Evaluation of gene-based family-based methods to detect novel genes associated with familial late onset Alzheimer disease

AbstractGene-based tests to study the combined effect of rare variants towards a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially for complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We have examined the performance of several collapsing, variance-component and transmission disequilibrium tests across eight different software and twenty-two models utilizing a cohort of 285 families (N=1,235) with late-onset Alzheimer disease (LOAD). After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the studied phenotype with high confidence and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, MAS1L) as candidates genes for familial LOAD.</jats:p

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer disease

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations

A data quality control program for computer-assisted personal interviews

Researchers strive to optimize data quality in order to ensure that study findings are valid and reliable. In this paper, we describe a data quality control program designed to maximize quality of survey data collected using computer-assisted personal interviews. The quality control program comprised three phases: (1) software development, (2) an interviewer quality control protocol, and (3) a data cleaning and processing protocol. To illustrate the value of the program, we assess its use in the Translating Research in Elder Care Study. We utilize data collected annually for two years from computer-assisted personal interviews with 3004 healthcare aides. Data quality was assessed using both survey and process data. Missing data and data errors were minimal. Mean and median values and standard deviations were within acceptable limits. Process data indicated that in only 3.4% and 4.0% of cases was the interviewer unable to conduct interviews in accordance with the details of the program. Interviewers&rsquo; perceptions of interview quality also significantly improved between Years 1 and 2. While this data quality control program was demanding in terms of time and resources, we found that the benefits clearly outweighed the effort required to achieve high-quality data.<br /

The relationship between characteristics of context and research utilization in a pediatric setting

BackgroundResearch utilization investigators have called for more focused examination of the influence of context on research utilization behaviors. Yet, up until recently, lack of instrumentation to identify and quantify aspects of organizational context that are integral to research use has significantly hampered these efforts. The Alberta Context Tool (ACT) was developed to assess the relationships between organizational factors and research utilization by a variety of healthcare professional groups. The purpose of this paper is to present findings from a pilot study using the ACT to elicit pediatric and neonatal healthcare professionals\u27 perceptions of the organizational context in which they work and their use of research to inform practice. Specifically, we report on the relationship between dimensions of context, founded on the Promoting Action on Research Implementation in Health Services (PARIHS) framework, and self-reported research use behavior.MethodsA cross-sectional survey approach was employed using a version of the ACT, modified specifically for pediatric settings. The survey was administered to nurses working in three pediatric units in Alberta, Canada. Scores for three dimensions of context (culture, leadership and evaluation) were used to categorize respondent data into one of four context groups (high, moderately high, moderately low and low). We then examined the relationships between nurses` self-reported research use and their perceived context.ResultsA 69% response rate was achieved. Statistically significant differences in nurses\u27 perceptions of culture, leadership and evaluation, and self-reported conceptual research use were found across the three units. Differences in instrumental research use across the three groups of nurses by unit were not significant. Higher self-reported instrumental and conceptual research use by all nurses in the sample was associated with more positive perceptions of their context.ConclusionsOverall, the results of this study lend support to the view that more positive contexts are associated with higher reports of research use in practice. These findings have implications for organizational endeavors to promote evidence-informed practice and maximize the quality of care. Importantly, these findings can be used to guide the development of interventions to target modifiable characteristics of organizational context that are influential in shaping research use behavior.<br /

A protocol for advanced psychometric assessment of surveys

Background and Purpose. In this paper, we present a protocol for advanced psychometric assessments of surveys based on the Standards for Educational and Psychological Testing. We use the Alberta Context Tool (ACT) as an exemplar survey to which this protocol can be applied. Methods. Data mapping, acceptability, reliability, and validity are addressed. Acceptability is assessed with missing data frequencies and the time required to complete the survey. Reliability is assessed with internal consistency coefficients and information functions. A unitary approach to validity consisting of accumulating evidence based on instrument content, response processes, internal structure, and relations to other variables is taken. We also address assessing performance of survey data when aggregated to higher levels (e.g., nursing unit). Discussion. In this paper we present a protocol for advanced psychometric assessment of survey data using the Alberta Context Tool (ACT) as an exemplar survey; application of the protocol to the ACT survey is underway. Psychometric assessment of any survey is essential to obtaining reliable and valid research findings. This protocol can be adapted for use with any nursing survey.<br /

Dairy foods and dairy protein consumption is inversely related to markers of adiposity in obese men and women

A number of intervention studies have reported that the prevalence of obesity may be in part inversely related to dairy food consumption while others report no association. We sought to examine relationships between energy, protein and calcium consumption from dairy foods (milk, yoghurt, cheese, dairy spreads, ice-cream) and adiposity including body mass index (BMI), waist (WC) and hip circumference (HC), and direct measures of body composition using dual energy X-ray absorptiometry (% body fat and abdominal fat) in an opportunistic sample of 720 overweight/obese Australian men and women. Mean (SD) age, weight and BMI of the population were 51 ± 10 year, 94 ± 18 kg and 32.4 ± 5.7 kg/m2, respectively. Reduced fat milk was the most commonly consumed dairy product (235 ± 200 g/day), followed by whole milk (63 ± 128 g/day) and yoghurt (53 ± 66 g/day). Overall dairy food consumption (g/day) was inversely associated with BMI, % body fat and WC (all p < 0.05). Dairy protein and dairy calcium (g/day) were both inversely associated with all adiposity measures (all p < 0.05). Yoghurt consumption (g/day) was inversely associated with % body fat, abdominal fat, WC and HC (all p < 0.05), while reduced fat milk consumption was inversely associated with BMI, WC, HC and % body fat (all p < 0.05). Within a sample of obese adults, consumption of dairy products, dairy protein, and calcium was associated with more favourable body composition

Reliability and validity of the Alberta context tool (ACT) with professional nurses: Findings from a multi-study analysis

Although organizational context is central to evidence-based practice, underdeveloped measurement hindersitsassessment. The Alberta Context Tool, comprised of 59 items that tap10 modifiable contextual concepts, was developed to address this gap. The purpose of this study to examine the reliability and validity of scores obtained when the Alberta Context Tool is completed by professional nurses across different healthcare settings. Five separate studies (N = 2361 nurses across different care settings) comprised the study sample. Reliability and validity were assessed. Cronbach\u27s alpha exceeded 0.70 for9/10 Alberta Context Tool concepts. Item-total correlations exceeded acceptable standards for 56/59items. Confirmatory Factor Analysescoordinated acceptably with the Alberta Context Tool\u27s proposed latent structure. The mean values for each Alberta Context Tool concept increased from low to high levels of research utilization(as hypothesized) further supporting its validity. This study provides robust evidence forreliability and validity of scores obtained with the Alberta Context Tool when administered to professional nurses

Light scattering corrections to linear dichroism spectroscopy for liposomes in shear flow using calcein fluorescence and modified Rayleigh-Gans-Debye-Mie scattering

The interpretation of data from absorbance spectroscopy experiments of liposomes in flow systems is often complicated by the fact that there is currently no easy way to account for scattering artefacts. This has proved particularly problematic for linear dichroism (LD) spectroscopy, which may be used to determine binding modes of small molecules, peptides and proteins to liposomes if we can extract the absorbance signal from the combined absorbance/scattering experiment. Equations for a modified Rayleigh-Gans-Debye (RGD) approximation to the turbidity (scattering) LD spectrum are available in the literature though have not been implemented. This review summarises the literature and shows how it can be implemented. The implementation proceeds by first determining volume loss that occurs when a spherical liposome is subjected to flow. Calcein fluorescence can be used for this purpose since at high concentrations (> 60 mM) it has low intensity fluorescence with maxima at 525 and 563 nm whereas at low concentrations (<1 mM) the fluorescence intensity is enhanced and the band shifts to 536 nm. The scattering calculation process yields the average axis ratios of the distorted liposome ellipsoids and extent of orientation of the liposomes in flow. The scattering calculations require methods to estimate liposome integrity, volume loss, and orientation when subjected to shear stresses under flow

Innovative Insights: Leveraging Chatbots for Research Assistance in College Libraries

This presentation will showcase a chatbot designed by librarians to bolster research assistance services within college libraries. Attendees will witness the development journey of the chatbot, from conception to implementation, exploring its functionalities and user interface and detailing how prompt engineering can build a chatbot that leverages professional expertise without requiring advanced coding abilities. Presenters will illustrate how this technology can revolutionize information access and support scholarly endeavors. Participants will learn practical strategies for chatbot prompt engineering and applications for chatbots built with custom data. Join us to discover chatbots\u27 transformative potential in elevating the academic library research experience