Search

PURPOSE: Current clinical risk stratification methods for localized prostate cancer are suboptimal, leading to over- and undertreatment. Recently, machine learning approaches using digital histopathology have shown superior prognostic ability in phase III trials. This study aims to develop a clinically usable risk grouping system using multimodal artificial intelligence (MMAI) models that outperform current National Comprehensive Cancer Network (NCCN) risk groups. MATERIALS AND METHODS: The cohort comprised 9,787 patients with localized prostate cancer from eight NRG Oncology randomized phase III trials, treated with radiation therapy, androgen deprivation therapy, and/or chemotherapy. Locked MMAI models, which used digital histopathology images and clinical data, were applied to each patient. Expert consensus on cut points defined low-, intermediate-, and high-risk groups on the basis of 10-year distant metastasis rates of 3% and 10%, respectively. The MMAIs reclassification and prognostic performance were compared with the three-tier NCCN risk groups. RESULTS: The median follow-up for censored patients was 7.9 years. According to NCCN risk categories, 30.4% of patients were low-risk, 25.5% intermediate-risk, and 44.1% high-risk. The MMAI risk classification identified 43.5% of patients as low-risk, 34.6% as intermediate-risk, and 21.8% as high-risk. MMAI reclassified 1,039 (42.0%) patients initially categorized by NCCN. Despite the MMAI low-risk group being larger than the NCCN low-risk group, the 10-year metastasis risks were comparable: 1.7% (95% CI, 0.2 to 3.2) for NCCN and 3.2% (95% CI, 1.7 to 4.7) for MMAI. The overall 10-year metastasis risk for NCCN high-risk patients was 16.6%, with MMAI further stratifying this group into low-, intermediate-, and high-risk, showing metastasis rates of 3.4%, 8.2%, and 26.3%, respectively. CONCLUSION: The MMAI risk grouping system expands the population of men identified as having low metastatic risk and accurately pinpoints a high-risk subset with elevated metastasis rates. This approach aims to prevent both overtreatment and undertreatment in localized prostate cancer, facilitating shared decision making.

Abstract Background Previous research has shown that genetics and maternal medical, sociodemographic, lifestyle and psychosocial factors affect maternal and perinatal outcomes. Substantial research has been done on ethnic differences and maternal and perinatal outcomes in hospital settings. To our knowledge there are no studies about the associations between ethnicity and maternal and perinatal outcomes in a midwife-led care setting among low-risk women. Therefore, our study aimed to investigate possible ethnic associations between non-Western and Dutch women, and maternal and perinatal outcomes in a midwife-led care setting. Methods A retrospective cohort study was performed of low-risk pregnant women (n = 977) in midwife-led care. Data was collected from a medium-sized midwifery practice in an urban region near Amsterdam, the Netherlands. Regression analyses were performed to examine the effect of ethnicity on maternal and perinatal outcomes. Outcomes of interest were gestational age, mode of birth, perineal status, postpartum hemorrhage, birthweight, perinatal death and low Apgar score. Associations were corrected for deprived areas, body mass index (BMI), parity and maternal educational level. Potential effect modification for prenatal referral to obstetrician and parity were assessed. Results The study included 977 women, of whom 483 were non-Western, and 494 were Dutch. Regarding characteristics, compared to Dutch women, non-Western women were more likely to be multiparous (respectively 58.6% versus 49.2%; p = 0.003), live in a deprived area (34.0% versus 8.1%; p

Sea level rise is associated with increased coastal erosion and inundation. However, the effects of sea level change on the shoreline can be enhanced or counteracted by vertical land motion and morphological processes. Therefore, knowledge about the individual contributions of sea level change, vertical land motion and morphodynamics on shoreline changes is necessary to make informed choices for climate change adaptation, such as applying coastal defence measures. Here, we assess the potential of remote-sensing techniques to detect a geometrical relationship between sea level rise and shoreline retreat for a case study at the Terschelling barrier island at the northern Dutch coast. First, we find that sea level observations from satellite radar altimetry retracked with ALES can represent sea level variations between 2002 and 2022 at the shoreline when the region to extract altimetry time series is chosen carefully. Second, results for cross-shore time series of satellite-derived shorelines extracted from optical remote-sensing images can change considerably, depending on choices made for tidal correction and parameter settings during the computation of time series. While absolute shoreline positions can differ on average by more than 200 m, the average trend differences are below 1 m yr−1. Third, by intersecting the 1992 land elevation with time-variable sea level, we find that inundation through sea level rise caused on average −0.3 m yr−1 of shoreline retreat between 1992 and 2022. The actual shoreline movement in this period was on average between −2.8 and −3.2 m yr−1, leading to the interpretation that the larger part of shoreline changes at Terschelling is driven by morphodynamics. We conclude that the combination of sea level from radar altimetry, satellite-derived shorelines and land elevation provides valuable information about the influence of sea level rise, vertical land motion and morphodynamics on shoreline movements.

Abstract The adaptive capacity of ecosystems, or their ability to function despite altered environmental conditions, is crucial for resilience to climate change. However, the role of landscape complexity or species traits on adaptive capacity remains unclear. Here, we combine field experiments and morphodynamic modelling to investigate how ecosystem complexity shapes the adaptive capacity of intertidal salt marshes. We focus on the importance of tidal channel network complexity for sediment accumulation, allowing vertical accretion to keep pace with sea-level rise. The model showed that landscape-scale ecosystem complexity, more than species traits, explained higher sediment accumulation rates, despite complexity arising from these traits. Landscape complexity, reflected in creek network morphology, also improved resilience to rising water levels. Comparing model outcomes with real-world tidal networks confirmed that flow concentration, sediment transport and deposition increase with drainage complexity. These findings emphasize that natural pattern development and persistence are crucial to preserve resilience to climate change.

Objectives: Food and Alcohol Disturbance (FAD) is the phenomenon in which individuals exhibit co-occurring hazardous alcohol and eating behaviors to either negate caloric intake associated with alcohol and/or maximize intoxication. While the Compensatory Eating and Behaviors in Response to Alcohol Scale (CEBRACS) is the most widely used measure to assess FAD to date, its factor-structure has yet to be confirmed. Methods: The current study utilized confirmatory factor analysis (CFA) to examine the CEBRACS' four factor subscales as well as recently proposed alternative scoring structures. Participants: Participants (N = 582) were American college students from seven universities (18-24 years; 67% cisgender women; 70% non-Hispanic White). Results: The CFA failed to provide optimal fit for all models tested. Results of invariance testing found no measurement variance by sex, suggesting the failure of the four-factor solution was not due to noninvariance. Conclusions: Overall, findings do not support continued use of the original 21-item CEBRACS.

Differences in the management of atrial fibrillation (AF) between men and women were investigated by using Gulf SAFE data in the Middle East. The study included 2,043 patients presenting with AF to emergency room (ER) were prospectively enrolled and followed for one-year. Women were older, have higher body mass index (BMI), comorbidities, and health complications than men. With regard to management of AF, cardioversion was recommended more often for men (16.7% vs. 9.3%), and underwent electrical cardioversion (2.2% vs. 1.1%). Women were prescribed digoxin more frequently than men (25.6% vs. 17.4%) and a significant number women received warfarin alone (31.1% vs. 8.7%). No difference between the sexes was noticed in One-year rates of stroke/transient ischemic attacks (TIA) and all-cause of mortality after one-year follow-up (3.1% men vs. 3.3% women, and 7.5% vs. 7.4%). Older age (≥ 65 years), smoking, alcohol use, CHADS2 scores ≥5 were some of the significant risk factors in men with AF. Suboptimal use of anticoagulants, higher mortality and stroke/TIA events at one year are high but similar between the sexes. ER management revealed high use of rate control strategy and high rate of hospital admission was noticed in women.

Abstract Background Movement links the distribution of habitats with the social environment of animals using those habitats. Despite the links between movement, habitat selection, and socioecology, their integration remains a challenge due to lack of shared vocabulary across fields, methodological gaps, and the implicit (rather than explicit) historical development of theory in the fields of social and spatial ecology. Given these challenges can be addressed, opportunity for further study will provide insight about the links between social, spatial, and movement ecology. Here, our objective was to disentangle the roles of habitat selection and social association as drivers of movement in caribou (Rangifer tarandus). Methods To accomplish our objective, we modelled the relationship between collective movement and selection of foraging habitats using socially informed integrated step selection function (iSSF). Using iSSF, we modelled the effect of social processes, i.e., nearest neighbour distance and social preference, and movement behaviour on patterns of habitat selection. Results By unifying social network analysis with iSSF, we identified movement-dependent social association, where individuals took shorter steps in lichen habitat and foraged in close proximity to more familiar individuals. Conclusions Our study demonstrates that social preference is context-dependent based on habitat selection and foraging behaviour. We therefore surmise that habitat selection and social association are drivers of collective movement, such that movement is the glue between habitat selection and social association. Here, we put these concepts into practice to demonstrate that movement is the glue connecting individual habitat selection to the social environment.

Abstract Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p

Abstract During the repair of interstrand crosslinks (ICLs) a DNA double-strand break (DSB) is generated. The Fanconi anemia (FA) core complex, which is recruited to ICLs, promotes high-fidelity repair of this DSB by homologous recombination (HR). However, whether the FA core complex also promotes HR at ICL-independent DSBs, for example induced by ionizing irradiation or nucleases, remains controversial. Here, we identified the FA core complex members FANCL and Ube2T as HR-promoting factors in a CRISPR/Cas9-based screen. Using isogenic cell line models, we further demonstrated an HR-promoting function of FANCL and Ube2T, and of their ubiquitination substrate FANCD2. We show that FANCL and Ube2T localize at DSBs in a FANCM-dependent manner, and are required for the DSB accumulation of FANCD2. Mechanistically, we demonstrate that FANCL ubiquitin ligase activity is required for the accumulation of CtIP at DSBs, thereby promoting end resection and Rad51 loading. Together, these data demonstrate a dual genome maintenance function of the FA core complex and FANCD2 in promoting repair of both ICLs and DSBs.

During the glacial cycles of the past 800 000 years, Eurasia and North America were periodically covered by large ice sheets, causing up to 100 m of sea-level change. While Late Pleistocene glacial cycles typically lasted 80 000–120 000 years, the termination phases were completed in only 10 000 years. During these glacial terminations, the North American and Eurasian ice sheets retreated, which created large proglacial lakes in front of the ice-sheet margin. Proglacial lakes accelerate deglaciation as they facilitate the formation of ice shelves at the southern margins of the North American and Eurasian ice sheets. These ice shelves are characterized by basal melting, low surface elevations, and negligible friction at the base. Here, we use an ice-sheet model to quantify the (combined) effects of proglacial lakes on Late Pleistocene glacial terminations by examining their interplay with glacial isostatic adjustment (GIA) and basal sliding. We find that proglacial lakes accelerate the deglaciation of ice sheets mainly because there is an absence of basal friction underneath ice shelves. If friction underneath grounded ice is applied to floating ice, full deglaciation is postponed by a few millennia, resulting in more ice remaining during interglacial periods and no extensive ice shelves forming. Additionally, the large uncertainty in melt rates underneath lacustrine ice shelves translates to an uncertainty in the timing of the termination of up to a millennium. Proglacial lakes are created by depressions in the landscape that remain after an ice sheet has retreated. The depth, size, and timing of proglacial lakes depend on the rate of bedrock rebound. We find that if bedrock rebounds within a few centuries (rather than a few millennia), the mass loss rate of the ice sheet is substantially reduced. This is because fast bedrock rebound prevents the formation of extensive proglacial lakes. Additionally, a decrease in ice thickness is partly compensated for by faster bedrock rebound, resulting in a higher surface elevation; lower temperatures; and a higher surface mass balance, which delays deglaciation. We find that a very long bedrock relaxation time does not substantially affect terminations, but it may lead to a delayed onset of the next glacial period. This is because inception regions, such as northwestern Canada, remain below sea level throughout the preceding interglacial period.

BACKGROUND: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life, and there remain no validated predictive models to guide its use. METHODS: We used digital pathology images from pretreatment prostate tissue and clinical data from 5727 patients enrolled in five phase 3 randomized trials, in which treatment was radiotherapy with or without ADT, as our data source to develop and validate an artificial intelligence (AI)–derived predictive patient-specific model that would determine which patients would develop the primary end point of distant metastasis. The model used baseline data to provide a binary output that a given patient will likely benefit from ADT or not. After the model was locked, validation was performed using data from NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 (n=1594), a trial that randomly assigned men to radiotherapy plus or minus 4 months of ADT. Fine–Gray regression and restricted mean survival times were used to assess the interaction between treatment and the predictive model and within predictive model–positive, i.e., benefited from ADT, and –negative subgroup treatment effects. RESULTS: Overall, in the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis. Of these enrolled patients, 543 (34%) were model positive, and ADT significantly reduced the risk of distant metastasis compared with radiotherapy alone. Of 1051 patients who were model negative, ADT did not provide benefit. CONCLUSIONS: Our AI-based predictive model was able to identify patients with a predominantly intermediate risk for prostate cancer likely to benefit from short-term ADT. (Supported by a grant [U10CA180822] from NRG Oncology Statistical and Data Management Center, a grant [UG1CA189867] from NCI Community Oncology Research Program, a grant [U10CA180868] from NRG Oncology Operations, and a grant [U24CA196067] from NRG Specimen Bank from the National Cancer Institute and by Artera, Inc. ClinicalTrials.gov numbers NCT00767286, NCT00002597, NCT00769548, NCT00005044, and NCT00033631.)