Consolidated guidance about materials licenses: Program-specific guidance about portable gauge licenses. Final report; Volume 1

As part of its redesign of the materials licensing process, NRC is consolidating and updating numerous guidance documents into a single comprehensive repository as described in NUREG-1539 and draft NUREG-1541. NUREG-1556, Vol. 1, is the first program-specific guidance developed for the new process and will serve as a template for subsequent program-specific guidance. This document is intended for use by applicants, licensees, and NRC staff and will also be available to Agreement States. This document supersedes the guidance previously found in draft Regulatory Guide DG-0008, ``Applications for the Use of Sealed Sources in Portable Gauging Devices,`` and in NMSs Policy and guidance Directive 2-07, ``Standard Review Plan for Applications for Use of Sealed Sources in Portable Gauging Devices.`` This final report takes a more risk-informed, performance-based approach to licensing portable gauges, and reduces the information(amount and level of detail) needed to support an application to use these devices. It incorporates many suggests submitted during the comment period on draft NUREG-1556, Volume 1. When published, this final report should be used in preparing portable gauge license applications. NRC staff will use this final report in reviewing these applications

Consolidated guidance about materials licenses: Program-specific guidance about portable gauge licenses. Final report; Volume 1

As part of its redesign of the materials licensing process, NRC is consolidating and updating numerous guidance documents into a single comprehensive repository as described in NUREG-1539 and draft NUREG-1541. NUREG-1556, Vol. 1, is the first program-specific guidance developed for the new process and will serve as a template for subsequent program-specific guidance. This document is intended for use by applicants, licensees, and NRC staff and will also be available to Agreement States. This document supersedes the guidance previously found in draft Regulatory Guide DG-0008, ``Applications for the Use of Sealed Sources in Portable Gauging Devices,`` and in NMSs Policy and guidance Directive 2-07, ``Standard Review Plan for Applications for Use of Sealed Sources in Portable Gauging Devices.`` This final report takes a more risk-informed, performance-based approach to licensing portable gauges, and reduces the information(amount and level of detail) needed to support an application to use these devices. It incorporates many suggests submitted during the comment period on draft NUREG-1556, Volume 1. When published, this final report should be used in preparing portable gauge license applications. NRC staff will use this final report in reviewing these applications

The asparagine-transamidosome from Helicobacter pylori: a dual-kinetic mode in non-discriminating aspartyl-tRNA synthetase safeguards the genetic code

Helicobacter pylori catalyzes Asn-tRNAAsn formation by use of the indirect pathway that involves charging of Asp onto tRNAAsn by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS), followed by conversion of the mischarged Asp into Asn by the GatCAB amidotransferase. We show that the partners of asparaginylation assemble into a dynamic Asn-transamidosome, which uses a different strategy than the Gln-transamidosome to prevent the release of the mischarged aminoacyl-tRNA intermediate. The complex is described by gel-filtration, dynamic light scattering and kinetic measurements. Two strategies for asparaginylation are shown: (i) tRNAAsn binds GatCAB first, allowing aminoacylation and immediate transamidation once ND-AspRS joins the complex; (ii) tRNAAsn is bound by ND-AspRS which releases the Asp-tRNAAsn product much slower than the cognate Asp-tRNAAsp; this kinetic peculiarity allows GatCAB to bind and transamidate Asp-tRNAAsn before its release by the ND-AspRS. These results are discussed in the context of the interrelation between the Asn and Gln-transamidosomes which use the same GatCAB in H. pylori, and shed light on a kinetic mechanism that ensures faithful codon reassignment for Asn

The effect of dose-interval on antibody response to mRNA COVID-19 vaccines: a prospective cohort study

BackgroundVaccination against COVID-19 is highly effective in preventing severe disease and hospitalization, but primary COVID mRNA vaccination schedules often differed from those recommended by the manufacturers due to supply chain issues. We investigated the impact of delaying the second dose on antibody responses to COVID mRNA-vaccines in a prospective cohort of health-care workers in Quebec.MethodsWe recruited participants from the McGill University Health Centre who provided serum or participant-collected dried blood samples (DBS) at 28-days, 3 months, and 6 months post-second dose and at 28-days after a third dose. IgG antibodies to SARS-CoV2 spike (S), the receptor-binding domain (RBD), nucleocapsid (N) and neutralizing antibodies to the ancestral strain were assessed by enzyme-linked immunosorbent assay (ELISA). We examined associations between long (≤89 days) versus short (<89 days) between-dose intervals and antibody response through multivariable mixed-effects models adjusted for age, sex, prior covid infection status, time since vaccine dose, and assay batch.FindingsThe cohort included 328 participants who received up to three vaccine doses (>80% Pfizer-BioNTech). Weighted averages of the serum (n=744) and DBS (n=216) cohort results from the multivariable models showed that IgG anti-S was 31% higher (95% CI: 12% to 53%) and IgG anti-RBD was 37% higher (95% CI: 14% to 65%) in the long vs. short interval participants, across all time points.InterpretationOur study indicates that extending the covid primary series between-dose interval beyond 89 days (approximately 3 months) provides stronger antibody responses than intervals less than 89 days. Our demonstration of a more robust antibody response with a longer between dose interval is reassuring as logistical and supply challenges are navigated in low-resource settings

A Randomised Experiment Evaluating the Mindful Raisin Practice as a Method of Reducing Chocolate Consumption During and After a Mindless Activity

The present study investigated the impact of the mindful raisin exercise on overeating during and after the experiment while controlling for wellbeing. One-hundred and twenty-eight participants were recruited and completed a questionnaire on wellbeing (i.e. depression, anxiety and stress) and state mindfulness. Participants were randomly allocated to either the mindful raisin exercise or a newspaper reading control condition. The State Mindfulness Scale was then completed again, and participants watched a neutral video while exposed to chocolate for 10 min. For those 10 min, results showed that the mindfulness condition translated into lower food consumption during the mindless activity when compared to the control condition. Post experiment, participants were asked to wait for 5 min, and any extra chocolate consumption during this time was recorded. Post-consumption was non-significantly different between the two groups, with those in the mindfulness condition consuming 1.3 g less than those in the control group. Controlling for wellbeing did not alter the impact of the mindfulness intervention on consumption. Implications for future work and practical applications for weight regulation are discussed

Predicting Weight Outcomes in Preadolescence: The Role of Toddlers? Self-regulation Skills and the Temperament Dimension of Pleasure

Objective To investigate the role of toddlers? self-regulation skills and temperament in predicting weight outcomes in preadolescence. Method Participants for this study included 195 children (114 girls) obtained from three different cohorts participating in a larger ongoing longitudinal study. At 2 years of age, participants participated in several laboratory tasks designed to assess their self-regulation abilities, including emotion regulation, sustained attention, and delay of gratification, while parents filled out a temperament questionnaire to assess toddlers? pleasure expression. Height and weight measures were collected when children were 4, 5, 7, and 10 years of age. Children also filled out a body image and eating questionnaire at the 10 year visit. Results Self-regulation skills in toddlers were associated with both BMI development, pediatric obesity, and body image/eating concerns. The temperament dimension of pleasure was also associated with BMI development and pediatric obesity but not body image/eating concerns. Conclusion Self-regulation difficulties across domains as well as temperament based pleasure in toddlers represented significant individual risk factors for the development of pediatric obesity eight years later. Early self-regulation difficulties also contributed to body image and eating concerns that typically accompanied overweight children. The mechanisms by which early self-regulation skills and temperament based pleasure may contribute to the development of pediatric obesity and associated weight concerns are discussed

Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

International audienceBACKGROUND:Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought.METHODOLOGY/PRINCIPAL FINDINGS:Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.CONCLUSIONS/SIGNIFICANCE:This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development

Changing perceptions of hunger on a high nutrient density diet

<p>Abstract</p> <p>Background</p> <p>People overeat because their hunger directs them to consume more calories than they require. The purpose of this study was to analyze the changes in experience and perception of hunger before and after participants shifted from their previous usual diet to a high nutrient density diet.</p> <p>Methods</p> <p>This was a descriptive study conducted with 768 participants primarily living in the United States who had changed their dietary habits from a low micronutrient to a high micronutrient diet. Participants completed a survey rating various dimensions of hunger (physical symptoms, emotional symptoms, and location) when on their previous usual diet versus the high micronutrient density diet. Statistical analysis was conducted using non-parametric tests.</p> <p>Results</p> <p>Highly significant differences were found between the two diets in relation to all physical and emotional symptoms as well as the location of hunger. Hunger was not an unpleasant experience while on the high nutrient density diet, was well tolerated and occurred with less frequency even when meals were skipped. Nearly 80% of respondents reported that their experience of hunger had changed since starting the high nutrient density diet, with 51% reporting a dramatic or complete change in their experience of hunger.</p> <p>Conclusions</p> <p>A high micronutrient density diet mitigates the unpleasant aspects of the experience of hunger even though it is lower in calories. Hunger is one of the major impediments to successful weight loss. Our findings suggest that it is not simply the caloric content, but more importantly, the micronutrient density of a diet that influences the experience of hunger. It appears that a high nutrient density diet, after an initial phase of adjustment during which a person experiences "toxic hunger" due to withdrawal from pro-inflammatory foods, can result in a sustainable eating pattern that leads to weight loss and improved health. A high nutrient density diet provides benefits for long-term health as well as weight loss. Because our findings have important implications in the global effort to control rates of obesity and related chronic diseases, further studies are needed to confirm these preliminary results.</p

'Yeah that made a big difference!': The importance of the relationship between health professionals and fathers who have a child with Down Syndrome

Evidence suggests that medical services do not reflect the increased involvement of fathers in childcare, a discrepancy that can often lead to feelings of exclusion and inequality. Fathers who have a child with Down syndrome may encounter many different health professionals during their child’s life, therefore it is important to consider this relationship, and investigate the factors that influence their experiences. This is particularly important because the limited research focusing on fathers suggest that those who have a child with Down syndrome can experience increased stress levels and lasting feelings of loss and grief. It is therefore important to address their relationships with health professionals, as these may be a significant resource to prevent these feelings. This study used interpretative phenomenological analysis (IPA) to explore the experiences of seven fathers who have a child with Down syndrome, focusing on their interactions with health professionals. The analysis showed that the major factors associated with negative experiences were feelings of exclusion, receiving overly negative information about the condition and a perceived lack of on-going support. Positive experiences were associated with being made to feel like an equal parent, being given direct/clear information and being congratulated on the birth of their child. These results provide an insight into what fathers expect in terms of their own and their child’s care and highlight that health professionals have an important and extensive role in influencing fathers’ experiences of Down syndrome