Pulse oximetry values from 33,080 participants in the Apple Heart & Movement Study.

Wearable devices that include pulse oximetry (SpO2) sensing afford the opportunity to capture oxygen saturation measurements from large cohorts under naturalistic conditions. We report here a cross-sectional analysis of 72 million SpO2 values collected from 33,080 individual participants in the Apple Heart and Movement Study, stratified by age, sex, body mass index (BMI), home altitude, and other demographic variables. Measurements aggregated by hour of day into 24-h SpO2 profiles exhibit similar circadian patterns for all demographic groups, being approximately sinusoidal with nadir near midnight local time, zenith near noon local time, and mean 0.8% lower saturation during overnight hours. Using SpO2 measurements averaged for each subject into mean nocturnal and daytime SpO2 values, we employ multivariate ordinary least squares regression to quantify population-level trends according to demographic factors. For the full cohort, regression coefficients obtained from models fit to daytime SpO2 are in close quantitative agreement with the corresponding values from published reference models for awake arterial oxygen saturation measured under controlled laboratory conditions. Regression models stratified by sex reveal significantly different age- and BMI-dependent SpO2 trends for females compared with males, although constant terms and regression coefficients for altitude do not differ between sexes. Incorporating categorical variables encoding self-reported race/ethnicity into the full-cohort regression models identifies small but statistically significant differences in daytime SpO2 (largest coefficient corresponding to 0.13% lower SpO2, for Hispanic study participants compared to White participants), but no significant differences between groups for nocturnal SpO2. Additional stratified analysis comparing regression models fit independently to subjects in each race/ethnicity group is suggestive of small differences in age- and sex-dependent trends, but indicates no significant difference in constant terms between any race/ethnicity groups for either daytime or nocturnal SpO2. The large diverse study population and study design employing automated background SpO2 measurements spanning the full 24-h circadian cycle enables the establishment of healthy population reference trends outside of clinical settings.

Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Effects of 6-month episodic future thinking training on delay discounting, weight loss and HbA1c changes in individuals with prediabetes.

People with prediabetes are at risk for type 2 diabetes. They may discount the future delay discounting (DD), and not engage in preventive health behaviors. Episodic future thinking (EFT) can reduce DD when future scenarios are cued, but research is needed to assess long-term effects of EFT and when EFT is not cued. This study tested EFT training compared to control for people with prediabetes enrolled in a 6-month weight loss program on DD, weight, HbA1c, and physical activity. Results showed a reliable EFT effect on reducing DD in cued (p = 0.0035), and uncued DD tasks (p = 0.048), and significant overall changes in weight (p < 0.001), HbA1c (p, 0.001) and physical activity (p = 0.003), but no significant differences in these outcomes by group (p's > 0.05). Sixty-eight percent of the sample ended below the prediabetes HbA1c range. These results suggest that DD can be modified over extended periods, and the effects of EFT can be observed without EFT cues. However, these data do not suggest that changes in weight, HbA1c or physical activity were due to EFT training. The study was initiated before the COVID-19 pandemic which provided the opportunity to compare differences for people treated in-person or remotely. Analyses showed no differences in DD, weight, HBA1c or physical activity outcomes were observed between in-person and remote treatment, suggesting telehealth is a scalable approach to treating prediabetes.

The Predictive Utility of Valuing the Future for Smoking Cessation: Findings from the ITC 4 Country Surveys.

BACKGROUND: Delay discounting (DD) and time perspective (TP) are conceptually related constructs that are theorized as important determinants of the pursuit of future outcomes over present inclinations. This study explores their predictive relationships for smoking cessation. METHODS: 5006 daily smokers at a baseline wave provided 6710 paired observations of quitting activity between two waves. Data are from the International Tobacco Control (ITC) smoking and vaping surveys with samples from the USA, Canada, England, and Australia, across three waves conducted in 2016, 2018 and 2020. Smokers were assessed for TP and DD, plus smoking-specific predictors at one wave of cessation outcomes defined as either making a quit attempt and/or success among those who tried to quit which was ascertained at the subsequent survey wave. RESULTS: TP and DD were essentially uncorrelated. TP predicted making quit attempts, both on its own and controlling for other potential predictors but was negatively associated with quit success. By contrast, DD was not related to making quit attempts, but high DD predicted relapse. The presence of financial stress at baseline resulted in some moderation of effects. CONCLUSIONS: Understanding the mechanisms of action of TP and DD can advance our understanding of, and ability to enhance, goal-directed behavioural change. TP appears to contribute to future intention formation, but not necessarily practical thought of how to achieve goals. DD is more likely an index of capacity to effectively generate competing future possibilities in response to immediate gratification.

Role of delay discounting in predicting change in HBA1c for individuals with prediabetes.

The majority of people with prediabetes transition to type 2 diabetes. Weight gain is a known predictor of increasing the risk of diabetes, but another reason may be a focus on immediate rewards and discounting of the future. Delay discounting (DD: devaluation of future consequences) is related to obesity and poor glycemic control in persons with type 2 diabetes. This study was designed to assess whether changes in DD are associated with HbA1c change beyond BMI change in individuals with prediabetes. Hierarchical regression showed changes in BMI (p = 0.008) and the $1000 DD task (p = 0.04) were associated with HbA1c change beyond demographic characteristics, with the full model accounting for 25.8% of the variance. Those with greater BMI increases and greater increases in discounting of the future showed the greatest increases in HbA1c. DD represents a novel target to prevent progression from prediabetes to type 2 diabetes.

Treatment options for unresectable HCC with a focus on SIRT with Yttrium-90 resin microspheres.

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the second leading cause of cancer-related deaths across the globe. Only a small percentage of HCC patients (~20%-30%) are diagnosed at an early stage when first-line treatment options may be effective. The majority of HCC patients (>70%) are diagnosed with unresectable disease and given a poor overall prognosis. Current treatment guidelines recommend locoregional therapy with transarterial chemoembolisation (TACE) and systemic therapy with sorafenib as first-line treatment for patients with intermediate and advanced stage HCC. However, multiple factors including contraindications, technical considerations and treatment-related toxicities pose significant challenges in achieving favourable treatment outcomes, underscoring the need for a paradigm shift in managing these patients. In 2002, yttrium-90 (Y-90) resin microspheres was approved by the U.S. Food and Drug Administration (FDA) for the treatment of unresectable metastatic colorectal cancer to the liver with adjuvant floxuridine chemotherapy. However, thousands of patients with unresectable HCC have also been treated with resin Y-90. For over two decades, several small-scale prospective trials and retrospective studies have investigated and reported on the efficacy of locoregional selective internal radiation therapy (SIRT) with Y-90 microspheres in treating unresectable HCC. Although it is currently a treatment option for intermediate-stage HCC patients, mainstream clinical application of resin Y-90 has been largely limited because of the lack of sufficient clinical data from a randomised controlled trial. This could change with the imminent announcement of results from the phase 3 Sorafenib vs Radioembolization in Advanced Hepatocellular carcinoma (SARAH) trial. To provide the foundation and context for interpreting results from the SARAH trial, this article provides an overview of treatment modalities and current challenges in managing unresectable HCC. There is also a review of key prospective and retrospective studies evaluating the use of Y-90 SIRT, specifically Y-90 resin microspheres in unresectable HCC, which led to the development of the SARAH trial. METHODS: To identify relevant publications, the PubMed database was queried using one or more of the following search terms alone or in combination with Boolean operators: epidemiology, hepatocellular, hepatocellular cancer, hepatocellular carcinoma, unresectable, radioembolisation, selective internal radiation therapy, SIR-Spheres, yttrium 90, TACE, and sorafenib. The results were sorted or filtered by "Author", "Publication dates" or "Article types" to identify articles relevant to each section of the review. To ensure that information on ongoing clinical trials involving Y-90 resin was included, we conducted a search on "ClinicalTrials.gov", by combining the search terms "HCC" OR "hepatocellular carcinoma" with "Y 90" OR "yttrium 90" OR "radioembo", and screened for studies that involved treatment with Y-90 resin microspheres.

Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) often present at stages where patients have limited treatment options. Use of selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) resin microspheres has progressed as data increasingly speak to its utility in patients with both intermediate and late stage disease in these cancers. In anticipation of the pending completion of several prospective randomized controlled multicenter studies exploring the use of Y-90 resin microspheres in primary liver cancers, this article outlines mechanisms involved in SIRT administration and reviews key efficacy and safety data that are currently available in the literature involving use of this therapy in both HCC and ICC.

Fluvastatin inhibits intimal hyperplasia in wild-type but not Thbs1-null mice.

BACKGROUND: Thrombospondin-1 (TSP-1) is functionally important to intimal hyperplasia (IH) development. Statin drugs have beneficial pleiotropic effects, including reduced IH; however, the effect of statins on IH in a TSP-1-independent setting is unknown. HYPOTHESIS: Statins will be less effective in attenuating IH after vascular injury in TSP-1-null (Thbs1-/-) mice compared with wild-type (WT) mice. MATERIALS AND METHODS: Carotid artery ligation was performed on WT and Thbs1-/- mice. Each strain was divided into two groups: no statin control or standard chow containing fluvastatin (10 or 40 mg/kg/d). After 28 d, analysis included morphometric analysis and real-time quantitative reverse transcription polymerase chain reaction on the arteries and enzyme-linked immunosorbent assay on plasma (TSP-1 WT, TSP-2 WT, and Thbs1-/-). Comparisons were made by analysis of variance, with P < 0.05 considered significant. RESULTS: In no statin controls, WT mice had more IH than Thbs1-/- mice (0.46 ± 0.09 versus 0.15 ± 0.04). Fluvastatin reduced IH in the WT (0.46 ± 0.09 versus 0.23 ± 0.06), but not in Thbs1-/- groups (0.15 ± 0.04 versus 0.22 ± 0.07). No difference in IH existed between Thbs1-/- no statin controls and fluvastatin WT and Thbs1-/- groups. Statin dose did not affect IH. TSP-1 plasma levels were increased in fluvastatin WT. TSP-2 levels were decreased in fluvastatin WT and elevated in fluvastatin Thbs1-/-. Fluvastatin had no effect on tissue Thbs1 or Thbs2 gene expression. CONCLUSIONS: TSP-1 is necessary for robust IH after arterial injury. Because fluvastatin had no effect on IH in Thbs1-/-, the data suggest that the statin effect on IH may be largely TSP-1 dependent. Both statins and the presence of TSP-1 affect TSP-1 and TSP-2 plasma levels.

Aversive properties of negative incentive shifts in Fischer 344 and Lewis rats.

Research on incentive contrast highlights that reward value is not absolute but rather is based upon comparisons we make to rewards we have received and expect to receive. Both human and nonhuman studies on incentive contrast show that shifting from a larger more-valued reward to a smaller less-valued reward is associated with long periods of nonresponding - a negative contrast effect. In this investigation, we used two different genetic rat strains, Fischer 344 and Lewis rats that putatively differ in their sensitivity to aversive stimulation, to assess the aversive properties of large-to-small reward shifts (negative incentive shifts). Additionally, we examined the extent to which increasing cost (fixed-ratio requirements) modulates negative contrast effects. In the presence of a cue that signaled the upcoming reward magnitude, lever pressing was reinforced with one of two different magnitudes of food (large or small). This design created two contrast shifts (small-to-large, large-to-small) and two shifts used as control conditions (small-to-small, large-to-large). Results showed a significant interaction between rat strain and cost requirements only during the negative incentive shift with the emotionally reactive Fischer 344 rats exhibiting significantly longer response latencies with increasing cost, highlighting greater negative contrast. These findings are more consistent with emotionality accounts of negative contrast and results of neurophysiological research that suggests shifting from a large to a small reward is aversive. Findings also highlight how subjective reward value and motivation is a product of gene-environment interactions.

Assessment of Magnetic Resonance Imaging Artifact Following Cervical Total Disc Arthroplasty.

BACKGROUND: Cervical disc arthroplasty has become a technique for the treatment of cervical degenerative disc disease. Clinically, the need to accurately assess the neural elements at the operative and adjacent levels is critical postoperatively. The purpose of this study was to quantitatively and qualitatively measure the amount of MRI artifact produced by various cervical total disc replacements. METHODS: T1 and T2-weighted turbo spin-echo MRI sequences were collected on the cervical spine (C2-T1) of a 68 year-old unembalmed male cadaver. A discectomy was performed at C5-6, followed by successive implantation of six different total disc replacements. The scans were quantitatively evaluated by three of the authors. The volume of artifact was measured using image analysis software. Qualitative analysis of the adjacent and index neural elements was performed. RESULTS: The artifact in the T2 weighted images was noted to be 58.6±7.3 cm3 for Prestige ST, 14.2±1.3 cm3 for ProDisc-C, 7.5±0.8 cm3 for Discover, 8.0±0.3 cm3 for Prestige LP, 6.6±0.7 cm3 for Bryan, and 7.3±0.6 cm3 for ProDisc-C titanium prototype. Acceptable intraobserver and excellent interobsever correlation was demonstrated using Pearson Correlation and Concordance Correlation Coefficient analysis. The adjacent and implanted level neural elements (spinal cord and neuroforamina) were easily visualized on the T2 weighted images after the implantation of titanium devices (ProDisc-C titanium prototype, Discover, Prestige LP and Bryan). After implantation of a cobalt chrome implant (ProDisc-C), the adjacent level neural elements were easily visualized but the implanted level could not be fully visualized due to distortion of the images. The quality of the distortion was least favorable after the implantation of the stainless steel implant (Prestige ST), where neither the adjacent nor the index level could be fully visualized. CONCLUSION: The volume of the artifact seen following cervical total disc arthroplasty is highly dependent upon the material property of the implant. Quantitative analysis described in this study demonstrated sufficiently low intraobserver and interobserver variability to be considered a reliable technique.

Regulatory considerations surrounding the deployment of Bt-expressing cowpea in Africa: report of the deliberations of an expert panel.

Cowpea (Vigna unguiculata spp unguiculata) is adapted to the drier agro-ecological zones of West Africa where it is a major source of dietary protein and widely used as a fodder crop. Improving the productivity of cowpea can enhance food availability and security in West Africa. Insect predation--predominately from the legume pod borer (Maruca vitrata), flower thrips (Megalurothrips sjostedti) and a complex of pod-sucking bugs (e.g., Clavigralla spp)--is a major yield-limiting factor in West African cowpea production. Dramatic increases in yield are shown when M. vitrata is controlled with insecticides. However, availability, costs, and safety considerations limit pesticides as a viable option for boosting cowpea production. Development of Bt-cowpea through genetic modification (GM) to control the legume pod borer is a promising approach to cowpea improvement. Cowpea expressing the lepidopteran-active Cry1Ab protein from Bacillus thuringiensis is being developed as a first generation Bt-cowpea crop for West Africa. Appropriate stewardship of Bt-cowpea to assure its sustainability under West African conditions is critical to its successful development. A first step in this process is an environmental risk assessment to determine the likelihood and magnitude of adverse effects of the Cry1Ab protein on key environmental protection goals in West Africa. Here we describe the results of an expert panel convened in 2009 to develop the problem formulation phase for Bt-cowpea and to address specific issues around gene flow, non-target arthropods, and insect resistance management.

Silicone foul release coatings: effect of the interaction of oil and coating functionalities on the magnitude of macrofouling attachment strengths.

Silicone biofouling release coatings have been shown to be an effective method of combating fouling. Nearly all silicone foul release coatings are augmented with an oil additive to decrease macrofouling attachment strength. This paper addresses the effect of the type of oil that is incorporated into the silicone coating and the type of silicone coating itself (silica vs calcium carbonate filled) on macrofouling adhesion strengths to the coating. It was found that not only are the main effects of oil type and silicone coating type important in determining the magnitude of the attachment strength of the organism, but the interaction term (oil type crossed with coating type) is highly significant for all organisms studied, except oysters at the University of Hawaii test site (Oahu, Hawaii) which has a significance level of alpha = 0.1. Each of the organisms exhibited a unique response to the various silicone fouling release coatings. Thus, in order to predict the effectives of foul release coatings, the composition variables of the coatings and the type of target organisms must be considered.