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Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.
Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.
Staphylococcus aureus nasal carriers were randomized (1:1) to XF-73 or placebo nasal gel, administered 5x over ∼24hrs pre-cardiac surgery. S. aureus burden rapidly decreased after 2 doses (–2.2log10 CFU/mL; placebo –0.01log10 CFU/mL) and was maintained to 6 days post-surgery. Among XF-73 patients, 46.5% received post-operative anti-staphylococcal antibiotics versus 70% in placebo (P = 0.045).
Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.
Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
We studied 83 cardiac-surgery patients with nasal S. aureus carriage who received 4 intranasal administrations of XF-73 nasal gel or placebo <24 hours before surgery. One hour before surgery, patients exhibited a S. aureus nasal carriage reduction of 2.5 log10 with XF-73 compared to 0.4 log10 CFU/mL for those who received placebo (95% CI, −2.7 to −1.5; P < .0001).
Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.
Written by academics from different disciplines and backgrounds, this book offers an international practical guide to doing diversity in the social sciences.