Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

Memory development: implications for adults recalling childhood experiences in the courtroom

Adults frequently provide compelling, detailed accounts of early childhood experiences in the courtroom. Judges and jurors are asked to decide guilt or innocence based solely on these decades-old memories using 'common sense' notions about memory. However, these notions are not in agreement with findings from neuroscientific and behavioural studies of memory development. Without expert guidance, judges and jurors may have difficulty in properly adjudicating the weight of memory evidence in cases involving adult recollections of childhood experiences

Patterns of care and emergency presentations for people with non-small cell lung cancer in New South Wales, Australia: A population-based study

Introduction Little is known about population-wide emergency presentations and patterns of care for people diagnosed with non-small cell lung cancer (NSCLC) in Australia. We examined patients’ characteristics associated with presenting to an emergency department around the time of diagnosis (“emergency presenters”), and receiving anti-cancer treatment within 12 months of diagnosis. Materials and Methods Participants in the 45 and Up Study who were newly diagnosed with NSCLC during 2006–2010 were included. We used linked data from population-wide health databases including Medicare and pharmaceutical claims, inpatient hospitalisations and emergency department presentations to follow participants to June 2014. Patients’ characteristics associated with being an emergency presenter and receiving any anti-cancer treatment were examined. Results A total of 647 NSCLC cases were included (58.6% male, median age 73 years). Emergency presenters (34.5% of cases) were more likely to have a high Charlson comorbidity index score, be an ex-smoker who had quit in the past 15 years and to be diagnosed with distant metastases. Almost all patients had visited their general practitioner ≥3 times in the 6 months prior to diagnosis. Nearly one-third (29.5%) of patients did not receive any anti-cancer treatment, however, there were no differences between emergency and non-emergency presenters in the likelihood of receiving treatment. Those less likely to be treated were older, had no private health insurance, and had unknown stage disease recorded. Conclusion Our results indicate the difficulties in diagnosing lung cancer at an early stage and inequities in NSCLC treatment. Future research should address opportunities to diagnose lung cancer earlier and to optimise treatment pathways

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

"What do i think about implementing lung cancer screening? It all depends on how." Acceptability and feasibility of lung cancer screening in Australia: The view of key stakeholders about health system factors

Background: Lung cancer is the number one cause of cancer death worldwide. Although international trials demonstrate that targeted screening using low dose computed tomography (LDCT) significantly reduces lung cancer mortality, implementation of screening in the high-risk population presents complex health system challenges that need to be thoroughly understood to support policy change. Aim: To elicit health care providers' and policymakers' views about the acceptability and feasibility of lung cancer screening (LCS) and barriers and enablers to implementation in the Australian setting. Methods: We conducted 24 focus groups and three interviews (22 focus groups and all interviews online) in 2021 with 84 health professionals, researchers, and current cancer screening program managers and policy makers across all Australian states and territories. Focus groups included a structured presentation about lung cancer and screening and lasted approximately one hour each. A qualitative approach to analysis was used to map topics to the Consolidated Framework for Implementation Research. Results: Nearly all participants considered LCS to be acceptable and feasible but identified a wide range of implementation challenges. Topics (five specific to health systems and five crosscutting with participant factors) identified were mapped to CFIR constructs, of which 'readiness for implementation', 'planning' and 'executing' were most salient. Health system factor topics included delivery of the LCS program, cost, workforce considerations, quality assurance and complexity of health systems. Participants strongly advocated for streamlined referral processes. Practical strategies to address equity and access, such as using mobile screening vans, were emphasised. Conclusions: Key stakeholders readily identified the complex challenges associated with the acceptability and feasibility of LCS in Australia. The barriers and facilitators across health system and cross-cutting topics were clearly elicited. These findings are highly relevant to the scoping of a national LCS program by the Australian Government and a subsequent recommendation for implementation

“We need to work towards it, whatever it takes.”—participation factors in the acceptability and feasibility of lung cancer screening in Australia: the perspectives of key stakeholders

Background: Low dose computed tomography (LDCT) screening, targeted at those at high-risk, has been shown to significantly reduce lung cancer mortality and detect cancers at an early stage. Practical, attitudinal and demographic factors can inhibit screening participation in high-risk populations. This study aimed to explore stakeholders’ views about barriers and enablers (determinants) to participation in lung cancer screening (LCS) in Australia. Methods: Twenty-four focus groups (range 2–5 participants) were conducted in 2021 using the Zoom platform. Participants were 84 health professionals, researchers, policy makers and program managers of current screening programs. Focus groups consisted of a structured presentation with facilitated discussion lasting about 1 hour. The content was analysed thematically and mapped to the Consolidated Framework for Implementation Research (CFIR). Results: Screening determinants were identified across each stage of the proposed screening and assessment pathway. Challenges included participant factors such as encouraging participation for individuals at high-risk, whilst ensuring that access and equity issues were carefully considered in program design. The development of awareness campaigns that engaged LCS participants and health professionals, as well as streamlined referral processes for initial entry and follow-up, were strongly advocated for. Considering practical factors included the use of mobile vans in convenient locations. Conclusions: Participants reported that LCS in Australia was acceptable and feasible. Participants identified a complex set of determinants across the proposed screening and assessment pathway. Strategies that enable the best chance for program success must be identified prior to implementation of a national LCS program

ILC3 function as a double-edged sword in inflammatory bowel diseases

Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Search for lepton-flavour-violating decays of the Higgs and Z bosons with the ATLAS detector

Direct searches for lepton flavour violation in decays of the Higgs and Z bosons with the ATLAS detector at the LHC are presented. The following three decays are considered: H→eτ, H→μτ, and Z→μτ. The searches are based on the data sample of proton–proton collisions collected by the ATLAS detector corresponding to an integrated luminosity of 20.3 fb−1 at a centre-of-mass energy of s√=8 TeV. No significant excess is observed, and upper limits on the lepton-flavour-violating branching ratios are set at the 95 % confidence level: Br (H→eτ)<1.04%, Br (H→μτ)<1.43%, and Br (Z→μτ)<1.69×10−5