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

Electronic health record-based clinical decision support (CDS) tools can facilitate the adoption of evidence into practice. Yet, the impact of CDS beyond single-site implementation is often limited by dissemination and implementation barriers related to site- and user-specific variation in workflows and behaviors. The translation of evidence-based CDS from initial development to implementation in heterogeneous environments requires a framework that assures careful balancing of fidelity to core functional elements with adaptations to ensure compatibility with new contexts. This study aims to develop and apply a framework to guide tailoring and implementing CDS across diverse clinical settings. In preparation for a multisite trial implementing CDS for pediatric overweight or obesity in primary care, we developed the User-Centered Framework for Implementation of Technology (UFIT), a framework that integrates principles from user-centered design (UCD), human factors/ergonomics theories, and implementation science to guide both CDS adaptation and tailoring of related implementation strategies. Our transdisciplinary study team conducted semistructured interviews with pediatric primary care clinicians and a diverse group of stakeholders from 3 health systems in the northeastern, midwestern, and southeastern United States to inform and apply the framework for our formative evaluation. We conducted 41 qualitative interviews with primary care clinicians (n=21) and other stakeholders (n=20). Our workflow analysis found 3 primary ways in which clinicians interact with the electronic health record during primary care well-child visits identifying opportunities for decision support. Additionally, we identified differences in practice patterns across contexts necessitating a multiprong design approach to support a variety of workflows, user needs, preferences, and implementation strategies. UFIT integrates theories and guidance from UCD, human factors/ergonomics, and implementation science to promote fit with local contexts for optimal outcomes. The components of UFIT were used to guide the development of Improving Pediatric Obesity Practice Using Prompts, an integrated package comprising CDS for obesity or overweight treatment with tailored implementation strategies. ClinicalTrials.gov NCT05627011; https://clinicaltrials.gov/study/NCT05627011.

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (79Br, 81Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues.

In vivo biomarkers that can detect long-term neuropathologies from repetitive head impact (RHI) exposure are needed, especially for the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). Here, we evaluated plasma p-tau217 as a potential biomarker for CTE p-tau pathology, and examined the concordance between plasma p-tau217 and Aβ pathology in an at-risk for CTE sample. The sample included 180 male former football players (120 professional, 60 college), and 56 asymptomatic men without RHI (i.e., controls). Participants completed blood draws, 18F-florbetapir (Aβ+=SUVR≥1.10), and 18F-flortaucipir PET. Traumatic encephalopathy syndrome (TES) diagnoses were made. Single molecule array for plasma p-tau217 (ALZpath) was performed (≥0.6 cutoff used to maximize sensitivity). Nine participants had post-mortem tissue. ANCOVA examined group differences in p-tau217 (football vs controls; TES-CTE no, TES-CTE suggestive, TES-CTE possible/probable). Multivariable regression models tested associations between p-tau217 and florbetapir/flortaucipir PET. Covariates included age, race and APOE e4. Sample characteristics are in Table 1. p-tau217 concentrations were higher in former football players compared to controls (est. marginal mean difference=-0.217, p = 0.005). There were no group differences in Aβ-PET SUVR. No differences were found across TES-CTE certainty levels. In football players, higher p-tau217 was associated with higher Aβ-PET SUVR (B=1.380, 95%CI[0.597-2.155], p = 0.001) but not when Aβ+ (n = 17) participants and those with kidney/liver disease (n = 5) were excluded. Aβ+ participants had the highest p-tau217 (Figure 1). When compared against Aβ-PET, several false Aβ-positives (high p-tau217, Aβ-) were identified, including one extreme outlier (assay related) and a cluster of Aβ- participants with p-tau217 between 0.60-1.0. There were no associations with flortaucipir SUVR (frontal, mesial temporal, left parietal). Two extreme p-tau217 outliers had autopsy-confirmed CTE stage III (AD-, Table 2). Of the remaining donors, all were AD- and four had CTE (stages II-IV) with ptau217 between 0.125-0.449. Plasma p-tau217 has usefulness in quantifying Aβ pathology but restricted utility for detection of CTE. In this at-risk for CTE sample, p-tau217 and Aβ-PET were associated at the group level. At the individual level, false Aβ-positives (and negatives) existed, including Aβ- participants with high p-tau217. We will explore whether this discrepancy is due to disease or peripheral interference with the N-terminal binding in p-tau assays.

Background In vivo biomarkers that can detect long‐term neuropathologies from repetitive head impact (RHI) exposure are needed, especially for the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). Here, we evaluated plasma p‐tau217 as a potential biomarker for CTE p‐tau pathology, and examined the concordance between plasma p‐tau217 and Aβ pathology in an at‐risk for CTE sample. Method The sample included 180 male former football players (120 professional, 60 college), and 56 asymptomatic men without RHI (i.e., controls). Participants completed blood draws, 18F‐florbetapir (Aβ+=SUVR≥1.10), and 18F‐flortaucipir PET. Traumatic encephalopathy syndrome (TES) diagnoses were made. Single molecule array for plasma p‐tau217 (ALZpath) was performed (≥0.6 cutoff used to maximize sensitivity). Nine participants had post‐mortem tissue. ANCOVA examined group differences in p‐tau217 (football vs controls; TES‐CTE no, TES‐CTE suggestive, TES‐CTE possible/probable). Multivariable regression models tested associations between p‐tau217 and florbetapir/flortaucipir PET. Covariates included age, race and APOE e4. Result Sample characteristics are in Table 1. p‐tau217 concentrations were higher in former football players compared to controls (est. marginal mean difference=‐0.217, p = 0.005). There were no group differences in Aβ‐PET SUVR. No differences were found across TES‐CTE certainty levels. In football players, higher p‐tau217 was associated with higher Aβ‐PET SUVR (B=1.380, 95%CI[0.597‐2.155], p = 0.001) but not when Aβ+ (n = 17) participants and those with kidney/liver disease (n = 5) were excluded. Aβ+ participants had the highest p‐tau217 (Figure 1). When compared against Aβ‐PET, several false Aβ‐positives (high p‐tau217, Aβ‐) were identified, including one extreme outlier (assay related) and a cluster of Aβ‐ participants with p‐tau217 between 0.60–1.0. There were no associations with flortaucipir SUVR (frontal, mesial temporal, left parietal). Two extreme p‐tau217 outliers had autopsy‐confirmed CTE stage III (AD‐, Table 2). Of the remaining donors, all were AD‐ and four had CTE (stages II‐IV) with ptau217 between 0.125‐0.449. Conclusion Plasma p‐tau217 has usefulness in quantifying Aβ pathology but restricted utility for detection of CTE. In this at‐risk for CTE sample, p‐tau217 and Aβ‐PET were associated at the group level. At the individual level, false Aβ‐positives (and negatives) existed, including Aβ‐ participants with high p‐tau217. We will explore whether this discrepancy is due to disease or peripheral interference with the N‐terminal binding in p‐tau assays.

The Greenland GPS Network (GNET) uses the Global Positioning System (GPS) to measure the displacement of bedrock exposed near the margins of the Greenland ice sheet. The entire network is uplifting in response to past and present-day changes in ice mass. Crustal displacement is largely accounted for by an annual oscillation superimposed on a sustained trend. The oscillation is driven by earth's elastic response to seasonal variations in ice mass and air mass (i.e., atmospheric pressure). Observed vertical velocities are higher and often much higher than predicted rates of postglacial rebound (PGR), implying that uplift is usually dominated by the solid earth's instantaneous elastic response to contemporary losses in ice mass rather than PGR. Superimposed on longer-term trends, an anomalous 'pulse' of uplift accumulated at many GNET stations during an approximate six-month period in 2010. This anomalous uplift is spatially correlated with the 2010 melting day anomaly.

The United States needs many different types of forests: some managed for wood products plus other benefits, and some managed for nonconsumptive uses and benefits. The objective of reducing global greenhouse gases (GHG) requires increasing carbon storage in pools other than the atmosphere. Growing more forests and keeping forests as forests are only part of the solution, because focusing solely on the sequestration benefits of the forests misses the important (and substantial) carbon storage and substitution GHG benefits of harvested forest products, as well as other benefits of active forest management. Forests and global climate are closely linked in terms of carbon storage and releases, water fluxes from the soil and into the atmosphere, and solar energy capture. Understanding how carbon dynamics are affected by stand age, density, and management and will evolve with climate change is fundamental to exploiting the capacity for sustainably managed forests to remove carbon dioxide from the atmosphere. For example, even though temperate forests continue to be carbon sinks, in western North America forest fires and tree mortality from insects are converting some forests into net carbon sources. Expanding forest biomass use for biofuels and energy generation will compete with traditional forest products, but it may also produce benefits through competition and market efficiency. Short-rotation woody crops, as well as landowners' preferences-based on investment-return expectations and environmental considerations, both of which will be affected by energy and environmental policies-have the potential to increase biomass supply. Unlike metals, concrete, and plastic, forest products store atmospheric carbon and have low embodied energy (the amount of energy it takes to make products), so there is a substitution effect when wood is used in place of other building materials. Wood used for energy production also provides substitution benefits by reducing the flow of fossil fuel-based carbon emissions to the atmosphere. The value of carbon credits generated by forest carbon offset projects differs dramatically, depending on the sets of carbon pools allowed by the protocol and baseline employed. The costs associated with establishing and maintaining offset projects depend largely on the protocols' specifics. Measurement challenges and relatively high transaction costs needed for forest carbon offsets warrant consideration of other policies that promote climate benefits from forests and forest products but do not require project-specific accounting. Policies can foster changes in forest management and product manufacture that reduce carbon emissions over time while maintaining forests for environmental and societal benefits. US policymakers should take to heart the finding of the Intergovernmental Panel on Climate Change in its Fourth Assessment Report when it concluded that \"In the long term, a sustainable forest management strategy aimed at maintaining or increasing forest carbon stocks, while producing an annual sustained yield of timber, fibre, or energy from the forest, will generate the largest sustained mitigation benefit.\" A rational energy and environmental policy framework must be based on the premise that atmospheric greenhouse gas levels are increasing primarily because of the addition of geologic fossil fuel-based carbon into the carbon cycle. Forest carbon policy that builds on the scientific information summarized in this article can be a significant and important part of a comprehensive energy policy that provides for energy independence and carbon benefits while simultaneously providing clean water, wildlife habitat, recreation, and other uses and values.

Medical student reflection is integral for professional development. Preliminary findings suggest that short-format writing promotes reflection and identifies impactful experiences. We sought to determine whether reflective writing could be used as a clerkship needs assessment. During their surgical clerkship, medical students submitted “tweet”-format reflections and completed a standardized evaluation. “Tweet” content was analyzed using modified grounded theory methods and coded by valence, content, and reflection. Sub-coding was conducted to compare feedback between “tweets” and evaluations. We analyzed 286 reflections and 214 evaluation comments; 176 “tweets” were reflective (62%). “Tweets” commented on “patient interaction” (53%), “educational experience” (38%), “physician interaction” (26%), and “career decisions” (10%). A significant difference was observed between “tweets” and evaluations with regard to the number that provided feedback on experiences with “critically ill or dying patients.” Reflections provided real-time reactions to impactful clerkship events, notably those involving critically ill or dying patients. This focus on illness may represent an unmet need for discussions related to end of life care. Overall, reflections provided more actionable feedback compared to evaluations. •Students can reflect using short-format writing.•Students reflected on impactful clerkship experiences.•Impactful experiences provide more actionable feedback compared to evaluations.•Student reflections can be used as a clerkship needs assessment.

Habitat degradation and harvest have upset the natural buffering mechanism (i.e., portfolio effects) of many large-scale multi-stock fisheries by reducing spawning stock diversity that is vital for generating population stability and resilience. The application of portfolio theory offers a means to guide management activities by quantifying the importance of multi-stock dynamics and suggesting conservation and restoration strategies to improve naturally occurring portfolio effects. Our application of portfolio theory to Lake Erie Sander vitreus (walleye), a large population that is supported by riverine and open-lake reef spawning stocks, has shown that portfolio effects generated by annual inter-stock larval fish production are currently suboptimal when compared to potential buffering capacity. Reduced production from riverine stocks has resulted in a single open-lake reef stock dominating larval production, and in turn, high inter-annual recruitment variability during recent years. Our analyses have shown (1) a weak average correlation between annual river and reef larval production (ρ̄ = 0.24), suggesting that a natural buffering capacity exists in the population, and (2) expanded annual production of larvae (potential recruits) from riverine stocks could stabilize the fishery by dampening inter-annual recruitment variation. Ultimately, our results demonstrate how portfolio theory can be used to quantify the importance of spawning stock diversity and guide management on ecologically relevant scales (i.e., spawning stocks) leading to greater stability and resilience of multi-stock populations and fisheries.