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PurposeThe aim of this study was to develop a prioritization strategy for scheduling immediate screening mammographic interpretation and possible diagnostic evaluation.MethodsA population-based cohort with screening mammograms performed from 2012 to 2020 at 126 radiology facilities from 7Breast Cancer Surveillance Consortium registries was identified. Classification trees identified combinations of clinical history (age, BI-RADS® density, time since prior mammogram, history of false-positive recall or biopsy result), screening modality (digital mammography, digital breast tomosynthesis), and facility characteristics (profit status, location, screening volume, practice type, academic affiliation) that grouped screening mammograms by recall rate, with ≥12/100 considered high and ≥16/100 very high. An efficiency ratio was estimated as the percentage of recalls divided by the percentage of mammograms.ResultsThe study cohort included 2,674,051 screening mammograms in 925,777 women, with 235,569 recalls. The most important predictor of recall was time since prior mammogram, followed by age, history of false-positive recall, breast density, history of benign biopsy, and screening modality. Recall rates were very high for baseline mammograms (21.3/100; 95% confidence interval, 19.7-23.0) and high for women with ≥5 years since prior mammogram (15.1/100; 95% confidence interval, 14.3-16.1). The 9.2% of mammograms in subgroups with very high and high recall rates accounted for 19.2% of recalls, an efficiency ratio of 2.1 compared with a random approach. Adding women

Background: Machine learning (ML) approaches facilitate risk prediction model development using high-dimensional predictors and higher-order interactions at the cost of model interpretability and transparency. We compared the relative predictive performance of statistical and ML models to guide modeling strategy selection for surveillance mammography outcomes in women with a personal history of breast cancer (PHBC). Methods: We cross-validated seven risk prediction models for two surveillance outcomes, failure (breast cancer within 12 months of a negative surveillance mammogram) and benefit (surveillance-detected breast cancer). We included 9,447 mammograms (495 failures, 1,414 benefits, and 7,538 nonevents) from years 1996 to 2017 using a 1:4 matched case–control samples of women with PHBC in the Breast Cancer Surveillance Consortium. We assessed model performance of conventional regression, regularized regressions (LASSO and elastic-net), and ML methods (random forests and gradient boosting machines) by evaluating their calibration and, among well-calibrated models, comparing the area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CI). Results: LASSO and elastic-net consistently provided well-calibrated predicted risks for surveillance failure and benefit. The AUCs of LASSO and elastic-net were both 0.63 (95% CI, 0.60–0.66) for surveillance failure and 0.66 (95% CI, 0.64–0.68) for surveillance benefit, the highest among well-calibrated models. Conclusions: For predicting breast cancer surveillance mammography outcomes, regularized regression outperformed other modeling approaches and balanced the trade-off between model flexibility and interpretability. Impact: Regularized regression may be preferred for developing risk prediction models in other contexts with rare outcomes, similar training sample sizes, and low-dimensional features.

Background and ObjectivesBrain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI.MethodsAdults aged 18–75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies.ResultsFrom 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device.DiscussionThe BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development.Trial Registration InformationClinicalTrials.gov Identifier:NCT00912041.Classification of EvidenceThis study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.

Programmable genome integration of large, diverse DNA cargo without DNA repair of exposed DNA double-strand breaks remains an unsolved challenge in genome editing. We present programmable addition via site-specific targeting elements (PASTE), which uses a CRISPR-Cas9 nickase fused to both a reverse transcriptase and serine integrase for targeted genomic recruitment and integration of desired payloads. We demonstrate integration of sequences as large as ~36 kilobases at multiple genomic loci across three human cell lines, primary T cells and non-dividing primary human hepatocytes. To augment PASTE, we discovered 25,614 serine integrases and cognate attachment sites from metagenomes and engineered orthologs with higher activity and shorter recognition sequences for efficient programmable integration. PASTE has editing efficiencies similar to or exceeding those of homology-directed repair and non-homologous end joining-based methods, with activity in non-dividing cells and in vivo with fewer detectable off-target events. PASTE expands the capabilities of genome editing by allowing large, multiplexed gene insertion without reliance on DNA repair pathways.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.Over the past decade there has been increased attention on the need for highly skilled and trained pharmacy technicians; however, few best practices to assist health-system pharmacies in meeting technician workforce challenges have been identified. These challenges have been further revealed since 2019 through rising inflation, increased cost of living, and competing opportunities for skilled technical workers. This article describes an 18-hospital academic health system's experience implementing an innovative pharmacy technician career structure focused on increasing pharmacy technician engagement as well as improving recruitment and retention.Prior to creating a new career structure, the department of pharmacy had one development track for pharmacy technicians, which included only 2 nonsupervisory job titles. Due to recruitment, retention, and employee engagement challenges, the department of pharmacy, in collaboration with the human resources department, developed a new pharmacy technician structure that included 3 pharmacy technician tracks and 4 nonsupervisory levels. Outcomes collected to determine the success of the program included pharmacy technician engagement survey scores, annual voluntary turnover rate, rolling 12-month voluntary turnover rate, monthly vacancy rate, and average years of service at termination. The monthly discharge prescription capture rate was also measured to support efforts to keep th e cost of the new structure budget neutral.The change in career structure assisted in the improvement of each outcome identified. The close collaboration of the departments of pharmacy and human resources can lead to positive solutions of national problems and have a sustained impact on department operations.

Patients may present to the emergency department for sexual assault care under the influence of drugs or alcohol. However, many emergency nurses are not prepared to meet their unique needs or aware of follow-up behavioral health resources. The purpose of this study was to (1) summarize current resources provided to patients and processes for referral to behavioral health services after sexual assault care, (2) explore emergency nurses' attitudes and behaviors toward patient substance use, and (3) explore nurses' perceptions of adjunct mobile health interventions for follow-up behavioral health care and describe anticipated barriers to use.Fifteen emergency nurses participated in semi-structured qualitative interviews.Participants had mixed perceptions of patient intoxication during sexual assault care. They felt that conversations about substance use may be more appropriate after the ED visit. Participants recognized the opportunity to connect ED patients with substance use treatment or prevention resources but perceived that there are few local service providers. Most participants were not referring patients with substance use issues to behavioral health services after sexual assault care and said that their emergency departments did not have processes for referral to these services. Acceptability of mobile health for follow-up behavioral health care was high, but participants had concerns for patient privacy and internet access. Participants gave recommendations to improve referral practices and patient engagement with mobile health interventions.This study highlights the need for emergency nurses to consider patient intoxication during sexual assault care and opportunities to connect patients with resources post-assault.

Animal conservation requires a sound understanding of movement ecology and habitat selection. A key component of this is identifying habitats that animals actively seek or avoid. We quantified habitat selection and investigated the drivers of variability in the short-term activity area of a small, endangered mesopredator, the northern quoll (Dasyurus hallucatus), in the Pilbara region of Western Australia. We collated, standardised, and analysed 14 northern quoll GPS tracking events from four studies conducted between 2014 and 2018. Northern quolls selected activity areas in locations that were more topographically rugged than the broader landscape, characterised by a higher percentage cover of rocky habitat and riverbed, and a lower percentage cover of spinifex sandplain. The size of their activity area also increased with higher percentage cover of non-preferred spinifex sandplain. Therefore, the destruction of habitats preferred by northern quolls – such as mining of rocky habitat – and introduction of structurally simple habitat like spinifex sandplain, is likely to negatively impact resource availability and lead to altered movement patterns that could decrease survival. Future conservation planning should place emphasis on the protection of rugged rocky habitat for northern quolls, as well as efficient movement pathways between patches of this critical habitat.

A diverse collection of dinosaur tracks and trackways preserved on a single bedding plane record activities of many animals over a very short time, possibly just a few days or less. The assemblage is exposed on a detached slab of siltstone from the Campanian–Maastrichtian St. Mary River Formation in southwestern Alberta, Canada. Members of four different groups of dinosaurs are identified as the makers of either isolated tracks, or trackways of varying lengths, and include inferred hatchling tyrannosaurids, medium and large ornithomimids, small and medium-sized ornithopods, and a small hadrosaurid. All but one of the seven trackways attributed to hatchling tyrannosaurids occur as codirectional, equally spaced pairs, but one pair walked in the opposite direction, albeit parallel, to the other two. The pair of ornithomimid trackways also appears to represent two animals walking at the same speed, in the same direction, and turning together. The trackway attributed to a medium-sized biped, possibly Parksosaurus warreni, is the first evidence for the presence of these dinosaurs in the environment recorded by the St. Mary River Formation.

Objective This study aimed to investigate the use of the head and neck cancer risk calculator version 2 in a primary care setting and to evaluate the impact of the risk calculator on the number of referrals stratified by urgency and cancer yield. Method Referrals between April 2019 and August 2019, April 2020 and July 2020 (pre-risk calculator) and August 2020 and July 2021 (post-risk calculator) were analysed. Referral urgency, head and neck cancer risk calculator version 2 score, cancer diagnosis, cancer type and further investigations were recorded. Results The 2023 patient encounters were analysed; there were 1110 (55 per cent) referrals before head and neck cancer risk calculator version 2 use and 913 (45 per cent) after head and neck cancer risk calculator version 2 use. A higher proportion of older (p < 0.001) and male (p < 0.013) patients were seen post-head and neck cancer risk calculator version 2 use. All cancer cases were seen on the urgent suspicion of cancer pathway post-head and neck cancer risk calculator version 2 use; however, a higher proportion of patients were seen as urgent suspicion of cancer (51.1 vs 83.5 per cent; p < 0.001). Overall, the cancer diagnosis rate increased from 2.7 to 4.1 per cent. Conclusion The head and neck cancer risk calculator version 2 had high sensitivity in cancer diagnosis. More studies are required to optimise the predicted versus actual cancer probability gap.

The aim of this study was to determine the frequency, components of, and factors associated with shared decision-making (SDM) discussions according to electronic health record (EHR) documentation among individuals undergoing lung cancer screening (LCS).A prospective observational cohort study was conducted of individuals undergoing LCS between February 2015 and June 2020 at four LCS centers. The primary outcome was EHR-documented SDM, defined using Medicare-designated components. A multivariable logistic regression model was used to examine predictors of EHR-documented SDM. A secondary outcome was agreement of individual's self-report of SDM and EHR-documented SDM, evaluated using Cohen's κ statistic.Among screened individuals, 41.9% (243 of 580) had EHR-documented SDM, and 71.1% (295 of 415) had self-reported SDM. Decision aids were used in 55.6% of EHR-documented SDM encounters (135 of 243), and 21.8% of documented SDM encounters (53 of 243) included all Medicare-designated components. SDM was documented more frequently in individuals with body mass index ≥ 25 versus25 kg/mAlthough EHR-documented SDM occurred in fewer than half of individuals undergoing LCS, self-reported SDM rates were higher, suggesting that SDM may be underdocumented in the EHR. In addition, EHR-documented SDM was more likely in individuals with higher body mass index and those referred for LCS by pulmonary clinicians. These findings indicate areas for improvement in the implementation and documentation of SDM.

Context Coral reef resilience is the product of multiple interacting processes that occur across various interacting scales. This complexity presents challenges for identifying solutions to the ongoing worldwide decline of coral reef ecosystems that are threatened by both local and global human stressors. Objectives We highlight how coral reef resilience is studied at spatial, temporal, and functional scales, and explore emerging technologies that are bringing new insights to our understanding of reef resilience. We then provide a framework for integrating insights across scales by using new and existing technological and analytical tools. We also discuss the implications of scale on both the ecological processes that lead to declines of reefs, and how we study those mechanisms. Methods To illustrate, we present a case study from Kāneʻohe Bay, Hawaiʻi, USA, linking remotely sensed hyperspectral imagery to within-colony symbiont communities that show differential responses to stress. Results In doing so, we transform the scale at which we can study coral resilience from a few individuals to entire ecosystems. Conclusions Together, these perspectives guide best practices for designing management solutions that scale from individuals to ecosystems by integrating multiple levels of biological organization from cellular processes to global patterns of coral degradation and resilience.

Models of visual search in scenes include image salience as a source of attentional guidance. However, because scene meaning is correlated with image salience, it could be that the salience predictor in these models is driven by meaning. To test this proposal, we generated meaning maps that represented the spatial distribution of semantic informativeness in scenes, and salience maps which represented the spatial distribution of conspicuous image features and tested their influence on fixation densities from two object search tasks in real-world scenes. The results showed that meaning accounted for significantly greater variance in fixation densities than image salience, both overall and in early attention across both studies. Here, meaning explained 58% and 63% of the theoretical ceiling of variance in attention across both studies, respectively. Furthermore, both studies demonstrated that fast initial saccades were not more likely to be directed to higher salience regions than slower initial saccades, and initial saccades of all latencies were directed to regions containing higher meaning than salience. Together, these results demonstrated that even though meaning was task-neutral, the visual system still selected meaningful over salient scene regions for attention during search.

The Cape Bathurst polynya and flaw lead (CBP) are major, predictable habitat features with ≤15% ice cover in an otherwise ice-covered Beaufort Sea, and thought to provide hunting opportunities for polar bears (Ursus maritimus Phipps, 1774). We assessed 78 adult (female; with and without cubs) and subadult (male and female) polar bears’ use of the CBP from October to June 2007–2014. The CBP was up to 725 km wide in autumn, ice-covered in winter, and

Humans rapidly process and understand real-world scenes with ease. Our stored semantic knowledge gained from experience is thought to be central to this ability by organizing perceptual information into meaningful units to efficiently guide our attention in scenes. However, the role stored semantic representations play in scene guidance remains difficult to study and poorly understood. Here, we apply a state-of-the-art multimodal transformer trained on billions of image-text pairs to help advance our understanding of the role semantic representations play in scene understanding. We demonstrate across multiple studies that this transformer-based approach can be used to automatically estimate local scene meaning in indoor and outdoor scenes, predict where people look in these scenes, detect changes in local semantic content, and provide a human-interpretable account of why one scene region is more meaningful than another. Taken together, these findings highlight how multimodal transformers can advance our understanding of the role scene semantics play in scene understanding by serving as a representational framework that bridges vision and language.

Supplementary Table 12 includes the one-year cumulative incidences for HCC surveillance overall and by insurance type, by calendar year of cirrhosis diagnosis, excluding individuals with decompensated cirrhosis (% and 95% confidence intervals).

Supplementary Table 7 includes baseline characteristics of individuals with cirrhosis eligible for HCC surveillance – Medicare only (N, %) (N=32,723).

The Supplementary Methods includes detailed descriptions for calculating the Proportion of Time Covered measures.

Supplementary Table 5 includes baseline characteristics of individuals with cirrhosis eligible for HCC surveillance – private insurance only (N, %) (N=6,530).

Supplementary Table 9 includes two-year cumulative incidences for HCC surveillance overall and by insurance type, by calendar year of cirrhosis diagnosis (% and 95% confidence intervals).

Supplementary Table 8 includes one-year cumulative incidences for HCC surveillance overall and by insurance type, by calendar year of cirrhosis diagnosis (% and 95% confidence intervals).