lordif: An R Package for Detecting Differential Item Functioning Using Iterative Hybrid Ordinal Logistic Regression/Item Response Theory and Monte Carlo Simulations

Logistic regression provides a flexible framework for detecting various types of differential item functioning (DIF). Previous efforts extended the framework by using item response theory (IRT) based trait scores, and by employing an iterative process using group--specific item parameters to account for DIF in the trait scores, analogous to purification approaches used in other DIF detection frameworks. The current investigation advances the technique by developing a computational platform integrating both statistical and IRT procedures into a single program. Furthermore, a Monte Carlo simulation approach was incorporated to derive empirical criteria for various DIF statistics and effect size measures. For purposes of illustration, the procedure was applied to data from a questionnaire of anxiety symptoms for detecting DIF associated with age from the Patient--Reported Outcomes Measurement Information System.

Isometric Embedding of BPS Branes in Flat Spaces with Two Times

We show how non-near horizon p-brane theories can be obtained from two embedding constraints in a flat higher dimensional space with 2 time directions. In particular this includes the construction of D3 branes from a flat 12-dimensional action, and M2 and M5 branes from 13 dimensions. The worldvolume actions are determined by constant forms in the higher dimension, reduced to the usual expressions by Lagrange multipliers. The formulation affords insight in the global aspects of the spacetime geometries and makes contact with recent work on two-time physics.Comment: 29 pages, 10 figures, Latex using epsf.sty and here.sty; v2: reference added and some small correction

lordif: An R Package for Detecting Differential Item Functioning Using Iterative Hybrid Ordinal Logistic Regression/Item Response Theory and Monte Carlo Simulations

Logistic regression provides a flexible framework for detecting various types of differential item functioning (DIF). Previous efforts extended the framework by using item response theory (IRT) based trait scores, and by employing an iterative process using group--specific item parameters to account for DIF in the trait scores, analogous to purification approaches used in other DIF detection frameworks. The current investigation advances the technique by developing a computational platform integrating both statistical and IRT procedures into a single program. Furthermore, a Monte Carlo simulation approach was incorporated to derive empirical criteria for various DIF statistics and effect size measures. For purposes of illustration, the procedure was applied to data from a questionnaire of anxiety symptoms for detecting DIF associated with age from the Patient--Reported Outcomes Measurement Information System

The Long-Term Conditions Questionnaire (LTCQ): Conceptual framework and item development

Purpose: To identify the main issues of importance when living with long-term conditions to refine a conceptual framework for informing the item development of a patient-reported outcome measure for long-term conditions. Methods: Semi-structured qualitative interviews (n=48) were conducted with people living with at least one long-term condition. Participants were recruited through primary care. The interviews were transcribed verbatim and analysed by thematic analysis. The analysis served to refine the conceptual framework, based on reviews of the literature and stakeholder consultations, for developing candidate items for a new measure for long-term conditions. Results: Three main organising concepts were identified ‘Impact of long-term conditions’, ‘Experience of services and support’ and ‘Self-care’. The findings helped to refine a conceptual framework leading to the development of 23 items that represent issues of importance in long-term conditions. The 23 candidate items formed the first draft of the measure, currently named the Long-Term Conditions Questionnaire (LTCQ). Conclusions: The aim of this study was to refine the conceptual framework and develop items for a patient-reported outcome measure for long-term conditions, including single and multiple morbidities, and physical and mental health conditions. Qualitative interviews identified the key themes for assessing outcomes in long-term conditions and these underpinned the development of the initial draft of the measure. These initial items will undergo cognitive testing to refine the items prior to further validation in a survey

Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding

Purpose Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke. Methods For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study–Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other. Results Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0–2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not. Conclusions Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions

Impact of Home Visit Capacity on Genetic Association Studies of Late-Onset Alzheimer\u27s Disease

INTRODUCTION—Findings for genetic correlates of late-onset Alzheimer\u27s disease (LOAD) in studies that rely solely on clinic visits may differ from those with capacity to follow participants unable to attend clinic visits. METHODS—We evaluated previously identified LOAD-risk single nucleotide variants in the prospective Adult Changes in Thought study, comparing hazard ratios (HRs) estimated using the full data set of both in-home and clinic visits (n = 1697) to HRs estimated using only data that were obtained from clinic visits (n = 1308). Models were adjusted for age, sex, principal components to account for ancestry, and additional health indicators. RESULTS—LOAD associations nominally differed for 4 of 21 variants; CR1 and APOE variants were significant after Bonferroni correction. DISCUSSION—Estimates of genetic associations may differ for studies limited to clinic-only designs. Home visit capacity should be explored as a possible source of heterogeneity and potential bias in genetic studies

Gene-based GWAS and -biological pathway analysis of the resilience of executive functioning

Resilience in executive functioning (EF) is characterized by high EF measured by neuropsychological test performance despite structural brain damage from neurodegenerative conditions. We previously reported single nucleotide polymorphism (SNP) genome-wide association study (GWAS) results for EF resilience. Here, we report gene- and pathway-based analyses of the same resilience phenotype, using an optimal SNP-set (Sequence) Kernel Association Test (SKAT) for gene-based analyses (conservative threshold for genome-wide significance = 0.05/18,123=2.8×10−6) and the gene-set enrichment package GSA-SNP for biological pathway analyses (False discovery rate (FDR) < 0.05). Gene-based analyses found a genome-wide significant association between RNASE13 and EF resilience (p=1.33×10−7). Genetic pathways involved with dendritic/neuron spine, presynaptic membrane, postsynaptic density etc. were enriched with association to EF resilience. Although replication of these results is necessary, our findings indicate the potential value of gene- and pathway-based analyses in research on determinants of cognitive resilience

Longitudinal Cognitive Performance of Alzheimer\u27s Disease Neuropathological Subtypes

Introduction: Alzheimer\u27s disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments. Methods: Two hundred ninety-two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed-effects models that included subtype, time, and a subtype-time interaction as predictors and four cognitive domain factor scores (memory, executive function, language, visuospatial) and a global score as outcomes. To assess if memory was relatively preserved in HpSpAD, non-memory factor scores were included as covariates in the mixed-effects model with memory as the outcome. Results: There were 57 (20%) with lpAD, 22 (8%) with HpSpAD and 213 (73%) with tAD. LpAD died significantly later than the participants with tAD (2.4 years, P = .01) and with HpSpAD (3.8 years, P = .03). Compared to tAD, HpSpAD, but not lpAD, performed significantly worse in all cognitive domains at the time of initial impairment and declined significantly faster in memory, language, and globally. HpSpAD did not have relatively preserved memory performance at any time point. Conclusion: The relative frequencies of AD neuropathological subtypes in an epidemiological sample were consistent with a previous report in a convenience sample. People with HpSpAD decline rapidly, but may not have a memory-sparing clinical syndrome. Cohort-specific differences in regional tau burden and comorbid neuropathology may explain the lack of clinicopathological correlation

High Rate of Microbleed Formation Following Primary Intracerebral Hemorrhage

Background We sought to investigate the frequency of microbleed development following intracerebral hemorrhage in a predominantly African-American population and to identify predictors of new microbleed formation. Aims and/or hypothesis To investigate the frequency and predictors of new microbleeds following intracerebral hemorrhage. Methods The DECIPHER study was a prospective, longitudinal, magnetic resonance-based cohort study designed to evaluate racial/ethnic differences in risk factors for microbleeds and to evaluate the prognostic impact of microbleeds in this intracerebral hemorrhage population. We evaluated new microbleed formation in two time periods: from baseline to 30 days and from 30 days to year 1. Results Of 200 subjects enrolled in DECIPHER, 84 had magnetic resonance imaging at all required time points to meet criteria for this analysis. In the baseline to day 30 analysis, 11 (13·1%) had new microbleeds, compared with 25 (29·8%) in the day 30 to year 1 analysis. Logistic regression analysis demonstrated that baseline number of microbleeds [odds ratio 1·05 (95% confidence interval 1·01, 1·08), P = 0·01] was associated with new microbleed formation at 30 days. A logistic regression model predicting new microbleed at one-year included baseline number of microbleeds [odds ratio 1·05 (1·00, 1·11), P = 0·046], baseline age [odds ratio 1·05 (1·00, 1·10), P = 0·04], and white matter disease score [odds ratio 1·18 (0·96, 1·45). P = 0·115]. Overall, 28 of 84 (33·3%) intracerebral hemorrhage subjects formed new microbleeds at some point in the first year post-intracerebral hemorrhage. Conclusions We found that one-third of intracerebral hemorrhage subjects in this cohort surviving one-year developed new microbleeds, which suggests a dynamic and rapidly progressive vasculopathy. Future studies are needed to examine the impact of new microbleed formation on patient outcomes

Incidence of cognitively defined late-onset Alzheimer's dementia subgroups from a prospective cohort study

INTRODUCTION: There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. METHODS: We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. RESULTS: During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants. DISCUSSION: A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia