Executive functioning as a moderator of flossing behaviour among young adults: a temporal self-regulation theory perspective

Background - Flossing among young adults is often infrequent and barriers not completely understood. One explanation concerns the capacity for executive functioning (EF) during the self-regulation of behaviour. Methods - Using Temporal Self-Regulation Theory (TST) as a framework to explore EF, young adults from Norwegian universities completed a survey that measured monthly flossing frequency, flossing-related intentions and behavioural prepotency (BP), and EF using the Behaviour Rating Inventory of Executive Function – Adult Version (BRIEF-A). Results - Data from 362 participants were analysed. The TST-model explained a substantial proportion of variance in monthly flossing (R2 = 0.74), and flossing was associated directly with intention and BP, and interactions between intention and both BP and global-EF. Sub-domains of EF were explored using the same model, revealing that behavioural regulation processes, specifically those related to emotional control and shifting between tasks, offered better fit. Simple slopes revealed that moderation effects were only present at lower levels of BP. Conclusion - EF plays a role in moderating the translation of intentions into flossing behaviour. Specifically, emotional control and task-shifting appear to be influential, and this influence increases when habitual and environmental support (i.e. BP) is reduced. Overcoming EF-barriers may represent a key step in establishing flossing behaviours

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Publisher Correction: Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

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31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Exploring psychological correlates of toothbrushing behaviour - a systematic review of current research and a qualitative exploration of real-time influences

© 2019 Adam Austin RogersThis thesis explores the psychological mechanisms of toothbrushing routines among younger adults. With individual attitudes and beliefs linked to toothbrushing engagement, an improved understanding of these mechanisms is expected to have benefits for preventive oral health efforts. Current limitations are that: a) there is little agreement regarding the psychological constructs that best correlate with toothbrushing, and b) there is little explanation around the dynamic, real-time influences that may influence toothbrushing on a daily basis. Two projects were designed: a systematic review of the current literature to determine the psychological constructs that best correlate with toothbrushing, and a qualitative exploration of how real-time variables may impact toothbrushing. The systematic review screened 1117 articles. Analysis of the final sample (N=13) found that variables related to attitudes (r=0.30), self-efficacy (r=0.48), and intentions (r=0.59) had significant correlations with toothbrushing behaviour. However, findings were distorted by observations that methodology was poor/average, with the use of validated measures and reporting of statistics lacking across all studies. The qualitative study consisted of in-depth interviews (N=23) that discussed toothbrushing routines, perceived attitudes and norms related to toothbrushing, and if toothbrushing routines ever changed from day-to-day. Individuals reported that routines were subject to change, with morning toothbrushing often skipped due to stress, and night-time due to exhaustion. Those who rarely neglected brushing reported being motivated by personal reasons rather than social pressures. Findings suggest the locus of motivations and ability to self-regulate during stress and/or feelings of tiredness may play a role in the experience of real-time barriers to toothbrushing. This thesis highlights the importance of exploring psychological mechanisms within the oral health field. Future research might attempt to quantify how self-regulation relates to toothbrushing engagement in terms of real-time decision making. Researchers are suggested to investigate the role of social pressures relative to more intrinsic motivations, and are advised to focus on study design, validated measures and the use of past literature. Clinicians are advised to be conscious of the role that situational barriers may have on toothbrushing behaviour, and should consider fostering intrinsic motivation within patients, rather than using fear or social norms to elicit improved toothbrushing. Limitations to the thesis and additional suggestions for research and further exploration within this field are discussed

Top-down self-regulation processes as determinants of oral hygiene self-care behaviour: A systematic scoping review

Objectives Understanding the psychological mechanisms that moderate oral hygiene self-care behavior is anticipated to benefit efforts to change such behavior. Top-down self-regulatory (TSR) processes represent one group of relatively unexplored, yet potentially influential, moderating factors. This systematic scoping review aims to explore whether there is evidence that TSR processes moderate oral hygiene self-care engagement within the current literature. Methods CINAHL, The Cochrane Library, Embase, MEDLINE, PsycINFO, Scopus, and Web of Science databases were searched up to April 2020 for articles that compared measures of TSR processes (such as self-monitoring, inhibitory control, and task switching) to oral hygiene self-care behavior, or tested interventions that aimed to change or support TSR processes. Results The search returned 6626 articles, with 25 included in the final sample. Weak evidence supported both the role of TSR processes as moderators of interdental cleaning and the value of interventions targeting self-monitoring of interdental cleaning behavior. Overall, methodological limitations rendered the findings somewhat inconclusive, with an absence of objective assessments of TSR capacity, and little focus on TSR processes as moderators of intervention effects. Conclusions The inconclusive, but reasonably promising, findings point to the value of continuing to apply TSR processes within studies of oral hygiene behavior. Exploring why interdental cleaning appears more reliant on TSR processes than toothbrushing, employing objective neuropsychological assessment, and measuring TSR constructs within interventions targeting TSR processes, are encouraged. As a scoping review, the study hopes to generate interest and serve as a starting point for further investigation