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River water in Kosovo is exposed to various discharges from industrial and agricultural activities as well as to urban wastewater. Rivers Sitnica and Drenica are among the most affected ones and water samples drawn from these rivers show the presence of various toxic substances. Genotoxic effects are seen in fish living in these rivers indicating a cytotoxic and mutagenic potential of the river water. Aiming at substantiating these observations, we assessed cyto- and genotoxic effects of water samples collected at different locations from Drenica and Sitnica river. Samples drawn from Lake Badovc served for comparison. To address seasonal effects, samples were collected at different seasons/time points during the period summer 2016 - spring 2018. The water samples were analyzed employing primary rat hepatocytes as reliable in vitro cell model for the assessment of cytotoxic effects (mitotic arrest and cell death) and DNA damage/genotoxicity (micronucleus assay, Comet assay). The results do not account for significant effects associated with specific locations but demonstrate seasonal differences of the genotoxic potential of the water samples collected along both rivers, which are accompanied by a limited cytotoxic potential. Our data provide substantial support to earlier observations and strongly warrant the need for continuous chemical as well as biological monitoring of the river water in Kosovo, focusing on an improved toxicant profiling of the river water and investigations addressing the observed seasonal variations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: This study aimed to assess the factors influencing bone erosion (BE) in patients with gout using dual-energy gemstone spectral imaging computer tomography., Methods: We compared the clinical data, laboratory indices, and tissue urate levels at the monosodium urate (MSU) bone interface measured by dual-energy gemstone spectral imaging computed tomography of 87 gout patients with (n = 41) and without (n = 46) BE. Logistic regression analysis was used to investigate the risk factors associated with BE., Results: In total, 47.1% of patients with gout had BE. The disease duration, serum uric acid, tissue urate levels, and the presence of tophi were significantly higher (p < .05) in gout patients with BE than in those without BE. Longer disease duration (odds ratio = 1.11, 95% confidence interval: 1.00-1.24, p < .05) and increased tissue urate levels (odds ratio = 1.01, 95% confidence interval: 1.00-1.02, p < .05) were independently associated with BE. Tissue urate levels at the MSU-bone interface were correlated with the presence of tophi (r = 0.62, p < .001), BE (r = 0.51, p < .001), renal calculus (r = 0.24, p = .03), and serum uric acid levels (r = 0.23, p = .03)., Conclusions: This study found that longer disease duration and elevated tissue urate concentrations at the MSU-bone interface were associated with BE in patients with gout., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, prostate acid phosphatase, or prostate-specific antigen., (© The Author(s) 2021. Published by Oxford University Press.)

Fungicides reduce fungal pathogen populations and are essential to food security. Understanding the impacts of fungicides on crop microbiomes is vital to minimizing unintended consequences while maintaining their use for plant protection. However, fungicide disturbance of plant microbiomes has received limited attention, and has not been examined in different agricultural management systems. We used amplicon sequencing of fungi and prokaryotes in maize and soybean microbiomes before and after foliar fungicide application in leaves and roots from plots under long-term no-till and conventional tillage management. We examined fungicide disturbance and resilience, which revealed consistent non-target effects and greater resiliency under no-till management. Fungicides lowered pathogen abundance in maize and soybean and decreased the abundance of Tremellomycetes yeasts, especially Bulleribasidiaceae, including core microbiome members. Fungicide application reduced network complexity in the soybean phyllosphere, which revealed altered co-occurrence patterns between yeast species of Bulleribasidiaceae, and Sphingomonas and Hymenobacter in fungicide treated plots. Results indicate that foliar fungicides lower pathogen and non-target fungal abundance and may impact prokaryotes indirectly. Treatment effects were confined to the phyllosphere and did not impact belowground microbial communities. Overall, these results demonstrate the resilience of no-till management to fungicide disturbance, a potential novel ecosystem service provided by no-till agriculture.

Abiotic stresses such as drought result in large annual economic losses around the world. As sessile organisms, plants cannot escape the environmental stresses they encounter but instead must adapt to survive. Studies investigating plant responses to osmotic and/or salt stress have largely focused on short-term systemic responses, leaving our understanding of intermediate to longer-term adaptation (24 h to d) lacking. In addition to protein abundance and phosphorylation changes, evidence suggests reversible lysine acetylation may also be important for abiotic stress responses. Therefore, to characterize the protein-level effects of osmotic and salt stress, we undertook a label-free proteomic analysis of Arabidopsis thaliana roots exposed to 300 mM mannitol and 150 mM NaCl for 24 h. We assessed protein phosphorylation, lysine acetylation and changes in protein abundance, detecting significant changes in 245, 35 and 107 total proteins, respectively. Comparison with available transcriptome data indicates that transcriptome- and proteome-level changes occur in parallel, while post-translational modifications (PTMs) do not. Further, we find significant changes in PTMs, and protein abundance involve different proteins from the same networks, indicating a multifaceted regulatory approach to prolonged osmotic and salt stress. In particular, we find extensive protein-level changes involving sulfur metabolism under both osmotic and salt conditions as well as changes in protein kinases and transcription factors that may represent new targets for drought stress signaling. Collectively, we find that protein-level changes continue to occur in plant roots 24 h from the onset of osmotic and salt stress and that these changes differ across multiple proteome levels., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Natural rubber is an important industrial raw material and is commercially produced by rubber trees (Hevea brasiliensis). The sucrose transporter HbSUT3 plays an essential role in rubber production. Its expression in latex (cytoplasm of rubber-producing laticifers) is induced by bark treatment with Ethrel, an ethylene releaser, and the inducing effect correlates well with Ethrel-stimulated rubber yield increase. However, the mechanisms of ethylene induction on HbSUT3 expression are not known. Here, five Ethylene Response Factor (ERF) genes were identified from the cDNA library of Hevea latex by yeast one-hybrid screening with the promoter of HbSUT3 gene as bait. As revealed in a tobacco (Nicotiana tabacum) protoplast transient expression system, these HbERFs were mainly localized in the nucleus and four of them exhibited apparent transactivation activity. Of the five HbERF genes, HbERF-IXc4 was the most frequently screened in yeast one-hybrid, accounting for 65% of the ERF clones obtained. Moreover, among the five HbERFs, HbERF-IXc4 showed the strongest transactivation capacity when expressed in tobacco protoplast, the highest transcript abundance in latex and a close expressional correlation with its target gene, HbSUT3, in response to the Ethrel treatment. Taken together, our results indicate that ERFs, especially HbERF-IXc4, are critically involved in the activation of HbSUT3 expression in latex after Ethrel treatment on Hevea bark, and thus the stimulated latex yield., (Published by Oxford University Press 2021.)

Objective: The aim of this study is to determine the association of intrapartum risk factors and infant clinical indicators using the National Institute for Health and Care Excellence (NICE) criteria with culture-positive early-onset neonatal sepsis (EONS) from a rural secondary healthcare facility where intrapartum prophylactic antibiotics are routinely administered to high-risk mothers., Methods: A single-center prospective observational study was conducted between July 2017 and September 2018. All intramural neonates with at least one NICE criteria at less than 72 h of life, were included. Univariate logistic regression and multivariable logistic backward elimination analyses were conducted to investigate individual risk factors and predictive models for culture proven EONS., Results: Of 236 newborns who were at risk for EONS by NICE criteria, 32 (13.8%) had positive blood cultures. Klebsiella species (n = 13, 39.4%) and Acinetobacter species (n = 11, 33.3%) were the most common isolated bacteria. In univariate analysis, the number of infant clinical indicators were associated with culture positive EONS (OR 1.36; 95% CI 1.01-1.81), but not the number of intrapartum risk factors (OR 0.76; 95% CI 0.4-1.29). The multivariate logistic regression with backward elimination procedure suggested that a model including absolute neutrophil count [adjusted OR (aOR) 0.81; 95% CI 0.72-0.92], C-reactive protein (aOR 1.24; 95% CI 1.08-1.43) and the number of clinical indicators (aOR 1.29; 95% CI 0.93-1.80) could be useful to predict culture positive EONS in our setting., Conclusion: In this maternal and neonatal cohort, infant clinical indicators rather than intrapartum risk factors were associated with culture confirmed EONS., (© The Author(s) [2020]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship., Results: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years., Conclusions: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients-individuals with an active or prior cancer history and with or at risk of cardiovascular disease-are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Care coordination challenges for patients with cancer continue to grow as expanding treatment options, multimodality treatment regimens, and an aging population with comorbid conditions intensify demands for multidisciplinary cancer care. Effective teamwork is a critical yet understudied cornerstone of coordinated cancer care delivery. For example, comprehensive lung cancer care involves a clinical "team of teams"-or clinical multiteam system (MTS)-coordinating decisions and care across specialties, providers, and settings. The teamwork processes within and between these teams lay the foundation for coordinated care. Although the need to work as a team and coordinate across disciplinary, organizational, and geographic boundaries increases, evidence identifying and improving the teamwork processes underlying care coordination and delivery among the multiple teams involved remains sparse. This commentary synthesizes MTS structure characteristics and teamwork processes into a conceptual framework called the cancer MTS framework to advance future cancer care delivery research addressing evidence gaps in care coordination. Included constructs were identified from published frameworks, discussions at the 2016 National Cancer Institute-American Society of Clinical Oncology Teams in Cancer Care Workshop, and expert input. A case example in lung cancer provided practical grounding for framework refinement. The cancer MTS framework identifies team structure variables and teamwork processes affecting cancer care delivery, related outcomes, and contextual variables hypothesized to influence coordination within and between the multiple clinical teams involved. We discuss how the framework might be used to identify care delivery research gaps, develop hypothesis-driven research examining clinical team functioning, and support conceptual coherence across studies examining teamwork and care coordination and their impact on cancer outcomes., (Published by Oxford University Press 2020.)

Mouse lemurs (Microcebus) are a radiation of morphologically cryptic primates distributed throughout Madagascar for which the number of recognized species has exploded in the past two decades. This taxonomic revision has prompted understandable concern that there has been substantial oversplitting in the mouse lemur clade. Here, we investigate mouse lemur diversity in a region in northeastern Madagascar with high levels of microendemism and predicted habitat loss. We analyzed RADseq data with multispecies coalescent (MSC) species delimitation methods for two pairs of sister lineages that include three named species and an undescribed lineage previously identified to have divergent mtDNA. Marked differences in effective population sizes, levels of gene flow, patterns of isolation-by-distance, and species delimitation results were found among the two pairs of lineages. Whereas all tests support the recognition of the presently undescribed lineage as a separate species, the species-level distinction of two previously described species, M. mittermeieri and M. lehilahytsara is not supported-a result that is particularly striking when using the genealogical discordance index (gdi). Nonsister lineages occur sympatrically in two of the localities sampled for this study, despite an estimated divergence time of less than 1 Ma. This suggests rapid evolution of reproductive isolation in the focal lineages and in the mouse lemur clade generally. The divergence time estimates reported here are based on the MSC calibrated with pedigree-based mutation rates and are considerably more recent than previously published fossil-calibrated relaxed-clock estimates. We discuss the possible explanations for this discrepancy, noting that there are theoretical justifications for preferring the MSC estimates in this case. [Cryptic species; effective population size; microendemism; multispecies coalescent; speciation; species delimitation.]., (© The Author(s) 2020. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: With the advent of primary human papillomavirus testing followed by cytology for cervical cancer screening, visual interpretation of cytology slides remains the last subjective analysis step and suffers from low sensitivity and reproducibility., Methods: We developed a cloud-based whole-slide imaging platform with a deep-learning classifier for p16/Ki-67 dual-stained (DS) slides trained on biopsy-based gold standards. We compared it with conventional Pap and manual DS in 3 epidemiological studies of cervical and anal precancers from Kaiser Permanente Northern California and the University of Oklahoma comprising 4253 patients. All statistical tests were 2-sided., Results: In independent validation at Kaiser Permanente Northern California, artificial intelligence (AI)-based DS had lower positivity than cytology (P < .001) and manual DS (P < .001) with equal sensitivity and substantially higher specificity compared with both Pap (P < .001) and manual DS (P < .001), respectively. Compared with Pap, AI-based DS reduced referral to colposcopy by one-third (41.9% vs 60.1%, P < .001). At a higher cutoff, AI-based DS had similar performance to high-grade squamous intraepithelial lesions cytology, indicating a risk high enough to allow for immediate treatment. The classifier was robust, showing comparable performance in 2 cytology systems and in anal cytology., Conclusions: Automated DS evaluation removes the remaining subjective component from cervical cancer screening and delivers consistent quality for providers and patients. Moving from Pap to automated DS substantially reduces the number of colposcopies and also achieves excellent performance in a simulated fully vaccinated population. Through cloud-based implementation, this approach is globally accessible. Our results demonstrate that AI not only provides automation and objectivity but also delivers a substantial benefit for women by reduction of unnecessary colposcopies., (© The Author(s) 2020. Published by Oxford University Press.)

Background: There is no standard of care with respect to the use of neoadjuvant chemotherapy (NAC) in resectable malignant pleural mesothelioma (MPM). We performed an intention-to-treat analysis with data from a single institution and the National Cancer Database (NCDB) to identify whether the use of NAC impacts survival in resectable MPM., Methods: Patients with MPM who had surgery with curative intent at Duke University from 1995 to 2017 were selected, and the 2004-2015 NCDB was used to identify MPM patients with clinical stage I-IIIB who underwent definitive surgery. For both cohorts, patients were stratified by receipt of NAC. Primary outcomes were overall survival and postresection survival (RS), which were estimated using Kaplan-Meier and multivariable Cox proportional hazards models., Results: A total of 257 patients met inclusion criteria in the Duke cohort. Compared with immediate resection (IR), NAC was associated with similar overall survival but an increased risk for postresection mortality in both unmatched (adjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.21 to 2.83) and propensity-matched (HR = 1.62, 95% CI = 1.03 to 2.55) cohorts. A total of 1949 NCDB patients were included: 1597 (81.9%) IR and 352 (18.1%) NAC. RS was worse for patients undergoing NAC in both unmatched (HR = 1.85, 95% CI = 1.21 to 2.83) and propensity-matched (HR = 1.29, 95% CI = 1.06 to 1.57) analyses compared with patients receiving IR., Conclusions: In this intention-to-treat study, NAC was associated with worse RS compared with IR in patients with MPM. The risks and benefits of induction therapy should be weighed before offering it to patients with resectable MPM., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Rapid access to pancreatic imaging and regular pancreatic surveillance may help identify stage I pancreatic cancer. We investigated recent trends in the stage of newly diagnosed pancreatic ductal adenocarcinoma (PDACs), age at diagnosis, and survival., Methods: Trends in age-adjusted incidence of stage IA PDAC between 2004 and 2016 were determined from the National Cancer Institute's Surveillance, Epidemiology and End Results database. All tests were two-sided., Results: The incidence of stage IA PDAC cases diagnosed increased statistically significantly from 2004 to 2016 (annual percent change = 14.5, 95% confidence interval [CI] = 11.4 to 17.7; P < .001). During the study period, average age at diagnosis for stage IA and IB casesAQ3 declined by 3.5 years (95% CI = 1.2 to 5.9; P = .004) and 5.5 years (95% CI = 3.4 to 7.6; P < .001), whereas average age increased for higher-stage cases (by 0.6 to 1.4 years). Among stage IA cases, the proportion of blacks was smaller (10.2% vs 12.5%), and the proportion of other non-Caucasians was higher compared with higher-stage cases (11.9% vs 8.4%; P < .001). Stage IA cases were more likely to carry insurance (vs Medicaid or none) than higher-stage cases (cases aged younger than 65 years; odds ratio = 2.45, 95% CI = 1.96 to 3.06; P < .001). The 5-year overall survival for stage IA PDAC improved from 44.7% (95% CI = 31.4 to 63.7) in 2004 to 83.7% (95% CI = 78.6% to 89.2%) in 2012; 10-year survival improved from 36.7% (95% CI = 24.1 to 55.8) in 2004 to 49.0% (95% CI = 37.2% to 64.6%) in 2007., Conclusions: In recent years, the proportion of patients diagnosed with stage IA PDAC has increased, their average age at diagnosis has decreased, and their overall survival has improved. These trends may be the result of improved early diagnosis and early detection., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Although adolescent and young adult (AYA) cancers represent a unique spectrum of malignancies, epidemiological studies of cancer incidence often group AYAs together with younger or older populations, obscuring patterns specific to this population., Methods: We examined AYA cancer incidence trends in 41 countries over a 15-year period using the CI5plus database. Truncated age-standardized incidence rates were calculated and the annual percentage change was assessed, with statistical significance corresponding to a 95% confidence interval that does not include zero., Results: From 1998 to 2012, the 41 included countries contributed a total of 1 846 588 cancer cases and 3.1 billion person-years among AYAs. Although statistically significant increases in the overall cancer burden were observed in 23 countries, the magnitude varied considerably, with the greatest increase in incidence observed in South Korea (annual percentage change2002-2012 = 8.5%, 95% confidence interval = 7.6% to 9.4%) due to thyroid cancer. Notable trends included sharp increases in the incidence of obesity-related malignancies among AYAs; indeed, statistically significant increases were observed among AYAs for 10 of 11 and 9 of 11 obesity-related cancer sites in the US and UK, respectively, with at least five obesity-related cancers statistically significantly increasing in Canada, Japan, South Korea, Australia, and the Netherlands. Other striking trends were noted for thyroid and testicular cancer, with statistically significantly increasing rates observed in 33 and 22 countries, respectively, whereas statistically significant declines in incidence were observed for smoking-related cancers, cervical cancer, and Kaposi sarcoma in many countries., Conclusions: Our results highlight the future health-care needs related to treatment as well as the urgency for public health initiatives that can mitigate the increasing burden of cancer in AYAs., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Health care and the Veterans Health Administration have adopted many initiatives to improve patient care, including efforts to create a "Just Culture" environment for patient safety and quality outcomes. Despite significant resources and efforts on these initiatives and some temporary improvements, we continue to struggle to make significant and sustainable improvements. At the Veterans Administration North Texas Health Care System, we see that our efforts have addressed the wrong thing. By focusing our efforts to shift the underlying mindset that drives behavior, we expect to create the foundation that will help us truly achieve a High Reliability and Just Culture organization that provides the care and outcomes our patients and staff deserve., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Regular exercise has multiple benefits for physical and mental health, including the body's ability to combat infections. The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers. The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period. The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes.

Objective: The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose-response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population., Methods: PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose-response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio., Results: Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response pattern, with the lowest risk observed at HDL-C levels of 54-58 mg/dL, 68-71 mg/dL and 64-68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality., Conclusions: In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.

Introduction: Because of the rigorous mental and physical health requirements for Naval Aviation, all applicants and designated personnel must meet physical standards, including initial and periodic screening for anemia. Most standards, including for accession to the U.S. Navy, use hemoglobin as the standard marker to screen for anemia. Moreover, previous literature generally supports the assertion that hemoglobin is more reliable and accurate than hematocrit. However, the U.S. Navy Aeromedical Reference and Waiver Guide uses a hematocrit standard for anemia screening. The purpose of this study was to determine whether hemoglobin or hematocrit correlates better with clinical anemia and evaluate which index is a more accurate indicator for anemia screening in Naval Aviation personnel., Materials and Methods: This is a retrospective cross-sectional study of Naval Aviation applicants (N = 95) who were evaluated by the Human Performance and Aeromedical Qualifications department at Naval Aerospace Medical Institute Clinic in Pensacola, Florida, from January 1, 2015 to September 30, 2018. Data were collected from electronic medical records in a de-identified manner that included demographics, class designations, labs results, diagnoses, and final disposition. Logistic regression was used to analyze whether hemoglobin (using the U.S. Navy standard of 13.5 g/dL for men and 12.0 g/dL for women) or hematocrit (using the Naval Aviation standard of 40% for men and 37% for women) predicted the diagnosis of anemia for subjects having at least one lab sample (1-sample) and for those having three samples (3-samples). Sensitivity and specificity values were calculated for hemoglobin and hematocrit as tools to predict a diagnosis of anemia using the same standards in the 1-sample and 3-sample groups., Results: Data were collected for 95 subjects, 53 of whom had three sets of paired hemoglobin/hematocrit values. Using logistic regression, hemoglobin was found to be a statistically significant predictor of anemia for both the 1-sample group (odds ratio 3.4, confidence interval [1.130-10.196], P < 0.05) and the 3-sample group (odds ratio 10.5, confidence interval [1.776-62.580], P < 0.01). Hematocrit was not a significant predictor in either group. Hemoglobin was 80% sensitive and 52.3% specific for a diagnosis of anemia in the 1-sample group and 91.3% sensitive and 50.0% specific in the 3-samples group. Hematocrit was 86.7% sensitive and 35.4% specific for a diagnosis of anemia in the 1-sample group and 91.3% sensitive and 23.3% specific in the 3-samples group., Conclusions: This study found that hemoglobin correlates better with the diagnosis of anemia than hematocrit. When three samples are analyzed, hemoglobin is equally sensitive and more specific than hematocrit. Based on these results and the U.S. Navy accession standards using hemoglobin as the standard index for anemia, the U.S. Navy Aeromedical Reference and Waiver Guide should consider using hemoglobin instead of hematocrit to screen for anemia. Future research should focus on prospective research to determine whether hemoglobin or hematocrit is a better indicator of anemia in screening military personnel., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Attempting to expedite delivery of care to wounded war fighters, this study aimed to quantify the ability of medical and surgical teams to perform lifesaving damage control and resuscitation procedures aboard nontraditional US Navy Vessels on high seas. Specifically, it looked at the ability of the teams to perform procedures in shipboard operating and emergency rooms by analyzing motion of personnel during the procedures., Methods: One hundred and twelve damage control and resuscitation procedures were performed during a voyage of the US Naval Ship Brunswick in transit from Norfolk, Virginia, to San Diego, California. The ability of personnel to perform these procedures was quantified by the use of motion link analysis designed to track the movement of each participant as they completed their assigned tasks., Results: The link analysis showed no significant change in the number of movements of participants from the beginning to the end of the study. However, there was a learning effect observed during the study, with teams completing tasks faster at the end of the study than at the beginning., Conclusion: This shows that the working conditions aboard the US Naval Ship Brunswick were satisfactory for the assigned tasks, indicating that these medical operations may be feasible aboard nontraditional US Navy vessels., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Youth with autism spectrum disorder (ASD) face high rates of unemployment, with unique challenges for military-dependent and -connected youth with ASD. This paper reports preliminary findings from Year One of a randomized waitlist controlled trial investigating the efficacy of the Project SEARCH + ASD Supports (PS + ASD) intervention model for military-dependent and -connected youth with ASD., Methods: Treatment group participants (n = 6) participated in internships at a military installation in the southeastern United States; waitlist group participants (n = 8) received special education transition services at their local high schools. Employment outcome data were collected at 12 months for both groups., Results: Fourteen unique internship experiences were developed across seven business partner organizations on the military installation during Year One. Five of six PS + ASD treatment group participants obtained competitive integrated employment for an overall employment rate of 83.3%. Four of the positions were federal jobs. None of the waitlist group participants obtained competitive integrated employment during the same period., Conclusions: Initial results are promising and suggest that the PS + ASD model may help to meet the transition needs of military-dependent and -connected youth with ASD and the employment needs of local military communities., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Leptospirosis is a global zoonotic disease spread through contact with contaminated water/soil. The US soldiers at the military bases in these countries are extremely vulnerable, as most of them are immunologically naïve to the responsible pathogen. No recent sero-epidemiological data of leptospirosis among US Marines stationed in Japan were available., Materials and Methods: In this study, we analyzed the presence of leptospirosis in US Marines stationed in Japan. One thousand posttour sera samples were analyzed by enzyme-linked immunosorbent assay for Leptospira-specific Immunoglobulin G., Results: Among these 1,000 posttour samples, 85 of them were positive and corresponding pretour samples were analyzed by enzyme-linked immunosorbent assay also. Seroconversion occurred for 35 (3.5%) Marines during their assignment to Japan. These results also indicate that 50 Marine personnels were exposed to leptospires before their assignment to Japan, perhaps because of previous exposure to leptospires at home., Conclusion: The 5% rate of seroconversion in 2013 and 2014 suggests that leptospirosis is a potential threat for Marines in the endemic region in Japan., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Service members are exposed to ambient airborne pollutants that have been linked to adverse health effects; however, capabilities to identify and characterize exposures across multi-domain operations are currently lacking. Occupational and environmental exposure monitoring is problematic because there is not a single simple solution, and current technological limitations suggest that simultaneous deployment of multiple devices may be the most effective near-term strategy., Materials and Methods: A broad industry scan of wearable, handheld, or portable occupational and environmental exposure monitoring devices was conducted, and subject matter experts were interviewed about the state of the field., Results: This survey identified limitations including the inability to detect multiple analytes or analyte classes, size and weight, and detection limits, but multiple implementation strategies could be employed to meet a variety of combat needs. Device types could be layered, or specific device types could be deployed in acute toxic exposure environments such as dense urban population centers or subterranean spaces., Conclusions: Evolving technologies and data management strategies may advance personal exposure monitoring in the future. These new devices and methods will likely supplant current technologies, while still using the programmatic and data framework established with early implementation of current commercial off the shelf devices., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Tissue injuries are often associated with abnormal blood flow (BF). The ability to assess BF distributions in injured tissues enables objective evaluation of interventions and holds the potential to improve the acute management of these injuries on battlefield., Materials and Methods: We have developed a novel speckle contrast diffuse correlation tomography (scDCT) system for noncontact 3D imaging of tissue BF distributions. In scDCT, a galvo mirror was used to remotely project near-infrared point light to different source positions and an electron multiplying charge-coupled-device was used to detect boundary diffuse speckle contrasts. The normalized boundary data were then inserted into a modified Near-Infrared Fluorescence and Spectral Tomography program for 3D reconstructions of BF distributions. This article reports the first application of scDCT for noncontact 3D imaging of BF distributions in burn wounds., Results: Significant lower BF values were observed in the burned areas/volumes compared to surrounding normal tissues., Conclusions: The unique noncontact 3D imaging capability makes the scDCT applicable for intraoperative assessment of burns/wounds, without risk of infection and without interfering with sterility of the surgical field. The portable scDCT device holds the potential to be used by surgeons in combat surgical hospitals to improve the acute management of battlefield burn injuries., (© Association of Military Surgeons of the United States 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In plants, parasitism triggers the reductive evolution of plastid genomes (plastomes). To disentangle the molecular evolutionary associations between feeding on other plants below- or aboveground and general transitions from facultative to obligate parasitism, we analyzed 34 complete plastomes of autotrophic, root- and stem-feeding hemiparasitic, and holoparasitic Santalales. We observed inexplicable losses of housekeeping genes and tRNAs in hemiparasites and dramatic genomic reconfiguration in holoparasitic Balanophoraceae, whose plastomes have exceptionally low GC contents. Genomic changes are related primarily to the evolution of hemi- or holoparasitism, whereas the transition from a root- to a stem-feeding mode plays no major role. In contrast, the rate of molecular evolution accelerates in a stepwise manner from autotrophs to root- and then stem-feeding parasites. Already the ancestral transition to root-parasitism coincides with a relaxation of selection in plastomes. Another significant selectional shift in plastid genes occurs as stem-feeders evolve, suggesting that this derived form coincides with trophic specialization despite the retention of photosynthetic capacity. Parasitic Santalales fill a gap in our understanding of parasitism-associated plastome degeneration. We reveal that lifestyle-genome associations unfold interdependently over trophic specialization and feeding mode transitions, where holoparasitic Balanophoraceae provide a system for exploring the functional realms of plastomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Cancer-related cognitive impairment (CRCI) is a concerning problem for many cancer survivors. Evaluating patients for CRCI has been a challenge, in part because of a lack of standardized practices. Self-report instruments are often used to assess CRCI, but there are no validated cutpoints. We present the results of receiver operating characteristic curve analysis identifying cutpoints of the Functional Assessment of Cancer Therapy-Cognition perceived cognitive impairment (PCI) in female breast cancer survivors for identifying CRCI cases. We defined presence of CRCI based on elevated complaints on the Patient's Assessment of Own Functioning Inventory compared with healthy control scores. Our results indicate that scores less than 54 in PCI scores using 18 items and scores less than 60 in PCI scores using 20 items exhibited good ability to discriminate CRCI cases from noncases (area under the receiver operating characteristic curve was 0.84 [95% CI = 0.73 to 0.94]). These preliminary results represent an important contribution toward standardizing practices across CRCI studies., (© The Author(s) 2020. Published by Oxford University Press.)

Epigenome-wide association studies (EWASs) have become increasingly popular for studying DNA methylation (DNAm) variations in complex diseases. The Illumina methylation arrays provide an economical, high-throughput and comprehensive platform for measuring methylation status in EWASs. A number of software tools have been developed for identifying disease-associated differentially methylated regions (DMRs) in the epigenome. However, in practice, we found these tools typically had multiple parameter settings that needed to be specified and the performance of the software tools under different parameters was often unclear. To help users better understand and choose optimal parameter settings when using DNAm analysis tools, we conducted a comprehensive evaluation of 4 popular DMR analysis tools under 60 different parameter settings. In addition to evaluating power, precision, area under precision-recall curve, Matthews correlation coefficient, F1 score and type I error rate, we also compared several additional characteristics of the analysis results, including the size of the DMRs, overlap between the methods and execution time. The results showed that none of the software tools performed best under their default parameter settings, and power varied widely when parameters were changed. Overall, the precision of these software tools were good. In contrast, all methods lacked power when effect size was consistent but small. Across all simulation scenarios, comb-p consistently had the best sensitivity as well as good control of false-positive rate., (© The Author(s) 2018. Published by Oxford University Press.)

Background: Observational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood., Methods: In a phase II trial, stage I-III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements. Analyses used linear mixed models., Results: In total, 139 patients were randomly assigned; 91 (65%) completed follow-up assessments. Fasting insulin levels statistically significantly decreased in all three intervention arms (-2.47 μU/mL combination arm, -0.08 μU/mL exercise only, -1.16 μU/mL metformin only, + 2.79 μU/mL control arm). Compared with the control arm, all groups experienced statistically significant weight loss between baseline and 12 weeks (-1.8% combination arm, -0.22% exercise only, -1.0% metformin only, +1.55% control). The combination arm also experienced statistically significant improvements in the homeostatic model assessment for insulin resistance (-30.6% combination arm, +61.2% control) and leptin (-42.2% combination arm, -0.8% control), compared with the control arm. The interventions did not change insulin-like growth factor-1 or insulin-like growth factor binding protein-3 measurements as compared with the control arm. Tolerance to metformin limited compliance (approximately 50% of the participants took at least 75% of the planned dosages in both treatment arms)., Conclusions: The combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing. Larger efforts are warranted to determine if such a combined modality intervention can improve outcomes in colorectal and breast cancer survivors., (© The Author(s) 2020. Published by Oxford University Press.)

Background: The National Comprehensive Cancer Network (NCCN) recommends germline testing for pathogenic BRCA1/2 mutations identified by somatic tumor sequencing. The aim of this study was to explore whether patients at Stanford with somatic BRCA1/2 mutations were recommended germline testing in accordance with NCCN guidelines., Methods: We retrospectively collected all Stanford patients with BRCA1/2 mutations found by tumor sequencing. Medical records were reviewed for each patient to identify those recommended germline testing. A multivariable logistic regression model was fit associating baseline characteristics with whether or not a recommendation was made., Results: Of 164 participants, 51 (31.1%) had no recommendation for germline testing. Of the 97 available germline-testing results, 54 (55.7%) were positive for pathogenic BRCA1/2 mutations. After adjusting for possible confounders, patients with genitourinary cancer (odds ratio [OR] = 0.03, 95% confidence interval [CI] = 0.00 to 0.03; P  =   .003), lung cancer (OR = 0.04, 95% CI = 0.01 to 0.21; P  <   .001), sarcoma (OR = 0.02, 95% CI = 0.00 to 0.14; P  <   .001), skin cancer (OR = 0.01, 95% CI = 0.98 to 1.03; P  =   .002), or "other" diagnoses (OR = 0.01, 95% CI = 0.00 to 0.16; P  <   .001) were statistically significantly less likely to be recommended germline testing compared with patients with breast or gynecological cancers., Conclusions: Our study highlights the importance of provider education outside of the oncologic specialties typically associated with BRCA -related cancers and continued exploration of referrals to genetics for germline testing on the basis of somatic findings., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer (CRC) is less clear., Methods: This cohort study was nested within a randomized trial of first-line chemotherapy and bevacizumab and/or cetuximab for advanced or metastatic CRC. Patients were enrolled at 508 community and academic centers throughout the National Clinical Trials Network. The primary exposure was physician-documented diabetes at the time of enrollment. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and adverse events. Tests of statistical significance were two-sided., Results: Among 2326 patients, 378 (16.3%) had diabetes. The median follow-up time was 6.0 years. We observed 1973 OS events and 2173 PFS events. The median time to an OS event was 22.7 months among those with diabetes and 27.1 months among those without diabetes (HR = 1.27, 95% CI = 1.13 to 1.44; P  <   .001). The median time to a PFS event was 9.7 months among those with diabetes and 10.8 months among those without diabetes (HR = 1.16, 95% CI = 1.03 to 1.30; P  =   .02). Patients with diabetes were more likely to experience no less than grade 3 hypertension (8.1% vs 4.4%; P  =   .054) but were not more likely to experience other adverse events, including neuropathy., Conclusions: Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic CRC. Patients with diabetes tolerate first-line treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be., Methods: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years)., Results: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation., Conclusions: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Ovarian cancer remains a leading cause of death from gynecological malignancies. Race, socioeconomic status (SES), and access to health care are important predictors of quality treatment and survival. We provide a systematic review and meta-analysis on the role of these predictors on disparities in ovarian cancer treatment and mortality., Methods: Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched PubMed, EMBASE, and Scopus for relevant articles published between January 2000 and March 2017. We selected studies published in the United States that evaluated the role of race, SES, or health-care access on disparities in ovarian cancer treatment or survival. Pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated for each outcome using a random-effects model., Results: A total of 41 studies met the inclusion criteria for systematic review. In meta-analysis, there was a 25% decrease (RR = 0.75, 95% CI = 0.66 to 0.84) in receipt of adherent ovarian cancer treatment and 18% increased risk (RR = 1.18, 95% CI = 1.11 to 1.26) of mortality for blacks compared to whites. Receipt of adherent ovarian cancer treatment was 15% lower (RR = 0.85, 95% CI = 0.77 to 0.94) in the lowest vs highest SES group and 30% lower (RR = 0.70, 95% CI = 0.58 to 0.85) among patients at lower vs higher hospital volumes., Conclusion: We found consistent and strong evidence for continued lack of quality ovarian cancer treatment and higher mortality among ovarian cancer patients who are black, are of low SES, and/or have poor access to care. Interventions focused on these groups targeting specific barriers to care are needed to reduce disparities in ovarian cancer treatment and mortality., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman's subsequent risk of hormone-sensitive cancer., Methods: This population-based cohort study included women aged 12-55 years who underwent prenatal screening between 11 weeks + 0 days of gestation to 20 weeks + 6 days of gestation in Ontario, Canada, 1993-2011, where universal health care is available. The hazard ratio of newly diagnosed breast, ovarian, endometrial, and thyroid cancer-arising at 21 weeks + 0 days of gestation or thereafter-was estimated in association with an abnormally low (≤5th) or high (>95th) percentile multiple of the median (MoM) for alpha-fetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol, pregnancy-associated plasma protein A, and dimeric inhibin A., Results: Among 677 247 pregnant women followed for a median of 11.0 years (interquartile range = 7.5-16.1), 7231 (1.07%) developed breast cancer, 515 (0.08%) ovarian cancer, 508 (0.08%) endometrial cancer, and 4105 (0.61%) thyroid cancer. In multivariable adjusted models, abnormally high hCG greater than the 95th percentile MoM was associated with a doubling in the risk of endometrial cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.33 to 2.95), and abnormally low AFP at the fifth percentile or less MoM conferred a moderately greater risk of thyroid cancer (aHR = 1.21, 95% CI = 1.07 to 1.38). Abnormally low pregnancy-associated plasma protein A at the fifth percentile or less MoM was not statistically significantly associated with breast cancer after multivariable adjustment (aHR = 1.19, 95% CI = 0.98 to 1.36)., Conclusions: Women with abnormally high levels of serum hCG or low AFP in early pregnancy may be at a greater future risk of certain types of hormone-sensitive cancers., (© The Author(s) 2020. Published by Oxford University Press.)

Important oncological management decisions rely on kidney function assessed by serum creatinine-based estimated glomerular filtration rate (eGFR). However, no large-scale multicenter comparisons of methods to determine eGFR in patients with cancer are available. To compare the performance of formulas for eGFR based on routine clinical parameters and serum creatinine not calibrated with isotope dilution mass spectrometry, we studied 3620 patients with cancer and 166 without cancer who had their glomerular filtration rate (GFR) measured with an exogenous nuclear tracer at one of seven clinical centers. The mean measured GFR was 86 mL/min. Accuracy of all models was center dependent, reflecting intercenter variability of isotope dilution mass spectrometry-creatinine measurements. CamGFR was the most accurate model for eGFR (root-mean-squared error 17.3 mL/min) followed by the Chronic Kidney Disease Epidemiology Collaboration model (root-mean-squared error 18.2 mL/min)., (© The Author(s) 2019. Published by Oxford University Press.)

Background: iPrevent is an online breast cancer (BC) risk management decision support tool. It uses an internal switching algorithm, based on a woman's risk factor data, to estimate her absolute BC risk using either the International Breast Cancer Intervention Study (IBIS) version 7.02, or Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 3 models, and then provides tailored risk management information. This study assessed the accuracy of the 10-year risk estimates using prospective data., Methods: iPrevent-assigned 10-year invasive BC risk was calculated for 15 732 women aged 20-70 years and without BC at recruitment to the Prospective Family Study Cohort. Calibration, the ratio of the expected (E) number of BCs to the observed (O) number and discriminatory accuracy were assessed., Results: During the 10 years of follow-up, 619 women (3.9%) developed BC compared with 702 expected (E/O = 1.13; 95% confidence interval [CI] =1.05 to 1.23). For women younger than 50 years, 50 years and older, and BRCA1/2 -mutation carriers and noncarriers, E/O was 1.04 (95% CI = 0.93 to 1.16), 1.24 (95% CI = 1.11 to 1.39), 1.13 (95% CI = 0.96 to 1.34), and 1.13 (95% CI = 1.04 to 1.24), respectively. The C-statistic was 0.70 (95% CI = 0.68 to 0.73) overall and 0.74 (95% CI = 0.71 to 0.77), 0.63 (95% CI = 0.59 to 0.66), 0.59 (95% CI = 0.53 to 0.64), and 0.65 (95% CI = 0.63 to 0.68), respectively, for the subgroups above. Applying the newer IBIS version 8.0b in the iPrevent switching algorithm improved calibration overall (E/O = 1.06, 95% CI = 0.98 to 1.15) and in all subgroups, without changing discriminatory accuracy., Conclusions: For 10-year BC risk, iPrevent had good discriminatory accuracy overall and was well calibrated for women aged younger than 50 years. Calibration may be improved in the future by incorporating IBIS version 8.0b., (© The Author(s) 2019. Published by Oxford University Press.)