Establishing In-House Cutoffs of CSF Alzheimer’s Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort

Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST^® ELISA and Lumipulse G^® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815⁻²⁷). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.     

Effect of freezing treatments and yeast amount on sensory and physical properties of sweet bakery products

The frozen bakery market has grown significantly in developed countries over the past decade.     

Analysis of the changes in quality in mandarin fruit,produced by deficit irrigation treatments

‘Clemenules’ mandarin citrus trees, grafted on Cleopatra and Carrizo rootstocks, were subjected to three irrigation treatments: the control (100% ETc), and phases II and III treatments (non-irrigation during phases II and III, respectively). The two deficit irrigation (DI) treatments affected in different ways some fruit quality parameters and these effects were also dependent on the rootstock. Although phase II treatment increased total soluble solids (TSS) and titratable acidity (TA), it delayed the maturation process. Phase II-stressed fruits on Carrizo had more fructose and glucose but less sucrose in relation to control fruits, thus increasing the reducing sugars. Phase II-stressed fruits on Cleopatra had more glucose, fructose and sucrose, for osmotic adjustment, also increasing the reducing sugars in these fruits. Phase III-stressed fruits had greater acidity, TSS, total phenolics, lycopene, glucose and sucrose than control fruits, but the same maturation state. In conclusion, DI in phase III improved fruit quality, by increasing the values of important quality parameters related to taste, flavour and nutritional benefits, but DI in phase II produced a drastic delay in the maturation process that made fruits non-commercial.     

Distribution planning with reliability options for distributed generation

The promotion of electricity generation from renewable energy sources (RES) and combined heat and power (CHP) has resulted in increasing penetration levels of distributed generation (DG). However, large-scale connection of DG involves profound changes in the operation and planning of electricity distribution networks. Distribution System Operators (DSOs) play a key role since these agents have to provide flexibility to their networks in order to integrate DG. Article 14.7 of EU Electricity Directive states that DSOs should consider DG as an alternative to new network investments. This is a challenging task, particularly under the current regulatory framework where DSOs must be legally and functionally unbundled from other activities in the electricity sector. This paper proposes a market mechanism, referred to as reliability options for distributed generation (RODG), which provides DSOs with an alternative to the investment in new distribution facilities. The mechanism proposed allocates the firm capacity required to DG embedded in the distribution network through a competitive auction. Additionally, RODG make DG partly responsible for reliability and provide DG with incentives for a more efficient operation taking into account the network conditions.     

Energy Partitions and Image Segmentation

We address the issue of low-level segmentation for real-valued images. The proposed approach relies on the formulation of the problem in terms of an energy partition of the image domain. In this framework, an energy is defined by measuring a pseudo-metric distance to a source point. Thus, the choice of an energy and a set of sources determines a tessellation of the domain. Each energy acts on the image at a different level of analysis; through the study of two types of energies, two stages of the segmentation process are addressed. The first energy considered, the path variation, belongs to the class of energies determined by minimal paths. Its application as a pre-segmentation method is proposed. In the second part, where the energy is induced by a ultrametric, the construction of hierarchical representations of the image is discussed.     

On Nirenberg-type conditions for higher-order systems on time scales

We study the existence of periodic solutions for a nonlinear system of nth-order differential equations on time scales. Assuming a suitable Nirenberg-type condition, we prove the existence of at least one solution of the problem using Mawhin’s coincidence degree.     

Improving the performance and functionality of Mondrian open‐source OLAP systems

For a long time, the design of relational databases has focused on the optimization of atomic transactions (insert, select, update or delete). Currently, relational databases store tactical information of data warehouses, mainly for select‐like operations. However, the database paradigm has evolved, and nowadays on‐line analytical processing (OLAP) systems handle strategic information for further analysis. These systems enable fast, interactive and consistent information analysis of data warehouses, including shared calculations and allocations. OLAP and data warehouses jointly allow multidimensional data views, turning raw data into knowledge. OLAP allows ‘slice and dice’ navigation and a top‐down perspective of data hierarchies. In this paper, we describe our experience in the migration from a large relational database management system to an OLAP system on top of a relational layer (the data warehouse), and the resulting contributions in open‐source ROLAP optimization. Existing open‐source ROLAP technologies rely on summarized tables with materialized aggregate views to improve system performance (in terms of response time). The design and maintenance of those tables are cumbersome. Instead, we intensively exploit cache memory, where key data reside, yielding low response times. A cold start process brings summarized data from the relational database to cache memory, subsequently reducing the response time. We ensure concurrent access to the summarized data, as well as consistency when the relational database updates data. We also improve the OLAP functionality, by providing new features for automating the creation of calculated members. This makes it possible to define new measures on the fly using virtual dimensions, without re‐designing the multidimensional cube. We have chosen the XML/A de facto standard for service provision. Copyright © 2008 John Wiley & Sons, Ltd.     

MegaViews: Scalable Many‐View Rendering With Concurrent Scene‐View Hierarchy Traversal

We present a scalable solution to render complex scenes from a large amount of viewpoints. While previous approaches rely either on a scene or a view hierarchy to process multiple elements together, we make full use of both, enabling sublinear performance in terms of views and scene complexity. By concurrently traversing the hierarchies, we efficiently find shared information among views to amortize rendering costs. One example application is many‐light global illumination. Our solution accelerates shadow map generation for virtual point lights, whose number can now be raised to over a million while maintaining interactive rates.     

Convergence of a lowest-order finite element method for the transmission eigenvalue problem

The transmission eigenvalue problem arises in scattering theory. The main difficulty in its analysis is the fact that, depending on the chosen formulation, it leads either to a quadratic eigenvalue problem or to a non-classical mixed problem. In this paper we prove the convergence of a mixed finite element approximation. This approach, which is close to the Ciarlet–Raviart discretization of biharmonic problems, is based on Lagrange finite elements and is one of the less expensive methods in terms of the amount of degrees of freedom. The convergence analysis is based on classical abstract spectral approximation result and the theory of mixed finite element methods for solving the stream function–vorticity formulation of the Stokes problem. Numerical experiments are reported in order to assess the efficiency of the method.     

IPTV: challenges and future directions

The move to IP Protocol Television (IPTV) has challenged the traditional television industry by opening the Internet to high quality real time television content delivery. Thus it has provided an enabling set of key technologies to understand and foster further innovations in the multimedia landscape and to create dynamics in the TV value chain. This editorial provides a brief overview of this special issue. It begins with a short introduction to IPTV Technology and then summarizes the main contributions of the selected papers for this special issue, highlighting their salient features and novel results.