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ObjectivesPhysical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.MethodsWe performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.ResultsGreater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).ConclusionOur study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

BackgroundThe literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.ObjectivesTo complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).MethodsTwo-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.ResultsNominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.ConclusionsThese results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

National professional capabilities for Australian Diagnostic Radiography (DR) graduates require computed tomography (CT) scanning competence. Clinical placements have varied success in achiveing CT learning experiences and dedicated simulation at university can aid development of clinical skills. This study explored DR undergraduate students' attitudes, confidence and experiences of using a remote access simulation facility equipped with a live radiation commercial scanner. A pre- and post-clinical placement survey, with Likert scales and open-ended questions, was employed. Students in their third year of study undertook formal simulation CT learning using the NETRAD CT facility, prior to a four week off-campus clinical placement. Results indicate students (pre n = 21; post n = 23) had mixed levels of satisfaction when using NETRAD CT even though learning outcomes and relevance was clear. Comparison of pre- and post-matched statements reveals a significant decrease in students' perception of confidence in their skills post-clinical placement, reduced satisfaction with remote learning and increased preference for hands-on experiences. Open-ended responses were polarised to either positive simulation themes of convenience and repeatability, alongside negative themes with remote access and lack of facilitation. While students considered CT simulation to be educationally engaging, the technology-rich learning environment presented challenges and believed interactive simulation is inferior to real clinical experiences.

Objectives: This study explored the familiarity, perceptions and confidence of Australian radiology clinicians involved in reading screening mammograms, regarding artificial intelligence (AI) applications in breast cancer detection. Methods: Sixty-five radiologists, breast physicians and radiology trainees participated in an online survey that consisted of 23 multiple choice questions asking about their experience and familiarity with AI products. Furthermore, the survey asked about their confidence in using AI outputs and their preference for AI modes applied in a breast screening context. Participants' responses to questions were compared using Pearson's χ 2 test. Bonferroni-adjusted significance tests were used for pairwise comparisons. Results: Fifty-five percent of respondents had experience with AI in their workplaces, with automatic density measurement powered by machine learning being the most familiar AI product (69.4%). The top AI outputs with the highest ranks of perceived confidence were 'Displaying suspicious areas on mammograms with the percentage of cancer possibility' (67.8%) and 'Automatic mammogram classification (normal, benign, cancer, uncertain)' (64.6%). Radiology and breast physicians preferred using AI as second-reader mode (75.4% saying 'somewhat happy' to 'extremely happy') over triage (47.7%), pre-screening and first-reader modes (both with 26.2%) (P < 0.001). Conclusion: The majority of screen readers expressed increased confidence in utilising AI for highlighting suspicious areas on mammograms and for automatically classifying mammograms. They considered AI as an optimal second-reader mode being the most ideal use in a screening program. The findings provide valuable insights into the familiarities and expectations of radiologists and breast clinicians for the AI products that can enhance the effectiveness of the breast cancer screening programs, benefitting both healthcare professionals and patients alike. What is known about the topic? Artificial intelligence (AI) holds promise in providing computer-aided detection in health care, however, current research suggests that standalone AI applications in clinical practice fall short of matching the accuracy of a single radiologist. What does this paper add? The study showed a significant preference among clinicians for using AI as a supplementary tool, serving as a second-reader. Such an integrated approach, where AI aids in flagging suspicious areas on mammograms or offers automatic classification, reflects the ideal cooperation between breast screening readers and AI systems. What are the implications for practitioners? These insights shed light on clinicians' familiarity with and expectations of AI tools that can boost the effectiveness of breast screening programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is one of the leading causes of cancer-related death in women. The early detection of breast cancer with screening mammograms plays a pivotal role in reducing mortality rates. Although population-based double-reading screening mammograms have reduced mortality by over 31% in women with breast cancer in Europe, continuing this program is difficult due to the shortage of radiologists. Artificial intelligence (AI) is an emerging technology that has provided promising results in medical imaging for disease detection. This study investigates the performance of AI models on an Australian mammographic database, demonstrating how transfer learning from a USA mammographic database to an Australian one, contrast enhancement on mammographic images and the quality of training data according to radiologists' concordance can improve breast cancer diagnosis. Our proposed methodology offers a more efficacious approach for AI to contribute to radiologists' decision making when interpreting mammography images. This paper investigates the adaptability of four state-of-the-art artificial intelligence (AI) models to the Australian mammographic context through transfer learning, explores the impact of image enhancement on model performance and analyses the relationship between AI outputs and histopathological features for clinical relevance and accuracy assessment. A total of 1712 screening mammograms (n = 856 cancer cases and n = 856 matched normal cases) were used in this study. The 856 cases with cancer lesions were annotated by two expert radiologists and the level of concordance between their annotations was used to establish two sets: a 'high-concordances subset' with 99% agreement of cancer location and an 'entire dataset' with all cases included. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of Globally aware Multiple Instance Classifier (GMIC), Global-Local Activation Maps (GLAM), I&H and End2End AI models, both in the pretrained and transfer learning modes, with and without applying the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm. The four AI models with and without transfer learning in the high-concordance subset outperformed those in the entire dataset. Applying the CLAHE algorithm to mammograms improved the performance of the AI models. In the high-concordance subset with the transfer learning and CLAHE algorithm applied, the AUC of the GMIC model was highest (0.912), followed by the GLAM model (0.909), I&H (0.893) and End2End (0.875). There were significant differences (p < 0.05) in the performances of the four AI models between the high-concordance subset and the entire dataset. The AI models demonstrated significant differences in malignancy probability concerning different tumour size categories in mammograms. The performance of AI models was affected by several factors such as concordance classification, image enhancement and transfer learning. Mammograms with a strong concordance with radiologists' annotations, applying image enhancement and transfer learning could enhance the accuracy of AI models. [ABSTRACT FROM AUTHOR]

Objective Radiologists can detect the gist of abnormal based on their rapid initial impression on a mammogram (ie, global gist signal [GGS]). This study explores (1) whether global radiomic (ie, computer-extracted) features can predict the GGS; and if so, (ii) what features are the most important drivers of the signals. Methods The GGS of cases in two extreme conditions was considered: when observers detect a very strong gist (high-gist) and when the gist of abnormal was not/poorly perceived (low-gist). Gist signals/scores from 13 observers reading 4191 craniocaudal mammograms were collected. As gist is a noisy signal, the gist scores from all observers were averaged and assigned to each image. The high-gist and low-gist categories contained all images in the fourth and first quartiles, respectively. One hundred thirty handcrafted global radiomic features (GRFs) per mammogram were extracted and utilized to construct eight separate machine learning random forest classifiers (All , Normal , Cancer , Prior-1 , Prior-2 , Missed , Prior-Visible , and Prior-Invisible) for characterizing high-gist from low-gist images. The models were trained and validated using the 10-fold cross-validation approach. The models' performances were evaluated by the area under receiver operating characteristic curve (AUC). Important features for each model were identified through a scree test. Results The Prior-Visible model achieved the highest AUC of 0.84 followed by the Prior-Invisible (0.83), Normal (0.82), Prior-1 (0.81), All (0.79), Prior-2 (0.77), Missed (0.75), and Cancer model (0.69). Cluster shade , standard deviation , skewness , kurtosis , and range were identified to be the most important features. Conclusions Our findings suggest that GRFs can accurately classify high- from low-gist images. Advances in knowledge Global mammographic radiomic features can accurately predict high- from low-gist images with five features identified to be valuable in describing high-gist images. These are critical in providing better understanding of the mammographic image characteristics that drive the strength of the GGSs which could be exploited to advance breast cancer (BC) screening and risk prediction, enabling early detection and treatment of BC thereby further reducing BC-related deaths. [ABSTRACT FROM AUTHOR]

Objectives: To determine the UK prevalence of behavioral problems in 5-year-old children born with isolated or syndromic cleft lip and/or palate (CL/P) compared to the general population and identify potentially associated factors. Design: Observational study using questionnaire data from the Cleft Collective 5-Year-Old Cohort study and three general population samples. Main Outcome Measure: The Strengths and Difficulties Questionnaire (SDQ). Participants: Mothers of children (age: 4.9-6.8 years) born with CL/P (n = 325). UK general population cohorts for SDQ scores were: Millennium Cohort Study (MCS) (n = 12 511), Office of National Statistics (ONS) normative school-age SDQ data (n = 5855), and Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 9386). Results: By maternal report, 14.2% of children born with CL/P were above clinical cut-off for behavioral problems, which was more likely than in general population samples: 7.5% of MCS (OR = 2.05 [1.49-2.82], P < 0.001), 9.8% of ONS (OR = 1.52 [1.10-2.09], P = 0.008), and 6.6% of ALSPAC (OR = 2.34 [1.70-3.24], P < 0.001). Children in the Cleft Collective had higher odds for hyperactivity, emotional and peer problems, and less prosocial behaviors. Maternal stress, lower maternal health-related quality of life and family functioning, receiving government income support, and maternal smoking showed evidence of association (OR range: 4.41-10.13) with behavioral problems, along with maternal relationship status, younger age, and lower education (OR range: 2.34-3.73). Conclusions: Findings suggest elevated levels of behavioral problems in children born with CL/P compared to the general population with several associated maternal factors similar to the general population. [ABSTRACT FROM AUTHOR]

Background: Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. Methods: We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. Results: A 1-standard deviation (SD: 1.5h/day) increment in hours of television watching increased risk of breast cancer (OR per 1-SD: 1.15, 95% confidence interval [CI]: 1.05–1.26) and colorectal cancer (OR per 1-SD: 1.32, 95% CI: 1.16– 1.49) while there was little evidence of an association for prostate cancer risk (OR per 1-SD: 0.94, 95% CI: 0.84–1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1-SD: 1.08, 95% CI: 0.92–1.27; colorectal cancer, OR per 1-SD: 1.08, 95% CI: 0.90–1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk. Conclusions: Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development. [ABSTRACT FROM AUTHOR]

Meta-analyses combine the results of multiple studies of a common question. Approaches based on effect size estimates from each study are generally regarded as the most informative. However, these methods can only be used if comparable effect sizes can be computed from each study, and this may not be the case due to variation in how the studies were done or limitations in how their results were reported. Other methods, such as vote counting, are then used to summarize the results of these studies, but most of these methods are limited in that they do not provide any indication of the magnitude of effect. We propose a novel plot, the albatross plot, which requires only a 1-sided P value and a total sample size from each study (or equivalently a 2-sided P value, direction of effect and total sample size). The plot allows an approximate examination of underlying effect sizes and the potential to identify sources of heterogeneity across studies. This is achieved by drawing contours showing the range of effect sizes that might lead to each P value for given sample sizes, under simple study designs. We provide examples of albatross plots using data from previous meta-analyses, allowing for comparison of results, and an example from when a meta-analysis was not possible.