)3-kinase inhibitors. It is unclear, however, which of the three classes of PI3-kinases is required for insulin-stimulated apoB100 degradation, as well as the proteolytic machinery underlying this response. Class III PI3-kinase is not activated by insulin, but the other two classes are. By using a class I-specific inhibitor and siRNA to the major class II isoform in liver, we now show that it is class II PI3-kinase that is required for insulin-stimulated apoB100 degradation in primary mouse hepatocytes. Because the insulin-stimulated process resembles other examples of apoB100 post-ER proteolysis mediated by autophagy, we hypothesized that the effects of insulin in autophagy-deficient mouse primary hepatocytes would be attenuated. Indeed, apoB100 degradation in response to insulin was significantly impaired in two types of autophagy-deficient hepatocytes. Together, our data demonstrate that insulin-stimulated apoB100 degradation in the liver requires both class II PI3-kinase activity and autophagy. © 2013 Andreo et al

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Testing Nelder-Mead based repulsion algorithms for multiple roots of nonlinear systems via a two-level factorial design of experiments

This paper addresses the challenging task of computing multiple roots of a system of nonlinear equations. A repulsion algorithm that invokes the Nelder-Mead (N-M) local search method and uses a penalty-type merit function based on the error function, known as 'erf', is presented. In the N-M algorithm context, different strategies are proposed to enhance the quality of the solutions and improve the overall efficiency. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm.Fundação para a Ciência e Tecnologia (FCT