Post-fire stabilization of thaw-affected permafrost terrain in northern Alaska.

In 2007, the Anaktuvuk River fire burned more than 1000 km2 of arctic tundra in northern Alaska, ~ 50% of which occurred in an area with ice-rich syngenetic permafrost (Yedoma). By 2014, widespread degradation of ice wedges was apparent in the Yedoma region. In a 50 km2 area, thaw subsidence was detected across 15% of the land area in repeat airborne LiDAR data acquired in 2009 and 2014. Updating observations with a 2021 airborne LiDAR dataset show that additional thaw subsidence was detected in < 1% of the study area, indicating stabilization of the thaw-affected permafrost terrain. Ground temperature measurements between 2010 and 2015 indicated that the number of near-surface soil thawing-degree-days at the burn site were 3 × greater than at an unburned control site, but by 2022 the number was reduced to 1.3 × greater. Mean annual ground temperature of the near-surface permafrost increased by 0.33 °C/yr in the burn site up to 7-years post-fire, but then cooled by 0.15 °C/yr in the subsequent eight years, while temperatures at the control site remained relatively stable. Permafrost cores collected from ice-wedge troughs (n = 41) and polygon centers (n = 8) revealed the presence of a thaw unconformity, that in most cases was overlain by a recovered permafrost layer that averaged 14.2 cm and 18.3 cm, respectively. Taken together, our observations highlight that the initial degradation of ice-rich permafrost following the Anaktuvuk River tundra fire has been followed by a period of thaw cessation, permafrost aggradation, and terrain stabilization.

Predicting non-response to ketamine for depression: An exploratory symptom-level analysis of real-world data among military veterans.

Ketamine helps some patients with treatment resistant depression (TRD), but reliable methods for predicting which patients will, or will not, respond to treatment are lacking. Herein, we aim to inform prediction models of non-response to ketamine/esketamine in adults with TRD. This is a retrospective analysis of PHQ-9 item response data from 120 patients with TRD who received repeated doses of intravenous racemic ketamine or intranasal eskatamine in a real-world clinic. Regression models were fit to patients' symptom trajectories, showing that all symptoms improved on average, but depressed mood improved relatively faster than low energy. Principal component analysis revealed a first principal component (PC) representing overall treatment response, and a second PC that reflects variance across affective versus somatic symptom subdomains. We then trained logistic regression classifiers to predict overall response (improvement on PC1) better than chance using patients' baseline symptoms alone. Finally, by parametrically adjusting the classifier decision thresholds, we identified optimal models for predicting non-response with a negative predictive value of over 96 %, while retaining a specificity of 22 %. Thus, we could identify 22 % of patients who would not respond based purely on their baseline symptoms. This approach could inform rational treatment recommendations to avoid additional treatment failures.

Effectiveness of Colonoscopy Screening vs Sigmoidoscopy Screening in Colorectal Cancer.

Importance: Randomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking. Objective: To estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy. Design, Setting, and Participants: This comparative effectiveness simulation study pooled data on 358 204 men and women randomly assigned to sigmoidoscopy screening or usual care in 4 randomized sigmoidoscopy screening trials conducted in Norway, Italy, the US, and UK with inclusion periods in the years 1993 to 2001. The primary analysis of the study was conducted from January 19 to December 30, 2021. Intervention: Invitation to endoscopic screening. Main Outcomes and Measures: Primary outcomes were CRC incidence and mortality. Using pooled 15-year follow-up data, colonoscopy screening effectiveness was estimated assuming that the efficacy of colonoscopy in the proximal colon was similar to that observed in the distal colon in the sigmoidoscopy screening trials. The simulation model was validated using data from Norwegian participants in a colonoscopy screening trial. Results: This analysis included 358 204 individuals (181 971 women [51%]) aged 55 to 64 years at inclusion with a median follow-up time ranging from 15 to 17 years. Compared with usual care, colonoscopy prevented an estimated 50 (95% CI, 42-58) CRC cases per 100 000 person-years, corresponding to 30% incidence reduction (rate ratio, 0.70 [95% CI, 0.66-0.75]), and prevented an estimated 15 (95% CI, 11-19) CRC deaths per 100 000 person-years, corresponding to 32% mortality reduction (rate ratio, 0.68 [95% CI, 0.61-0.76]). The additional benefit of colonoscopy screening compared with sigmoidoscopy was 12 (95% CI, 10-14) fewer CRC cases and 4 (95% CI, 3-5) fewer CRC deaths per 100 000 person-years, corresponding to percentage point reductions of 6.9 (95% CI, 6.0-7.9) for CRC incidence and 7.6 (95% CI, 5.7-9.6) for CRC mortality. The number needed to switch from sigmoidoscopy to colonoscopy screening was 560 (95% CI, 486-661) to prevent 1 CRC case and 1611 (95% CI, 1275-2188) to prevent 1 CRC death. Conclusions and Relevance: The findings of this comparative effectiveness study assessing long-term follow-up after CRC screening suggest that there was an additional preventive effect on CRC incidence and mortality associated with colonoscopy screening compared with sigmoidoscopy screening, but the additional preventive effect was less than what was achieved by introducing sigmoidoscopy screening where no screening existed. The results probably represent the upper limit of what may be achieved with colonoscopy screening compared with sigmoidoscopy screening.

High-Throughput Screening of Streptavidin-Binding Proteins in Self-Assembled Solid Films for Directed Evolution of Materials.

Evolution has shaped the development of proteins with an incredible diversity of properties. Incorporating proteins into materials is desirable for applications including biosensing; however, high-throughput selection techniques for screening protein libraries in materials contexts is lacking. In this work, a high-throughput platform to assess the binding affinity for ordered sensing proteins was established. A library of fusion proteins, consisting of an elastin-like polypeptide block, one of 22 variants of rcSso7d, and a coiled-coil order-directing sequence, was generated. All selected variants had high binding in films, likely due to the similarity of the assay to magnetic bead sorting used for initial selection, while solution binding was more variable. From these results, both the assembly of the fusion proteins in their operating state and the functionality of the binding protein are key factors in the biosensing performance. Thus, the integration of directed evolution with assembled systems is necessary to the design of better materials.

Changes in uptake of stool-based colorectal cancer screening during the Covid-19 pandemic.

PURPOSE: Colorectal cancer (CRC) screening is underutilized and endoscopic colon screening includes a number of barriers that were exacerbated by the Covid-19 pandemic. At-home stool-based screening (SBS) increased during the pandemic and potentially reached eligible adults hesitant to be screened by endoscopy. The purpose of this analysis was to examine the change in uptake of SBS during the pandemic among adults not screened within guidelines by endoscopy. METHODS: We used data from the 2019 and 2021 National Health Interview Surveys to estimate uptake of SBS among adults aged 50-75 years, without a previous diagnosis of CRC and without guideline-concordant endoscopic screening. We also examined provider recommendations for screening tests. To examine if changes in uptake differed during the pandemic by demographic and health characteristics, we combined survey years and ran logistic regression models with an interaction term for each factor and survey year. RESULTS: In our study population, SBS increased 74% overall from 2019 to 2021 (8.7% to 15.1%; p < 0.001), with the largest percent increase among those aged 50-52 years (3.5% to 9.9%; p < 0.001). Among those aged 50-52 years, the ratio of endoscopy to SBS changed from 83%/17% in 2019 to 55%/45% in 2021. Cologuard was the only screening test where recommendations by healthcare providers significantly increased from 2019 (10.6% to 16.1%; p = 0.002). CONCLUSIONS: Use and recommendations for SBS increased substantially during the pandemic. Increased awareness among patients could potentially improve future CRC screening rates if uptake of SBS occurs among those unable or unwilling to be screened by endoscopy.

Depression and anxiety among multiethnic middle school students: Age, gender, and sociocultural environment.

BACKGROUND: Depression and anxiety-related disorders are common among adolescents. Research attention to early adolescence and low-income ethnically diverse populations is limited. AIM: To conduct screening for depression and anxiety at an early age with attention to gender and socioenvironmental context within a low-income setting. METHOD: Mixed methods included the PHQ-9A and GAD-10 screening instruments and ethnographic interviews. RESULTS: 75 ethnically diverse middle school students were included. Mean years age was 11.2 (0.74). Females had higher PHQ-9A sum scores than males (p = .002, Mann-Whitney test) and higher GAD-10 sum scores than males (p = .016, Mann-Whitney test). After controlling for multiple comparisons, girls had higher mean responses on three PHQ-9A items (p < .006, two-sided t-test) and only one GAD-10 item (p < .005, two-sided t-test). Ethnographic interviews revealed contexts associated with girls' experiences of depression and anxiety, including gender-based violence in both school and home environments. Salient for girls and boys alike were worries about consequences of COVID-19 for family with respect to illness, death, job loss, economic hardship. Fears over student perceptions of intensified discrimination and racism in school and community were prominent. These problems were experienced by students as barriers to educational engagement. CONCLUSION: Specific attention to early adolescence is needed to identify emergence of subsyndromal conditions which may benefit from therapeutic attention to reduce symptom severity, identify sociocultural, structural, and gender-specific stressors, and to enhance educational engagement.

Cervical cancer screening and predictors of screening by diabetes status.

PURPOSE: Women with diabetes have lower survival rates after a cervical cancer diagnosis compared to women without diabetes. Pap smears and human papilloma virus (HPV) testing are highly effective screening tests for cervical cancer, therefore, it is important to know the prevalence of guideline-concordant screening among women with diabetes and understand if their predictors of screening differ. The purpose of this analysis was to assess guideline-concordant cervical cancer screening and predictors by diabetes status. METHODS: We used the 2019 National Health Interview Survey data, limited to women aged 21-65 years without a previous diagnosis of cancer, a hysterectomy, or diagnosed with diabetes in the year prior to the survey. We considered the Pap and HPV tests together and concordance as being tested within the past 3 years as part of a routine exam. We calculated weighted, adjusted prevalence, and prevalence ratios (PRs) of screening concordance comparing women with diabetes to those without. RESULTS: The unadjusted prevalence of concordant screening was 66.5% for women with diabetes compared to 73.3% for women without diabetes (PR = 0.91 95% CI 0.84-0.98). In the fully adjusted model adjusting for factors known to be associated with diabetes and access to healthcare, the association was attenuated and no longer statistically significant (PR = 0.96 95% CI 0.89-1.04). CONCLUSION: Cervical cancer screening concordance was lower in women with diabetes compared to those without overall but the deficit appears to be due primarily to underlying differences in sociodemographic characteristics and access to healthcare and not diabetes independently.

Spatial preferences account for inter-animal variability during the continual learning of a dynamic cognitive task.

Understanding the complexities of behavior is necessary to interpret neurophysiological data and establish animal models of neuropsychiatric disease. This understanding requires knowledge of the underlying information-processing structure-something often hidden from direct observation. Commonly, one assumes that behavior is solely governed by the experimenter-controlled rules that determine tasks. For example, differences in tasks that require memory of past actions are often interpreted as exclusively resulting from differences in memory. However, such assumptions are seldom tested. Here, we provide a comprehensive examination of multiple processes that contribute to behavior in a prevalent experimental paradigm. Using a combination of behavioral automation, hypothesis-driven trial design, and reinforcement learning modeling, we show that rats learn a spatial alternation task consistent with their drawing upon spatial preferences in addition to memory. Our approach also distinguishes learning based on established preferences from generalization of task structure, providing further insights into learning dynamics.

Development and translation of a paper-based top readout vertical flow assay for SARS-CoV-2 surveillance.

Surveillance of SARS-CoV-2 infection is critical for controlling the current pandemic. Antigen rapid tests (ARTs) provide a means for surveillance. Available lateral flow assay format ARTs rely heavily on nitrocellulose paper, raising challenges in supply shortage. Vertical flow assay (VFA) with cellulose paper as test material attracts much attention as a complementary test approach. However, current reported VFAs are facing challenges in reading the test signal from the bottom face of the test cassette, complicating the test workflow and hindering translation into rapid test application. Here, we address this gap with an enhanced VFA against SARS-CoV-2 N protein that adapts a cellulose pull-down test format allowing (1) one-step sample application at the top of the test cassette and (2) readout of the test signal from the top. We also demonstrate the feasibility of translating the enhanced VFA into a point-of-care application that can help in SARS-CoV-2 surveillance.

Differences in the relationship between diabetes and prostate cancer among Black and White non-Hispanic men.

PURPOSE: Studies finding lower incidence rates of prostate cancer among men with diabetes have been primarily conducted in White non-Hispanic (WNH) populations. The purpose of this analysis is to compare the relationship between diabetes and prostate cancer among Black (BNH) and White non-Hispanic men. METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2011 to 2015 to compare incidence rates and tumor characteristics between BNH and WNH men by diabetes status. Age-adjusted incidence rates and corresponding rate ratios (RR) by diabetes status were calculated overall and by tumor grade, stage, and PSA level separately for BNH and WNH men. We used multivariable logistic regression to compare tumor characteristics among men with prostate cancer in the numerator, both within and across race/ethnic groups. RESULTS: Overall age-adjusted incidence rates were significantly lower in men with diabetes compared to those without among WNH men [RR = 0.88 95% Confidence Interval (CI) 0.86-0.90] but there was no difference in rates by diabetes status among BNH men (RR = 1.01 95% CI 0.96-1.07). Men with diabetes were less likely to be diagnosed with distant-staged tumors compared to those without diabetes in both race/ethnic groups but the magnitude of difference by diabetes status was greater in BNH [Odds Ratio (OR) = 0.52 95% CI 0.42-0.64] than WNH (OR = 0.88 95% CI 0.81-0.95) men (p-value for interaction < 0.001). CONCLUSION: The relationship between diabetes and prostate cancer differed between BNH and WNH men. The differences could have implications in evaluating the effectiveness of prostate cancer screening in men with diabetes across racial/ethnic subgroups.

Developing a SARS-CoV-2 Antigen Test Using Engineered Affinity Proteins.

The ongoing COVID-19 pandemic has clearly established how vital rapid, widely accessible diagnostic tests are in controlling infectious diseases and how difficult and slow it is to scale existing technologies. Here, we demonstrate the use of the rapid affinity pair identification via directed selection (RAPIDS) method to discover multiple affinity pairs for SARS-CoV-2 nucleocapsid protein (N-protein), a biomarker of COVID-19, from in vitro libraries in 10 weeks. The pair with the highest biomarker sensitivity was then integrated into a 10 min, vertical-flow cellulose paper test. Notably, the as-identified affinity proteins were compatible with a roll-to-roll printing process for large-scale manufacturing of tests. The test achieved 40 and 80 pM limits of detection in 1× phosphate-buffered saline (mock swab) and saliva matrices spiked with cell-culture-generated SARS-CoV-2 viruses and is also capable of detection of N-protein from characterized clinical swab samples. Hence, this work paves the way toward the mass production of cellulose paper-based assays which can address the shortages faced due to dependence on nitrocellulose and current manufacturing techniques. Further, the results reported herein indicate the promise of RAPIDS and engineered binder proteins for the timely and flexible development of clinically relevant diagnostic tests in response to emerging infectious diseases.

Overwintering fires in boreal forests.

Forest fires are usually viewed within the context of a single fire season, in which weather conditions and fuel supply can combine to create conditions favourable for fire ignition-usually by lightning or human activity-and spread1-3. But some fires exhibit 'overwintering' behaviour, in which they smoulder through the non-fire season and flare up in the subsequent spring4,5. In boreal (northern) forests, deep organic soils favourable for smouldering6, along with accelerated climate warming7, may present unusually favourable conditions for overwintering. However, the extent of overwintering in boreal forests and the underlying factors influencing this behaviour remain unclear. Here we show that overwintering fires in boreal forests are associated with hot summers generating large fire years and deep burning into organic soils, conditions that have become more frequent in our study areas in recent decades. Our results are based on an algorithm with which we detect overwintering fires in Alaska, USA, and the Northwest Territories, Canada, using field and remote sensing datasets. Between 2002 and 2018, overwintering fires were responsible for 0.8 per cent of the total burned area; however, in one year this amounted to 38 per cent. The spatiotemporal predictability of overwintering fires could be used by fire management agencies to facilitate early detection, which may result in reduced carbon emissions and firefighting costs.

Developing a SARS-CoV-2 Antigen Test Using Engineered Affinity Proteins.

The ongoing COVID-19 pandemic has clearly established how vital rapid, widely accessible diagnostic tests are in controlling infectious diseases and how difficult and slow it is to scale existing technologies. Here, we demonstrate the use of the rapid affinity pair identification via directed selection (RAPIDS) method to discover multiple affinity pairs for SARS-CoV-2 nucleocapsid protein (N-protein), a biomarker of COVID-19, from in vitro libraries in 10 weeks. The pair with the highest biomarker sensitivity was then integrated into a 10-minute, vertical-flow cellulose paper test. Notably, the as-identified affinity proteins were compatible with a roll-to-roll printing process for large-scale manufacturing of tests. The test achieved 40 pM and 80 pM limits of detection in 1×PBS (mock swab) and saliva matrices spiked with cell-culture generated SARS-CoV-2 viruses and is also capable of detection of N-protein from characterized clinical swab samples. Hence, this work paves the way towards the mass production of cellulose paper-based assays which can address the shortages faced due to dependence on nitrocellulose and current manufacturing techniques. Further, the results reported herein indicate the promise of RAPIDS and engineered binder proteins for the timely and flexible development of clinically relevant diagnostic tests in response to emerging infectious diseases.

Vertical Flow Cellulose-Based Assays for SARS-CoV-2 Antibody Detection in Human Serum.

Rapid and inexpensive serological tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies are essential to conduct large-scale seroprevalence surveys and can potentially complement nucleic acid or antigen tests at the point of care. During the COVID-19 pandemic, extreme demand for traditional lateral flow tests has stressed manufacturing capacity and supply chains. Motivated by this limitation, we developed a SARS-CoV-2 antibody test using cellulose, an alternative membrane material, and a double-antigen sandwich format. Functionalized SARS-CoV-2 antigens were used as both capture and reporter binders, replacing the anti-human antibodies currently used in lateral flow tests. The test could provide enhanced sensitivity because it labels only antibodies against SARS-CoV-2 and the signal intensity is not diminished due to other human antibodies in serum. Three-dimensional channels in the assay were designed to have consistent flow rates and be easily manufactured by folding wax-printed paper. We demonstrated that this simple, vertical flow, cellulose-based assay could detect SARS-CoV-2 antibodies in clinical samples within 15 min, and the results were consistent with those from a laboratory, bead-based chemiluminescence immunoassay that was granted emergency use approval by the US FDA.

Robust and replicable measurement for prepulse inhibition of the acoustic startle response.

Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this phenomenon remains uncertain. Here, we deconstruct the phenomenon of PPI and confirm several limitations of the methodology traditionally utilized to describe PPI, including that the underlying startle response has a non-Gaussian distribution, and that the traditional PPI metric changes with different stimuli. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound processing. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared with wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In contrast, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.

Healthcare Access, Utilization, and Preventive Health Behaviors by Eligibility for Lung Cancer Screening.

In 2013, the US Preventive Services Task Force recommended low-dose computed tomography screening for smokers at high risk of lung cancer; however, use remains low. Efforts to promote lung cancer screening need to consider how receptive this population is to preventive healthcare and cancer screening. In addition, because of demonstrated heterogeneity in behaviors by smoking status, interventions may need to differ among eligible high-risk subgroups. To assess the engagement of high-risk smokers in other preventive healthcare behaviors, we examined healthcare use, including non-lung cancer screening, and healthcare provider discussions regarding screening by eligibility for lung cancer screening. We used the 2015 National Health Interview Survey to assess smoking history, healthcare use, cancer screening, vaccinations, and healthcare provider discussions regarding non-lung cancer screening. We calculated weighted prevalence estimates and prevalence ratios comparing eligible and ineligible current and former smokers to never smokers. Eligible current and former smokers had significantly different healthcare utilization and screening concordance compared to never smokers and to each other. Compared to never smokers, eligible current smokers were significantly less likely to be concordant with breast, colorectal, and cervical cancer screening while eligible former smokers were only less likely to be concordant with breast cancer screening. Eligible current smokers were less likely to report physician discussions about non-lung screening tests. Provider discussions about screening and engagement in preventive healthcare differed among current and former smokers eligible for lung cancer screening. Intervention efforts to increase lung cancer screening levels will likely need to differ as well.

Examining the relationship between diabetes and prostate cancer through changes in screening guidelines.

PURPOSE: Previous studies have found that men with diabetes are at reduced risk of prostate cancer compared to men without diabetes. The lower risk could be due to biologic differences and/or a diagnosis bias from use of the prostate-specific antigen (PSA) test as a screening and diagnostic tool. We sought to further examine the relationship between diabetes and incidence of prostate cancer and examine the potential impact of changes in PSA screening guidelines in 2008 and 2012. METHODS: We used 2004-2015 Surveillance, Epidemiology and End Results (SEER)-Medicare data and limited the study population to men aged 67-74 with at least 2 years of continuous enrollment. Using the 5% Medicare sample as the denominator and prostate cancer cases as the numerator, we calculated age-adjusted rate ratios (RR) in 2006-2011 and 2012-2015 by diabetes status, overall and by tumor grade. We used multivariable logistic regression to compare tumor characteristics by diabetes status. RESULTS: Men with diabetes had lower incidence rates of prostate cancer compared to men without diabetes in 2006-2011 [RR = 0.89 95% confidence interval (CI) 0.87-0.91] and 2012-2015 (RR = 0.92 95% CI 0.89-0.95) but the slight attenuation toward the null in 2012-2015 was primarily due to the change in RRs for low-grade tumors. CONCLUSION: We found differences in the risk and characteristics of prostate cancer by diabetes status and that some risks have changed over time as guidelines have changed. With lower PSA use in the more recent time-period, rates of low-grade tumors have become more similar by diabetes status.

Functional comparison of paper-based immunoassays based on antibodies and engineered binding proteins.

Binding protein scaffolds, such as rcSso7d, have been investigated for use in diagnostic tests; however, the functional performance of rcSso7d has not yet been studied in comparison to antibodies. Here, we assessed the analyte-binding capabilities of rcSso7d and antibodies on cellulose with samples in buffer and 100% human serum.

Breast cancer risk prediction models and subsequent tumor characteristics.

BACKGROUND: A previous study found evidence that a breast cancer risk prediction model preferentially selected for less aggressive tumors in Swedish women. In the US, the Gail model has been widely used and was used for entry criteria in two large breast cancer prevention trials. We assessed if higher risk levels from the Gail model were associated with less aggressive tumor characteristics and if risk levels were predictive of mortality and survival. METHODS: We used questionnaire data from women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to calculate Gail risk levels (low < 1.66%; moderate 1.66-2.99%; high ≥ 3.00%). Women aged 55-74 were enrolled between 1993 and 2001 and had detailed information on breast cancer incidence and tumors collected. We calculated breast cancer incidence and mortality rates among all women by risk levels and examined breast cancer survival and tumor characteristics among women diagnosed with breast cancer. We used Chi-squared tests and multivariable logistic regression to assess the association between risk levels and tumor characteristics. RESULTS: The study population for this analysis included 45,402 women with 1908 cases of breast cancer. Women at high risk were associated with higher risk of breast cancer mortality compared to women with low risk [rate ratio (RR) = 2.29 95% confidence interval (CI) 1.37-3.84)]. Higher risk levels were associated with lobular-type tumors [moderate: adjusted odds ratio (aOR) = 1.57 95% CI 1.13-2.17; high: aOR = 1.78 95% CI 1.25-2.54] but were not associated with any other tumor characteristics or breast cancer survival. CONCLUSIONS: We did not find evidence that higher risk levels from the Gail model are predictive of less aggressive breast cancer tumors.