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Policy Points This study examines the impact of several world-changing events in 2020, such as the pandemic and widespread racism protests, on the US population's comfort with the use of identifiable data for public health. Before the 2020 election, there was no significant difference between Democrats and Republicans. However, African Americans exhibited a decrease in comfort that was different from other subgroups. Our findings suggest that the public remained supportive of public health data activities through the pandemic and the turmoil of 2020 election cycle relative to other data use. However, support among African Americans for public health data use experienced a unique decline compared to other demographic groups. CONTEXT: Recent legislative privacy efforts have not included special provisions for public health data use. Although past studies documented support for public health data use, several global events in 2020 have raised awareness and concern about privacy and data use. This study aims to understand whether the events of 2020 affected US privacy preferences on secondary uses of identifiable data, focusing on public health and research uses. METHODS: We deployed two online surveys-in February and November 2020-on data privacy attitudes and preferences using a choice-based-conjoint analysis. Participants received different data-use scenario pairs-varied by the type of data, user, and purpose-and selected scenarios based on their comfort. A hierarchical Bayes regression model simulated population preferences. FINDINGS: There were 1,373 responses. There was no statistically significant difference in the population's data preferences between February and November, each showing the highest comfort with population health and research data activities and the lowest with profit-driven activities. Most subgroups' data preferences were comparable with the population's preferences, except African Americans who showed significant decreases in comfort with population health and research. CONCLUSIONS: Despite world-changing events, including a pandemic, we found bipartisan public support for using identifiable data for public health and research. The decreasing support among African Americans could relate to the increased awareness of systemic racism, its harms, and persistent disparities. The US population's preferences support including legal provisions that permit public health and research data use in US laws, which are currently lacking specific public health use permissions.

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The management of short-segment benign gastrointestinal (GI) strictures refractory to currently available endoscopic treatments (endoscopic balloon dilation, intralesional steroid injection, incisional therapy and fully covered self-expanding metal stents) proves to be challenging. Lumen-apposing metal stents (LAMS), originally developed for access to and drainage of pancreatic fluid collections, are being used in an off-label manner for the treatment of short GI luminal strictures. The short length and wide flanges make LAMS potentially suitable for this indication and may reduce complications and improve patient tolerance. In this article we review the published literature, including 138 patients from 4 retrospective studies and 13 case reports who received a LAMS for the treatment of a short GI luminal stricture. In the reviewed literature only 2 of the 138 cases had immediate adverse events warranting hospitalization: perforation and postoperative GI bleed. A total adverse event rate of 32.5% (45 of 138 cases) was reported. Migration was the most common adverse event, accounting for 40% of the total. Nearly 58% of reported patients had symptom and stricture resolution after stent removal in the reviewed studies. Follow up varied from 28-352 days after stent removal. Although more data are needed to determine their long-term safety and efficacy, LAMS represent an important alternative to traditional endoscopic options when approaching patients with short GI luminal strictures.

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The complexity of medical devices and the processes by which they are developed pose considerable challenges to producing safe designs and regulatory submissions that are amenable to effective reviews. Designing an appropriate and clearly documented architecture can be an important step in addressing this complexity. Best practices in medical device design embrace the notion of a safety architecture organized around distinct operation and safety requirements. By explicitly separating many safety-related monitoring and mitigation functions from operational functionality, the aspects of a device most critical to safety can be localized into a smaller and simpler safety subsystem, thereby enabling easier verification and more effective reviews of claims that causes of hazardous situations are detected and handled properly. This article defines medical device safety architecture, describes its purpose and philosophy, and provides an example. Although many of the presented concepts may be familiar to those with experience in realization of safety-critical systems, this article aims to distill the essence of the approach and provide practical guidance that can potentially improve the quality of device designs and regulatory submissions.

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High-oleic acid soybean oil (H-OSBO) is a trait-enhanced vegetable oil containing >70% oleic acid. Developed as an alternative for trans-FA (TFA)-containing vegetable oils, H-OSBO is predicted to replace large amounts of soybean oil in the US diet. However, there is little evidence concerning the effects of H-OSBO on coronary heart disease (CHD)(6) risk factors and CHD risk. We examined and quantified the effects of substituting high-oleic acid (HO) oils for fats and oils rich in saturated FAs (SFAs), TFAs, or n-6 (ω-6) polyunsaturated FAs (PUFAs) on blood lipids in controlled clinical trials. Searches of online databases through June 2014 were used to select studies that defined subject characteristics; described control and intervention diets; substituted HO oils compositionally similar to H-OSBO (i.e., ≥70% oleic acid) for equivalent amounts of oils high in SFAs, TFAs, or n-6 PUFAs for ≥3 wk; and reported changes in blood lipids. Studies that replaced saturated fats or oils with HO oils showed significant reductions in total cholesterol (TC), LDL cholesterol, and apolipoprotein B (apoB) (P < 0.05; mean percentage of change: -8.0%, -10.9%, -7.9%, respectively), whereas most showed no changes in HDL cholesterol, triglycerides (TGs), the ratio of TC to HDL cholesterol (TC:HDL cholesterol), and apolipoprotein A-1 (apoA-1). Replacing TFA-containing oil sources with HO oils showed significant reductions in TC, LDL cholesterol, apoB, TGs, TC:HDL cholesterol and increased HDL cholesterol and apoA-1 (mean percentage of change: -5.7%, -9.2%, -7.3%, -11.7%, -12.1%, 5.6%, 3.7%, respectively; P < 0.05). In most studies that replaced oils high in n-6 PUFAs with equivalent amounts of HO oils, TC, LDL cholesterol, TGs, HDL cholesterol, apoA-1, and TC:HDL cholesterol did not change. These findings suggest that replacing fats and oils high in SFAs or TFAs with either H-OSBO or oils high in n-6 PUFAs would have favorable and comparable effects on plasma lipid risk factors and overall CHD risk.

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BACKGROUND: The origins of life on the Earth required chemical entities to interact with their environments in ways that could respond to natural selection. The concept of interpretation, where biotic entities use signs in their environment as proxy for the existence of other items of selective value in their environment, has been proposed on theoretical grounds to be relevant to the origins and early evolution of life. However this concept has not been demonstrated empirically. RESULTS: Here, we present data that certain catalytic RNA sequences have properties that would enable interpretation of divalent cation levels in their environment. By assaying the responsiveness of two variants of the Tetrahymena ribozyme to the Ca(2+) ion as a sign for the more catalytically useful Mg(2+) ion, we show an empirical proof-of-principle that interpretation can be an evolvable trait in RNA, often suggested as a model system for early life. In particular we demonstrate that in vitro, the wild-type version of the Tetrahymena ribozyme is not interpretive, in that it cannot use Ca(2+) as a sign for Mg(2+). Yet a variant of this sequence containing five mutations that alter its ability to utilize the Ca(2+) ion engenders a strong interpretive characteristic in this RNA. CONCLUSIONS: We have shown that RNA molecules in a test tube can meet the minimum criteria for the evolution of interpretive behaviour in regards to their responses to divalent metal ion concentrations in their environment. Interpretation in RNA molecules provides a property entirely dependent on natural physico-chemical interactions, but capable of shaping the evolutionary trajectory of macromolecules, especially in the earliest stages of life's history.

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The dynamic nature of the medical domain is driving a need for continuous innovation and improvement in techniques for developing and assuring medical devices. Unfortunately, research in academia and communication between academics, industrial engineers, and regulatory authorities is hampered by the lack of realistic non-proprietary development artifacts for medical devices. In this paper, we give an overview of a detailed requirements document for a Patient-Controlled Analgesic (PCA) pump developed under the US NSF's Food and Drug Administration (FDA) Scholar-in-Residence (SIR) program. This 60+ page document follows the methodology outlined in the US Federal Aviation Administrations (FAA) Requirements Engineering Management Handbook (REMH) and includes a domain overview, use cases, statements of safety & security requirements, and formal top-level system architectural description. Based on previous experience with release of a requirements document for a cardiac pacemaker that spawned a number of research and pedagogical activities, we believe that the described PCA requirements document can be an important research enabler within the formal methods and software engineering communities.

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We describe the initial realization of behavior in the biosphere, which we term behavioral chemistry. If molecules are complex enough to attain a stochastic element to their structural conformation in such as a way as to radically affect their function in a biological (evolvable) setting, then they have the capacity to behave. This circumstance is described here as behavioral chemistry, unique in its definition from the colloquial chemical behavior.  This transition between chemical behavior and behavioral chemistry need be explicit when discussing the root cause of behavior, which itself lies squarely at the origins of life and is the foundation of choice.  RNA polymers of sufficient length meet the criteria for behavioral chemistry and therefore are capable of making a choice.

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BACKGROUND: Population-based studies have shown that vegetarians have lower body mass index than nonvegetarians, suggesting that vegetarian diet plans may be an approach for weight management. However, a perception exists that vegetarian diets are deficient in certain nutrients. OBJECTIVE: To compare dietary quality of vegetarians, nonvegetarians, and dieters, and to test the hypothesis that a vegetarian diet would not compromise nutrient intake when used to manage body weight. DESIGN: Cross-sectional analysis of National Health and Nutrition Examination Survey (1999-2004) dietary and anthropometric data. Diet quality was determined using United States Department of Agriculture's Healthy Eating Index 2005. Participants included adults aged 19 years and older, excluding pregnant and lactating women (N = 13,292). Lacto-ovo vegetarian diets were portrayed by intakes of participants who did not eat meat, poultry, or fish on the day of the survey (n = 851). Weight-loss diets were portrayed by intakes of participants who consumed 500 kcal less than their estimated energy requirements (n = 4,635). Mean nutrient intakes and body mass indexes were adjusted for energy, sex, and ethnicity. Using analysis of variance, all vegetarians were compared to all nonvegetarians, dieting vegetarians to dieting nonvegetarians, and nondieting vegetarians to nondieting nonvegetarians. RESULTS: Mean intakes of fiber, vitamins A, C, and E, thiamin, riboflavin, folate, calcium, magnesium, and iron were higher for all vegetarians than for all nonvegetarians. Although vegetarian intakes of vitamin E, vitamin A, and magnesium exceeded that of nonvegetarians (8.3 ± 0.3 vs 7.0 ± 0.1 mg; 718 ± 28 vs 603 ± 10 µg; 322 ± 5 vs 281 ± 2 mg), both groups had intakes that were less than desired. The Healthy Eating Index score did not differ for all vegetarians compared to all nonvegetarians (50.5 ± 0.88 vs 50.1 ± 0.33, P = 0.6). CONCLUSIONS: These findings suggest that vegetarian diets are nutrient dense, consistent with dietary guidelines, and could be recommended for weight management without compromising diet quality.

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The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5.5 % MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of beta-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source.

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As part of the workshop entitled "Early Risk Determinants and Later Health Outcomes: Implications for Research Prioritization and the Food Supply" (8-9 July 2008, Washington, DC), which was cosponsored by the International Life Sciences Institute of North America and the International Life Sciences Institute Research Foundation, representatives of the food industry discussed the practical application of nutrition science. Nutrition plays a key role in guiding health outcomes throughout the life cycle. In particular, the prenatal, postnatal, and early childhood periods are extremely sensitive to the presence of appropriate nutrition. A growing body of evidence shows that early nutrition may program the unborn and the infant's key physiologic systems, including the endocrine, cardiovascular, and central nervous systems, to influence later life outcomes. While scientists in academia continue to explore the multifactorial nature of early risk determinants and later life outcomes at a mechanistic and basic science level, it is important to understand the potential of the infant and child food industries to address questions such as what factors have been noted to drive research in these sectors of the food industry. How can scientists in these industries work alongside the scientists in academia and in government to set priorities, make decisions around these health issues, and translate academic insights into innovative nutritional solutions for the benefit of public health? Given the commitment of the infant and child food industries to deliver scientifically supported early life nutrition, it is easy to understand why this industry would work in partnership with both the scientists in academia and the government to identify a means of addressing the fundamental questions of this workshop.

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RNA and DNA oligonucleotides radiolabeled with (32)P or (33)P often require gel electrophoresis to remove undesired side and/or degradation products. Common ways to visualize these molecules after electrophoresis are by ultraviolet (UV) shadowing, which necessarily reduces the specific activity of the oligonucleotide, and by autoradiography using film, which is cumbersome and increases the cost of generating the radiolabeled molecule. A more cost-effective method is to physically inject the gel with a "Dip-N-Dot" solution of dye and radionuclide after electrophoresis but prior to phosphorimaging. The gel can be overlaid on its computer-generated image, allowing the labeled molecules to be visualized quickly.

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OBJECTIVE: The purpose of this study was to determine the microtensile bond strength of various resin composite/adhesive systems to alumina particle abraded Ti-6Al-4V substrate after aging for 24h, 10 days, and 30 days in distilled water at 37 degrees C. METHODS: Four laboratory resin composite veneering systems (Gradia, GR; Solidex, SOL; Ceramage, CER; and Sinfony, SF) were bonded to 25 mm diameter machined disks of Ti-6Al-4V with their respective adhesive and methodology, according to the manufacturer's instructions. Microtensile bars of approximate dimensions 1 mm x 1 mm x 6 mm were prepared for each resin composite/adhesive system. After cutting, groups (n=12) from each adhesive system were separated and either stored in water at 37 degrees C for 24h (baseline) or aged for 10 or 30 days prior to loading to failure under tension at a cross head speed of 1.0mm/min. Failure modes were determined by means of scanning electron microscopy (SEM). Statistical analysis was performed through one-way ANOVA and Tukey's test at 95% level of significance. RESULTS: Significant variation in microtensile bond strength was observed for the different systems and aging times. SOL and GR showed the highest mean bond strength values followed by SF and CER at baseline. Aging specimens in water had an adverse effect on bond strength for SOL and CER but not for the SF and GR groups. SIGNIFICANCE: In vitro bond strength of laboratory resin composites to Ti-6Al-4V suggests that strong bonds can be achieved and are stable for certain systems, making them useful as an alternative for esthetic fixed prosthetic restorations.

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This report reviews decade two of the lifetime diet restriction study of the dog. Labrador retrievers (n 48) were paired at age 6 weeks by sex and weight within each of seven litters, and assigned randomly within the pair to control-feeding (CF) or 25 % diet restriction (DR). Feeding began at age 8 weeks. The same diet was fed to all dogs; only the quantity differed. Major lifetime observations included 1.8 years longer median lifespan among diet-restricted dogs, with delayed onset of late life diseases, especially osteoarthritis. Long-term DR did not negatively affect skeletal maturation, structure or metabolism. Among all dogs, high static fat mass and declining lean body mass predicted death, most strongly at 1 year prior. Fat mass above 25 % was associated with increasing insulin resistance, which independently predicted lifespan and chronic diseases. Metabolizable energy requirement/lean body mass most accurately explained energy metabolism due to diet restriction; diet-restricted dogs required 17 % less energy to maintain each lean kilogram. Metabonomics-based urine metabolite trajectories reflected DR-related differences, suggesting that signals from gut microbiota may be involved in the DR longevity and health responses. Independent of feeding group, increased hazard of earlier death was associated with lower lymphoproliferative responses to phytohaemagglutinin, concanavalin A, and pokeweed mitogen; lower total lymphocytes, T-cells, CD4 and CD8 cells; lower CD8 percentages and higher B-cell percentages. When diet group was taken into account, PWM responses and cell counts and percentages remained predictive of earlier death.

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Long-term restriction of energy intake without malnutrition is a robust intervention that has been shown to prolong life and delay age-related morbidity. A 1H NMR-based metabonomic strategy was used to monitor urinary metabolic profiles throughout the lifetimes of control-fed and diet-restricted dogs. Urinary metabolic trajectories were constructed for each dog, and metabolic variation was found to be predominantly influenced by age. Urinary excretion of creatinine increased with age, reaching a maximum between ages 5 and 9 years and declining thereafter. Excretion of mixed glycoproteins was noted at earlier ages, which may be a reflection of growth patterns. In addition, consistent metabolic variation related to diet was also characterized, and energy-associated metabolites, such as creatine, 1-methylnicotinamide, lactate, acetate, and succinate, were depleted in urine from diet-restricted dogs. Both aging and diet restriction altered activities of the gut microbiotia, manifested by variation of aromatic metabolites and aliphatic amine compounds. This analysis allowed the metabolic response to two different physiological processes to be monitored throughout the lifetime of the canine population and may form part of a strategy to monitor and reduce the impact of age related diseases in the dog, as well as providing more general insights into extension of longevity in higher mammals.

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Effects of lifetime food restriction on erythrocytes and numerous clinical chemistry, thyroid, parathyroid, and acid-base variables are reported from a paired-feeding study of 25% diet restriction in dogs. The 48 dogs were paired by gender and weaning weight within litter, and 1 dog in each pair was fed 25% less than its pair mate, from age 8 weeks until death. Erythrocyte and serum biochemistry profiles were evaluated by annual sampling intervals and longitudinally. Erythrocyte variables were slightly higher among control-fed dogs, a possible reflection of the need to support both higher body fat mass and lean mass that uses energy less efficiently. Among serum biochemistry variables, glucose and triglyceride were lower among diet-restricted dogs, while creatinine was slightly higher in the absence of renal disease or failure, over the life spans of the dogs. Glucose outcomes reflect improved glucose tolerance that has been demonstrated with diet restriction protocols in several species, while triglyceride data may reflect the difference in total body fat cells between feeding groups. Creatinine outcomes may reflect lean mass responses to diet restriction or more efficient function of the intracellular proteasome. Serum triiodothyronine levels were lower among diet-restricted dogs. Other clinical chemistry and thyroid variables, parathyroid variables, and acid-base variables were not strongly influenced by diet restriction but revealed age-related effects.

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Traditional thinking views apparently non-programmed disruptions of aging, which medical science calls geriatric diseases, as separate from 'less harmful' morphological and physiological aging phenotypes that are more universally expected with passage of time (loss of skin elasticity, graying of hair coat, weight gain, increased sleep time, behavioral changes, etc). Late-life disease phenotypes, especially those involving chronic processes, frequently are complex and very energy-expensive. A non-programmed process of homeostatic disruption leading into a death trajectory seems inconsistent with energy intensive processes. That is, evolutionary mechanisms do not favor complex and prolonged energy investment in death. Taking a different view, the naturally occurring feline (Felis silvestris catus) renal model suggests that at least some diseases of late life represent only the point of failure in essentially survival-driven adaptive processes. In the feline renal model, individuals that succumbed to failure most frequently displayed progressive tubular deletion and peritubular interstitial fibrosis, but had longer mean life span than cats that died from other causes. Additionally, among cats that died from non-renal causes, those that had degrees of renal tubular deletion and peritubular interstitial fibrosis also had longer mean life span than those cats with no changes, even though causes of death differed minimally between these latter two groups. The data indicate that selective tubular deletion very frequently begins early in adult life, without a clear initiating phase or event. The observations support a hypothesis that this prolonged process may be intrinsic and protective prior to an ultimate point of failure. Moreover, given the genetic complexity and the interplay with associated risk factors, existing data also do not support the ideas that these changes are simple compensatory responses and that breed- or strain-based 'default' diseases are inevitable results of increasing individual longevity. Emerging molecular technology offers the future potential to further evaluate and refine these observations. At present, the existence of plastic and adaptive aging programming is suggested by these findings.

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OBJECTIVE: To describe effects of lifetime food restriction on causes of death and the association between body-mass characteristics and time of death in dogs. DESIGN: Paired-feeding study. ANIMALS: 48 dogs from 7 litters. PROCEDURES: Dogs were paired, and 1 dog in each pair was fed 25% less food than its pair mate from 8 weeks of age until death. Numerous morphometric and physiologic measures were obtained at various intervals throughout life. Associations of feeding group to time and causes of death were evaluated, along with important associated factors such as body composition components and insulin-glucose responses. RESULTS: Median life span was significantly longer for the group that was fed 25% less food, whereas causes of death were generally similar between the 2 feeding groups. High body-fat mass and declining lean mass significantly predicted death 1 year prior to death, and lean body composition was associated with metabolic responses that appeared to be integrally involved in health and longevity. CONCLUSIONS AND CLINICAL RELEVANCE: Results were similar to results of diet restriction studies in rodents and primates, reflecting delayed death from species- and strain-specific intrinsic causes. Clinicians should be aware that unplanned body mass changes during mid- and later life of dogs may indicate the need for thorough clinical evaluation.

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OBJECTIVE: To compare preferences of dogs for 2 similar foods by use of 2 distinct methods (the cognitive palatability assessment protocol [CPAP] and the 2-pan test). ANIMALS: 13 Beagles. PROCEDURE: 6 dogs were trained in a 3-choice object-discrimination-learning task in which their nonpreferred objects were associated with a reward of a lamb-based or chicken-based food. The number of choices for each object was used to determine food preferences. Preference of the same foods was also assessed by use of a 2-pan test in which all 13 dogs were provided the 2 foods in identical bowls. The amount of each food consumed in 10 minutes was used to determine food preference. RESULTS: All dogs had a noticeable preference for the chicken-based food during the CPAP. Once established, preferences remained consistent and were not affected by satiety. The 2-pan test identified a preference for the chicken-based food in dogs with previous exposure to the food but only a weak and nonsignificant preference for the same food in dogs without previous exposure. Food preferences in the 2-pan test varied considerably. Total food consumption and the ability to detect a preference were reduced when dogs were fed prior to testing. CONCLUSIONS AND CLINICAL RELEVANCE: The CPAP provides a reliable measure of food preference that requires few test subjects. The 2-pan test reveals similar preferences but with variability in data that requires larger numbers of subjects and is susceptible to effects from prior exposure and feeding of the test foods to the subjects.

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Labrador retrievers (42 of original 48) were used to assess the effects of lifetime diet restriction on glucose tolerance at ages 9-12 y. Restricted-fed (RF) dogs were fed 75% of the same diet consumed by control-fed (CF) pair-mates. An intravenous glucose tolerance test was done annually (maximal stimulation, nonsteady-state). Diet treatment, age, and interactions were fixed effects. Statistical procedures used included mixed-model, repeated-measures ANOVA; least-squares means; Tukey's multiple comparison; paired t tests; and Spearman rank correlations. Glucose k-value and half-life, and insulin sensitivity (total, and 9, 10, 11 y, and per lean mass) were higher (P < 0.05) in RF than in CF dogs. Late-phase insulin release [area under the curve (AUC) 30-120 min] was less (P < 0.05) in RF than in CR dogs. Early-phase insulin release (AUC 0-5 min), y 12 insulin sensitivity and insulinogenic index did not differ between RF and CF dogs. Insulin peak, delta and total AUC increased (P < 0.05) with age, whereas the glucose k-value and glucose half-life were not affected by age. Insulin sensitivity was negatively, and insulin AUC 30-120 min, peak and delta glucose were positively correlated with body weight, body condition score, fat mass, percentage of fat and abdominal fat/total tissue. Higher insulinogenic indices tended (P = 0.053) to be associated with greater median survival and dogs with higher insulin sensitivity were at lower (P < 0.05) risk of dying or receiving chronic disease treatment. Time to first osteoarthritis treatment or death was greater with lower basal glucose and higher insulin sensitivity (P < 0.05), but diet restriction explained most of this relationship's variation. Glucose disposal efficiency and insulin response were associated with increased quality and length of life in diet-restricted dogs.

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