CD161(+) Tconv and CD161(+) Treg Share a Transcriptional and Functional Phenotype despite Limited Overlap in TCR beta Repertoire

Human regulatory T cells (Treg) are important in immune regulation, but can also show plasticity in specific settings. CD161 is a lectin-like receptor and its expression identifies an effector-like Treg population. Here, we determined how CD161+ Treg relate to CD161+ conventional T cells (Tconv). Transcriptional profiling identified a shared transcriptional signature between CD161+ Tconv and CD161+ Treg, which is associated with T helper (Th)1 and Th17 cells, and tissue homing, including high expression of gut-homing receptors. Upon retinoic acid (RA) exposure, CD161+ T cells were more enriched for CCR9+ and integrin α4+β7+ cells than CD161− T cells. In addition, CD161+ Tconv and CD161+ Treg were enriched at the inflamed site in autoimmune arthritis, and both CD161+ and CD161− Treg from the inflamed site were suppressive in vitro. CD161+ T cells from the site of autoimmune arthritis showed a diminished gut-homing phenotype and blunted response to RA suggesting prior imprinting by RA in the gut or at peripheral sites rather than during synovial inflammation. TCRβ repertoires of CD161+ and CD161− Tconv and Treg from blood showed limited overlap whereas there was clear overlap between CD161+ and CD161− Tconv, and CD161+ and CD161− Treg from the inflamed site suggesting that the inflamed environment may alter CD161 levels, potentially contributing to disease pathogenesis

Marketing authorization procedures for advanced cancer drugs: exploring the views of patients, oncologists, healthcare decision makers and citizens in France

International audienceBackground. The past decades have seen advances in cancer treatments in terms of toxicity and side effects but progress in the treatment of advanced cancer has been modest. New drugs have emerged improving progression free survival but with little impact on overall survival, raising questions about the criteria on which to base decisions to grant marketing authorizations and about the authorization procedure itself. For decisions to be fair, transparent and accountable, it is necessary to consider the views of those with relevant expertise and experience. Methods. We conducted a Q-study to explore the views of a range of stakeholders in France, involving: 54 patients (18 months after diagnosis); 50 members of the general population; 27 oncologists; 19 healthcare decision makers; and 2 individuals from the pharmaceutical industry. Results. Three viewpoints emerged, focussing on different dimensions entitled: 1) ‘Quality of life (QoL), opportunity cost and participative democracy’; 2)‘QoL and patient-centeredness’; and 3) ‘Length of life’. Respondents from all groups were associated with each viewpoint, except for healthcare decision makers, who were only associated with the first one. Conclusion. Our results highlight plurality in the views of stakeholders, emphasize the need for transparency in decision making processes, and illustrate the importance of a re-evaluation of treatments for all 3 viewpoints. In the context of advanced cancer, our results suggest that QoL should be more prominent amongst authorization criteria, as it is a concern for 2 of the 3 viewpoints

Examining ‘gender-sensitive’ approaches to nuclear weapons policy: a study of the Non-Proliferation Treaty

The past decade has seen a push for ‘gender sensitive’ approaches within nuclear policy-making. Yet the significance of this approach, and how it understands ‘gender sensitivity’ are unclear and have not been studied. This article asks the question: how does work done on ‘gendering’ nuclear policy to date understand what a gender sensitive approach to nuclear weapons means and requires? The article provides an overview of the movement to include gender in nuclear policymaking before conducting an analysis of the discourse on gender in a core institution of nuclear politics, the Nuclear Non-Proliferation Treaty (NPT). Through qualitative analysis of five years of NPT texts, we find that dominant understandings of a ‘gender sensitive approach’ centre on the inclusion of women. We further find that there is almost no mention of men and masculinity in the NPT discourse; women are constructed as a homogenous category of outsiders; and women's inclusion is understood mainly as a means of increasing institutional efficiency. We suggest that the next steps in ‘gendering’ nuclear policy engage more with feminist policy analysis and the experiences of those already working within the policy space, and consider further how and if one can meaningfully link gender sensitive approaches to the practice of nuclear deterrence. The findings of this study also have significance beyond nuclear weapons, illuminating the broader dynamics and challenges of ‘gendering’ international security spaces

Radiation-induced root surface caries restored with glass-ionomer cement placed in conventional and ART cavity preparations: Results at two years

The document attached has been archived with permission from the Australian Dental Association (8th Jan 2008). An external link to the publisher’s copy is included.Background: There are no published studies comparing the clinical performances of more-viscous glass-ionomer cement (GIC) restorations when placed using conventional and atraumatic restorative treatment (ART) cavity preparation methods to restore root surface caries. Methods: One dentist used encapsulated Fuji IX GP and Ketac-Molar to restore 72 conventional and 74 ART cavity preparations for 15 patients who had received cervicofacial radiation therapy. Two assessors evaluated the restorations at six, 12, and 24 months for retention, marginal defects and surface wear, and recurrent caries. Results: After two years, the cumulative restoration successes were 65.2 per cent for the conventional and 66.2 per cent for the ART cavity preparations, without statistical or clinical significance (P>0.50). Restoration dislodgement accounted for 82.8 per cent and marginal defects for 17.2 per cent of all failures. There were no instances of unsatisfactory restoration wear or recurrent caries observed. Teeth with three or more restored cervical surfaces accounted for 79.3 per cent of all failures (P<0.0001). Conclusions: For root surface caries restored with GIC, the use of hand instruments only with the ART method was an equally effective alternative to conventional rotary instrumentation for cavity preparation. Larger restorations had higher failures, usually from dislodgement.JY Hu, XC Chen, YQ Li, RJ Smales and KH Yi

Effects of patient health literacy, patient engagement and a system-level health literacy attribute on patient-reported outcomes: A representative statewide survey

BACKGROUND: The effects of health literacy are thought to be based on interactions between patients’ skill levels and health care system demands. Little health literacy research has focused on attributes of health care organizations. We examined whether the attribute of individuals’ experiences with front desk staff, patient engagement through bringing questions to a doctor visit, and health literacy skills were related to two patient-reported outcomes. METHODS: We administered a telephone survey with two sampling frames (i.e., household landline, cell phone numbers) to a randomly selected statewide sample of 3358 English-speaking adult residents of Missouri. We examined two patient-reported outcomes – whether or not respondents reported knowing more about their health and made better choices about their health following their last doctor visit. Multivariable logistic regression models were used to examine the independent contributions of predictor variables (i.e., front desk staff, bringing questions to a doctor visit, health literacy skills). RESULTS: Controlling for self-reported health, having a personal doctor, time since last visit, number of chronic conditions, health insurance, and sociodemographic characteristics, respondents who had a good front desk experience were 2.65 times as likely (95% confidence interval [CI]: 2.13, 3.30) and those who brought questions were 1.73 times as likely (95% CI: 1.32, 2.27) to report knowing more about their health after seeing a doctor. In a second model, respondents who had a good front desk experience were 1.57 times as likely (95% CI: 1.26, 1.95) and those who brought questions were 1.66 times as likely (95% CI: 1.29, 2.14) to report making better choices about their health after seeing a doctor. Patients’ health literacy skills were not associated with either outcome. CONCLUSIONS: Results from this representative statewide survey may indicate that one attribute of a health care organization (i.e., having a respectful workforce) and patient engagement through question asking may be more important to patient knowledge and health behaviors than patients’ health literacy skills. Findings support focused research to examine the effects of organizational attributes on patient health outcomes and system-level interventions that might enhance patient health

Fatigue and Recovery Time Course After Female Soccer Matches: A Systematic Review And Meta-analysis.

BACKGROUND: This study aimed to analyze the extent of fatigue responses after female soccer matches and the ensuing recovery time course of performance, physiological, and perceptual responses. METHODS: Three databases (PubMed, Web of Science, and SPORTDiscus) were searched in October 2020 and updated in November 2021. Studies were included when participants were female soccer players, regardless of their ability level. Further, the intervention was an official soccer match with performance, physiological, or perceptual parameters collected pre- and post-match (immediately, 12 h, 24 h, 48 h, or 72 h-post). RESULTS: A total of 26 studies (n = 465 players) were included for meta-analysis. Most performance parameters showed some immediate post-match reduction (effect size [ES] = - 0.72 to - 1.80), apart from countermovement jump (CMJ; ES = - 0.04). Reduced CMJ performance occurred at 12 h (ES = - 0.38) and 24 h (ES = - 0.42) and sprint at 48 h post-match (ES = - 0.75). Inflammatory and immunological parameters responded acutely with moderate-to-large increases (ES = 0.58-2.75) immediately post-match. Creatine kinase and lactate dehydrogenase alterations persisted at 72 h post-match (ES = 3.79 and 7.46, respectively). Small-to-moderate effects were observed for increased cortisol (ES = 0.75) and reduced testosterone/cortisol ratio (ES = -0.47) immediately post-match, while negligible to small effects existed for testosterone (ES = 0.14) and estradiol (ES = 0.34). Large effects were observed for perceptual variables, with increased fatigue (ES = 1.79) and reduced vigor (ES = - 0.97) at 12 h post-match, while muscle soreness was increased immediately post (ES = 1.63) and at 24 h post-match (ES = 1.00). CONCLUSIONS: Acute fatigue exists following female soccer matches, and the performance, physiological, and perceptual parameters showed distinctive recovery timelines. Importantly, physical performance was recovered at 72 h post-match, whereas muscle damage markers were still increased at this time point. These timelines should be considered when planning training and match schedules. However, some caution should be advised given the small number of studies available on this population. REGISTRATION: The protocol for this systematic review was pre-registered on the International Prospective Register of Systematic Reviews (PROSPERO, Registration Number: CRD42021237857)

Unicellular cyanobacteria are important components of phytoplankton communities in Australia's northern oceanic ecoregions

© 2019 Moore, Huang, Ostrowski, Mazard, Kumar, Gamage, Brown, Messer, Seymour and Paulsen. The tropical marine environments of northern Australia encompasses a diverse range of geomorphological and oceanographic conditions and high levels of productivity and nitrogen fixation. However, efforts to characterize phytoplankton assemblages in these waters have been restricted to studies using microscopic and pigment analyses, leading to the current consensus that this region is dominated by large diatoms, dinoflagellates, and the marine cyanobacterium Trichodesmium. During an oceanographic transect from the Arafura Sea through the Torres Strait to the Coral Sea, we characterized prokaryotic and eukaryotic phytoplankton communities in surface waters using a combination of flow cytometry and Illumina based 16S and 18S ribosomal RNA amplicon sequencing. Similar to observations in other marine regions around Australian, phytoplankton assemblages throughout this entire region were rich in unicellular picocyanobacterial primary producers while picoeukaryotic phytoplankton formed a consistent, though smaller proportion of the photosynthetic biomass. Major taxonomic groups displayed distinct biogeographic patterns linked to oceanographic and nutrient conditions. Unicellular picocyanobacteria dominated in both flow cytometric abundance and carbon biomass, with members of the Synechococcus genus dominating in the shallower Arafura Sea and Torres Strait where chlorophyll a was relatively higher (averaging 0.4 ± 0.2 mg m-3), and Prochlorococcus dominating in the oligotrophic Coral Sea where chlorophyll a averaged 0.13 ± 0.07 mg m-3. Consistent with previous microscopic and pigment-based observations, we found from sequence analysis that a variety of diatoms (Bacillariophyceae) exhibited high relative abundance in the Arafura Sea and Torres Strait, while dinoflagellates (Dinophyceae) and prymnesiophytes (Prymnesiophyceae) were more abundant in the Coral Sea. Ordination analysis identified temperature, nutrient concentrations and water depth as key drivers of the region's assemblage composition. This is the first molecular and flow cytometric survey of the abundance and diversity of both prokaryotic and picoeukaryotic phytoplankton in this region, and points to the need to include the picocyanobacterial populations as an essential oceanic variable for sustained monitoring in order to better understand the health of these important coastal waters as global oceans change

Comparison of Cross-Sectional and Daily Reports in Studying the Relationship Between Depression and Use of Alcohol in Response to Stress in College Students

Alcohol use in response to stress in college students may be affected by the presence of symptoms of depression. However, this is a challenging issue to study due to the various methodologies used as well as the possible effect of depressed mood on the accuracy of self-report. This study focused on methodological issues as possible sources of equivocal findings regarding the relationship between depressed mood and alcohol use in response to stress in a college student population. Findings may differ when these variables are examined cross-sectionally versus longitudinally. Methods : Depressed mood and alcohol coping were assessed both cross-sectionally and repeatedly over time in 125 college students. Participants were assessed at baseline using a diagnostic self-report measure of depression as well as a measure of typical coping style. In addition, daily measures of stress, symptoms of depression, and coping were completed for 45 consecutive days. Results : Different relationships between depressed mood and alcohol coping were found when depressed individuals were analyzed separately from those who were not depressed. Although a significant correlation between daily use of alcohol coping and daily depressed mood was found, there were no differences between depressed and nondepressed participants (as assessed at baseline) on daily alcohol coping. Conclusions : These findings have implications for research design as well as clinical assessment regarding the relationships between mood and use of alcohol for coping; the findings suggest that cross-sectional measures of mood and alcohol use may obscure differences as assessed repeatedly over time. In addition, these findings support the utility of frequent assessment of depressive symptoms when implementing or evaluating programs that target coping skills in college students.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65757/1/j.1530-0277.2000.tb04552.x.pd

Mathematically gifted and talented learners: Theory and practice

This is an Author's Accepted Manuscript of an article published in International Journal of Mathematical Education in Science and Technology, 40(2), 213-228, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/00207390802566907.There is growing recognition of the special needs of mathematically gifted learners. This article reviews policy developments and current research and theory on giftedness in mathematics. It includes a discussion of the nature of mathematical ability as well as the factors that make up giftedness in mathematics. The article is set in the context of current developments in Mathematics Education and Gifted Education in the UK and their implications for Science and Technology. It argues that early identification and appropriate provision for younger mathematically promising pupils capitalizes on an intellectual resource which could provide future mathematicans as well as specialists in Science or Technology. Drawing on a Vygotskian framework, it is suggested that the mathematically gifted require appropriate cognitive challenges as well as attitudinally and motivationally enhancing experiences. In the second half of this article we report on an initiative in which we worked with teachers to identify mathematically gifted pupils and to provide effective enrichment support for them, in a number of London Local Authorities. A number of significant issues are raised relating to the identification of mathematical talent, enrichment provision for students and teachers’ professional development