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1.
Psychol Res ; 88(1): 39-80, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37314574

ABSTRACT

The ability to sustain attention consistency is frequently assessed using either objective behavioral measures, such as reaction time (RT) variability, or subjective self-report measures, such as rates of task-unrelated thought (TUT). The current studies examined whether the individual-difference covariation in these measures provides a more construct valid assessment of attention consistency than does either alone. We argue that performance and self-report measures mutually validate each other; each measurement approach has its own sources of error, so their shared variance should best reflect the attention consistency construct. We reanalyzed two latent-variable studies where RT variability and TUTs were measured in multiple tasks (Kane et al. in J Exp Psychol Gen 145:1017-1048, 2016; Unsworth et al. in J Exp Psychol Gen 150:1303-1331, 2021), along with several nomological network constructs to test the convergent and discriminant validity of a general attention consistency factor. Confirmatory factor analyses assessing bifactor (preregistered) and hierarchical (non-preregistered) models suggested that attention consistency can be modeled as the shared variance among objective and subjective measures. This attention consistency factor was related to working memory capacity, attention (interference) control, processing speed, state motivation and alertness, and self-reported cognitive failures and positive schizotypy. Although bifactor models of general attention consistency provide the most compelling construct validity evidence for a specific ability to sustain attention, multiverse analyses of outlier decisions suggested they are less robust than hierarchical models. The results provide evidence for the general ability to sustain attention consistency and suggestions for improving its measurement.


Subject(s)
Attention , Thinking , Humans , Self Report , Reaction Time , Memory, Short-Term
2.
Atten Percept Psychophys ; 86(1): 109-145, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38012476

ABSTRACT

The ability to sustain attention is often measured with either objective performance indicators, like within-person RT variability, or subjective self-reports, like mind wandering propensity. A more construct valid approach, however, may be to assess the covariation in these performance and self-report measures, given that each of these is influenced by different sources of measurement error. If the correlation between performance-variability and self-report measures reflects the sustained attention construct, then task manipulations aimed at reducing the sustained attention demands of tasks should reduce the correlation between them (in addition to reducing mean levels of variability and mind wandering). The current study investigated this claim with a combined experimental-correlation approach. In two experiments (Ns ~ 1,500 each), participants completed tasks that either maximized or minimized the demand for sustained attention. Our demand manipulations successfully reduced the mean levels of sustained attention failures in both the objective and subjective measures, in both experiments. In neither experiment, however, did the covariation between these measures change as a function of the sustained attention demands of the tasks. We can therefore claim only minimal support for the construct validity of our measurement approach to sustained attention.


Subject(s)
Attention , Humans , Self Report
3.
BMC Bioinformatics ; 24(1): 482, 2023 Dec 17.
Article in English | MEDLINE | ID: mdl-38105180

ABSTRACT

This paper presents novel datasets providing numerical representations of ICD-10-CM codes by generating description embeddings using a large language model followed by a dimension reduction via autoencoder. The embeddings serve as informative input features for machine learning models by capturing relationships among categories and preserving inherent context information. The model generating the data was validated in two ways. First, the dimension reduction was validated using an autoencoder, and secondly, a supervised model was created to estimate the ICD-10-CM hierarchical categories. Results show that the dimension of the data can be reduced to as few as 10 dimensions while maintaining the ability to reproduce the original embeddings, with the fidelity decreasing as the reduced-dimension representation decreases. Multiple compression levels are provided, allowing users to choose as per their requirements, download and use without any other setup. The readily available datasets of ICD-10-CM codes are anticipated to be highly valuable for researchers in biomedical informatics, enabling more advanced analyses in the field. This approach has the potential to significantly improve the utility of ICD-10-CM codes in the biomedical domain.


Subject(s)
Electronic Health Records , International Classification of Diseases , Language , Machine Learning , Natural Language Processing
4.
medRxiv ; 2023 May 15.
Article in English | MEDLINE | ID: mdl-37162903

ABSTRACT

This paper presents novel datasets providing numerical representations of ICD-10-CM codes by generating description embeddings using a large language model followed by a dimension reduction via autoencoder. The embeddings serve as informative input features for machine learning models by capturing relationships among categories and preserving inherent context information. The model generating the data was validated in two ways. First, the dimension reduction was validated using an autoencoder, and secondly, a supervised model was created to estimate the ICD-10-CM hierarchical categories. Results show that the dimension of the data can be reduced to as few as 10 dimensions while maintaining the ability to reproduce the original embeddings, with the fidelity decreasing as the reduced-dimension representation decreases. Multiple compression levels are provided, allowing users to choose as per their requirements. The readily available datasets of ICD-10-CM codes are anticipated to be highly valuable for researchers in biomedical informatics, enabling more advanced analyses in the field. This approach has the potential to significantly improve the utility of ICD-10-CM codes in the biomedical domain.

5.
Behav Res Methods ; 55(1): 327-347, 2023 01.
Article in English | MEDLINE | ID: mdl-35381956

ABSTRACT

Mind-wandering assessment relies heavily on the thought probe technique as a reliable and valid method to assess momentary task-unrelated thought (TUT), but there is little guidance available to help researchers decide how many probes to include within a task. Too few probes may lead to unreliable measurement, but too many probes might artificially disrupt normal thought flow and produce reactive effects. Is there a "Goldilocks zone" for how few thought probes can be used to reliably and validly assess individual differences in mind-wandering propensity? We address this question by reanalyzing two published datasets (Study 1, n = 541; Study 2, ns ≈ 260 per condition) in which thought probes were presented in multiple tasks. Our primary analyses randomly sampled probes in increments of two for each subject in each task. A series of confirmatory factor analyses for each probe "bin" size tested whether the latent correlations between TUT rate and theoretically relevant constructs like working memory capacity, attention-control ability, disorganized schizotypy, and retrospective self-reported mind wandering changed as more probes assessed the TUT rate. TUT rates were remarkably similar across increasing probe-bin sizes and zero-order correlations within and between tasks stabilized at 8-10 probes; moreover, TUT-rate correlations with other latent variables stabilized at about 8 thought probes. Our provisional recommendation (with caveats) is that researchers may use as few as 8 thought probes in prototypical cognitive tasks to gain reliable and valid information about individual differences in TUT rate.


Subject(s)
Secondary Data Analysis , Thinking , Humans , Retrospective Studies , Attention , Memory, Short-Term
6.
Article in English | MEDLINE | ID: mdl-36078698

ABSTRACT

The Matsigenka people living traditional lifestyles in remote areas of the Amazon rely on a fish-based diet that exposes them to methylmercury (MeHg) at levels that have been associated with decreased IQ scores. In this study, the association between Hg levels and working memory was explored using the framework of the Multicomponent Model. Working memory tasks were modified to fit the culture and language of the Matsigenka when needed and included measures for verbal storage (Word Span) visuospatial storage (Corsi Block Task) and a measure of executive functions, the Self-Ordered Pointing Task (SOPT). An innovation of the Trail Making Tests A & B (TMT A & B) was pilot tested as another potential measure of executive functions. The mean hair Hg levels of 30 participants, ages 12 to 55 years, from three different communities (Maizal, Cacaotal and Yomibato) was 7.0 ppm (sd = 2.40), well above the World Health Organization (WHO) limit for hair of 2.0 ppm and ranged from 1.8 to 14.2 ppm, with 98% of a broader sample of 152 individuals exceeding the WHO limit. Hair Hg levels showed significant associations with cognitive performance, but the degree varied in magnitude according to the type of task. Hg levels were negatively associated with executive functioning performance (SOPT errors), while Hg levels and years of education predicted visuospatial performance (Corsi Block accuracy). Education was the only predictor of Word Span accuracy. The results show that Hg exposure is negatively associated with working memory performance when there is an increased reliance on executive functioning. Based on our findings and the review of the experimental research, we suggest that the SOPT and the Corsi Block have the potential to be alternatives to general intelligence tests when studying remote groups with extensive cultural differences.


Subject(s)
Memory, Short-Term , Mercury , Animals , Executive Function , Humans , Indigenous Peoples , Mercury/analysis , Neuropsychological Tests , Peru
7.
Cogn Res Princ Implic ; 7(1): 26, 2022 03 26.
Article in English | MEDLINE | ID: mdl-35348931

ABSTRACT

Considerable research has examined the prevalence and apparent consequences of task-unrelated thoughts (TUTs) in both laboratory and authentic educational settings. Few studies, however, have explored methods to reduce TUTs during learning; those few studies tested small samples or used unvalidated TUT assessments. The present experimental study attempted to conceptually replicate or extend previous findings of interpolated testing and pretesting effects on TUT and learning. In a study of 195 U.S. undergraduates, we investigated whether interpolated testing (compared to interpolated restudy) and pretesting on lecture-relevant materials (compared to pretesting on conceptually related but lecture-irrelevant materials) would reduce TUTs during a video lecture on introductory statistics. Subjects completed either a content-matched or content-mismatched pretest on statistics concepts and then watched a narrated lecture slideshow. During the lecture, half of the sample completed interpolated tests on the lecture material and half completed interpolated restudy of that material. All subjects responded to unpredictably presented thought probes during the video to assess their immediately preceding thoughts, including TUTs. Following the lecture, students reported on their situational interest elicited by the lecture and then completed a posttest. Interpolated testing significantly reduced TUT rates during the lecture compared to restudying, conceptually replicating previous findings-but with a small effect size and no supporting Bayes-factor evidence. We found statistical evidence for neither an interpolated testing effect on learning, nor an effect of matched-content pretesting on TUT rates or learning. Interpolated testing might have limited utility to support students' attention, but varying effect sizes across studies warrants further work.


Subject(s)
Attention , Learning , Bayes Theorem , Humans , Microsurgery , Students
8.
Clin Trials ; 19(3): 297-306, 2022 06.
Article in English | MEDLINE | ID: mdl-35128970

ABSTRACT

BACKGROUND: Recent advances in developing "tumor agnostic" oncology therapies have identified molecular targets that define patient subpopulations in a manner that supersedes conventional criteria for cancer classification. These successes have produced effective targeted therapies that are administered to patients regardless of their tumor histology. Trials have evolved as well with master protocol designs. By blending translational and clinical science, basket trials in particular are well-suited to investigate and develop targeted therapies among multiple cancer histologies. However, basket trials intrinsically involve more complex design decisions, including issues of multiple testing across baskets, and guidance for investigators is needed. METHODS: The sensitivity of the multisource exchangeability model to prior specification under differing degrees of response heterogeneity is explored through simulation. Then, a multisource exchangeability model design that incorporates control of the false-discovery rate is presented and a simulation study compares the operating characteristics to a design where the family-wise error rate is controlled and to the frequentist approach of treating the baskets as independent. Simulations are based on the original design of a real-world clinical trial, the SUMMIT trial, which investigated Neratinib treatment for a variety of solid tumors. The methods studied here are specific to single-arm phase II trials with binary outcomes. RESULTS: Values of prior probability of exchangeability in the multisource exchangeability model between 0.1 and 0.3 provide the best trade-offs between gain in precision and bias, especially when per-basket sample size is below 30. Application of these calibration results to a re-analysis of the SUMMIT trial showed that the breast basket exceeded the null response rate with posterior probability of 0.999 while having low posterior probability of exchangeability with all other baskets. Simulations based on the design of the SUMMIT trial revealed that there is meaningful improvement in power even in baskets with small sample size when the false-discovery rate is controlled as opposed to the family-wise error rate. For example, when only the breast basket was active, with a sample size of 25, the power was 0.76 when the false-discovery rate was controlled at 0.05 but only 0.56 when the family-wise error rate was controlled at 0.05, indicating that impractical sample sizes for the phase II setting would be needed to achieve acceptable power while controlling the family-wise error rate in this setting of a trial with 10 baskets. CONCLUSION: Selection of the prior exchangeability probability based on calibration and incorporation of false-discovery rate control result in multisource exchangeability model designs with high power to detect promising treatments in the context of phase II basket trials.


Subject(s)
Clinical Trials as Topic , Research Design , Bayes Theorem , Clinical Trials as Topic/methods , Humans , Neoplasms/drug therapy , Sample Size
10.
J Exp Psychol Learn Mem Cogn ; 47(9): 1383-1402, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34197169

ABSTRACT

We used a technique known as reach tracking to investigate how individual differences in working memory capacity (WMC) relate to the functioning of two processes proposed to underlie cognitive control: a threshold adjustment process that temporarily inhibits motor output in response to signals of conflict and a controlled selection process that recruits top-down control to guide stimulus-response translation. Undergraduates (N = 135) performed two WMC tasks (updating counters and symmetry span) and a reach-tracking version of the Eriksen flanker task. Consistent with previous research using button-press flanker tasks, WMC significantly correlated with response time (RT) performance, with higher WMC scores corresponding to smaller congruency effects. Given that RTs reflect the combined functioning of multiple processes underlying cognitive control, we interpreted this effect to reflect a general link between WMC and both the threshold adjustment process and controlled selection process. We also found a significant association between WMC and participants' reach trajectories, with higher WMC scores corresponding to more direct reach movements on incongruent trials involving stimulus-response overlap with the preceding trial. We interpreted this effect to reflect a more specific link between WMC and the functioning of the controlled selection process. We discuss the observed links between WMC and cognitive control in relation to the unity and diversity of executive functions framework and in relation to the role of prefrontal and striatal dopamine in supporting adaptive cognitive control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Individuality , Memory, Short-Term , Cognition , Executive Function , Humans , Reaction Time
11.
Mem Cognit ; 49(6): 1247-1266, 2021 08.
Article in English | MEDLINE | ID: mdl-33890247

ABSTRACT

This study investigated what academic traits, attitudes, and habits predict individual differences in task-unrelated thought (TUT) during lectures, and whether this TUT propensity mediates associations between academic individual differences and course outcomes (final grade and situational interest evoked by material). Undergraduates (N = 851) from ten psychology classes at two US universities responded to thought probes presented during two early-course lectures; they also indicated sitting in the front, middle, or back of the classroom. At each probe, students categorized their thought content, such as indicating on-task thought or TUT. Students also completed online, academic-self-report questionnaires at the beginning of the course and a situational interest questionnaire at the end. Average TUT rate was 24% but individuals' rates varied widely (SD = 18%). TUT rates also increased substantially from the front to back of the classroom, and modestly from the first to second half of class periods. Multiple-group analyses (with ten classroom groups) indicated that: (a) classroom media-multitasking habits, initial interest in the course topic, and everyday propensity for mind-wandering and boredom accounted for unique variance in TUT rate (beyond other predictors); (b) TUT rate accounted for unique (modest) variance in course grades and situational interest; and (c) classroom media multitasking and propensity for mind-wandering and boredom had indirect associations with course grades via TUT rate, and these predictor variables, along with initial interest, had indirect associations with end-of-term situational interest via TUT rate. Some academic traits and behaviors predict course outcomes in part because they predict off-task thought during class.


Subject(s)
Individuality , Universities , Attention , Cognition , Humans , Thinking
12.
Behav Res Methods ; 53(6): 2372-2411, 2021 12.
Article in English | MEDLINE | ID: mdl-33835393

ABSTRACT

Psychology faces a measurement crisis, and mind-wandering research is not immune. The present study explored the construct validity of probed mind-wandering reports (i.e., reports of task-unrelated thought [TUT]) with a combined experimental and individual-differences approach. We examined laboratory data from over 1000 undergraduates at two U.S. institutions, who responded to one of four different thought-probe types across two cognitive tasks. We asked a fundamental measurement question: Do different probe types yield different results, either in terms of average reports (average TUT rates, TUT-report confidence ratings), or in terms of TUT-report associations, such as TUT rate or confidence stability across tasks, or between TUT reports and other consciousness-related constructs (retrospective mind-wandering ratings, executive-control performance, and broad questionnaire trait assessments of distractibility-restlessness and positive-constructive daydreaming)? Our primary analyses compared probes that asked subjects to report on different dimensions of experience: TUT-content probes asked about what they'd been mind-wandering about, TUT-intentionality probes asked about why they were mind-wandering, and TUT-depth probes asked about the extent (on a rating scale) of their mind-wandering. Our secondary analyses compared thought-content probes that did versus didn't offer an option to report performance-evaluative thoughts. Our findings provide some "good news"-that some mind-wandering findings are robust across probing methods-and some "bad news"-that some findings are not robust across methods and that some commonly used probing methods may not tell us what we think they do. Our results lead us to provisionally recommend content-report probes rather than intentionality- or depth-report probes for most mind-wandering research.


Subject(s)
Attention , Executive Function , Consciousness , Humans , Individuality , Retrospective Studies
13.
Emotion ; 21(2): 297-314, 2021 Mar.
Article in English | MEDLINE | ID: mdl-30883149

ABSTRACT

[Correction Notice: An Erratum for this article was reported online in Emotion on Jan 7 2021 (see record 2021-06077-001). In the article, in the Results and Discussion sections for Study 2 and in Table 6, it was stated that RSPAN scores predicted spontaneous down-regulation of negative affect from one diary signal to the next. However, because RSPAN scores are a person-level variable, it is an error to describe the results in that way. RSPAN scores cannot predict variability within person (i.e., signal to signal) but rather predict variability between person (i.e., person to person). Hence, a corrected interpretation would be to state that the RSPAN predicted levels of negative affect across the experience sampling diary, even when considering trait and state levels of affect and variability in daily stress. The analysis remains correct and the findings remain meaningful.] We tested the association of 2 versions of the Reading Span Task of working memory capacity, a conventional neutral version (RSPAN-N) and an adapted task with incidental negative content (RSPAN-E), for predicting objective indicators (behavioral displays; autonomic activation) of negative emotion regulation during a laboratory provocation, as well as reported negative emotion in daily life experience sampling. Across 2 samples, both tasks demonstrated utility as estimates of spontaneous negative emotion regulation capacity, predicting down-regulation of negative emotion in daily life and during a lab challenge. In addition, scores from both tasks appear to be independent of self-reported distress, a confound often present in studies of emotion regulation. There was some incremental evidence that the RSPAN-E may have advantages over the RSPAN-N for predicting some indices of emotion processing. Together these findings provide further evidence for the role of working memory (among other executive-control abilities) in emotion regulatory processing and suggest that RSPAN tasks may have considerable potential as tools in research on emotion processing and emotion regulation in psychological health and adjustment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Emotional Regulation/physiology , Memory, Short-Term/physiology , Adult , Female , Humans , Male , Young Adult
14.
J Exp Psychol Gen ; 150(4): 609-632, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33119355

ABSTRACT

Are intelligence and creativity distinct abilities, or do they rely on the same cognitive and neural systems? We sought to quantify the extent to which intelligence and creative cognition overlap in brain and behavior by combining machine learning of fMRI data and latent variable modeling of cognitive ability data in a sample of young adults (N = 186) who completed a battery of intelligence and creative thinking tasks. The study had 3 analytic goals: (a) to assess contributions of specific facets of intelligence (e.g., fluid and crystallized intelligence) and general intelligence to creative ability (i.e., divergent thinking originality), (b) to model whole-brain functional connectivity networks that predict intelligence facets and creative ability, and (c) to quantify the degree to which these predictive networks overlap in the brain. Using structural equation modeling, we found moderate to large correlations between intelligence facets and creative ability, as well as a large correlation between general intelligence and creative ability (r = .63). Using connectome-based predictive modeling, we found that functional brain networks that predict intelligence facets overlap to varying degrees with a network that predicts creative ability, particularly within the prefrontal cortex of the executive control network. Notably, a network that predicted general intelligence shared 46% of its functional connections with a network that predicted creative ability-including connections linking executive control and salience/ventral attention networks-suggesting that intelligence and creative thinking rely on similar neural and cognitive systems. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Cognition , Connectome , Creativity , Functional Neuroimaging , Intelligence , Magnetic Resonance Imaging , Adult , Brain/diagnostic imaging , Executive Function , Female , Humans , Latent Class Analysis , Machine Learning , Male , Prefrontal Cortex/diagnostic imaging , Young Adult
15.
J Intell ; 8(2)2020 Jun 02.
Article in English | MEDLINE | ID: mdl-32498311

ABSTRACT

The worst performance rule (WPR) is a robust empirical finding reflecting that people's worst task performance shows numerically stronger correlations with cognitive ability than their average or best performance. However, recent meta-analytic work has proposed this be renamed the "not-best performance" rule because mean and worst performance seem to predict cognitive ability to similar degrees, with both predicting ability better than best performance. We re-analyzed data from a previously published latent-variable study to test for worst vs. not-best performance across a variety of reaction time tasks in relation to two cognitive ability constructs: working memory capacity (WMC) and propensity for task-unrelated thought (TUT). Using two methods of assessing worst performance-ranked-binning and ex-Gaussian-modeling approaches-we found evidence for both the worst and not-best performance rules. WMC followed the not-best performance rule (correlating equivalently with mean and longest response times (RTs)) but TUT propensity followed the worst performance rule (correlating more strongly with longest RTs). Additionally, we created a mini-multiverse following different outlier exclusion rules to test the robustness of our findings; our findings remained stable across the different multiverse iterations. We provisionally conclude that the worst performance rule may only arise in relation to cognitive abilities closely linked to (failures of) sustained attention.

16.
J Exp Psychol Gen ; 149(3): 580-584, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31318255

ABSTRACT

Intimates often discuss the causes of, and solutions to, their relationship problems with their partners, and this information can shape partners' behavior and thus facilitate problem resolution. Partners' ability to encode and later recall such discussions should lead to greater declines in the severity of those problems. This brief report presents the results from a broader longitudinal study in which newlywed couples completed tasks assessing their working memory capacity (WMC), engaged in problem-solving discussions, recalled those discussions after a short delay, and then reported the severity of the problems discussed over the course of a year. Greater WMC among partners was associated with greater declines in the severity of a relationship problem, mediated by partners' recall of the discussion of that problem, suggesting that WMC facilitated the long-term memory encoding of the problem discussion. This study is among the first to suggest that individual differences in basic cognitive abilities may affect conversation processing and recall, and thereby close relationships. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Subject(s)
Interpersonal Relations , Memory, Short-Term/physiology , Mental Recall/physiology , Problem Solving/physiology , Sexual Partners/psychology , Adult , Communication , Female , Humans , Longitudinal Studies , Male , Young Adult
17.
Mem Cognit ; 47(4): 619-642, 2019 05.
Article in English | MEDLINE | ID: mdl-30725377

ABSTRACT

We examined the effects of interpolated retrieval from long-term memory (LTM) and short-term memory (STM) on list isolation in dual-list free recall and whether individual differences in working memory capacity (WMC) moderated those effects. Ninety-seven subjects completed study-test trials that included two study lists separated by either an exemplar generation task (LTM retrieval) or a two-back task (STM retrieval). Subjects then completed an externalized free recall task that allowed for the examination of response accessibility and monitoring. Individual differences in WMC were assessed using three complex span tasks: operation span, reading span, and rotation span. Correct recall and intratrial intrusion summary scores showed no effect of interpolated retrieval on either response accessibility or monitoring. However, serial-position curves for correct recall of List 1 showed larger primacy in the two-back than in the exemplar generation task for high-WMC subjects. We interpreted these results from a context change perspective, as showing that interpolated LTM retrieval accelerated context change for subjects who processed the context more effectively. We consider the implications of these findings for models of memory.


Subject(s)
Attention/physiology , Individuality , Memory, Long-Term/physiology , Memory, Short-Term/physiology , Mental Recall/physiology , Adolescent , Adult , Female , Humans , Male , Young Adult
18.
JCO Precis Oncol ; 3: 1-9, 2019 Dec.
Article in English | MEDLINE | ID: mdl-35100726

ABSTRACT

Progress in the areas of genomics, disease pathways, and drug discovery has advanced into clinical and translational cancer research. The latest innovations in clinical trials have followed with master protocols, which are defined by inclusive eligibility criteria and devised to interrogate multiple therapies for a given tumor histology and/or multiple histologies for a given therapy under one protocol. The use of master protocols for oncology has become more common with the desire to improve the efficiency of clinical research and accelerate overall drug development. Basket trials have been devised to ascertain the extent to which a treatment strategy offers benefit to various patient subpopulations defined by a common molecular target. Conventionally conducted within the phase II setting, basket designs have become popular as drug developers seek to effectively evaluate and identify preliminary efficacy signals among clinical indications identified as promising in preclinical study. This article reviews basket trial designs in oncology settings and discusses several issues that arise with their design and analysis.

20.
J Mol Neurosci ; 66(1): 114-120, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30105628

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disease for which there is currently no effective treatment. The progression of ALS includes loss of motor neurons controlling the voluntary muscles, with much of this loss occurring at the neuromuscular junction. In an effort to better understand changes at the neuromuscular junction, we utilized the wobbler mouse model of motor neuron loss. We examined biceps and end plate morphologies and monitored selected factors involved in end plate function. Structural volumes were determined from 3D reconstructions that were generated for the end plates. Wobbler mice exhibited size reductions of both the muscle fibers and the end plates within the biceps, and we found that the end plate volumes were the most sensitive indicator of the degeneration. Concurrently, we found increases in calcitonin gene-related peptide (CGRP) and its receptor in wobbler biceps and spinal cord. We also found increases in gene expression of two acetylcholine receptors within the wobbler biceps, which may be a result of altered CGRP/CALCRL (calcitonin receptor-like receptor) expression.


Subject(s)
Motor Endplate/pathology , Neurodegenerative Diseases/pathology , Vesicular Transport Proteins/genetics , Animals , Calcitonin Gene-Related Peptide/genetics , Calcitonin Gene-Related Peptide/metabolism , Mice , Motor Endplate/metabolism , Motor Neurons/metabolism , Motor Neurons/pathology , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism , Receptors, Cholinergic/genetics , Receptors, Cholinergic/metabolism
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