Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1

Peer reviewedPublisher PD

Ecosystem Resilience and Threshold Response in the Galápagos Coastal Zone

Background: The Intergovernmental Panel on Climate Change (IPCC) provides a conservative estimate on rates of sea-level rise of 3.8 mm yr⁻¹ at the end of the 21st century, which may have a detrimental effect on ecologically important mangrove ecosystems. Understanding factors influencing the long-term resilience of these communities is critical but poorly understood. We investigate ecological resilience in a coastal mangrove community from the Galápagos Islands over the last 2700 years using three research questions: What are the 'fast and slow' processes operating in the coastal zone? Is there evidence for a threshold response? How can the past inform us about the resilience of the modern system?Methodology/Principal Findings: Palaeoecological methods (AMS radiocarbon dating, stable carbon isotopes (δ13C)) were used to reconstruct sedimentation rates and ecological change over the past 2,700 years at Diablas lagoon, Isabela, Galápagos. Bulk geochemical analysis was also used to determine local environmental changes, and salinity was reconstructed using a diatom transfer function. Changes in relative sea level (RSL) were estimated using a glacio-isostatic adjustment model. Non-linear behaviour was observed in the Diablas mangrove ecosystem as it responded to increased salinities following exposure to tidal inundations. A negative feedback was observed which enabled the mangrove canopy to accrete vertically, but disturbances may have opened up the canopy and contributed to an erosion of resilience over time. A combination of drier climatic conditions and a slight fall in RSL then resulted in a threshold response, from a mangrove community to a microbial mat.Conclusions/Significance: Palaeoecological records can provide important information on the nature of non-linear behaviour by identifying thresholds within ecological systems, and in outlining responses to 'fast and slow' environmental change between alternative stable states. This study highlights the need to incorporate a long-term ecological perspective when designing strategies for maximizing coastal resilience.</p

An anatomically-based masking protocol for the assessment of in-shoe plantar pressure measurement of the forefoot

Background The area beneath the metatarsal heads is a common location of foot pain, which is often associated with high plantar pressures. Current plantar pressure assessment protocols focus mainly on the gross area of the forefoot with minimal attention paid to specific areas such as the metatarsal heads. The aim of this study was to develop and assess a new anatomically-based masking protocol that is clinically relevant to measure forefoot plantar pressure during shod conditions based on the anatomical positions of the metatarsal heads. Methods Initially, we developed a masking protocol to measure forefoot plantar pressure during shod conditions based on the anatomical positions of the metatarsal heads. This new masking protocol divided the forefoot into three sub-areas (proximal, beneath, and distal to the metatarsal heads) as determined by the position of each metatarsal head. Following development of the new masking protocol, we compared the new protocol against a traditional protocol, which defines the forefoot as between 51 and 81% of the foot length. To compare the two masking protocols, we tested two experimental conditions: (i) a control condition (i.e. no metatarsal pad), and (ii) a metatarsal pad condition. We then compared plantar pressure differences between the two experimental conditions for the two masking protocols. Participants for this component of the study included 36 community dwelling older adults (mean age 75.6 years ±5.4) with a history of forefoot pain. Forefoot plantar pressure data were measured while walking using the pedar®-X in-shoe system. Peak pressure, maximum force and contact area at the time of peak pressure were determined and results were compared between the two masking protocols. Results The traditional masking protocol showed that the metatarsal pad significantly decreased peak pressure and increased contact area in the forefoot area (i.e. within the entire mask area), but maximum force was not significantly different between the two conditions. In contrast, the newly developed anatomically-based masking protocol indicated that the metatarsal pad decreased peak plantar pressures distal to and beneath the metatarsal heads by increasing force and contact area proximal to the metatarsal heads. Conclusions An anatomically-based masking protocol that is clinically relevant was developed to assess forefoot plantar pressure during shod conditions based on the anatomical positions of metatarsal heads. We propose that the new forefoot masking protocol will provide greater interpretability of forefoot plantar pressure data, which will aid clinicians and researchers for diagnostic, prognostic and therapeutic purposes

Reduced Protein Expression of the Na+/Ca2++K+-Exchanger (SLC24A4) in Apical Plasma Membranes of Maturation Ameloblasts of Fluorotic Mice

Exposure of forming enamel to fluoride results into formation of hypomineralized enamel. We tested whether enamel hypomineralization was caused by lower expression of the NCKX4/SLC24A4 Ca2+-transporter by ameloblasts. Three commercial antibodies against NCKX4 were tested on enamel organs of wild-type and Nckx4-null mice, one of which (a mouse monoclonal) was specific. This antibody gave a prominent staining of the apical plasma membranes of maturation ameloblasts, starting at early maturation. The layer of immuno-positive ameloblasts contained narrow gaps without immunostaining or with reduced staining. In fluorotic mouse incisors, the quantity of NCKX4 protein in ameloblasts as assessed by western blotting was not different from that in non-fluorotic ameloblasts. However, immunostaining of the apical plasma membranes of fluorotic ameloblasts was strongly reduced or absent suggesting that trafficking of NCKX4 to the apical membrane was strongly reduced. Exposure to fluoride may reduce NCKX4-mediated transport of Ca2+ by maturation stage ameloblasts which delays ameloblast modulation and reduces enamel mineralization

Survival Analysis of Patients with Heart Failure: Implications of Time-Varying Regression Effects in Modeling Mortality

Background: Several models have been designed to predict survival of patients with heart failure. These, while available and widely used for both stratifying and deciding upon different treatment options on the individual level, have several limitations. Specifically, some clinical variables that may influence prognosis may have an influence that change over time. Statistical models that include such characteristic may help in evaluating prognosis. The aim of the present study was to analyze and quantify the impact of modeling heart failure survival allowing for covariates with time-varying effects known to be independent predictors of overall mortality in this clinical setting. Methodology: Survival data from an inception cohort of five hundred patients diagnosed with heart failure functional class III and IV between 2002 and 2004 and followed-up to 2006 were analyzed by using the proportional hazards Cox model and variations of the Cox's model and also of the Aalen's additive model. Principal Findings: One-hundred and eighty eight (188) patients died during follow-up. For patients under study, age, serum sodium, hemoglobin, serum creatinine, and left ventricular ejection fraction were significantly associated with mortality. Evidence of time-varying effect was suggested for the last three. Both high hemoglobin and high LV ejection fraction were associated with a reduced risk of dying with a stronger initial effect. High creatinine, associated with an increased risk of dying, also presented an initial stronger effect. The impact of age and sodium were constant over time. Conclusions: The current study points to the importance of evaluating covariates with time-varying effects in heart failure models. The analysis performed suggests that variations of Cox and Aalen models constitute a valuable tool for identifying these variables. The implementation of covariates with time-varying effects into heart failure prognostication models may reduce bias and increase the specificity of such models.CNPq Brazilian Foundation for Scientific and Technological DevelopmentCNPq - Brazilian Foundation for Scientific and Technological Development [150653/2008-5

The Formation of the First Massive Black Holes

Supermassive black holes (SMBHs) are common in local galactic nuclei, and SMBHs as massive as several billion solar masses already exist at redshift z=6. These earliest SMBHs may grow by the combination of radiation-pressure-limited accretion and mergers of stellar-mass seed BHs, left behind by the first generation of metal-free stars, or may be formed by more rapid direct collapse of gas in rare special environments where dense gas can accumulate without first fragmenting into stars. This chapter offers a review of these two competing scenarios, as well as some more exotic alternative ideas. It also briefly discusses how the different models may be distinguished in the future by observations with JWST, (e)LISA and other instruments.Comment: 47 pages with 306 references; this review is a chapter in "The First Galaxies - Theoretical Predictions and Observational Clues", Springer Astrophysics and Space Science Library, Eds. T. Wiklind, V. Bromm & B. Mobasher, in pres

Tobacco control policies in hospitals before and after the implementation of a national smoking ban in Catalonia, Spain

Background: Diverse projects and guidelines to assist hospitals towards the attainment of comprehensive smoke-free policies have been developed. In 2006, Spain government passed a new smoking ban that reinforce tobacco control policies and banned completely smoking in hospitals. This study assesses the progression of tobacco control policies in the Catalan Network of Smokefree Hospitals before and after a comprehensive national smoking ban. Methods: We used the Self-Audit Questionnaire of the European Network for Smoke-free Hospitals to score the compliance of 9 policy standards (global score = 102). We used two crosssectional surveys to evaluate tobacco control policies before (2005) and after the implementation of a national smoking ban (2007) in 32 hospitals of Catalonia, Spain. We compared the means of the overall score in 2005 and 2007 according to the type of hospital, the number of beds, the prevalence of tobacco consumption, and the number of years as a smoke-free hospital. Results: The mean of the implementation score of tobacco control policies was 52.4 (95% CI:45.4-59.5) in 2005 and 71.6 (95% CI: 67.0-76.2) in 2007 with an increase of 36.7% (p 300 beds (41.1% increase; p < 0.01), hospitals with employees' tobacco consumption prevalence 35-39% (72.2% increase; p < 0.05) and hospitals that had recently implemented smoke-free policies (74.2% increase; p < 0.01). Conclusion: The national smoking ban appears to increase tobacco control activities in hospitals combined with other non-bylaw initiatives such as the Smoke-free Hospital Network

IL-4Rα-Independent Expression of Mannose Receptor and Ym1 by Macrophages Depends on their IL-10 Responsiveness

IL-4Rα-dependent responses are essential for granuloma formation and host survival during acute schistosomiasis. Previously, we demonstrated that mice deficient for macrophage-specific IL-4Rα (LysMcreIl4ra−/lox) developed increased hepatotoxicity and gut inflammation; whereas inflammation was restricted to the liver of mice lacking T cell-specific IL-4Rα expression (iLckcreIl4ra−/lox). In the study presented here we further investigated their role in liver granulomatous inflammation. Frequencies and numbers of macrophage, lymphocyte or granulocyte populations, as well as Th1/Th2 cytokine responses were similar in Schistosoma mansoni-infected LysMcreIl4ra−/lox liver granulomas, when compared to Il4ra−/lox control mice. In contrast, a shift to Th1 responses with high IFN-γ and low IL-4, IL-10 and IL-13 was observed in the severely disrupted granulomas of iLckcreIl4ra−/lox and Il4ra−/− mice. As expected, alternative macrophage activation was reduced in both LysMcreIl4ra−/lox and iLckcreIl4ra−/lox granulomas with low arginase 1 and heightened nitric oxide synthase RNA expression in granuloma macrophages of both mouse strains. Interestingly, a discrete subpopulation of SSChighCD11b+I-A/I-EhighCD204+ macrophages retained expression of mannose receptor (MMR) and Ym1 in LysMcreIl4ra−/lox but not in iLckcreIl4ra−/lox granulomas. While aaMφ were in close proximity to the parasite eggs in Il4ra−/lox control mice, MMR+Ym1+ macrophages in LysMcreIl4ra−/lox mice were restricted to the periphery of the granuloma, indicating that they might have different functions. In vivo IL-10 neutralisation resulted in the disappearance of MMR+Ym1+ macrophages in LysMcreIl4ra−/lox mice. Together, these results show that IL-4Rα-responsive T cells are essential to drive alternative macrophage activation and to control granulomatous inflammation in the liver. The data further suggest that in the absence of macrophage-specific IL-4Rα signalling, IL-10 is able to drive mannose receptor- and Ym1-positive macrophages, associated with control of hepatic granulomatous inflammation

Magnitude, precision, and realism of depth perception in stereoscopic vision

Our perception of depth is substantially enhanced by the fact that we have binocular vision. This provides us with more precise and accurate estimates of depth and an improved qualitative appreciation of the three-dimensional (3D) shapes and positions of objects. We assessed the link between these quantitative and qualitative aspects of 3D vision. Specifically, we wished to determine whether the realism of apparent depth from binocular cues is associated with the magnitude or precision of perceived depth and the degree of binocular fusion. We presented participants with stereograms containing randomly positioned circles and measured how the magnitude, realism, and precision of depth perception varied with the size of the disparities presented. We found that as the size of the disparity increased, the magnitude of perceived depth increased, while the precision with which observers could make depth discrimination judgments decreased. Beyond an initial increase, depth realism decreased with increasing disparity magnitude. This decrease occurred well below the disparity limit required to ensure comfortable viewing