Comparison of the Usability and Reliability of Answers to Clinical Questions: AI-Generated ChatGPT versus a Human-Authored Resource.

OBJECTIVES: Our aim was to compare the usability and reliability of answers to clinical questions posed of Chat-Generative Pre-Trained Transformer (ChatGPT) compared to those of a human-authored Web source (www.Pearls4Peers.com) in response to "real-world" clinical questions raised during the care of patients. METHODS: Two domains of clinical information quality were studied: usability, based on organization/readability, relevance, and usefulness, and reliability, based on clarity, accuracy, and thoroughness. The top 36 most viewed real-world questions from a human-authored Web site (www.Pearls4Peers.com [P4P]) were posed to ChatGPT 3.5. Anonymized answers by ChatGPT and P4P (without literature citations) were separately assessed for usability by 18 practicing physicians ("clinician users") in triplicate and for reliability by 21 expert providers ("content experts") on a Likert scale ("definitely yes," "generally yes," or "no") in duplicate or triplicate. Participants also directly compared the usability and reliability of paired answers. RESULTS: The usability and reliability of ChatGPT answers varied widely depending on the question posed. ChatGPT answers were not considered useful or accurate in 13.9% and 13.1% of cases, respectively. In within-individual rankings for usability, ChatGPT was inferior to P4P in organization/readability, relevance, and usefulness in 29.6%, 28.3%, and 29.6% of cases, respectively, and for reliability, inferior to P4P in clarity, accuracy, and thoroughness in 38.1%, 34.5%, and 31% of cases, respectively. CONCLUSIONS: The quality of ChatGPT responses to real-world clinical questions varied widely, with nearly one-third or more answers considered inferior to a human-authored source in several aspects of usability and reliability. Caution is advised when using ChatGPT in clinical decision making.

Adaptive penalties for generalized Tikhonov regularization in statistical regression models with application to spectroscopy data.

Tikhonov regularization was proposed for multivariate calibration by Andries and Kalivas [1]. We use this framework for modeling the statistical association between spectroscopy data and a scalar outcome. In both the calibration and regression settings this regularization process has advantages over methods of spectral pre-processing and dimension-reduction approaches such as feature extraction or principal component regression. We propose an extension of this penalized regression framework by adaptively refining the penalty term to optimally focus the regularization process. We illustrate the approach using simulated spectra and compare it with other penalized regression models and with a two-step method that first pre-processes the spectra then fits a dimension-reduced model using the processed data. The methods are also applied to magnetic resonance spectroscopy data to identify brain metabolites that are associated with cognitive function.

Age-related effects on circadian phase in the sleep of patients with depression and insomnia.

We examined whether an age-related phase advance was present in 60 patients with depression and insomnia (mean age 41.5 [12.5] years) using diaries and 5 weekdays of actigraphy. Actigraphy was analyzed with functional data analysis. The low point of activity (bathyphase) for each subject was fitted by cosine function with 24-hr cycle time. Linear regression analysis revealed that increasing age was associated with earlier bedtimes (p < 0.001), shorter sleep latencies (p < 0.05), and earlier bathyphase (p < 0.001). These findings are consistent with prior reports of age-dependent phase-advances in sleep behavior in self-reported good sleepers and reinforce the premise that individualized behavioral therapy of older persons with insomnia may require prescription of earlier bedtimes and earlier rise times than would be employed in younger persons with insomnia. Further, we demonstrate that aging of the sleep system, at least as reflected in actigraphy, occurs as early as the third decade.

Bivariate correlation coefficients in family-type clustered studies.

We propose a unified approach based on a bivariate linear mixed effects model to estimate three types of bivariate correlation coefficients (BCCs), as well as the associated variances between two quantitative variables in cross-sectional data from a family-type clustered design. These BCCs are defined at different levels of experimental units including clusters (e.g., families) and subjects within clusters and assess different aspects on the relationships between two variables. We study likelihood-based inferences for these BCCs, and provide easy implementation using standard software SAS. Unlike several existing BCC estimators in the literature on clustered data, our approach can seamlessly handle two major analytic challenges arising from a family-type clustered design: (1) many families may consist of only one single subject; (2) one of the paired measurements may be missing for some subjects. Hence, our approach maximizes the use of data from all subjects (even those missing one of the two variables to be correlated) from all families, regardless of family size. We also conduct extensive simulations to show that our estimators are superior to existing estimators in handling missing data or/and imbalanced family sizes and the proposed Wald test maintains good size and power for hypothesis testing. Finally, we analyze a real-world Alzheimer's disease dataset from a family clustered study to investigate the BCCs across different modalities of disease markers including cognitive tests, cerebrospinal fluid biomarkers, and neuroimaging biomarkers.

Measuring the impact of apnea and obesity on circadian activity patterns using functional linear modeling of actigraphy data.

BACKGROUND: Actigraphy provides a way to objectively measure activity in human subjects. This paper describes a novel family of statistical methods that can be used to analyze this data in a more comprehensive way. METHODS: A statistical method for testing differences in activity patterns measured by actigraphy across subgroups using functional data analysis is described. For illustration this method is used to statistically assess the impact of apnea-hypopnea index (apnea) and body mass index (BMI) on circadian activity patterns measured using actigraphy in 395 participants from 18 to 80 years old, referred to the Washington University Sleep Medicine Center for general sleep medicine care. Mathematical descriptions of the methods and results from their application to real data are presented. RESULTS: Activity patterns were recorded by an Actical device (Philips Respironics Inc.) every minute for at least seven days. Functional linear modeling was used to detect the association between circadian activity patterns and apnea and BMI. Results indicate that participants in high apnea group have statistically lower activity during the day, and that BMI in our study population does not significantly impact circadian patterns. CONCLUSIONS: Compared with analysis using summary measures (e.g., average activity over 24 hours, total sleep time), Functional Data Analysis (FDA) is a novel statistical framework that more efficiently analyzes information from actigraphy data. FDA has the potential to reposition the focus of actigraphy data from general sleep assessment to rigorous analyses of circadian activity rhythms.

Synthesis, Electronic Structure, and Electrochemical Properties of the Cubic Mg2MnO4 Spinel with Porous-Spongy Structure.

Mg2MnO4 nanoparticles with cubic spinel structure were synthesized by the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. X-ray powder diffraction, infrared spectrum (IR), scanning electron microscope (SEM), and transmission electron microscope (TEM) were used to characterize the crystalline phase and particle size of as-synthesized nanoparticles. The electronic structure of Mg2MnO4 spinel was studied by X-ray photoelectron spectroscopy (XPS). The results showed that pure cubic Mg2MnO4 spinel nanoparticles were obtained when the annealing temperature was 500-700 °C. The samples had a porous-spongy structure assembled by nanoparticles. XPS studies indicated that Mg2MnO4 nanoparticles were mixed spinel structures and the degree of cation inversion decreased with increasing annealing temperature. Furthermore, the performance of Mg2MnO4 as lithium anode material was studied. The results showed that Mg2MnO4 samples had good cycle stability except for the slight decay in the capacity at 50 cycles. The coulombic efficiency (ratio of discharge and charge capacity) in most cycles was near 100%. The sample annealed at 600 °C exhibited good electrochemical properties, the first discharge capacity was 771.5 mAh/g, and the capacity remained 340 mAh/g after 100 cycles. The effect of calcination temperature on the charge-discharge performance of the samples was studied and discussed.

Modeling longitudinal data with nonparametric multiplicative random effects jointly with survival data.

In clinical studies, longitudinal biomarkers are often used to monitor disease progression and failure time. Joint modeling of longitudinal and survival data has certain advantages and has emerged as an effective way to mutually enhance information. Typically, a parametric longitudinal model is assumed to facilitate the likelihood approach. However, the choice of a proper parametric model turns out to be more elusive than models for standard longitudinal studies in which no survival endpoint occurs. In this article, we propose a nonparametric multiplicative random effects model for the longitudinal process, which has many applications and leads to a flexible yet parsimonious nonparametric random effects model. A proportional hazards model is then used to link the biomarkers and event time. We use B-splines to represent the nonparametric longitudinal process, and select the number of knots and degrees based on a version of the Akaike information criterion (AIC). Unknown model parameters are estimated through maximizing the observed joint likelihood, which is iteratively maximized by the Monte Carlo Expectation Maximization (MCEM) algorithm. Due to the simplicity of the model structure, the proposed approach has good numerical stability and compares well with the competing parametric longitudinal approaches. The new approach is illustrated with primary biliary cirrhosis (PBC) data, aiming to capture nonlinear patterns of serum bilirubin time courses and their relationship with survival time of PBC patients.

Amino acid sources in the adult diet do not affect life span and fecundity in the fruit-feeding butterfly Bicyclus anynana.

1. In tropical forests, the adults of many butterfly species feed on fruits rather than nectar from flowers and have long life spans. Rotting fruit and nectar differ from each other in many respects, including sources of amino acids and microbial life. If amino acids in the adult diet can be used for reproduction, this may have facilitated the evolution of extended life spans in this guild.2. This issue was addressed by investigating effects of banana, yeast, and amino acids in the adult diet of the fruit-feeding butterfly Bicyclus anynana (Lepidoptera) on longevity and female reproductive output in two experiments.3. Results showed that in the fruit-feeding butterfly B. anynana: (i) banana juice, but not sliced banana or added amino acids extend life span compared with a sugar solution of similar composition; (ii) compared with this sugar solution, other cohorts (banana juice-amino acid enriched) did not have significantly higher reproductive outputs; (iii) yeast does not represent a valuable source of nutrients; (iv) caloric restriction may cause decreased life span and rate of reproduction; and (v) increased rates of reproduction have a life span cost.

Adult diet affects lifespan and reproduction of the fruit-feeding butterfly Charaxes fulvescens.

Fruit-feeding butterflies are among the longest lived Lepidoptera. While the use of pollen-derived amino acids by Heliconius butterflies has been interpreted as important for the evolution of extended lifespans, very little is known about the life-history consequences of frugivory. This issue is addressed by investigating effects of four adult diets (sugar, sugar with amino acids, banana, and moistened banana) on lifespan and reproduction in the fruit-feeding butterfly Charaxes fulvescens Aurivillius (Lepidoptera: Nymphalidae). Female butterflies were collected from Kibale National Park, Uganda, and kept individually in cages near their natural habitat and data were collected on lifespan, oviposition, and hatching of eggs. Lifespan in captivity was longer for the sugar and the amino acid cohort, than for the banana cohorts. The longitudinal pattern of oviposition was erratic, with many days without oviposition and few periods with high numbers of eggs laid. Butterflies typically did not lay eggs during their 1st week in captivity and the length of the period between capture and first reproduction was significantly shorter for butterflies fed moistened banana. The length of the reproduction period (first reproduction-last reproduction in captivity) and the reproduction rate (total number of eggs/length of the reproduction period) did not differ significantly between the diet treatments. Those fed with amino acid and moistened banana had significantly higher egg hatchability than those fed with sugar and banana. We found no evidence for a lifespan cost of reproduction. Our results show that (1) female C. fulvescens can use amino acids in their diet for laying fertile eggs, (2) more wing-wear does correlate with lower survival in captivity (indicating aging in the wild), but not with intensity of reproduction (providing no evidence for reproductive aging), and (3) fruit-feeding butterflies may be dietary restricted in the field.

Challenging the validity of the EPO index.

BACKGROUND: With use of recombinant erythropoietin (EPO) and intravenous iron, the majority of hemodialysis patients can achieve target hemoglobin concentrations. EPO resistance arises as a consequence of inflammation and other processes that can adversely affect survival. We hypothesized that the EPO dose-hematocrit (EPO/Hct) ratio, also known as the EPO index, may be a surrogate for inflammation and that greater EPO/Hct ratios would be associated with decreased survival. METHODS: We used proportional hazards regression models and time-varying logistic models to analyze the association between EPO index and survival in US hemodialysis patients initiating hemodialysis therapy between January 1, 1999, and December 31, 2000, and followed up for up to 3 years until December 31, 2001. RESULTS: We found an unexpected and consistent association between greater EPO index and survival in all models. The associations of EPO/Hct ratio were most prominent at intermediate Hct values and with longer dialysis vintage. Iron administration was associated with a lower risk for death independent of Hct. Conversely, greater average prior EPO dose was associated with a greater risk for death. CONCLUSION: EPO resistance may be reflected better by total cumulative EPO dose than the EPO/Hct ratio. The mechanism(s) responsible for the association between a greater EPO/Hct ratio and survival remains to be established, but may be a result of nonerythrogenic effects of EPO.

Nutrients in fruit increase fertility in wild-caught females of large and long-lived Euphaedra species (Lepidoptera, Nymphalidae).

Fruit-feeding butterflies can experience a more nutrient rich adult diet than nectar-feeding species, and can be expected to use these nutrients for egg production. Here we compare life span, and reproduction parameters of wild-caught females of large and long-lived species on either a sucrose or a mashed banana diet. With small sample sizes per species, but rich longitudinal data for each individual, we examined the longitudinal reproduction pattern, egg size and hatchability of these butterflies in captivity. Diet significantly affected mortality in captivity in a time-dependent manner. On average, we found that butterflies fed mashed banana laid 1.855 times more eggs than those fed sugar. They laid significantly more eggs when they laid and conserved egg size with age while butterflies fed sucrose showed significantly declining egg sizes. Egg hatchability was not significantly affected by diet. Long pre-oviposition periods, significantly smaller first eggs, and absence of age at capture effects on intensity of reproduction indicate low reproduction rates in the field that are due to low food availability. With our small sample sizes, we did not detect significant differences between the species in their response to the diet treatments.

Does dietary restriction reduce life span in male fruit-feeding butterflies?

Male life history and resource allocation is not frequently studied in aging and life span research. Here, we verify that males of long-lived fruit-feeding butterfly species have reduced longevity on restricted diets [Beck, J., 2007. The importance of amino acids in the adult diet of male tropical rainforest butterflies. Oecologia 151, 741-747], in contrast to the common finding of longevity extension in dietary restriction experiments in Drosophila and some other organisms. Males of some of the most long-lived species of fruit-feeding butterflies were collected from Kibale Forest, Uganda, and kept on diets of either sugar or mashed banana. Seven out of eight species had non-significantly longer life spans on mashed banana diets. Data analysis using a time-varying Cox-model with species as covariate showed that males had reduced survival on the sugar diet during the first 35 days of captive life, but the effect was absent or reversed at more advanced ages. These results challenge the generality of dietary restriction as a way to extend life span in animals. We argue that such studies on males are promising tools for better understanding life history evolution and aging because males display a wider variety of tactics for obtaining reproductive success than females.