Abstract
In this article we address a number of important issues that arise in the analysis of nonindependent data. Such data are common in studies in which predictors vary within "units" (e.g., ...within-subjects, within-classrooms). Most researchers analyze categorical within-unit predictors with repeated-measures ANOVAs, but continuous within-unit predictors with linear mixed-effects models (LMEMs). We show that both types of predictor variables can be analyzed within the LMEM framework. We discuss designs with multiple sources of nonindependence, for example, studies in which the same subjects rate the same set of items or in which students nested in classrooms provide multiple answers. We provide clear guidelines about the types of random effects that should be included in the analysis of such designs. We also present a number of corrective steps that researchers can take when convergence fails in LMEM models with too many parameters. We end with a brief discussion on the trade-off between power and generalizability in designs with "within-unit" predictors.
Translational Abstract
Researchers and practitioners sometimes want to analyze data that are "nonindependent." Data are said to be nonindependent when the study is designed such that certain data points can be expected to be on average more similar to each other than other data points. This is usually the case when each subject provides multiple data points (so-called within-subject designs), when subjects belonging to higher-order units influence each other (e.g., students clustered in classrooms, employees clustered in teams), or when subjects react to or evaluate the same set of items (e.g., pictures, words, sentences, products, art works, target individuals). In the present article, we propose that all types of nonindependent data can be analyzed with the same statistical technique called "linear mixed-effects models." Compared to standard statistical tests belonging to the family of "General Linear Models" (e.g., ANOVA, regression), linear mixed-effects models have a "complex error term," i.e., the data analyst has to explicitly include all possible reasons for why the predictions of the statistical model may be wrong (these possible reasons are called "random effects"). It is not always obvious how to identify all possible sources of error. In this article, we provide clear guidelines on the type of random effects that researchers and practitioners should include when estimating linear mixed-effects models. Failure to include the appropriate random effects leads to an unacceptable false positive rate (or "type I error rate"), i.e., a high proportion of statistically significant results for effects that do not exist in reality.
Melanomas on mucosal membranes, acral skin (soles, palms, and nail bed), and skin with chronic sun-induced damage have infrequent mutations in BRAF and NRAS, genes within the mitogen-activated ...protein (MAP) kinase pathway commonly mutated in melanomas on intermittently sun-exposed skin. This raises the question of whether other aberrations are occurring in the MAP kinase cascade in the melanoma types with infrequent mutations of BRAF and NRAS.
We analyzed array comparative genomic hybridization data from 102 primary melanomas (38 from mucosa, 28 from acral skin, and 18 from skin with and 18 from skin without chronic sun-induced damage) for DNA copy number aberrations specific to melanoma subtypes where mutations in BRAF and NRAS are infrequent. A narrow amplification on 4q12 was found, and candidate genes within it were analyzed.
Oncogenic mutations in KIT were found in three of seven tumors with amplifications. Examination of all 102 primary melanomas found mutations and/or copy number increases of KIT in 39% of mucosal, 36% of acral, and 28% of melanomas on chronically sun-damaged skin, but not in any (0%) melanomas on skin without chronic sun damage. Seventy-nine percent of tumors with mutations and 53% of tumors with multiple copies of KIT demonstrated increased KIT protein levels.
KIT is an important oncogene in melanoma. Because the majority of the KIT mutations we found in melanoma also occur in imatinib-responsive cancers of other types, imatinib may offer an immediate therapeutic benefit for a significant proportion of the global melanoma burden.
Advances in cognitive and affective neuroscience come largely from within-subjects comparisons, in which the functional significance of neural activity is determined by contrasting two or more ...experimental conditions. Clinical and social neuroscience studies have attempted to leverage between-subject variability in such condition differences to better understand psychopathology and other individual differences. Shifting from within-to between-subjects comparisons requires that measures have adequate internal consistency to function as individual difference variables. This is particularly relevant for difference scores—which have lower reliability. The field has assumed reasonable internal consistency of neural measures based on consistent findings across studies (i.e., if a within-subject difference in neural activity is robust, then it must be reliable). Using one of the most common fMRI paradigms in the clinical neuroscience literature (i.e., a face- and shape-matching task), in a large sample of adolescents (N = 139) we replicate a robust finding: amygdala activation is greater for faces than shapes. Moreover, we demonstrate that the internal consistency of the amygdala in face and shape blocks was excellent (Spearman-Brown corrected reliability SB > .94). However, the internal consistency of the activation difference between faces and shapes was nearly zero (SB = −.06). This reflected the fact that the amygdala response to faces and shapes was highly correlated (r = .97) across individuals. Increased neural activation to faces versus shapes could not possibly function as an individual difference measure in these data—illustrating how neural activation can be robust within subjects, but unreliable as an individual difference measure. Strong and reproducible condition differences in neural activity are not necessarily well-suited for individual differences research—and neuroimaging studies should always report the internal consistency of, and correlations between, activations used in individual differences research.
•Robust within-subject differences are often used as individual difference measures.•A robust within-subject difference may not be internally consistent.•Difference scores are problematic when constituent measures are highly correlated.•Subtraction-based measures should report the correlation between the two variables.•Internal consistencies should be reported for difference and constituent scores
The relationship between eczema, wheeze or asthma, and rhinitis is complex, and epidemiology and mechanisms of their comorbidities is unclear.
To investigate within-individual patterns of morbidity ...of eczema, wheeze, and rhinitis from birth to adolescence/early adulthood.
We investigated onset, progression, and resolution of eczema, wheeze, and rhinitis using descriptive statistics, sequence mining, and latent Markov modeling in four population-based birth cohorts. We used logistic regression to ascertain if early-life eczema or wheeze, or genetic factors (
mutations and 17q21 variants), increase the risk of multimorbidity.
Single conditions, although the most prevalent, were observed significantly less frequently than by chance. There was considerable variation in the timing of onset/remission/persistence/intermittence. Multimorbidity of eczema+wheeze+rhinitis was rare but significantly overrepresented (three to six times more often than by chance). Although infantile eczema was associated with subsequent multimorbidity, most children with eczema (75.4%) did not progress to any multimorbidity pattern.
mutations and rs7216389 were not associated with persistence of eczema/wheeze as single conditions, but both increased the risk of multimorbidity (
by 2- to 3-fold, rs7216389 risk variant by 1.4- to 1.7-fold). Latent Markov modeling revealed five latent states (no disease/low risk, mainly eczema, mainly wheeze, mainly rhinitis, multimorbidity). The most likely transition to multimorbidity was from eczema state (0.21). However, although this was one of the highest transition probabilities, only one-fifth of those with eczema transitioned to multimorbidity.
Atopic diseases fit a multimorbidity framework, with no evidence for sequential atopic march progression. The highest transition to multimorbidity was from eczema, but most children with eczema (more than three-quarters) had no comorbidities.
There is currently inconclusive evidence regarding the relationship between recidivism and mental illness. This retrospective study aimed to use rigorous machine learning methods to understand the ...unique predictive utility of mental illness for recidivism in a general population (i.e.; not only those with mental illness) prison sample in the United States.
Participants were adult men (n = 322) and women (n = 72) who were recruited from three prisons in the Midwest region of the United States. Three model comparisons using Bayesian correlated t-tests were conducted to understand the incremental predictive utility of mental illness, substance use, and crime and demographic variables for recidivism prediction. Three classification statistical algorithms were considered while evaluating model configurations for the t-tests: elastic net logistic regression (GLMnet), k-nearest neighbors (KNN), and random forests (RF).
Rates of substance use disorders were particularly high in our sample (86.29%). Mental illness variables and substance use variables did not add predictive utility for recidivism prediction over and above crime and demographic variables. Exploratory analyses comparing the crime and demographic, substance use, and mental illness feature sets to null models found that only the crime and demographics model had an increased likelihood of improving recidivism prediction accuracy.
Despite not finding a direct relationship between mental illness and recidivism, treatment of mental illness in incarcerated populations is still essential due to the high rates of mental illnesses, the legal imperative, the possibility of decreasing institutional disciplinary burden, the opportunity to increase the effectiveness of rehabilitation programs in prison, and the potential to improve meaningful outcomes beyond recidivism following release.
Background Psychopathic behavior is generally attributed to a fundamental, amygdala-mediated deficit in fearlessness that undermines social conformity. An alternative view is that psychopathy ...involves an attention-related deficit that undermines the processing of peripheral information, including fear stimuli. Methods We evaluated these alternative hypotheses by measuring fear-potentiated startle (FPS) in a group of 125 prisoners under experimental conditions that 1) focused attention directly on fear-relevant information or 2) established an alternative attentional focus. Psychopathy was assessed using Hare's Psychopathy Checklist-Revised (PCL-R). Results Psychopathic individuals displayed normal FPS under threat-focused conditions but manifested a significant deficit in FPS under alternative-focus conditions. Moreover, these findings were essentially unchanged when analyses employed the interpersonal/affective factor of the PCL-R instead of PCL-R total scores. Conclusions The results provide unprecedented evidence that higher-order cognitive processes moderate the fear deficits of psychopathic individuals. These findings suggest that psychopaths' diminished reactivity to fear stimuli, and emotion-related cues more generally, reflect idiosyncrasies in attention that limit their processing of peripheral information. Although psychopathic individuals are commonly described as cold-blooded predators who are unmotivated to change, the attentional dysfunction identified in this study supports an alternative interpretation of their chronic disinhibition and insensitive interpersonal style.
Maximal lung function in early adulthood is an important determinant of mortality and COPD. We investigated whether distinct trajectories of lung function are present during childhood and whether ...these extend to adulthood and infancy.
To ascertain trajectories of FEV
, we studied two population-based birth cohorts (MAAS and ALSPAC) with repeat spirometry from childhood into early adulthood (1046 participants from 5-16 years and 1390 participants from 8-24 years). We used a third cohort (PIAF) with repeat lung function measures in infancy (V'
) and childhood (FEV
; 196 participants from 1 month to 18 years of age) to investigate whether these childhood trajectories extend from early life. We identified trajectories using latent profile modelling. We created an allele score to investigate genetic associations of trajectories, and constructed a multivariable model to identify their early-life predictors.
We identified four childhood FEV
trajectories: persistently high, normal, below average, and persistently low. The persistently low trajectory (129 5% of 2436 participants) was associated with persistent wheezing and asthma throughout follow-up. In genetic analysis, compared with the normal trajectory, the pooled relative risk ratio per allele was 0·96 (95% CI 0·92-1·01; p=0·13) for persistently high, 1·01 (0·99-1·02; p=0·49) for below average, and 1·05 (0·98-1·13; p=0·13) for persistently low. Most children in the low V'
trajectory in infancy did not progress to the low FEV
trajectory in childhood. Early-life factors associated with the persistently low trajectory included recurrent wheeze with severe wheezing exacerbations, early allergic sensitisation, and tobacco smoke exposure.
Reduction of childhood smoke exposure and minimisation of the risk of early-life sensitisation and wheezing exacerbations might reduce the risk of diminished lung function in early adulthood.
None.
Leishmaniasis, a chronic and persistent intracellular protozoal infection caused by many different species within the genus
, is an unfamiliar disease to most North American providers. Clinical ...presentations may include asymptomatic and symptomatic visceral leishmaniasis (so-called Kala-azar), as well as cutaneous or mucosal disease. Although cutaneous leishmaniasis (caused by
in the United States) is endemic in some southwest states, other causes for concern include reactivation of imported visceral leishmaniasis remotely in time from the initial infection, and the possible long-term complications of chronic inflammation from asymptomatic infection. Climate change, the identification of competent vectors and reservoirs, a highly mobile populace, significant population groups with proven exposure history, HIV, and widespread use of immunosuppressive medications and organ transplant all create the potential for increased frequency of leishmaniasis in the U.S. Together, these factors could contribute to leishmaniasis emerging as a health threat in the U.S., including the possibility of sustained autochthonous spread of newly introduced visceral disease. We summarize recent data examining the epidemiology and major risk factors for acquisition of cutaneous and visceral leishmaniasis, with a special focus on implications for the United States, as well as discuss key emerging issues affecting the management of visceral leishmaniasis.
Gonorrhea is the second most common bacterial sexually transmitted infection in the United States. Rates are increasing, and multiple challenges compound management, including worsening antimicrobial ...resistance. New therapeutics, enhanced screening and partner notification, and treatment through point-of-care testing and expedited partner therapy, as well as primary prevention efforts provide opportunities for success in combating these trends.
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