Alzheimer’s disease cerebrospinal fluid biomarkers are not influenced by gravity drip or aspiration extraction methodology

Introduction: Cerebrospinal fluid (CSF) biomarkers, although of established utility in the diagnostic evaluation of Alzheimer's disease (AD), are known to be sensitive to variation based on pre-analytical sample processing. We assessed whether gravity droplet collection versus syringe aspiration was another factor influencing CSF biomarker analyte concentrations and reproducibility. Methods: Standardized lumbar puncture using small calibre atraumatic spinal needles and CSF collection using gravity fed collection followed by syringe aspirated extraction was performed in a sample of elderly individuals participating in a large long-term observational research trial. Analyte assay concentrations were compared. Results: For the 44 total paired samples of gravity collection and aspiration, reproducibility was high for biomarker CSF analyte assay concentrations (concordance correlation [95%CI]: beta-amyloid1-42 (Aβ42) 0.83 [0.71 - 0.90]), t-tau 0.99 [0.98 - 0.99], and phosphorylated tau (p-tau) 0.82 [95 % CI 0.71 - 0.89]) and Bonferroni corrected paired sample t-tests showed no significant differences (group means (SD): Aβ42 366.5 (86.8) vs 354.3 (82.6), p = 0.10; t-tau 83.9 (46.6) vs 84.7 (47.4) p = 0.49; p-tau 43.5 (22.8) vs 40.0 (17.7), p = 0.05). The mean duration of collection was 10.9 minutes for gravity collection and <1 minute for aspiration. Conclusions: Our results demonstrate that aspiration of CSF is comparable to gravity droplet collection for AD biomarker analyses but could considerably accelerate throughput and improve the procedural tolerability for assessment of CSF biomarkers

The role of emotion, values, and beliefs in the construction of innovative work realities

Traditional approaches to requirements elicitation stress systematic and rational analysis and representation of organizational context and system requirements. This paper argues that (1) for an organization, a software system implements a shared vision of a future work reality and that (2) understanding the emotions, feelings, values, beliefs, and interests that drive organizational human action is needed in order to invent the requirements of such a software system. This paper debunks some myths about how organizations transform themselves through the adoption of Information and Communication Technology; describes the concepts of emotion, feeling, value, and belief; and presents some constructionist guidelines for the process of eliciting requirements for a software system that helps an organization to fundamentally change its work patterns.(undefined

The role of the facilitator in distributed teamwork

SIGLEAvailable from British Library Document Supply Centre-DSC:D200001 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Sex pheromone and visual trap interactions in mate location strategies and aggregation by host-alternating aphids in the field

Field observations were made on the responses of males and gynoparae of three host-alternating aphid species, the blackberry-cereal aphid, Sitobion fragariae (Walker), the bird cherry-oat aphid, Rhopalosiphum padi (L.) and the damson-hop aphid, Phouodon humuli (Schrank) to species-specific sex pheromones released from transparent and coloured water traps. Pheromone traps caught significantly more males than did control traps without pheromone, whereas transparent, light green, yellow and orange traps caught most insects. Measurements of the distance over which sex pheromones function indicated that male P. humuli detect the pheromone 2-6 m from the source and can fly upwind to a source in wind speeds of less than or equal to 0.7 m s(-1). In all three species significantly more gynoparae were caught in pheromone traps than in control traps, suggesting that pheromone released by adult sexual females may assist late-flying gynoparae to locate a suitable host plant on which to deposit their progeny. The response is relatively stronger for males than gynoparae, but the pheromones appear to act as both sex and aggregation pheromones

74th ENMC International Workshop: Mitochondrial Diseases

Item does not contain fulltex

A methodology for the selection of requirements engineering techniques

The complexity of software projects as well as the multidisciplinary nature of requirements engineering (RE) requires developers to carefully select RE techniques and practices during software development. Nevertheless, the selection of RE techniques is usually based on personal preference or existing company practice rather than on characteristics of the project at hand. Furthermore, there is a lack of guidance on which techniques are suitable for a certain project context. So far, only a limited amount of research has been done regarding the selection of RE techniques based on the attributes of the project under development. The few approaches that currently exist for the selection of RE techniques provide only little guidance for the actual selection process. We believe that the evaluation of RE techniques in the context of an application domain and a specific project is of great importance. This paper describes a Methodology for Requirements Engineering Techniques Selection (MRETS) as an approach that helps requirements engineers select suitable RE techniques for the project at hand. The MRETS has three aspects: Firstly, it aids requirements engineers in establishing a link between the attributes of the project and the attributes of RE techniques. Secondly, based on the evaluation schema proposed in our research, MRETS provides an opportunity to analyze RE techniques in detail using clustering. Thirdly, the objective function used in our approach provides an effective decision support mechanism for the selection of RE techniques. This paper makes contributions to RE techniques analysis, the application of RE techniques in practice, RE research, and software engineering in general. The application of the proposed methodology to an industrial project provides preliminary information on the effectiveness of MRETS for the selection of RE techniques.Li Jiang, Armin Eberlein, Behrouz H. Far and Majid Mousav

Concordance between cerebrospinal fluid biomarkers with Alzheimer’s disease pathology between three independent assay platforms

Background:To enhance the accuracy of clinical diagnosis for Alzheimer’s disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in vivo quantification of different AD pathological hallmarks in the brains of affected subjects; however, consensus around the best platform, most informative biomarker and correlations across different methodologies are controversial. Objective:Assessing levels of Aβ-amyloid and tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET Aβ-amyloid (32 Aβ-amyloid–and 45 Aβ-amyloid+), as well as concordance between CSF biomarker levels and PET Aβ-amyloid imaging. Methods:Prediction and concordance analyses were performed using a sub-cohort of 77 individuals (48 healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the Australian Imaging Biomarker and Lifestyle study of aging. Results:Across all three platforms, the T-tau/Aβ42 ratio biomarker had modestly higher correlation with SUVR/BeCKeT (ρ= 0.69–0.8) as compared with Aβ42 alone (ρ= 0.66–0.75). Differences in CSF biomarker levels between the PET Aβ-amyloid–and Aβ-amyloid+ groups were strongest for the Aβ42/Aβ40 and T-tau/Aβ42 ratios (p < 0.0001); however, comparison of predictive models for PET Aβ-amyloid showed no difference between Aβ42 alone and the T-tau/Aβ42 ratio. Conclusion:This study confirms strong concordance between CSF biomarkers and PET Aβ-amyloid status is independent of immunoassay platform, supporting their utility as biomarkers in clinical practice for the diagnosis of AD and for participant enrichment in clinical trials

Alzheimer’s Disease Normative Cerebrospinal Fluid Biomarkers Validated in PET Amyloid-β Characterized Subjects from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study

Background: The cerebrospinal fluid (CSF) amyloid-β (Aβ)1-42, total-tau (T-tau), and phosphorylated-tau (P-tau181P) profile has been established as a valuable biomarker for Alzheimer’s disease (AD). Objective: The current study aimed to determine CSF biomarker cut-points using positron emission tomography (PET) Aβ imaging screened subjects from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, as well as correlate CSF analyte cut-points across a range of PET Aβ amyloid ligands. Methods: Aβ pathology was determined by PET imaging, utilizing 11C-Pittsburgh Compound B, 18F-flutemetamol, or 18F-florbetapir, in 157 AIBL participants who also underwent CSF collection. Using an INNOTEST assay, cut-points were established (Aβ1-42 >544 ng/L, T-tau <407 ng/L, and P-tau181P <78 ng/L) employing a rank based method to define a “positive” CSF in the sub-cohort of amyloid-PET negative healthy participants (n = 97), and compared with the presence of PET demonstrated AD pathology. Results: CSF Aβ1-42 was the strongest individual biomarker, detecting cognitively impaired PET positive mild cognitive impairment (MCI)/AD with 85% sensitivity and 91% specificity. The ratio of P-tau181P or T-tau to Aβ1-42 provided greater accuracy, predicting MCI/AD with Aβ pathology with ≥92% sensitivity and specificity. Cross-validated accuracy, using all three biomarkers or the ratio of P-tau or T-tau to Aβ1-42 to predict MCI/AD, reached ≥92% sensitivity and specificity. Conclusions: CSF Aβ1-42 levels and analyte combination ratios demonstrated very high correlation with PET Aβ imaging. Our study offers additional support for CSF biomarkers in the early and accurate detection of AD pathology, including enrichment of patient cohorts for treatment trials even at the pre-symptomatic stage