CSF protein biomarkers predicting longitudinal reduction of CSF β-amyloid42 in cognitively healthy elders.

β-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD). It is believed to start many years prior to symptoms and is reflected by reduced cerebrospinal fluid (CSF) levels of the peptide Aβ1-42 (Aβ42). Here we tested the hypothesis that baseline levels of CSF proteins involved in microglia activity, synaptic function and Aβ metabolism predict the development of Aβ plaques, assessed by longitudinal CSF Aβ42 decrease in cognitively healthy people. Forty-six healthy people with three to four serial CSF samples were included (mean follow-up 3 years, range 2-4 years). There was an overall reduction in Aβ42 from a mean concentration of 211-195 pg ml(-1) after 4 years. Linear mixed-effects models using longitudinal Aβ42 as the response variable, and baseline proteins as explanatory variables (n=69 proteins potentially relevant for Aβ metabolism, microglia or synaptic/neuronal function), identified 10 proteins with significant effects on longitudinal Aβ42. The most significant proteins were angiotensin-converting enzyme (ACE, P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL, P=0.009). Receiver-operating characteristic analysis identified 11 proteins with significant effects on longitudinal Aβ42 (largely overlapping with the proteins identified by linear mixed-effects models). Several proteins (including ACE, CgA and AXL) were associated with Aβ42 reduction only in subjects with normal baseline Aβ42, and not in subjects with reduced baseline Aβ42. We conclude that baseline CSF proteins related to Aβ metabolism, microglia activity or synapses predict longitudinal Aβ42 reduction in cognitively healthy elders. The finding that some proteins only predict Aβ42 reduction in subjects with normal baseline Aβ42 suggest that they predict future development of the brain Aβ pathology at the earliest stages of AD, prior to widespread development of Aβ plaques

Proportionate and disproportionate policy responses to climate change: core concepts and empirical applications

A fresh perspective on policy-making and planning has emerged which views disproportionate policy as an intentional policy response. A disproportionate policy response is understood to be a lack of‘fit’or balance between the costs of a public policy and the benefits that are derived from this policy, and between policy ends and means. This paper applies this new perspective on the proportionality of policy-making to the area of climate change. The first part of the paper discusses the underlying causes of disproportionate policy responses in broad terms and then applies the theoretical reasoning to understand the conditions in which they are likely to appear in relation to climate change. These conditions are hypothesized to relate to four main factors: economic considerations; levels of public demand; focusing events; and strategic considerations. It concludes with the suggestion that societal actors may be able to manipulate these four factors to encourage politicians to adopt policies that mitigate climate change more rapidly than is currently the case in most countries

Accelerated swell testing of artificial sulfate bearing lime stabilised cohesive soils

This paper reports on the physico-chemical response of two lime stabilised sulfate bearing artificial soils subject to the European Accelerated Volumetric Swell Test (EN13286-49). At various intervals during the test, a specimen was removed and subject to compositional and microstructural analysis. Ettringite was formed by both soils types, but with significant differences in crystal morphology. Ettringite crystals formed from kaolin based soils were very small, colloidal in size and tended to form on the surface of other particles. Conversely, those formed from montmorillonite were relatively large and typically formed away from the surface in the pore solution. It was concluded that the mechanism by which ettringite forms is determined by the hydroxide ion concentration in the pore solution and the fundamental structure of the bulk clay. In the kaolin soil, ettringite forms by a topochemical mechanism and expands by crystal swelling. In the montmorillonite soil, it forms by a through-solution mechanism and crystal growth

Grain rotation and lattice deformation during perovskite spray coating and annealing probed in situ by GI-WAXS

We report for the first time on grain rotation in CH3NH3PbI3 perovskite films for ∼12% efficient planar solar cells and present a new method for investigating their texture evolution during thermal annealing. Our technique is based on in situ 2D grazing incidence wide-angle X-ray scattering (GI-WAXS) and employs a 10 keV wide-focussed X-ray beam to simultaneously probe a large number of grains. The ability to track the texture dynamics from a statistically relevant number of spots diffracting from single grains during thermal annealing and in grazing incidence geometry can have applications understanding the processing dynamics of a range of new materials

Structural and magnetic properties of Co-V nanoparticles

We have investigated the structural and magnetic properties of Co1-xVx nanoparticles (NPs) with composition x = 0.25 (stoichiometric) and 0.29 (under-stoichiometric) prepared by the cluster-beam deposition (CBD) technique. Our data shows that the as-made Co1-xVx NPs are a mixture of the high-temperature phase (HTP) and the low-temperature phase (LTP) of Co3V and the particles are superparamagnetic at room temperature (RT) with blocking temperatures (TB) of 90 and 137 K for x = 0.25 and 0.29, respectively. This behavior contrasts with the bulk which are paramagnetic down to 4.2 K. When the Co75V25 NPs are annealed at 573 K, they undergo a phase separation into a mixture of phases and become ferromagnetic at room temperature with Curie temperature (Tc) of 515 K

Engineering CAR-T therapies for autoimmune disease and beyond

Chimeric antigen receptor-T cell (CAR-T) therapy has transformed the management of refractory hematological malignancies. Now that targeting pathogenic cells of interest with antigen-directed cytotoxic T lymphocytes is possible, the field is expanding the reach of CAR-T therapy beyond oncology. Recently, breakthrough progress has been made in the application of CAR-T technology to autoimmune diseases, exploiting the same validated targets that were used by pioneering CAR-T therapies in hematology. Here, we discuss recent advances and outcomes that are paving the way for extension to new therapeutic areas, including autoimmunity

Sucrose in the concentrated solution or the supercooled “state” : a review of caramelisation reactions and physical behaviour

Sucrose is probably one of the most studied molecules by food scientists, since it plays an important role as an ingredient or preserving agent in many formulations and technological processes. When sucrose is present in a product with a concentration near or greater than the saturation point—i.e. in the supercooled state—it possesses high potentialities for the food industry in areas as different as pastry industry, dairy and frozen desserts or films and coatings production. This paper presents a review on critical issues and research on highly concentrated sucrose solutions—mainly, on sucrose thermal degradation and relaxation behaviour in such solutions. The reviewed works allow identifying several issues with great potential for contributing to significant advances in Food Science and Technology.Authors are grateful for the valuable discussions with Teresa S. Brandao and Rosiane Lopes da Cunha during this research. Author M. A. C. Quintas acknowledges the financial support of her research by FCT grant SFRH/BPD/41715/2007

Towards an operationalization of test-driven development skills: An industrial empirical study

Abstract Context: The majority of the empirical studies on Test-driven development (TDD) are concerned with verifying or refuting the effectiveness of the technique over a traditional approach, and they tend to neglect whether the subjects possess the necessary skills to apply TDD, though they argue such skills are necessary. Objective: We evaluate a set of minimal, a priori and in process skills necessary to apply TDD. We determine whether variations in external quality (i.e., number of defects) and productivity (i.e., number of features implemented) can be associated with different clusters of the TDD skills? set. Method: We executed a quasi-experiment involving 30 practitioners from industry. We first grouped the participants according to their TDD skills? set (consisting of a priori experience on programming and testing as well as in-process TDD conformance) into three levels (Low-Medium-High) using k-means clustering. We then applied ANOVA to compare the clusters in terms of external quality and productivity, and conducted post-hoc pairwise analysis. Results: We did not observe a statistically significant difference between the clusters either for external software quality ( F ( 2 , 27 = 1.44 , p = . 260 ), or productivity ( F ( 2 , 27 ) = 3.02 , p = . 065 ). However, the analysis of the effect sizes and their confidence intervals shows that the TDD skills? set is a factor that could account for up to 28% of the external quality, and 38% for productivity. Conclusion: We have reason to conclude that focusing on the improvement of TDD skills? set investigated in this study could benefit software developers in improving their baseline productivity and the external quality of the code they produce. However, replications are needed to overcome the issues related with the statistical power of this study. We suggest practical insights for future work to investigate the phenomenon further.hisresearchispartiallysupportedbytheAcademyofFinlandwithdecisionno.:278354,andbyFinnishDistinguishedProfessor(Fi.Di.Pro.) programme, ESEIL

The Importance of Fecaliths in the Aetiology of Acute Appendicitis

Aim: Fecaliths, lymphoid hyperplasia, parasites, undigested plant residues and foreign bodies are considered as part of the aetiology of acute appendicitis. In our article we discussed about fecaliths, fecalith formation, and its aetiological value. Methods: Patients which have been operated onfor acute appendicitis between 2009-2010 are analysed retrospectively. Results: The average age was 29,3. The number of cases with fecalith was 261 (36,1%). Out of these, 19 acute appendicites, 95 phlegmons, and 30 perforations were detected. Conclusions: Intraluminal pathologies probably play a major role in the development of acute appendicitis. Intraluminal pathological findings may also be seen in healthy persons without necessarily pointing toacute appendicitis. Disease progresses from intraluminal fecalith with no inflammation to perforation from the beginning. There are many explanations regarding the formation of fecaliths. Diagnosis of the fecalith may be decided with ultrasonography, computed tomography and magnetic resonance imaging techniques. In case of preoperatively demonstrated intraluminal fecalith through ultrasonographic examination with clinical symptoms of acute appendicitis, early appendectomy must be performed in our opinion. Early appendectomy lowers morbidity and mortalityrates

Options to Reform the European Union Legislation on GMOs: Scope and Definitions

We discuss options to reform the EU genetically modified organisms (GMO) regulatory framework, make risk assessment and decision-making more consistent with scientific principles, and lay the groundwork for international coherence. The first in a three-part series, this article focuses on reform options related to the scope of the legislation and the GMO definition