A half-second glimpse often lets radiologists identify breast cancer cases even when viewing the mammogram of the opposite breast

Humans are very adept at extracting the “gist” of a scene in a fraction of a second. We have found that radiologists can discriminate normal from abnormal mammograms at above-chance levels after a half-second viewing (d′ ∼ 1) but are at chance in localizing the abnormality. This pattern of results suggests that they are detecting a global signal of abnormality. What are the stimulus properties that might support this ability? We investigated the nature of the gist signal in four experiments by asking radiologists to make detection and localization responses about briefly presented mammograms in which the spatial frequency, symmetry, and/or size of the images was manipulated. We show that the signal is stronger in the higher spatial frequencies. Performance does not depend on detection of breaks in the normal symmetry of left and right breasts. Moreover, above-chance classification is possible using images from the normal breast of a patient with overt signs of cancer only in the other breast. Some signal is present in the portions of the parenchyma (breast tissue) that do not contain a lesion or that are in the contralateral breast. This signal does not appear to be a simple assessment of breast density but rather the detection of the abnormal gist may be based on a widely distributed image statistic, learned by experts. The finding that a global signal, related to disease, can be detected in parenchyma that does not contain a lesion has implications for improving breast cancer detection

Detecting the “gist” of breast cancer in mammograms three years before localized signs of cancer are visible

Objectives: After a 500 ms presentation, experts can distinguish abnormal mammograms at above chance levels even when only the breast contralateral to the lesion is shown. Here, we show that this signal of abnormality is detectable 3 years before localized signs of cancer become visible. Methods: In 4 prospective studies, 59 expert observers from 3 groups viewed 116–200 bilateral mammograms for 500 ms each. Half of the images were prior exams acquired 3 years prior to onset of visible, actionable cancer and half were normal. Exp. 1D included cases having visible abnormalities. Observers rated likelihood of abnormality on a 0–100 scale and categorized breast density. Performance was measured using receiver operating characteristic analysis. Results: In all three groups, observers could detect abnormal images at above chance levels 3 years prior to visible signs of breast cancer (p < 0.001). The results were not due to specific salient cases nor to breast density. Performance was correlated with expertise quantified by the number of mammographic cases read within a year. In Exp. 1D, with cases having visible actionable pathology included, the full group of readers failed to reliably detect abnormal priors; with the exception of a subgroup of the six most experienced observers. Conclusions: Imaging specialists can detect signals of abnormality in mammograms acquired years before lesions become visible. Detection may depend on expertise acquired by reading large numbers of cases. Advances in knowledge: Global gist signal can serve as imaging risk factor with the potential to identify patients with elevated risk for developing cancer, resulting in improved early cancer diagnosis rates and improved prognosis for females with breast cancer

The 2015-2016 El Nino and the Response of the Carbon Cycle: Findings from NASA's OCO-2 Mission

The El Nino Southern Oscillation (ENSO) is the most important mode of tropical climate variability on interannual to decadal time scales. Correlations between atmospheric CO2 growth rate and ENSO activity are relatively well known but the magnitude of this correlation, the contribution from tropical marine vs. terrestrial flux components, and the causal mechanisms, are poorly constrained in space and time. The launch of NASA's Orbiting Carbon Observatory-2 (OCO-2) mission in July 2014 was rather timely given the development of strong ENSO conditions over the tropical Pacific Ocean in 2015-2016. In this presentation, we will discuss how the high-density observations from OCO-2 provided us with a novel dataset to resolve the linkages between El Nino and atmospheric CO2. Along with information from in situ observations of CO2 from NOAA's Tropical Atmosphere Ocean (TAO) project and atmospheric CO2 from the Scripps CO2 Program, and other remote-sensing missions, we are able to piece together the time dependent response of atmospheric CO2 concentrations over the Tropics. Our findings confirm the hypothesis from studies following the 1997-1998 El Nino event that an early reduction in CO2 outgassing from the tropical Pacific Ocean is later reversed by enhanced net CO2 emissions from the terrestrial biosphere. This implies that a component of the interannual variability (IAV) in the growth rate of atmospheric CO2, which has typically been used to constrain the climate sensitivity of tropical land carbon fluxes, is strongly influenced and modified by ocean fluxes during the early phase of the ENSO event. Our analyses shed further light on the understanding of the marine vs. terrestrial partitioning of tropical carbon fluxes during El Nino events, their relative contributions to the global atmospheric CO2 growth rate, and provide clues about the sensitivity of the carbon cycle to climate forcing on interannual time scales

Intensity and timing of physical activity in relation to postmenopausal breast cancer risk: the prospective NIH-AARP diet and health study.

BACKGROUND: Despite strong evidence of an inverse association of physical activity with postmenopausal breast cancer risk, whether a certain intensity or time of life of physical activity is most effective for lowering breast cancer risk is not known. METHODS: In 118,899 postmenopausal women in the prospective NIH-AARP Diet and Health Study, we examined the relations of light and moderate-to-vigorous intensity physical activity during four periods of life ("historical": ages 15-18, 19-29, 35-39 years; "recent": past 10 years) to postmenopausal breast cancer risk. Physical activity was assessed by self-report at baseline, and 4287 incident breast cancers were identified over 6.6 years of follow-up. RESULTS: In age-adjusted and multivariate Cox regression models, >7 hours/week of moderate-to-vigorous activity during the past 10 years was associated with 16% reduced risk of postmenopausal breast cancer (RR:0.84; 95%CI:0.76,0.93) compared with inactivity. The association remained statistically significant after adjustment for BMI (RR:0.87; 95%CI:0.78,0.96). Neither moderate-to-vigorous activity during other periods of life nor light intensity activity during any period of life was related to breast cancer risk, and associations did not vary by tumor characteristics. CONCLUSION: A high level of recent, but not historical, physical activity of moderate-to-vigorous intensity is associated with reduced postmenopausal breast cancer risk. More precise recall of recent physical activity than activity in the distant past is one possible explanation for our findings.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Estrogen metabolism and mammographic density in postmenopausal women : a cross-sectional study

Background: Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD. Methods: Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm2) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use. Results: Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm2 (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI. Conclusion: In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD. Impact: Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD

Associations of Genetic Ancestry with Terminal Duct Lobular Unit Involution among Healthy Women

Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR](trend) = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (OR(trend) = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (OR(trend) = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk

Epidemiologic Risk Factors for In Situ and Invasive Breast Cancers Among Postmenopausal Women in the National Institutes of Health-AARP Diet and Health Study

Comparing risk factor associations between invasive breast cancers and possible precursors may further our understanding of factors related to initiation versus progression. Accordingly, among 190,325 postmenopausal participants in the National Institutes of Health-AARP Diet and Health Study (1995-2011), we compared the association between risk factors and incident ductal carcinoma in situ (DCIS; n = 1,453) with that of risk factors and invasive ductal carcinomas (n = 7,525); in addition, we compared the association between risk factors and lobular carcinoma in situ (LCIS; n = 186) with that of risk factors and invasive lobular carcinomas (n = 1,191). Hazard ratios and 95% confidence intervals were estimated from multivariable Cox proportional hazards regression models. We used case-only multivariable logistic regression to test for heterogeneity in associations. Younger age at menopause was associated with a higher risk of DCIS but lower risks of LCIS and invasive ductal carcinomas (P for heterogeneity < 0.01). Prior breast biopsy was more strongly associated with the risk of LCIS than the risk of DCIS (P for heterogeneity = 0.04). Increased risks associated with use of menopausal hormone therapy were stronger for LCIS than DCIS (P for heterogeneity = 0.03) and invasive lobular carcinomas (P for heterogeneity < 0.01). Associations were similar for race, age at menarche, age at first birth, family history, alcohol consumption, and smoking status, which suggests that most risk factor associations are similar for in situ and invasive cancers and may influence early stages of tumorigenesis. The differential associations observed for various factors may provide important clues for understanding the etiology of certain breast cancers

The 2015-2016 El Nino and the Response of the Carbon Cycle: Findings from NASA's OCO-2 Mission

The El Nino Southern Oscillation (ENSO) is the most important mode of tropical climate variability on interannual to decadal time scales. Correlations between atmospheric CO2 growth rate and ENSO activity are relatively well known but the magnitude of this correlation, the contribution from tropical marine vs. terrestrial flux components, and the causal mechanisms, are poorly constrained in space and time. The launch of NASA's Orbiting Carbon Observatory-2 (OCO-2) mission in July 2014 was rather timely given the development of strong ENSO conditions over the tropical Pacific Ocean in 2015-2016. In this presentation, we will discuss how the high-density observations from OCO-2 provided us with a novel dataset to resolve the linkages between El Nino and atmospheric CO2. Along with information from in situ observations of pCO2 from NOAA's Tropical Atmosphere Ocean (TAO) project and atmospheric CO2 from the Scripps CO2 Program, and other remote-sensing missions, we are able to piece together the time dependent response of atmospheric CO2 concentrations over the Tropics. Our findings confirm the hypothesis from studies following the 1997-1998 El Nino event that an early reduction in CO2 outgassing from the tropical Pacific Ocean is later reversed by enhanced net CO2 emissions from the terrestrial biosphere. This implies that a component of the interannual variability (IAV) in the growth rate of atmospheric CO2, which has typically been used to constrain the climate sensitivity of tropical land carbon fluxes, is strongly influenced and modified by ocean fluxes during the early phase of the ENSO event. Our analyses shed further light on the understanding of the marine vs. terrestrial partitioning of tropical carbon fluxes during El Nino events, their relative contributions to the global atmospheric CO2 growth rate, and provide clues about the sensitivity of the carbon cycle to climate forcing on interannual time scales