Human epididymis protein 4 reference limits and natural variation in a Nordic reference population

The objectives of this study are to establish reference limits for human epididymis protein 4, HE4, and investigate factors influencing HE4 levels in healthy subjects. HE4 was measured in 1,591 samples from the Nordic Reference Interval Project Bio-bank and Database biobank, using the manual HE4 EIA (Fujirebio) for 802 samples and the Architect HE4 (Abbott) for 792 samples. Reference limits were calculated using the statistical software R. The influence of donor characteristics such as age, sex, body mass index, smoking habits, and creatinine on HE4 levels was investigated using a multivariate model. The study showed that age is the main determinant of HE4 in healthy subjects, corresponding to 2% higher HE4 levels at 30 years (compared to 20 years), 9% at 40 years, 20% at 50 years, 37% at 60 years, 63% at 70 years, and 101% at 80 years. HE4 levels are 29% higher in smokers than in nonsmokers. In conclusion, HE4 levels in healthy subjects are associated with age and smoking status. Age-dependent reference limits are suggested

Identifying morphological indicators of aging with neural networks on large-scale whole-body MRI

A wealth of information is contained in images obtained by whole-body magnetic resonance imaging (MRI). Studying the link between the imaged anatomy and properties known from outside sources has the potential to give new insights into the underlying factors that manifest themselves in individual human morphology. In this work we investigate the expression of age-related changes in the whole-body image. A large dataset of about 32,000 subjects scanned from neck to knee and aged 44–82 years from the UK Biobank study was used for a machine-based analysis. We trained a convolutional neural network based on the VGG16 architecture to predict the age of a given subject based on image data from these scans. In 10-fold cross-validation on 23,000 of these images the network reached a mean absolute error (MAE) of 2.49 years (R 2 = 0.83) and showed consistent performance on a separate test set of another 8,000 images. On a second test set of 100 images the network outperformed the averaged estimates given by three experienced radiologists, which reached an MAE of 5.58 years (R 2 = 0.08), by more than three years on average. In an attempt to explain these findings, we employ saliency analysis that opens up the image-based criteria used by the automated method to human interpretation. We aggregate the saliency into a single anatomical visualization which clearly highlights structures in the aortic arch and knee as primary indicators of age

Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death-Results from the Norwegian Prostate Cancer Consortium

BACKGROUND: Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality.OBJECTIVE: To determine the association between midlife PSA levels 8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40-54 and 55-69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005.INTERVENTION: Baseline PSA.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5-0.9, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method.RESULTS AND LIMITATIONS: The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0-3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40-54 and 55-69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation.CONCLUSIONS: We replicated prior studies that baseline PSA at age 40-69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15-20 yr.PATIENT SUMMARY: A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man's risk of dying from prostate cancer in the next two decades