Trends in U.S. public confidence in science and opportunities for progress.

In recent years, many questions have been raised about whether public confidence in science is changing. To clarify recent trends in the public's confidence and factors that are associated with these feelings, an effort initiated by the National Academies' Strategic Council for Research Excellence, Integrity, and Trust (the Strategic Council) analyzed findings from multiple survey research organizations. The Strategic Council's effort, which began in 2022, found that U.S. public confidence in science, the scientific community, and leaders of scientific communities is high relative to other civic, cultural, and governmental institutions for which researchers regularly collect such data. However, confidence in these institutions has fallen during the previous 5 years. Science's decline, while real, is similar to or less than that in the other groups. A recent study goes into greater detail by exploring public views of science. From these data, we observe that many of the surveyed U.S. public question the extent to which scientists share their values or overcome personal biases when presenting conclusions. At the same time, large majorities agree on certain types of actions that they want scientists to take. For example, 84% respond that it is "somewhat important" or "very important" for scientists to disclose their funders. Ninety-two percent (92%) offer the same responses to scientists "being open to changing their minds based on new evidence." Collectively, these data clarify how the U.S. public views science and scientists. They also suggest actions that can affect public confidence in science and scientists in the years to come.

Reproduction has immediate effects on female mortality, but no discernible lasting physiological impacts: A test of the disposable soma theory.

The disposable soma theory (DST) posits that organisms age and die because of a direct trade-off in resource allocation between reproduction and somatic maintenance. DST predicts that investments in reproduction accentuate somatic damage which increase senescence and shortens lifespan. Here, we directly tested DST predictions in breeding and nonbreeding female C57BL/6J mice. We measured reproductive outputs, body composition, daily energy expenditure, and oxidative stress at peak lactation and over lifetime. We found that reproduction had an immediate and negative effect on survival due to problems encountered during parturition for some females. However, there was no statistically significant residual effect on survival once breeding had ceased, indicating no trade-off with somatic maintenance. Instead, higher mortality appeared to be a direct consequence of reproduction without long-term physiological consequences. Reproduction did not elevate oxidative stress. Our findings do not provide support for the predictions of the DST.

A Bayesian semi-parametric scalar-on-function regression with measurement error using instrumental variables.

Wearable devices such as the ActiGraph are now commonly used in research to monitor or track physical activity. This trend corresponds with the growing need to assess the relationships between physical activity and health outcomes, such as obesity, accurately. Device-based physical activity measures are best treated as functions when assessing their associations with scalar-valued outcomes such as body mass index. Scalar-on-function regression (SoFR) is a suitable regression model in this setting. Most estimation approaches in SoFR assume that the measurement error in functional covariates is white noise. Violating this assumption can lead to underestimating model parameters. There are limited approaches to correcting measurement errors for frequentist methods and none for Bayesian methods in this area. We present a non-parametric Bayesian measurement error-corrected SoFR model that relaxes all the constraining assumptions often involved with these models. Our estimation relies on an instrumental variable allowing a time-varying biasing factor, a significant departure from the current generalized method of moment (GMM) approach. Our proposed method also permits model-based grouping of the functional covariate following measurement error correction. This grouping of the measurement error-corrected functional covariate allows additional ease of interpretation of how the different groups differ. Our method is easy to implement, and we demonstrate its finite sample properties in extensive simulations. Finally, we applied our method to data from the National Health and Examination Survey to assess the relationship between wearable device-based measures of physical activity and body mass index in adults in the United States.

Not feeling the heat? Effects of dietary protein on satiation and satiety in mice are not due to its impact on body temperature.

Dietary protein modulates food intake (FI) via unclear mechanism(s). One possibility is that higher protein leads to greater post-ingestive heat production (Specific dynamic action: SDA) leading to earlier meal termination (increased satiation), and inhibition of further intake (increased satiety). The influence of dietary protein on feeding behaviour in C57BL/6J mice was tested using an automated FI monitoring system (BioDAQ), simultaneous to body temperature (Tb). Total FI, inter meal intervals (IMI, satiety) and meal size (MS, satiation) were related to changes in Tb after consuming low (5%, LP), moderate (15%, MP) and high (30%, HP) protein diets. Diets were tested over three conditions: 1) room temperature (RT, 21 ± 1 °C), 2) room temperature and running wheels (RTRW) and 3) low temperature (10 °C) and running wheels (LTRW). The differences between diets and conditions were also compared using mixed models. Mice housed at RT fed HP diet, reduced total FI compared with LP and MP due to earlier meal termination (satiation effect). FI was lowered in RTRW conditions with no differences between diets. FI significantly increased under LTRW conditions for all diets, with protein content leading to earlier meal termination (satiation) but not the intervals between feeding bouts (satiety). Tb fell immediately after feeding in all conditions. Despite a reduction in total FI in mice fed HP, mediated via increased satiation, this effect was not linked to increased Tb during meals. We conclude effects of dietary protein on intake are not mediated via SDA and Tb.

The Strategic Council for Research Excellence, Integrity, and Trust.

We announce the creation of a new body within the National Academies of Sciences, Engineering, and Medicine called the Strategic Council for Research Excellence, Integrity, and Trust, charged with advancing the overall health, quality, and effectiveness of the research enterprise across all domains that fund, execute, disseminate, and apply scientific work in the public interest. By promoting the alignment of incentives and policies, adoption of standard tools, and implementation of proven methods, the Strategic Council seeks to optimize the excellence and trustworthiness of research for the benefit of society.

Hidden: A Baker's Dozen Ways in Which Research Reporting is Less Transparent than it Could be and Suggestions for Implementing Einstein's Dictum.

The tutelage of our mentors as scientists included the analogy that writing a good scientific paper was an exercise in storytelling that omitted unessential details that did not move the story forward or that detracted from the overall message. However, the advice to not get lost in the details had an important flaw. In science, it is the many details of the data themselves and the methods used to generate and analyze them that give conclusions their probative meaning. Facts may sometimes slow or distract from the clarity, tidiness, intrigue, or flow of the narrative, but nevertheless they are important for the assessment of what was done, the trustworthiness of the science, and the meaning of the findings. Nevertheless, many critical elements and facts about research studies may be omitted from the narrative and become hidden from scholarly scrutiny. We describe a "baker's dozen" shortfalls in which such elements that are pertinent to evaluating the validity of scientific studies are sometimes hidden in reports of the work. Such shortfalls may be intentional or unintentional or lie somewhere in between. Additionally, shortfalls may occur at the level of the individual or an institution or of the entire system itself. We conclude by proposing countermeasures to these shortfalls.

Estimation of sparse functional quantile regression with measurement error: a SIMEX approach.

Quantile regression is a semiparametric method for modeling associations between variables. It is most helpful when the covariates have complex relationships with the location, scale, and shape of the outcome distribution. Despite the method's robustness to distributional assumptions and outliers in the outcome, regression quantiles may be biased in the presence of measurement error in the covariates. The impact of function-valued covariates contaminated with heteroscedastic error has not yet been examined previously; although, studies have investigated the case of scalar-valued covariates. We present a two-stage strategy to consistently fit linear quantile regression models with a function-valued covariate that may be measured with error. In the first stage, an instrumental variable is used to estimate the covariance matrix associated with the measurement error. In the second stage, simulation extrapolation (SIMEX) is used to correct for measurement error in the function-valued covariate. Point-wise standard errors are estimated by means of nonparametric bootstrap. We present simulation studies to assess the robustness of the measurement error corrected for functional quantile regression. Our methods are applied to National Health and Examination Survey data to assess the relationship between physical activity and body mass index among adults in the United States.

How do we operate a large monthly red blood cell exchange program.

BACKGROUND: Red blood cell (RBC) exchange for sickle cell disease presents unique difficulties due to RBC phenotyping, complex antibody work-ups, large number of RBC units required, and vascular access considerations, any of which can delay the procedure. Multidisciplinary coordination and systemic processes ensure that monthly appointments remain on schedule. STUDY DESIGN AND METHODS: A high-volume chronic RBC exchange program is described, highlighting the importance of multidisciplinary coordination and process improvement strategies involving initial referral, vascular access, order sets, and allocation of antigen-negative or phenotypically matched RBCs. RESULTS: Approximately 50 outpatient RBC exchanges are performed each month with an 82% kept-appointment rate. Specific factors for program success include open communication across services and improvements to referrals and standardized order sets. CONCLUSION: A combination of multidisciplinary coordination and process improvement can ensure the success of a high volume RBC exchange program. Frequent communication of upcoming appointments between the referring hematologists, the hemapheresis clinic, transfusion service, and interventional radiology is critical. Advance notice to the immunohematology reference lab of upcoming appointments is needed to allow enough time for allocating antigen-negative RBCs. Order sets can be leveraged to standardize and streamline RBC exchanges. Lastly, numerous mechanisms help patients compensate for the cognitive sequelae of stroke.

Toward more rigorous and informative nutritional epidemiology: The rational space between dismissal and defense of the status quo.

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rigor and adherence to scientific reporting commensurate with research methods used. Some commentators advocate jettisoning nutritional epidemiology entirely, perhaps believing improvements are impossible. Still others support only normative refinements. But neither abolition nor minor tweaks are appropriate. Nutritional epidemiology, in its present state, offers utility, yet also needs marked, reformational renovation. Changing the status quo will require ongoing, unflinching scrutiny of research questions, practices, and reporting-and a willingness to admit that "good enough" is no longer good enough. As such, a workshop entitled "Toward more rigorous and informative nutritional epidemiology: the rational space between dismissal and defense of the status quo" was held from July 15 to August 14, 2020. This virtual symposium focused on: (1) Stronger Designs, (2) Stronger Measurement, (3) Stronger Analyses, and (4) Stronger Execution and Reporting. Participants from several leading academic institutions explored existing, evolving, and new better practices, tools, and techniques to collaboratively advance specific recommendations for strengthening nutritional epidemiology.

Only one cluster per condition is an invalid design for a cluster randomized trial and should be re-labeled a quasi-experimental study. Response to: "Effect of behavioral activation on time and frequency domain heart rate variability in older adults with subthreshold depression: a cluster randomized controlled trial in Thailand".

Ayudhaya et al. examined the effect of Behavioral Activation on daily step count and heart rate variability among older adults with depression in a study labeled a cluster randomized controlled trial (cRCT). However, only one cluster was assigned to either of the study conditions. Such a design would have zero degrees of freedom for inferential testing, because the variation due to cluster membership cannot be estimated apart from the variation due to treatment assignment. Thus, the intervention effect is completely confounded with the cluster effect. The study should be labeled a quasi-experimental study, not a cRCT. Accordingly, the numerical results should be interpreted as associations but not evidence for causal relationships.

Corrected analysis of "the effects of bright light treatment on affective symptoms in people with dementia: a 24-week cluster randomized controlled trial" that accounts for clustering and nesting verifies conclusions.

In this correspondence, we explain the reasoning for invalidity of the analysis choices by Kolberg et al., and provide the results produced using correct statistical procedures for their study design. Reassuringly, we could verify the original conclusions. That is, results of the corrected statistical models are similar to the results of the original analysis. Regardless of the magnitude of difference that corrected statistical methods make, results and conclusions that are derived from invalid methods are unsubstantiated. By verifying the results, we allow the readers to be assured that the published conclusions in the study by Kolberg et al. now rest on a sound evidential basis.

Intraoperative transabdominal MEPs: four case reports.

Four recent cases utilizing transabdominal motor-evoked potentials (TaMEPs) are presented as illustrative of the monitoring technique during lumbosacral fusion, sciatic nerve tumor resection, cauda equina tumor resection, and lumbar decompression. Case 1: In a high-grade lumbosacral spondylolisthesis revision fusion, both transcranial motor-evoked potentials (TcMEPs) and TaMEPs detected a transient focal loss of left tibialis anterior response in conjunction with L5 nerve root decompression. Case 2: In a sciatic nerve tumor resection, TcMEPs responses were lost but TaMEPs remained unchanged, the patient was neurologically intact postoperatively. Case 3: TaMEPs were acquired during an L1-L3 intradural extramedullary cauda equina tumor resection utilizing a unique TaMEP stimulation electrode. Case 4: TaMEPs were successfully acquired with little anesthetic fade utilizing an anesthetic regimen of 1.1 MAC Sevoflurane during a lumbar decompression. While the first two cases present TaMEPs and TcMEPs side-by-side, demonstrating TaMEPs correlating to TcMEPs (Case 1) or a more accurate reflection of patient outcome (Case 2), no inference regarding the accuracy of TaMEPs to monitor nerve elements during cauda equina surgery (Cases 3) or the lumbar decompression presented in Case 4 should be made as these are demonstrations of technique, not utility.

Incorrect analysis in "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study" has resulted in incorrect conclusions of demonstrated effects where no such effects have been demonstrated.

In their 2023 Nutrition and Health paper "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study", Giacomello et al. investigated the effects of an educational intervention based on the Dietary Guidelines for the Brazilian Population among obese women. The authors concluded that the intervention significantly improved weight loss, quality of life, components of metabolic syndrome, and pain. However, we believe the statistical analysis employed in the study was flawed. The authors used within-group changes to draw conclusions, which is known as a difference in nominal significance error. This error has the potential to inflate Type I error rates substantially. To address this issue, we re-analyzed the data obtained from the authors. We focused on body mass and hip circumference and replicated the incorrectly chosen within-group analyses, which remained significant. However, to properly evaluate the intervention's effectiveness, it is essential to compare the differences between the groups directly. Therefore, we calculated change scores for each participant and used independent samples t-tests and linear mixed models to compare between-group differences. Both methods yielded similar non-significant p-values, indicating that there is no significant effect of treatment on body mass or hip circumference. The original paper's conclusions regarding the effectiveness of the intervention are not supported by the proper statistical analysis. The data should be re-analyzed using appropriate between-group comparisons, and the corrected results should be published, or the incorrect results and original paper should be retracted.

RELATIONSHIP BETWEEN REPRODUCTIVE AND BONE BIOMARKERS AND OSTEOARTHRITIS IN ZOO ASIAN (ELEPHAS MAXIMUS) AND AFRICAN (LOXODONTA AFRICANA) ELEPHANTS.

Osteoarthritis (OA) is common in zoo Asian (Elephas maximus) and African (Loxodonta africana) elephants. This study investigated the relationship between confirmed or suspected OA with ovarian cyclicity, gonadotropins, progestagens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and collagen type I (CTX-I) in zoo elephants. In Asian elephants, odds of having confirmed or suspected OA decreased with cycling (OR = 0.22, P = 0.016; OR = 0.29, P = 0.020, respectively), however, not when adjusted for age (odds ratio [OR] = 0.31, P = 0.112; OR = 0.58, P = 0.369, respectively). In African elephants, none of the models between confirmed OA and cycling status were significant (P > 0.060), while the odds of having suspected OA decreased with cycling (OR = 0.12, P = 0.001), even after adjusting for age (OR = 0.15, P = 0.005). Progestagens (Asian elephants P > 0.096; African elephants P > 0.415), LH (Asian P > 0.129; African P > 0.359), and FSH (Asian P > 0.738; African P > 0.231) did not differ with confirmed or suspected OA status, unadjusted. CTX-I concentrations were not related to OA status (P > 0.655). This study concluded hormonal changes may not have a strong impact on OA, so additional investigation into other serologic biomarkers is warranted.

Stimulated Insulin Secretion Predicts Changes in Body Composition Following Weight Loss in Adults with High BMI.

BACKGROUND: The aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals. OBJECTIVES: The goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss. METHODS: Exploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12-18% weight loss in ∼14 wk or 10-14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post-weight loss. Associations were analyzed using general linear models with adjustment for covariates. RESULTS: In FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 µIU/mL increment in baseline insulin-30; P = 0.005; -1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (-0.465 kg per 100 µIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (-3.37% per 100 µIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude. CONCLUSIONS: Baseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at clinicaltrials.gov as NCT03394664 and NCT02068885.

Risk of Type 2 Diabetes Among Individuals with Excess Weight: Weight Trajectory Effects.

PURPOSE OF REVIEW: Increased risk of type 2 diabetes mellitus (T2D) among individuals with overweight or obesity is well-established; however, questions remain about the temporal dynamics of weight change (gain or loss) on the natural course of T2D in this at-risk population. Existing epidemiologic evidence is limited to studies that discretely sample and assess excess weight and T2D risk at different ages with limited follow-up, yet changes in weight may have time-varying and possibly non-linear effects on T2D risk. Predicting the impact of weight change on the risk of T2D is key to informing primary prevention. We critically review the relationship between weight change, trajectory groups (i.e., distinct weight change patterns), and T2D risk among individuals with excess weight in recently published T2D prevention randomized controlled trials (RCTs) and longitudinal cohort studies. RECENT FINDINGS: Overall, weight trajectory groups have been shown to differ by age of onset, sex, and patterns of insulin resistance or beta-cell function biomarkers. Lifestyle (diet and physical activity), pharmacological, and surgical interventions can modify an individual's weight trajectory. Adolescence is a critical etiologically relevant window during which onset of excess weight may be associated with higher risk of T2D. Changes in insulin resistance and beta-cell function biomarkers are distinct but related correlates of weight trajectory groups that evolve contemporaneously over time. These multi-trajectory markers are differentially associated with T2D risk. T2D risk may differ by the age of onset and duration of excess body weight, and the type of weight loss intervention. A better understanding of the changes in weight, insulin sensitivity, and beta-cell function as distinct but related correlates of T2D risk that evolve contemporaneously over time has important implications for designing and targeting primary prevention efforts.

Kynurenine metabolism is altered in mdx mice: a potential muscle to brain connection.

NEW FINDINGS: What is the central question in this study? Promoting muscle health with regular aerobic exercise can improve mental health through a kynurenine metabolic pathway: do conditions of muscle disease such as muscular dystrophy negatively influence this pathway? What is the main finding and its importance? The DBA/2J mdx model of Duchenne muscular dystrophy exhibits altered kynurenine metabolism with less kynurenic acid and peroxisome proliferator-activated receptor-γ coactivator 1-α and higher levels of tumour necrosis factor α mRNA - results associated with anxiety-like behaviour. ABSTRACT: Regular exercise can direct muscle kynurenine (KYN) metabolism toward the neuroprotective branch of the kynurenine pathway thereby limiting the accumulation of neurotoxic metabolites in the brain and contributing to mental resilience. However, the effect of muscle disease on KYN metabolism has not yet been investigated. Previous work has highlighted anxiety-like behaviours in approximately 25% of patients with Duchenne muscular dystrophy (DMD), possibly due to altered KYN metabolism. Here, we characterized KYN metabolism in mdx mouse models of DMD. Young (8-10 week old) DBA/2J (D2) mdx mice, but not age-matched C57BL/10 (C57) mdx mice, had lower levels of circulating kynurenic acid (KYNA) and lower KYNA:KYN ratio compared with their respective wild-type (WT) controls. While both C57 and D2 mdx mice displayed signs of anxiety-like behaviour, spending more time in the corners of the arena during a novel object recognition test, this effect was more prominent in D2 mdx mice. Correlational analysis detected a significant negative association between KYNA:KYN levels and time spent in corners in D2 mice, but not C57 mice. In extensor digitorum longus muscles from D2 mdx mice, but not C57 mdx mice, we found lowered protein levels of peroxisome proliferator-activated receptor-γ coactivator 1-α and kynurenine amino transferase-1 enzyme when compared with WT. Furthermore, D2 mdx quadriceps muscles had the highest level of tumour necrosis factor α expression, which is suggestive of enhanced inflammation. Thus, our pilot work shows that KYN metabolism is altered in D2 mdx mice, with a potential contribution from altered muscle health.

Efficacy and safety of a specific commercial high-protein meal-replacement product line in weight management: meta-analysis of randomized controlled trials.

BACKGROUND: Protein is suggested to be the nutrient providing the most satiety and is frequently used in meal-replacement products to achieve weight loss. Commercial products such as Herbalife high-protein (HP) products have been studied in various clinical trials, but controversy remains regarding their efficacy and safety. METHODS: We searched the PubMed, Center for Clinical and Translational Research (CCTR), and Google Scholar databases for randomized controlled trials of Herbalife HP products used as meal replacement (MR) published through July 2019 in peer-reviewed journals. We reviewed changes in efficacy and safety-related outcomes in treatment and control groups, and we estimated the pooled standardized mean difference (SMD) and corresponding 95% confidence intervals (CIs) with a DerSimonian and Laird random-effects method. RESULTS: By pooling data from nine identified studies (934 participants: 463 in treatment groups and 471 in control groups), we found that participants who consumed HP products experienced significantly larger decreases in body weight (SMD = -0.24; 95% CI: -0.37 to -0.10), body mass index (SMD = -0.31; 95% CI: -0.50 to -0.11), and fat mass (SMD = -0.37; 95% CI: -0.65 to -0.09) than did individuals consuming control diets. Concerning safety outcomes, the participants in the treatment group had a significantly larger decrease in aspartate aminotransferase (SMD = -0.23; 95% CI: -0.42 to -0.03). There were no significant between-group differences in alanine aminotransferase or creatinine. However, blood urea nitrogen levels increased in both groups, with a significantly larger increase in the treatment group (SMD = 0.53; 95% CI: 0.15 to 0.92). CONCLUSIONS: Herbalife HP MR products appear effective and do not evidence significant risk in reducing body weight.

The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update.

STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The objective was to update the 2016 version of the Canadian clinical practice guidelines for the management of neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient, outpatient and community SCI rehabilitation settings in Canada. METHODS: The guidelines were updated in accordance with the Appraisal of Guidelines for Research and Evaluation II tool. A Steering Committee and Working Group reviewed the relevant evidence on neuropathic pain management (encompassing screening and diagnosis, treatment and models of care) after SCI. The quality of evidence was scored using Grading of Recommendations Assessment, Development and Evaluation (GRADE). A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: The working group identified and reviewed 46 additional relevant articles published since the last version of the guidelines. The panel agreed on 3 new screening and diagnosis recommendations and 8 new treatment recommendations. Two key changes to these treatment recommendations included the introduction of general treatment principles and a new treatment recommendation classification system. No new recommendations to model of care were made. CONCLUSIONS: The CanPainSCI recommendations for the management of neuropathic pain after SCI should be used to inform practice.