A Simulation Based Evaluation of Sample Size Methods for Biomarker Studies

Cancer researchers are often interested in identifying biomarkers that are indicative of poor outcomes (prognostic biomarkers) or response to specific therapies (predictive biomarkers). In designing a biomarker study, the first statistical issue encountered is the sample size requirement for adequate detection of a biomarker effect. In biomarker studies, the desired effect size is typically larger than those targeted in therapeutic trials and the biomarker prevalence is rarely near the optimal 50%. In this article, we review sample size formulas that are routinely used in designing therapeutic trials. We then conduct simulation studies to evaluate the performances of these methods when applied to biomarker studies. In particular, we examine the impact that deviations from certain statistical assumptions (i.e., biomarker positive prevalence and effect size) have on statistical power and type I error. Our simulation results indicate that when the true biomarker prevalence is close to 50%, all methods perform well in terms of power regardless of the magnitude of the targeted biomarker effect. However, when the biomarker positive prevalence rate deviates from 50%, the empirical power based on some existing methods may be substantially different from the nominal power, and this discrepancy becomes more profound for large biomarker effects. The type I error is maintained close to the 5% nominal level in all scenarios we investigate, although there is a slight inflation as the targeted effect size increases. Based on these results, we delineate the range of parameters within which the use of some sample size methods may be sufficiently robust

Changes in Ultra-Processed Food Consumption and Lifestyle Behaviors Following COVID-19 Shelter-in-Place: A Retrospective Study

Ultra-processed food (UPF) consumption poses a potential risk to public health and may be related to shelter-in-place orders. This study utilized the level of food processing as a lens by which to examine the relationships between diet, weight change, and lifestyle changes (including cooking, snacking, and sedentary activity) that occurred during regional shelter-in-place orders. This study used a cross-sectional, retrospective survey (n = 589) to assess baseline demographics, changes in lifestyle behaviors using a Likert scale, and changes in dietary behaviors using a modified food frequency questionnaire from mid-March to May 2020; data were collected in the California Bay Area from August to October 2020. Foods were categorized by level of processing (minimally processed, processed, and ultra-processed) using the NOVA scale. Stepwise multiple linear regression and univariate linear regression models were used to determine the associations between these factors. Increased snacking was positively associated with a change in the percent of the calories derived from UPF and weight gain (β = 1.0, p < 0.001; β = 0.8 kg, p < 0.001) and negatively associated with the share of MPF calories consumed (β = -0.9, p < 0.001). These relationships have public health implications as interventions designed around decreased snacking may positively impact diet and weight management and thereby mitigate negative health outcomes

Switching diets after 6-months does not result in renewed weight loss: a secondary analysis of a 12-month crossover randomized trial

Weight change trajectory from diet and lifestyle interventions typically involves rapid weight loss followed by a weight plateau after approximately 6 months. Changing from one weight-loss diet to another at the time of the plateau could instigate renewed weight loss. Therefore, our secondary analysis aimed to assess trajectory of weight loss in a 12-month, randomized, cross-over study. Forty-two adults were randomized to eat a healthy low-fat or healthy low-carbohydrate diet for 6 months then switched to the opposite diet for an additional 6 months. Regardless of diet assignment, participants experienced rapid initial weight loss, which slowed between 3 to 6 months. After switching diets at 6 months, weight modestly decreased until 9 months, but at a rate slower than the initial 3 months and slower than the rate from 3 to 6 months. This suggests that the weight loss plateau typically seen at 6 months is physiological and cannot be overcome by simply switching to a different weight-loss diet

Exploring Structural Parameters for Pretargeting Radioligand Optimization

Pretargeting offers a way to enhance target specificity while reducing off-target radiation dose to healthy tissue during payload delivery. We recently reported the development of an ¹⁸F-based pretargeting strategy predicated on the inverse electron demand Diels–Alder reaction as well as the use of this approach to visualize pancreatic tumor tissue in vivo as early as 1 h postinjection. Herein, we report a comprehensive structure: pharmacokinetic relationship study of a library of 25 novel radioligands that aims to identify radiotracers with optimal pharmacokinetic and dosimetric properties. This investigation revealed key relationships between molecular structure and in vivo behavior and produced two lead candidates exhibiting rapid tumor targeting with high target-to-background activity concentration ratios at early time points. We believe this knowledge to be of high value for the design and clinical translation of next-generation pretargeting agents for the diagnosis and treatment of disease

Effect of a ketogenic diet versus Mediterranean diet on glycated hemoglobin in individuals with prediabetes and type 2 diabetes mellitus: The interventional Keto-Med randomized crossover trial

BackgroundConsensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options.ObjectivesWe compared 2 low-carbohydrate diets with 3 key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and 3 key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM.MethodsKeto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the 3 key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake.ResultsThe primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, -16% (SEM, 4%) compared with -5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with -5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable.ConclusionsHbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable. This trial was registered at clinicaltrials.gov as NCT03810378

Preliminary study of tumor heterogeneity in imaging predicts two year survival in pancreatic cancer patients - Fig 2

<p>(a) Extracted CT slice after acquisition, (b) magnified view of tumor region with (top) and without (bottom) the manually drawn boundary, (c) 3-D view of manually segmented pancreas with tumor, (d) 2-D slices of tumor.</p

Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins

ImportanceIncreasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds).ObjectiveTo compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention.Design, setting, and participantsThis single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data.InterventionTwin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks.Main outcomes and measuresThe primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being.ResultsA total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] μIU/mL; 95% CI, -5.3 to -0.4 μIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg).Conclusions and relevanceIn this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients.Trial registrationClinicalTrials.gov Identifier: NCT05297825

List of features selected with >0.5 probability by the model.

<p>List of features selected with >0.5 probability by the model.</p

The area under ROC, classification accuracy (as a percentage), sensitivity, and specificity obtained with fMRMR feature selection and SVM classification using leave-one-image-out and three-fold cross-validation techniques.

<p>The maximum AUC and <i>Ac</i> are highlighted with bold face.</p