Breast Cancer Index is a predictive biomarker of treatment benefit and outcome from extended tamoxifen therapy: final analysis of the Trans-aTTom study

PURPOSE: The Breast Cancer Index (BCI) HOXB13/IL17BR (H/I) ratio predicts benefit from extended endocrine therapy in hormone receptor–positive (HR(+)) early-stage breast cancer. Here, we report the final analysis of the Trans-aTTom study examining BCI (H/I)'s predictive performance. EXPERIMENTAL DESIGN: BCI results were available for 2,445 aTTom trial patients. The primary endpoint of recurrence-free interval (RFI) and secondary endpoints of disease-free interval (DFI) and disease-free survival (DFS) were examined using Cox proportional hazards regression and log-rank test. RESULTS: Final analysis of the overall study population (N = 2,445) did not show a significant improvement in RFI with extended tamoxifen [HR, 0.90; 95% confidence interval (CI), 0.69–1.16; P = 0.401]. Both the overall study population and N0 group were underpowered due to the low event rate in the N0 group. In a pre-planned analysis of the N(+) subset (N = 789), BCI (H/I)-High patients derived significant benefit from extended tamoxifen (9.7% absolute benefit: HR, 0.33; 95% CI, 0.14–0.75; P = 0.016), whereas BCI (H/I)-Low patients did not (−1.2% absolute benefit; HR, 1.11; 95% CI, 0.76–1.64; P = 0.581). A significant treatment-to-biomarker interaction was demonstrated on the basis of RFI, DFI, and DFS (P = 0.037, 0.040, and 0.025, respectively). BCI (H/I)-High patients remained predictive of benefit from extended tamoxifen in the N(+)/HER2(−) subgroup (9.4% absolute benefit: HR, 0.35; 95% CI, 0.15–0.81; P = 0.047). A three-way interaction evaluating BCI (H/I), treatment, and HER2 status was not statistically significant (P = 0.849). CONCLUSIONS: Novel findings demonstrate that BCI (H/I) significantly predicts benefit from extended tamoxifen in HR(+) N(+) patients with HER2(−) disease. Moreover, BCI (H/I) demonstrates significant treatment to biomarker interaction across survival outcomes

Quantifying the impact of avian influenza on the northern gannet colony of Bass Rock using ultra-high-resolution drone imagery and deep learning

Drones are an increasingly popular choice for wildlife surveys due to their versatility, quick response capabilities, and ability to access remote areas while covering large regions. A novel application presented here is to combine drone imagery with neural networks to assess mortality within a bird colony. Since 2021, Highly Pathogenic Avian Influenza (HPAI) has caused significant bird mortality in the UK, mainly affecting aquatic bird species. The world’s largest northern gannet colony on Scotland’s Bass Rock experienced substantial losses in 2022 due to the outbreak. To assess the impact, RGB imagery of Bass Rock was acquired in both 2022 and 2023 by deploying a drone over the island for the first time. A deep learning neural network was subsequently applied to the data to automatically detect and count live and dead gannets, providing population estimates for both years. The model was trained on the 2022 dataset and achieved a mean average precision (mAP) of 37%. Application of the model predicted 18,220 live and 3761 dead gannets for 2022, consistent with NatureScot’s manual count of 21,277 live and 5035 dead gannets. For 2023, the model predicted 48,455 live and 43 dead gannets, and the manual count carried out by the Scottish Seabird Centre and UK Centre for Ecology and Hydrology (UKCEH) of the same area gave 51,428 live and 23 dead gannets. This marks a promising start to the colony’s recovery with a population increase of 166% determined by the model. The results presented here are the first known application of deep learning to detect dead birds from drone imagery, showcasing the methodology’s swift and adaptable nature to not only provide ongoing monitoring of seabird colonies and other wildlife species but also to conduct mortality assessments. As such, it could prove to be a valuable tool for conservation purposes

Total fluid intake and the risk of recurrence in patients with non-muscle invasive bladder cancer::a prospective cohort study

Objectives: To investigate the role of fluid intake from beverages before and after a diagnosis of bladder cancer in relation to the risk of developing bladder cancer recurrence. Study Design: Prospective cohort study. Methods: 716 patients with non-muscle invasive bladder cancer (NMIBC), who received transurethral resection of a primary bladder tumour (TURBT) and completed self-administrated questionnaires on usual fluid intake from beverages at time of diagnosis (over the year before diagnosis) and during follow-up (over the year after diagnosis), were included. Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals of developing recurrent bladder cancer in relation to the intake of total fluid, total alcohol, and individual beverages. Results: During 2,025 person-years of follow-up, 238 (33%) of the included 716 NMIBC patients developed one or more recurrences of bladder cancer. Total fluid intake before diagnosis was not associated with a first recurrence of bladder cancer when comparing the highest and lowest intake group (HR = 0.98, 95% C.I. 0.70-1.38, p = 0.91). Comparable results were obtained for total fluid intake pre-diagnosis and the risk of developing multiple recurrences of bladder cancer (HR = 1.01, 95% C. I. 0.87-1.19, p = 0.85). A total of 379 of the 716 patients reported on usual fluid intake within 1 year of diagnosis. No significant associations between total fluid intake 1 year after diagnosis and a first recurrence of bladder cancer were found when comparing the highest and lowest intake group (HR = 0.91; 95% C. I. 0.60-1.37, p = 0.65) or with multiple recurrences of bladder cancer (HR = 1.06; 95% C. I. 0.89-1.26, p = 0.54). In addition, total alcohol intake and individual beverages were not associated with bladder cancer recurrence. Conclusions: The results indicate that an individual's fluid intake from beverages is unlikely to have an important role in bladder cancer recurrence

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

The endurance of children's working memory : a recall time analysis.

We analyse the timing of recall as a source of information about children’s performance in complex working memory tasks. A group of 8-year- old children performed a traditional operation span task in which sequence length increased across trials and an operation period task in which processing requirements were extended across trials of constant sequence length. Interword pauses were larger than is commonly found in immediate serial recall tasks, yet shorter than for reading span. These pauses increased with the demands of recall, decreased across the output sequence and were to some extent predictive of scholastic ability. Overall, timing data illustrate that recall in working memory tasks involve subtle processes of item access rather than simple read-out of information from an immediate store

The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers

Abstract Background: Hepatocellular carcinoma is a common complication of chronic liver disease (CLD), and is conventionally diagnosed by radiological means. We aimed to build a statistical model that could determine the risk of hepatocellular carcinoma in individual patients with CLD using objective measures, particularly serological tumor markers. Methods: A total of 670 patients with either CLD alone or hepatocellular carcinoma were recruited from a single UK center into a case–control study. Sera were collected prospectively and specifically for this study. A logistic regression analysis was used to determine independent factors associated with hepatocellular carcinoma and a model built and assessed in terms of sensitivity, specificity, and proportion of correct diagnoses. Results: The final model involving gender, age, AFP-L3, α fetoprotein (AFP), and des-carboxy-prothrombin (“GALAD”) was developed in a “discovery” data set and validated in independent data sets both from the same institution and from an external institution. When optimized for sensitivity and specificity, the model gave values of more than 0.88 irrespective of the disease stage. Conclusions: The presence of hepatocellular carcinoma can be detected in patients with CLD on the basis of a model involving objective clinical and serological factors. It is now necessary to test the model's performance in a prospective manner and in a routine clinical practice setting, to determine if it may replace or, more likely, enhance current radiological approaches. Impact: Our data provide evidence that an entirely objective serum biomarker–based model may facilitate the detection and diagnosis of hepatocellular carcinoma and form the basis for a prospective study comparing this approach with the standard radiological approaches. Cancer Epidemiol Biomarkers Prev; 23(1); 144–53. ©2013 AACR.</jats:p

Correlative studies of the Breast Cancer Index (HOXB13/IL17BR) and ER, PR, AR, AR/ER ratio and Ki67 for prediction of extended endocrine therapy benefit:a Trans-aTTom study

BACKGROUND: Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. METHODS: Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson’s correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. RESULTS: EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = − 0.18), PR (r = − 0.25), and AR (r = − 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). CONCLUSION: These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01589-x

Participation of foreign players on team game performance in our highest competition for women.

Title: Participation of foreign players on team game performance in our highest competition for women. Objectives: The goal of this master's thesis is to compare game performance of foreign players with Czech players from season 1998/1999 to season 2017/2018 in the highest Czech basketball competition for women. The partial goal of the thesis is to find out and observe the evolution of number of foreign players participating in above stated twenty-year period. Methods: In our thesis we used a method of collecting secondary information, which means secondary statistical data analysis. Results: By data analysis we found out, that foreign players were more effective than Czech players in all monitored seasons while comparing played time and reached index of success. The number of foreign players in the highest league was gradually growing until reaching its peak in season 2014/2015. Keywords: globalization, migration in sport, basketball, Czech women's basketball league, foreign players, comparison, game performanc