ImageNet Large Scale Visual Recognition Challenge

The ImageNet Large Scale Visual Recognition Challenge is a benchmark in object category classification and detection on hundreds of object categories and millions of images. The challenge has been run annually from 2010 to present, attracting participation from more than fifty institutions. This paper describes the creation of this benchmark dataset and the advances in object recognition that have been possible as a result. We discuss the challenges of collecting large-scale ground truth annotation, highlight key breakthroughs in categorical object recognition, provide a detailed analysis of the current state of the field of large-scale image classification and object detection, and compare the state-of-the-art computer vision accuracy with human accuracy. We conclude with lessons learned in the five years of the challenge, and propose future directions and improvements.Comment: 43 pages, 16 figures. v3 includes additional comparisons with PASCAL VOC (per-category comparisons in Table 3, distribution of localization difficulty in Fig 16), a list of queries used for obtaining object detection images (Appendix C), and some additional reference

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.Comment: 45 pages 5 figure

Background risk of breast cancer and the association between physical activity and mammographic density

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Risk prediction models with incomplete data with application to prediction of estrogen receptor-positive breast cancer: prospective data from the Nurses' Health Study

Introduction A number of breast cancer risk prediction models have been developed to provide insight into a woman\u27s individual breast cancer risk. Although circulating levels of estradiol in postmenopausal women predict subsequent breast cancer risk, whether the addition of estradiol levels adds significantly to a model\u27s predictive power has not previously been evaluated. Methods Using linear regression, the authors developed an imputed estradiol score using measured estradiol levels (the outcome) and both case status and risk factor data (for example, body mass index) from a nested case-control study conducted within a large prospective cohort study and used multiple imputation methods to develop an overall risk model including both risk factor data from the main cohort and estradiol levels from the nested case-control study. Results The authors evaluated the addition of imputed estradiol level to the previously published Rosner and Colditz log-incidence model for breast cancer risk prediction within the larger Nurses\u27 Health Study cohort. The follow-up was from 1980 to 2000; during this time, 1,559 invasive estrogen receptor-positive breast cancer cases were confirmed. The addition of imputed estradiol levels significantly improved risk prediction; the age-specific concordance statistic increased from 0.635 ± 0.007 to 0.645 ± 0.007 (P \u3c 0.001) after the addition of imputed estradiol. Conclusion Circulating estradiol levels in postmenopausal women appear to add to other lifestyle factors in predicting a woman\u27s individual risk of breast cancer

Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies

INTRODUCTION: Although reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER(+)PR(+ )and ER(-)PR(- )cancer risk. MATERIALS AND METHODS: We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model. RESULTS: Each birth reduced the risk of ER(+)PR(+ )cancer by 11% (RR per birth = 0.89, 95% CI = 0.84–0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER(+)PR(+ )cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07–1.50). Neither parity nor age at first birth was associated with the risk of ER(-)PR(- )cancer (RR per birth = 0.99, 95% CI = 0.94–1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85–1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER(+)PR(+ )than ER(-)PR(- )cancer (RR = 0.72 for ER(+)PR(+ )cancer; RR = 0.84 for ER(-)PR(- )cancer, p for homogeneity = 0.006). CONCLUSION: Our findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth

Regulation of the Cardiac Na+/K+ ATPase by Phospholemman

Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe

Prioritization strategies in clinical practice guidelines development: a pilot study

Objective: Few methodological studies address the prioritization of clinical topics for the development of Clinical Practice Guidelines (CPGs). The aim of this study was to validate a methodology for Priority Determination of Topics (PDT) of CPGs. Methods and results: Firstly, we developed an instrument for PDT with 41 criteria that were grouped under 10 domains, based on a comprehensive systematic search. Secondly, we performed a survey of stakeholders involved in CPGs development, and end users of guidelines, using the instrument. Thirdly, a pilot testing of the PDT procedure was performed in order to choose 10 guideline topics among 34 proposed projects; using a multicriteria analysis approach, we validated a mechanism that followed five stages: determination of the composition of groups, item/domain scoring, weights determination, quality of the information used to support judgments, and finally, topic selection. Participants first scored the importance of each domain, after which four different weighting procedures were calculated (including the survey results). The process of weighting was determined by correlating the data between them. We also reported the quality of evidence used for PDT. Finally, we provided a qualitative analysis of the process. The main domains used to support judgement, having higher quality scores and weightings, were feasibility, disease burden, implementation and information needs. Other important domains suc

Risk factors for ductal and lobular breast cancer: results from the nurses' health study

Introduction Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses\u27 Health Study. Methods Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes. Results The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het \u3c 0.001) and postmenopausal hormone use (P-het \u3c 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors. Conclusions These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology

Ethnic differences in ovulatory function in nulliparous women

African-American women have a long-standing approximately 20% higher breast cancer incidence rate than USA White women under age 40 while rates among Latinas are lower than those of Whites. The reasons for this are not clear, however they may be due to ethnic differences in circulating oestradiol and progesterone levels. In a cross-sectional study, we investigated whether anovulation frequency and circulating serum oestradiol and/or progesterone levels vary among normally cycling nulliparous African-American (n=60), Latina (n=112) and non-Latina White (n=69) women. Blood and urine specimens were collected over two menstrual cycles among healthy 17- to 34-year-old women. Frequency of anovulation was greater among White women (nine out of 63, 14.3%) than African-American women (four out of 56, 7.1%) or Latina women (seven out of 102, 6.9%), although these differences were not statistically significant. African-American women had 9.9% (P=0.26) higher follicular phase oestradiol concentrations than Latina women and 17.4% (P=0.13) higher levels than White women. African-American women also had considerably higher levels of luteal phase oestradiol (vs Latinas, +9.4%, P=0.14; vs Whites, +25.3%, P=0.003) and progesterone (vs Latinas, +15.4%, P=0.07; vs Whites, +36.4%, P=0.002). Latina women were also observed to have higher follicular oestradiol, and luteal oestradiol and progesterone levels than White women (follicular oestradiol: +6.8%, P=0.48; luteal oestradiol: +14.6%, P=0.04; luteal progesterone: +18.2%, P=0.06). These results suggest that exposure to endogenous steroid hormones may be greater for young African-American and Latina women than for Whites