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Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P> 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Abstract The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10−8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

Abstract Background This paper explores whether plans to quit, wanting to quit, and quit efficacy add predictive value over measures of habit strength and dependence in making quit attempts and/or attaining smoking abstinence. Aims and Methods We used three waves of the International Tobacco Control (ITC) Four Country Smoking and Vaping Survey conducted in 2016, 2018, and 2020. Baseline daily smokers (N = 6710) who provided data for at least one wave-to-wave transition (W1 to W2, N = 3511 or W2 to W3, N = 3199) and provided outcome data at the next wave (follow-up) formed the analytic sample. Generalized estimating equations (GEE) logistic regression analyses examined predictors of quit attempts and abstinence at follow-up (1- and 6-month sustained abstinence). Results Wanting and planning to quit were significantly positively associated with making quit attempts, but negatively associated with smoking abstinence. A significant interaction between the Heaviness of Smoking Index and age warranted an age-stratified analysis for both abstinence outcomes. Lower HSI predicted abstinence in only the younger smokers Motivation and plans to quit were positively associated with abstinence in younger smokers, but surprisingly were negatively associated with abstinence in older smokers. Quit efficacy was associated with abstinence in the older, but not the younger smokers. Conclusions Models of smoking abstinence are significantly improved by including motivational predictors of smoking. Age was an important moderator of the association between abstinence for both dependence and motivational variables. Implications The findings from this large cohort study indicate there are age-related differences in predictors of smoking abstinence but not quit attempts. These associations may reflect differential experiences of older and younger cohorts of smokers, which may have implications for interventions to motivate and assist smokers in quitting.

AbstractThe international community, comprised of national governments, multilateral agencies and civil society organisations, has recently negotiated a set of 17 sustainable development goals (SDGs) and 169 targets to replace the Millennium Development Goals, which expired in 2015. For progress in implementing the SDGs, ensuring policy coherence for sustainable development will be essential. We conducted a health impact assessment to identify potential incoherences between contemporary regional trade agreements (RTAs) and nutrition and health-related SDGs. Our findings suggest that obligations in RTAs may conflict with several of the SDGs. Areas of policy incoherence include the spread of unhealthy commodities, threats to equitable access to essential health services, medicines and vaccines, and reduced government regulatory flexibility. Scenarios for future incoherence are identified, with recommendations for how these can be avoided or mitigated. While recognising that governments have multiple policy ...

Funding: Royal Society - UF150663, RGF\EA\180141; Wellcome Trust - 217065/Z/19/Z; H2020 European Research Council - 694189; NWO - 451-15-017; National Health and Medical Research Council - 1173896; Canadian Institute for Health Research - MOP-133440. Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6–19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06–1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions. Publisher PDF Peer reviewed

Background: Increasingly, it is being suggested that translational gaps might be eradicated or narrowed by\ud bringing research users and producers closer together, a theory that is largely untested. This paper reports a\ud national study to fill a gap in the evidence about the conditions, processes and outcomes related to collaboration\ud and implementation.\ud Methods: A longitudinal realist evaluation using multiple qualitative methods case studies was conducted with\ud three Collaborations for Leadership in Applied Health Research in Care (England). Data were collected over four\ud rounds of theory development, refinement and testing. Over 200 participants were involved in semi-structured\ud interviews, non-participant observations of events and meetings, and stakeholder engagement. A combined\ud inductive and deductive data analysis process was focused on proposition refinement and testing iteratively over\ud data collection rounds.\ud Results: The quality of existing relationships between higher education and local health service, and views about\ud whether implementation was a collaborative act, created a path dependency. Where implementation was\ud perceived to be removed from service and there was a lack of organisational connections, this resulted in a focus\ud on knowledge production and transfer, rather than co-production. The collaborations’ architectures were\ud counterproductive because they did not facilitate connectivity and had emphasised professional and epistemic\ud boundaries. More distributed leadership was associated with greater potential for engagement. The creation of\ud boundary spanning roles was the most visible investment in implementation, and credible individuals in these roles\ud resulted in cross-boundary work, in facilitation and in direct impacts. The academic-practice divide played out\ud strongly as a context for motivation to engage, in that ‘what’s in it for me’ resulted in variable levels of engagement\ud along a co-operation-collaboration continuum. Learning within and across collaborations was patchy depending on\ud attention to evaluation.\ud Conclusions: These collaborations did not emerge from a vacuum, and they needed time to learn and develop.\ud Their life cycle started with their position on collaboration, knowledge and implementation. More impactful\ud attempts at collective action in implementation might be determined by the deliberate alignment of a number of\ud features, including foundational relationships, vision, values, structures and processes and views about the nature of\ud the collaboration and implementation.