Neural regions associated with gain-loss frequency and average reward in older and younger adults

Research on the biological basis of reinforcement-learning has focused on how brain regions track expected value based on average reward. However, recent work suggests that humans are more attuned to reward frequency. Furthermore, older adults are less likely to use expected values to guide choice than younger adults. This raises the question of whether brain regions assumed to be sensitive to average reward, like the medial and lateral PFC, also track reward frequency, and whether there are age-based differences. Older (60-81 years) and younger (18-30 years) adults performed the Soochow Gambling task, which separates reward frequency from average reward, while undergoing fMRI. Overall, participants preferred options that provided negative net payoffs, but frequent gains. Older adults improved less over time, were more reactive to recent negative outcomes, and showed greater frequency-related activation in several regions, including DLPFC. We also found broader recruitment of prefrontal and parietal regions associated with frequency value and reward prediction errors in older adults, which may indicate compensation. The results suggest greater reliance on average reward for younger adults than older adults

The Effect of Acetaminophen on Temperature in Critically Ill Children: A Retrospective Analysis of Over 50,000 Doses

Objectives: Acetaminophen is widely used in PICUs. Although randomized controlled trials suggest that acetaminophen significantly reduces body temperature in adults, the effect of acetaminophen on temperature in critically ill children has not been previously quantified. Design: Retrospective observational cohort study. Setting: Single-center general and cardiac PICU in a specialist children’s hospital. Patients: All children who received acetaminophen or had a fever (temperature ≥ 38°C) while on the ICU over a 40-month period (September 2012 to December 2015). Interventions: None. Measurements and Main Results: In total, 58,177 doses of acetaminophen were administered, with temperature data available for analysis for 54,084 doses. Temperature decreased by 0.11°C (95% CI, 0.09–0.14°C) 4 hours post acetaminophen dose, after adjustment for weight and illness severity. In children who had a fever and were given acetaminophen, temperature decreased by 0.78°C (95% CI, 0.74–0.82°C). Temperature decreased by 0.88°C (95% CI, 0.85–0.92°C) in children who had fever but did not receive acetaminophen. The change in temperature associated with fever was significantly different between those who did and did not receive acetaminophen (likelihood ratio statistic 246.06; p < 2.2×10–16). Conclusions: Acetaminophen is associated with a significant decrease in temperature in children with fever. However, temperature may decrease following fever without acetaminophen in the PICU. The threshold to use acetaminophen must be understood to determine the true effect on temperature in any future trials

High temperature optical absorption investigation into the electronic transitions in sol–gel derived C12A7 thin films

Optical absorption into 6 mm thick sol–gel derived films, annealed at 1300 °C of 12CaO·7Al2O3 calcium aluminate binary compound on MgO〈100〉 single crystal substrates was studied at temperatures ranging from room temperature to 300 °C. Experimental data were analysed in both Tauc and Urbach regions. The optical band gap decreased from 4.088 eV at 25 °C to 4.051 eV at 300 °C, while Urbach energy increased from 0.191 eV at 25 °C to 0.257 eV at 300 °C. The relationship between the optical band gap and the Urbach energy at different temperatures showed an almost linear relationship from which the theoretical values of 4.156 and 0.065 eV were evaluated for the band gap energy and Urbach energy of a 12CaO·7Al2O3 crystal with zero structural disorder at 0 K

The missions of medical schools: the pursuit of health in the service of society

Mission statements and role documents of medical schools in the United Kingdom, United States, Canada and Australia have been examined on their Internet Web sites and categorised in purpose, content and presentation. The format and content are highly variable, but there is a common vision of three integral roles, namely, education, advancement of knowledge and service to society. Other frequent themes include tradition and historical perspective, service for designated communities, and benchmarking to accreditation standards. Differences in content reflect variable interpretation of the notion of "mission", and local or national characteristics such as institutional affiliations, the types, levels and organisation of medical education, relationships with health systems, and extent of multi-professional education. Outcomes data and measures of medical school performance referenced to the institution's stated missions are rarely encountered. Mission documents placed on the Internet are in the public domain. These Web sites and documents and linked information constitute a valuable new resource for international exchange of approaches and ideas in medical education and generally in academic medicine. Routine inclusion of outcome or performance data could help to demonstrate the community roles and social accountability of medical schools This paper proposes that partial standardisation of these Web documents could enhance their value both internally and for external readers. A generic descriptive statement template is offered

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Bony metastases from breast cancer - a study of foetal antigen 2 as a blood tumour marker

Background : Foetal antigen 2 (FA-2), first isolated in the amniotic fluid, was shown to be the circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I. Serum concentrations of FA-2 appeared to be elevated in a number of disorders of bone metabolism. This paper is the first report of its role as a marker of bone metabolism in metastatic breast cancer. Methods: Serum FA-2 concentrations were measured by radioimmunoassay in 153 women with different stages of breast cancer and in 34 normal controls. Results: Serum FA-2 was significantly elevated in women with bony metastases (p < 0.015). Its levels were not significantly different among women with non-bony metastases, with non-metastatic disease, as well as among normal controls. Conclusions: FA-2 is a promising blood marker of bone metabolism. Further studies to delineate its role in the diagnosis and management of bony metastases from breast cancer are required

Global distribution of two fungal pathogens threatening endangered sea turtles

This work was supported by grants of Ministerio de Ciencia e Innovación, Spain (CGL2009-10032, CGL2012-32934). J.M.S.R was supported by PhD fellowship of the CSIC (JAEPre 0901804). The Natural Environment Research Council and the Biotechnology and Biological Sciences Research Council supported P.V.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Thanks Machalilla National Park in Ecuador, Pacuare Nature Reserve in Costa Rica, Foundations Natura 2000 in Cape Verde and Equilibrio Azul in Ecuador, Dr. Jesus Muñoz, Dr. Ian Bell, Dr. Juan Patiño for help and technical support during samplingPeer reviewedPublisher PD

Oportunidades perdidas na prevenção da sífilis congênita e da transmissão vertical do HIV

OBJECTIVE: To estimate the prevalence of missed opportunities for congenital syphilis and HIV prevention in pregnant women who had access to prenatal care and to assess factors associated to non-testing of these infections. METHODS: Cross-sectional study comprising a randomly selected sample of 2,145 puerperal women who were admitted in maternity hospitals for delivery or curettage and had attended at least one prenatal care visit, in Brazil between 1999 and 2000. No syphilis and/or anti-HIV testing during pregnancy was a marker for missed prevention opportunity. Women who were not tested for either or both were compared to those who had at least one syphilis and one anti-HIV testing performed during pregnancy (reference category). The prevalence of missed prevention opportunity was estimated for each category with 95% confidence intervals. Factors independently associated with missed prevention opportunity were assessed through multinomial logistic regression. RESULTS: The prevalence of missed prevention opportunity for syphilis or anti-HIV was 41.2% and 56.0%, respectively. The multivariate analysis showed that race/skin color (non-white), schooling (OBJETIVO: Estimar la prevalencia de oportunidad de pérdida de prevención de la sífilis y el HIV entre gestantes que tuvieron acceso al pre-natal y factores asociados con la no evaluación de estos agravios. MÉTODOS: Se realizó estudio transversal con muestra aleatoria de 2.145 puérperas de Brasil, 1999 y 2000 admitidas en maternidades para parto o curetaje y que habían realizado al menos una consulta de pre-natal. La no realización del examen de prueba para sífilis y/o anti-HIV durante el embarazo fue usada como marcador para oportunidad de pérdida de prevención. Las mujeres que realizaron sólo examen de sífilis o sólo examen de anti-HIV, o que no realizaron ninguno, fueron comparadas con las que realizaron los dos (categoría de referencia). La prevalencia de oportunidad de pérdida de prevención fue estimada para cada categoría, con intervalo de confianza de 95%. Los factores asociados con la oportunidad de pérdida de prevención fueron analizados por medio de regresión logística multinomial. RESULTADOS: La prevalencia de oportunidad de pérdida de prevención para la realización de la prueba de sífilis o anti-HIV fue de 41,2% e 56,0%, respectivamente. El análisis multivariado indicó que raza/color (no blanca), escolaridad (< 8 años de estudio), estado civil (soltera), renta < 3 salarios mínimos, relación sexual durante el embarazo, no haber tenido sífilis anterior al embarazo actual, realización de seis o mas consultas de pre-natal y la realización de la última visita antes del tercer trimestre de embarazo, estaban asociados con mayor riesgo de tener oportunidad de pérdida de prevención. Se observó una asociación negativa entre estado civil (soltera), lugar de realización de pre-natal (hospital) y la realización de la primera consulta pre-natal en el tercer trimestre con oportunidad de pérdida de prevención. CONCLUSIONES: Altos porcentajes de gestantes no evaluadas señalan fallas en la prevención y control de la infección por HIV y de la sífilis congénita en los servicios de salud. Las gestantes continúan interrumpiendo el cuidado pre-natal precozmente y no logran realizar los procedimientos de selección para HIV y sífilis.OBJETIVO: Estimar a prevalência de oportunidade perdida de prevenção a sífilis e HIV entre gestantes que tiveram acesso ao pré-natal e fatores associados a não-testagem para esses agravos. MÉTODOS: Estudo transversal com amostra aleatória de 2.145 puérperas do Brasil, 1999 e 2000 admitidas em maternidades para parto ou curetagem e que haviam realizado pelo menos uma consulta de pré-natal. A não-realização de exame de teste para sífilis e/ou anti-HIV durante a gravidez foi usada como marcador para oportunidade perdida de prevenção. Mulheres que realizaram apenas exame de sífilis ou apenas o anti-HIV, ou não realizaram nenhum, foram comparadas àquelas que realizaram os dois (categoria de referência). A prevalência de oportunidade perdida de prevenção foi estimada para cada categoria, com intervalo de confiança de 95%. Os fatores associados com oportunidade perdida de prevenção foram analisados por meio de regressão logística multinomial. RESULTADOS: A prevalência de oportunidade perdida de prevenção para a realização do teste de sífilis ou anti-HIV foi de 41,2% e 56,0%, respectivamente. A análise multivariada indicou que raça/cor (não branca), escolaridade (< 8 anos de estudo), estado civil (solteira), rend

Control of Gastric H,K-ATPase Activity by Cations, Voltage and Intracellular pH Analyzed by Voltage Clamp Fluorometry in Xenopus Oocytes

Whereas electrogenic partial reactions of the Na,K-ATPase have been studied in depth, much less is known about the influence of the membrane potential on the electroneutrally operating gastric H,K-ATPase. In this work, we investigated site-specifically fluorescence-labeled H,K-ATPase expressed in Xenopus oocytes by voltage clamp fluorometry to monitor the voltage-dependent distribution between E1P and E2P states and measured Rb+ uptake under various ionic and pH conditions. The steady-state E1P/E2P distribution, as indicated by the voltage-dependent fluorescence amplitudes and the Rb+ uptake activity were highly sensitive to small changes in intracellular pH, whereas even large extracellular pH changes affected neither the E1P/E2P distribution nor transport activity. Notably, intracellular acidification by approximately 0.5 pH units shifted V0.5, the voltage, at which the E1P/E2P ratio is 50∶50, by −100 mV. This was paralleled by an approximately two-fold acceleration of the forward rate constant of the E1P→E2P transition and a similar increase in the rate of steady-state cation transport. The temperature dependence of Rb+ uptake yielded an activation energy of ∼90 kJ/mol, suggesting that ion transport is rate-limited by a major conformational transition. The pronounced sensitivity towards intracellular pH suggests that proton uptake from the cytoplasmic side controls the level of phosphoenzyme entering the E1P→E2P conformational transition, thus limiting ion transport of the gastric H,K-ATPase. These findings highlight the significance of cellular mechanisms contributing to increased proton availability in the cytoplasm of gastric parietal cells. Furthermore, we show that extracellular Na+ profoundly alters the voltage-dependent E1P/E2P distribution indicating that Na+ ions can act as surrogates for protons regarding the E2P→E1P transition. The complexity of the intra- and extracellular cation effects can be rationalized by a kinetic model suggesting that cations reach the binding sites through a rather high-field intra- and a rather low-field extracellular access channel, with fractional electrical distances of ∼0.5 and ∼0.2, respectively

Mannose-binding lectin-deficient genotypes as a risk factor of pneumococcal meningitis in infants

OBJECTIVES: The objective of this study was to evaluate to evaluate the role of mannose-binding-lectin deficient genotypes in pneumococcal meningitis (PM) in children. METHODS: We performed a 16-year retrospective study (January 2001 to March 2016) including patients ≤ 18 years with PM. Variables including attack rate of pneumococcal serotype (high or low invasive capacity) and MBL2 genotypes associated with low serum MBL levels were recorded. RESULTS: Forty-eight patients were included in the study. Median age was 18.5 months and 17/48 episodes (35.4%) occurred in children ≤ 12 months old. Serotypes with high-invasive disease potential were identified in 15/48 episodes (31.2%). MBL2 deficient genotypes accounted for 18.8% (9/48). Children ≤ 12 months old had a 7-fold risk (95% CI: 1.6-29.9; p 12 months old. A sub-analysis of patients by age group revealed significant proportions of carriers of MBL2 deficient genotypes among those ≤ 12 months old with PM caused by opportunistic serotypes (54.5%), admitted to the PICU (Pediatric Intensive Care Unit) (46.7%) and of White ethnicity (35.7%). These proportions were significantly higher than in older children (all p<0.05). CONCLUSIONS: Our results suggest that differences in MBL2 genotype in children ≤12 months old affects susceptibility to PM, and it may have an important role in the episodes caused by non-high invasive disease potential serotypes