Meta-Analysis of COVID-19 BAL Single-Cell RNA Sequencing Reveals Alveolar Epithelial Transitions and Unique Alveolar Epithelial Cell Fates.

Single-cell RNA sequencing (scRNA-seq) of BAL cells has provided insights into coronavirus disease (COVID-19). However, reports have been limited by small patient cohorts. We performed a meta-analysis of BAL scRNA-seq data from healthy control subjects (n = 13) and patients with COVID-19 (n = 20), sourced from six independent studies (167,280 high-quality cells in total). Consistent with the source reports, increases in infiltrating leukocyte subtypes were noted, several with type I IFN signatures and unique gene expression signatures associated with transcellular chemokine signaling. Noting dramatic reductions of inferred NKX2-1 and NR4A1 activity in alveolar epithelial type II (AT-II) cells, we modeled pseudotemporal AT-II-to-AT-I progression. This revealed changes in inferred AT-II cell metabolic activity, increased transitional cells, and a previously undescribed AT-I state. This cell state was conspicuously marked by the induction of genes of the epidermal differentiation complex, including the cornified envelope protein SPRR3 (small proline-rich protein 3), upregulation of multiple KRT (keratin) genes, inferred mitochondrial dysfunction, and cell death signatures including apoptosis and ferroptosis. Immunohistochemistry of lungs from patients with COVID-19 confirmed upregulation and colocalization of KRT13 and SPRR3 in the distal airspaces. Forced overexpression of SPRR3 in human alveolar epithelial cells ex vivo did not activate caspase-3 or upregulate KRT13, suggesting that SPRR3 marks an AT-I cornification program in COVID-19 but is not sufficient for phenotypic changes.

ORSO (Online Resource for Social Omics): A data-driven social network connecting scientists to genomics datasets.

High-throughput sequencing has become ubiquitous in biomedical sciences. As new technologies emerge and sequencing costs decline, the diversity and volume of available data increases exponentially, and successfully navigating the data becomes more challenging. Though datasets are often hosted by public repositories, scientists must rely on inconsistent annotation to identify and interpret meaningful data. Moreover, the experimental heterogeneity and wide-ranging quality of high-throughput biological data means that even data with desired cell lines, tissue types, or molecular targets may not be readily interpretable or integrated. We have developed ORSO (Online Resource for Social Omics) as an easy-to-use web application to connect life scientists with genomics data. In ORSO, users interact within a data-driven social network, where they can favorite datasets and follow other users. In addition to more than 30,000 datasets hosted from major biomedical consortia, users may contribute their own data to ORSO, facilitating its discovery by other users. Leveraging user interactions, ORSO provides a novel recommendation system to automatically connect users with hosted data. In addition to social interactions, the recommendation system considers primary read coverage information and annotated metadata. Similarities used by the recommendation system are presented by ORSO in a graph display, allowing exploration of dataset associations. The topology of the network graph reflects established biology, with samples from related systems grouped together. We tested the recommendation system using an RNA-seq time course dataset from differentiation of embryonic stem cells to cardiomyocytes. The ORSO recommendation system correctly predicted early data point sources as embryonic stem cells and late data point sources as heart and muscle samples, resulting in recommendation of related datasets. By connecting scientists with relevant data, ORSO provides a critical new service that facilitates wide-ranging research interests.

RATEmiRs: the rat atlas of tissue-specific and enriched miRNAs for discerning baseline expression exclusivity of candidate biomarkers.

MicroRNAs (miRNAs) are small RNAs that regulate mRNA expression and have been targeted as biomarkers of organ damage and disease. To explore the utility of miRNAs to assess injury to specific tissues, a tissue atlas of miRNA abundance was constructed. The Rat Atlas of Tissue-specific and Enriched miRNAs (RATEmiRs) catalogues miRNA sequencing data from 21 and 23 tissues in male and female Sprague-Dawley rats, respectively. RATEmiRs identifies tissue-enriched (TE), tissue-specific (TS), or organ-specific (OS) miRNAs via comparisons of one or more tissue or organ vs others. We provide a brief overview of RATEmiRs and present how to use it to detect miRNA expression abundance of candidate biomarkers as well as to compare the expression of miRNAs between rat and human. The database is available at https://www.niehs.nih.gov/ratemirs/.

RATEmiRs: the rat atlas of tissue-specific and enriched miRNAs database.

BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and have been targeted as indicators of environmental/toxicologic stressors. Using the data from our deep sequencing of miRNAs in an extensive sampling of rat tissues, we developed a database called RATEmiRs for the Rat Atlas of Tissue-specific and Enriched miRNAs to allow users to dynamically determine mature-, iso- and pre-miR expression abundance, enrichment and specificity in rat tissues and organs. RESULTS: Illumina sequencing count data from mapped reads and meta data from the miRNA body atlas consisting of 21 and 23 tissues (14 organs) of toxicologic interest from 12 to 13 week old male and female Sprague Dawley rats respectively, were managed in a relational database with a user-friendly query interface. Data-driven pipelines are available to tailor the identification of tissue-enriched (TE) and tissue-specific (TS) miRNAs. Data-driven organ-specific (OS) pipelines reveal miRNAs that are expressed predominately in a given organ. A user-driven approach is also available to assess the tissue expression of user-specified miRNAs. Using one tissue vs other tissues and tissue(s) of an organ vs other organs, we illustrate the utility of RATEmiRs to facilitate the identification of candidate miRNAs. As a use case example, RATEmiRs revealed two TS miRNAs in the liver: rno-miR-122-3p and rno-miR-122-5p. When liver is compared to just the brain tissues for example, rno-miR-192-5p, rno-miR-193-3p, rno-miR-203b-3p, rno-miR-3559-5p, rno-miR-802-3p and rno-miR-802-5p are also detected as abundantly expressed in liver. As another example, 55 miRNAs from the RATEmiRs query of ileum vs brain tissues overlapped with miRNAs identified from the same comparison of tissues in an independent, publicly available dataset of 10 week old male rat microarray data suggesting that these miRNAs are likely not age-specific, platform-specific nor pipeline-dependent. Lastly, we identified 10 miRNAs that have conserved tissue/organ-specific expression between the rat and human species. CONCLUSIONS: RATEmiRs provides a new platform for identification of TE, TS and OS miRNAs in a broad array of rat tissues. RATEmiRs is available at: https://www.niehs.nih.gov/ratemirs.

BioTIME: A database of biodiversity time series for the Anthropocene.

MOTIVATION: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. MAIN TYPES OF VARIABLES INCLUDED: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. SPATIAL LOCATION AND GRAIN: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2). TIME PERIOD AND GRAIN: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. MAJOR TAXA AND LEVEL OF MEASUREMENT: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. SOFTWARE FORMAT: .csv and .SQL.

Increasing confidence and changing behaviors in primary care providers engaged in genetic counselling.

BACKGROUND: Screening and counseling for genetic conditions is an increasingly important part of primary care practice, particularly given the paucity of genetic counselors in the United States. However, primary care physicians (PCPs) often have an inadequate understanding of evidence-based screening; communication approaches that encourage shared decision-making; ethical, legal, and social implication (ELSI) issues related to screening for genetic mutations; and the basics of clinical genetics. This study explored whether an interactive, web-based genetics curriculum directed at PCPs in non-academic primary care settings was superior at changing practice knowledge, attitudes, and behaviors when compared to a traditional educational approach, particularly when discussing common genetic conditions. METHODS: One hundred twenty one PCPs in California and Pennsylvania physician practices were randomized to either an Intervention Group (IG) or Control Group (CG). IG physicians completed a 6 h interactive web-based curriculum covering communication skills, basics of genetic testing, risk assessment, ELSI issues and practice behaviors. CG physicians were provided with a traditional approach to Continuing Medical Education (CME) (clinical review articles) offering equivalent information. RESULTS: PCPs in the Intervention Group showed greater increases in knowledge compared to the Control Group. Intervention PCPs were also more satisfied with the educational materials, and more confident in their genetics knowledge and skills compared to those receiving traditional CME materials. Intervention PCPs felt that the web-based curriculum covered medical management, genetics, and ELSI issues significantly better than did the Control Group, and in comparison with traditional curricula. The Intervention Group felt the online tools offered several advantages, and engaged in better shared decision making with standardized patients, however, there was no difference in behavior change between groups with regard to increases in ELSI discussions between PCPs and patients. CONCLUSION: While our intervention was deemed more enjoyable, demonstrated significant factual learning and retention, and increased shared decision making practices, there were few differences in behavior changes around ELSI discussions. Unfortunately, barriers to implementing behavior change in clinical genetics is not unique to our intervention. Perhaps the missing element is that busy physicians need systems-level support to engage in meaningful discussions around genetics issues. The next step in promoting active engagement between doctors and patients may be to put into place the tools needed for PCPs to easily access the materials they need at the point-of-care to engage in joint discussions around clinical genetics.

Impact of a randomized controlled educational trial to improve physician practice behaviors around screening for inherited breast cancer.

BACKGROUND: Many primary care physicians (PCPs) are ill-equipped to provide screening and counseling for inherited breast cancer. OBJECTIVE: To evaluate the outcomes of an interactive web-based genetics curriculum versus text curriculum for primary care physicians. DESIGN: Randomized two-group design. PARTICIPANTS: 121 California and Pennsylvania community physicians. INTERVENTION: Web-based interactive genetics curriculum, evaluated against a control group of physicians who studied genetics review articles. After education, physicians interacted with an announced standardized patient (SP) at risk for inherited breast cancer. MAIN MEASURES: Transcripts of visit discussions were coded for presence or absence of 69 topics relevant to inherited breast cancer. KEY RESULTS: Across all physicians, history-taking, discussions of test result implications, and exploration of ethical and legal issues were incomplete. Approximately half of physicians offered a genetic counseling referral (54.6%), and fewer (43.8%) recommended testing. Intervention physicians were more likely than controls to explore genetic counseling benefits (78.3% versus 60.7%, P = 0.048), encourage genetic counseling before testing (38.3% versus 21.3%, P = 0.048), ask about a family history of prostate cancer (25.0% versus 6.6%, P = 0.006), and report that a positive result indicated an increased risk of prostate cancer for male relatives (20.0% versus 1.6%, P = 0.001). Intervention-group physicians were less likely than controls to ask about Ashkenazi heritage (13.3% versus 34.4%, P = 0.01) or to reply that they would get tested when asked, "What would you do?" (33.3% versus 54.1%, P = 0.03). CONCLUSIONS: Physicians infrequently performed key counseling behaviors, and this was true regardless of whether they had completed the web-based interactive training or read clinical reviews.

Direct and legacy effects of long-term elevated CO2 on fine root growth and plant-insect interactions.

Increasing atmospheric CO2 concentrations alter leaf physiology, with effects that cascade to communities and ecosystems. Yet, responses over cycles of disturbance and recovery are not well known, because most experiments span limited ecological time. We examined the effects of CO2 on root growth, herbivory and arthropod biodiversity in a woodland from 1996 to 2006, and the legacy of CO2 enrichment on these processes during the year after the CO2 treatment ceased. We used minirhizotrons to study root growth, leaf censuses to study herbivory and pitfall traps to determine the effects of elevated CO2 on arthropod biodiversity. Elevated CO2 increased fine root biomass, but decreased foliar nitrogen and herbivory on all plant species. Insect biodiversity was unchanged in elevated CO2. Legacy effects of elevated CO2 disappeared quickly as fine root growth, foliar nitrogen and herbivory levels recovered in the next growing season following the cessation of elevated CO2. Although the effects of elevated CO2 cascade through plants to herbivores, they do not reach other trophic levels, and biodiversity remains unchanged. The legacy of 10 yr of elevated CO2 on plant-herbivore interactions in this system appear to be minimal, indicating that the effects of elevated CO2 may not accumulate over cycles of disturbance and recovery.

The effects of 11 yr of CO2 enrichment on roots in a Florida scrub-oak ecosystem.

Uncertainty surrounds belowground plant responses to rising atmospheric CO2 because roots are difficult to measure, requiring frequent monitoring as a result of fine root dynamics and long-term monitoring as a result of sensitivity to resource availability. We report belowground plant responses of a scrub-oak ecosystem in Florida exposed to 11 yr of elevated atmospheric CO2 using open-top chambers. We measured fine root production, turnover and biomass using minirhizotrons, coarse root biomass using ground-penetrating radar and total root biomass using soil cores. Total root biomass was greater in elevated than in ambient plots, and the absolute difference was larger than the difference aboveground. Fine root biomass fluctuated by more than a factor of two, with no unidirectional temporal trend, whereas leaf biomass accumulated monotonically. Strong increases in fine root biomass with elevated CO2 occurred after fire and hurricane disturbance. Leaf biomass also exhibited stronger responses following hurricanes. Responses after fire and hurricanes suggest that disturbance promotes the growth responses of plants to elevated CO2. Increased resource availability associated with disturbance (nutrients, water, space) may facilitate greater responses of roots to elevated CO2. The disappearance of responses in fine roots suggests limits on the capacity of root systems to respond to CO2 enrichment.

Cumulative response of ecosystem carbon and nitrogen stocks to chronic CO2 exposure in a subtropical oak woodland.

Rising atmospheric carbon dioxide (CO2) could alter the carbon (C) and nitrogen (N) content of ecosystems, yet the magnitude of these effects are not well known. We examined C and N budgets of a subtropical woodland after 11 yr of exposure to elevated CO2. We used open-top chambers to manipulate CO2 during regrowth after fire, and measured C, N and tracer (15) N in ecosystem components throughout the experiment. Elevated CO2 increased plant C and tended to increase plant N but did not significantly increase whole-system C or N. Elevated CO2 increased soil microbial activity and labile soil C, but more slowly cycling soil C pools tended to decline. Recovery of a long-term (15) N tracer indicated that CO2 exposure increased N losses and altered N distribution, with no effect on N inputs. Increased plant C accrual was accompanied by higher soil microbial activity and increased C losses from soil, yielding no statistically detectable effect of elevated CO2 on net ecosystem C uptake. These findings challenge the treatment of terrestrial ecosystems responses to elevated CO2 in current biogeochemical models, where the effect of elevated CO2 on ecosystem C balance is described as enhanced photosynthesis and plant growth with decomposition as a first-order response.

Fire, hurricane and carbon dioxide: effects on net primary production of a subtropical woodland.

Disturbance affects most terrestrial ecosystems and has the potential to shape their responses to chronic environmental change. Scrub-oak vegetation regenerating from fire disturbance in subtropical Florida was exposed to experimentally elevated carbon dioxide (CO2) concentration (+350 µl l(-1)) using open-top chambers for 11 yr, punctuated by hurricane disturbance in year 8. Here, we report the effects of elevated CO2 on aboveground and belowground net primary productivity (NPP) and nitrogen (N) cycling during this experiment. The stimulation of NPP and N uptake by elevated CO2 peaked within 2 yr after disturbance by fire and hurricane, when soil nutrient availability was high. The stimulation subsequently declined and disappeared, coincident with low soil nutrient availability and with a CO2 -induced reduction in the N concentration of oak stems. These findings show that strong growth responses to elevated CO2 can be transient, are consistent with a progressively limited response to elevated CO2 interrupted by disturbance, and illustrate the importance of biogeochemical responses to extreme events in modulating ecosystem responses to global environmental change.

Physician communication regarding prostate cancer screening: analysis of unannounced standardized patient visits.

PURPOSE: Prostate cancer screening with prostate-specific antigen (PSA) is a controversial issue. The present study aimed to explore physician behaviors during an unannounced standardized patient encounter that was part of a randomized controlled trial to educate physicians using a prostate cancer screening, interactive, Web-based module. METHODS: Participants included 118 internal medicine and family medicine physicians from 5 health systems in California, in 2007-2008. Control physicians received usual education about prostate cancer screening (brochures from the Center for Disease Control and Prevention). Intervention physicians participated in the prostate cancer screening module. Within 3 months, all physicians saw unannounced standardized patients who prompted prostate cancer screening discussions in clinic. The encounter was audio-recorded, and the recordings were transcribed. Authors analyzed physician behaviors around screening: (1) engagement after prompting, (2) degree of shared decision making, and (3) final recommendations for prostate cancer screening. RESULTS: After prompting, 90% of physicians discussed prostate cancer screening. In comparison with control physicians, intervention physicians showed somewhat more shared decision making behaviors (intervention 14 items vs control 11 items, P <.05), were more likely to mention no screening as an option (intervention 63% vs control 26%, P <.05), to encourage patients to consider different screening options (intervention 62% vs control 39%, P <.05) and seeking input from others (intervention 25% vs control 7%, P<.05). CONCLUSIONS: A brief Web-based interactive educational intervention can improve shared decision making, neutrality in recommendation, and reduce PSA test ordering. Engaging patients in discussion of the uses and limitations of tests with uncertain value can decrease utilization of the tests.

Pairing physician education with patient activation to improve shared decisions in prostate cancer screening: a cluster randomized controlled trial.

BACKGROUND: Most expert groups recommend shared decision making for prostate cancer screening. Most primary care physicians, however, routinely order a prostate-specific antigen (PSA) test with little or no discussion about whether they believe the potential benefits justify the risk of harm. We sought to assess whether educating primary care physicians and activating their patients to ask about prostate cancer screening had a synergistic effect on shared decision making, rates and types of discussions about prostate cancer screening, and the physician's final recommendations. METHODS: Our study was a cluster randomized controlled trial among primary care physicians and their patients, comparing usual education (control), with physician education alone (MD-Ed), and with physician education and patient activation (MD-Ed+A). Participants included 120 physicians in 5 group practices, and 712 male patients aged 50 to 75 years. The interventions comprised a Web-based educational program for all intervention physicians and MD-Ed+A patients compared with usual education (brochures from the Centers for Disease Control and Prevention). The primary outcome measure was patients' reported postvisit shared decision making regarding prostate cancer screening; secondary measures included unannounced standardized patients' reported shared decision making and the physician's recommendation for prostate cancer screening. RESULTS: Patients' ratings of shared decision making were moderate and did not differ between groups. MD-Ed+A patients reported that physicians had higher prostate cancer screening discussion rates (MD-Ed+A = 65%, MD-Ed = 41%, control=38%; P <.01). Standardized patients reported that physicians seeing MD-Ed+A patients were more neutral during prostate cancer screening recommendations (MD-Ed+A=50%, MD-Ed=33%, control=15%; P <.05). Of the male patients, 80% had had previous PSA tests. CONCLUSIONS: Although activating physicians and patients did not lead to significant changes in all aspects of physician attitudes and behaviors that we studied, interventions that involved physicians did have a large effect on their attitudes toward screening and in the discussions they had with patients, including their being more likely than control physicians to engage in prostate cancer screening discussions and more likely to be neutral in their final recommendations.

Implementation outcomes of a multiinstitutional web-based ethical, legal, and social implications genetics curriculum for primary care residents in three specialties.

PURPOSE: Medical genetics lends itself to disseminated teaching methods because of mismatches between numbers of physicians having patients with genetic disorders and availability of genetic specialists. METHOD: During 3 years, we implemented an interactive, web-based curriculum on ethical, legal, and social implications in medical genetics for primary care residents in three specialties at three institutions. Residents took five (of 10) cases and three (of five) tutorials that varied by specialty. We assessed changes in self-efficacy (primary outcome), knowledge, application, and viewpoints. RESULTS: Overall enrollment was 69% (279/403). One institution did not complete implementation and was dropped from pre-post comparisons. We developed a six-factor ethical, legal, and social implications self-efficacy scale (Cronbach α = 0.95). Baseline self-efficacy was moderate (71/115; range: 23-115) and increased 15% after participation. Pre-post knowledge scores were high and unchanged. Residents reported that this curriculum covered ethical, legal, and social implications/genetics better than their usual curricula. Most (68-91%) identified advantages, especially in providing flexibility and stimulating self-directed learning. After participation, residents reported creating learning goals (66%) and acting on those goals (62%). CONCLUSIONS: Ethical, legal, and social implications genetics curricular participation led to modest self-efficacy gains. Residents reported that the curriculum covered unique content areas, had advantages over traditional curriculum, and that they applied ethical, legal, and social implications content clinically. We share lessons from developing and implementing this complex web-based curriculum across multiple institutions.

'Annals of Emergency Medicine Journal Club: the measurement of reliability.

Editor's capsule summary for Cruz et al: (1) WHAT IS ALREADY KNOWN ON THIS TOPIC: Valid clinical research requires high-quality data collection. Physicians are commonly considered the standard by which valid prospective data are obtained. WHAT QUESTION THIS STUDY ADDRESSED: This study determined whether non-medically trained research assistants could reliably collect subjective historical data from emergency department patients with chest pain. WHAT THIS STUDY ADDS TO OUR KNOWLEDGE: This prospective comparative study included 33 research assistants, 39 physicians, and 143 patients. Research assistants demonstrated fair to excellent reliability (as defined by crude agreement and kappa) when obtaining cardiac histories and cardiac risk factors. HOW THIS MIGHT CHANGE CLINICAL PRACTICE: The results of this study will not change clinical practice. They do, however, provide evidence to support the use of trained research assistants for the collection of certain types of clinical data.

Feasibility study of an EHR-integrated mobile shared decision making application.

INTRODUCTION: Integrating mobile applications (apps) into users' standard electronic health record (EHR) workflows may be valuable, especially for apps that both read and write data. This report details the lessons learned during the integration of a patient decision aid - prostate specific antigen (PSA) testing for prostate cancer screening - into our users' standard EHR workflow for a small usability assessment. MATERIALS AND METHODS: This feasibility study included two steps. First we enabled realtime, secure bidirectional data exchange between the mobile app and EHR for 14 data elements, and second we pilot tested the production environment app with 9 primary care patients aged 60-65 years. Our primary usability metric was a net promoter score (NPS), based on users' recommendation of the app to a friend or family member; we also assessed the proportion of users who 1) updated their prostate cancer risk factor information present in the EHR and 2) submitted more than one unique response regarding their preference to have PSA testing. RESULTS: The seven web services necessary to read and write data required considerable configuration, but successfully delivered risk factor-specific educational content and recorded patients' values and decision preference directly within the EHR. Seven of the 9 patients (78%) would recommend this app to a friend/family member (NPS = 55.6%), one patient used the app to update risk factor information, and 4/9 (44%) changed their decision preference while using the app. CONCLUSIONS: It is feasible to implement a decision aid directly into users' standard EHR workflow for limited usability testing. Broad scale implementation may have a positive effect on patient engagement and improve shared decision making, but several challenges exist with proprietary EHR vendor application programming interfaces (API)s.

DNA methylation in mice is influenced by genetics as well as sex and life experience.

DNA methylation is an essential epigenetic process in mammals, intimately involved in gene regulation. Here we address the extent to which genetics, sex, and pregnancy influence genomic DNA methylation by intercrossing 2 inbred mouse strains, C57BL/6N and C3H/HeN, and analyzing DNA methylation in parents and offspring using whole-genome bisulfite sequencing. Differential methylation across genotype is detected at thousands of loci and is preserved on parental alleles in offspring. In comparison of autosomal DNA methylation patterns across sex, hundreds of differentially methylated regions are detected. Comparison of animals with different histories of pregnancy within our study reveals a CpG methylation pattern that is restricted to female animals that had borne offspring. Collectively, our results demonstrate the stability of CpG methylation across generations, clarify the interplay of epigenetics with genetics and sex, and suggest that CpG methylation may serve as an epigenetic record of life events in somatic tissues at loci whose expression is linked to the relevant biology.

Nitrogen cycling during seven years of atmospheric CO2 enrichment in a scrub oak woodland.

Experimentally increasing atmospheric CO2 often stimulates plant growth and ecosystem carbon (C) uptake. Biogeochemical theory predicts that these initial responses will immobilize nitrogen (N) in plant biomass and soil organic matter, causing N availability to plants to decline, and reducing the long-term CO2-stimulation of C storage in N limited ecosystems. While many experiments have examined changes in N cycling in response to elevated CO2, empirical tests of this theoretical prediction are scarce. During seven years of postfire recovery in a scrub oak ecosystem, elevated CO2 initially increased plant N accumulation and plant uptake of tracer 15N, peaking after four years of CO2 enrichment. Between years four and seven, these responses to CO2 declined. Elevated CO2 also increased N and tracer 15N accumulation in the O horizon, and reduced 15N recovery in underlying mineral soil. These responses are consistent with progressive N limitation: the initial CO2 stimulation of plant growth immobilized N in plant biomass and in the O horizon, progressively reducing N availability to plants. Litterfall production (one measure of aboveground primary productivity) increased initially in response to elevated CO2, but the CO2 stimulation declined during years five through seven, concurrent with the accumulation of N in the O horizon and the apparent restriction of plant N availability. Yet, at the level of aboveground plant biomass (estimated by allometry), progressive N limitation was less apparent, initially because of increased N acquisition from soil and later because of reduced N concentration in biomass as N availability declined. Over this seven-year period, elevated CO2 caused a redistribution of N within the ecosystem, from mineral soils, to plants, to surface organic matter. In N limited ecosystems, such changes in N cycling are likely to reduce the response of plant production to elevated CO2.

A test of knowledge about prostate cancer screening. Online pilot evaluation among Southern California Physicians.

BACKGROUND: Although the benefits of prostate cancer screening are uncertain and guidelines recommend that physicians share the screening decision with their patients, most U.S. men over age 50 are routinely screened, often without counseling. OBJECTIVE: To develop an instrument for assessing physicians' knowledge related to the U.S. Preventive Services Task Force recommendations on prostate cancer screening. PARTICIPANTS: Seventy internists, family physicians, and general practitioners in the Los Angeles area who deliver primary care to adult men. MEASUREMENTS: We assessed knowledge related to prostate cancer screening (natural history, test characteristics, treatment effects, and guideline recommendations), beliefs about the net benefits of screening, and prostate cancer screening practices for men in different age groups, using an online survey. We constructed a knowledge scale having 15 multiple-choice items. RESULTS: Participants' mean knowledge score was 7.4 (range 3 to 12) of 15 (Cronbach's alpha=0.71). Higher knowledge scores were associated with less belief in a mortality benefit from prostate-specific antigen (PSA) testing (r=-.49, P<.001). Participants could be categorized as low, age-selective, and high users of routine PSA screening. High users had lower knowledge scores than age-selective or low users, and they believed much more in mortality benefits from PSA screening. CONCLUSIONS: Based on its internal consistency and its correlations with measures of physicians' net beliefs and self-reported practices, the knowledge scale developed in this study holds promise for measuring the effects of professional education on prostate cancer screening. The scale deserves further evaluation in broader populations.

A comparison of Web-based and small-group palliative and end-of-life care curricula: a quasi-randomized controlled study at one institution.

PURPOSE: Few studies have compared the effect of Web-based eLearning versus small-group learning on medical student outcomes. Palliative and end-of-life (PEOL) education is ideal for this comparison, given uneven access to PEOL experts and content nationally. METHOD: In 2010, the authors enrolled all third-year medical students at the University of California, Davis School of Medicine into a quasi-randomized controlled trial of Web-based interactive education (eDoctoring) compared with small-group education (Doctoring) on PEOL clinical content over two months. Students participated in three 3-hour PEOL sessions with similar content. Outcomes included a 24-item PEOL-specific self-efficacy scale with three domains (diagnosis/treatment [Cronbach alpha=0.92; CI: 0.91-0.93], communication/prognosis [alpha=0.95; CI: 0.93-0.96], and social impact/self-care [alpha=0.91; CI: 0.88-0.92]); 8 knowledge items; 10 curricular advantage/disadvantages; and curricular satisfaction (both students and faculty). RESULTS: Students were randomly assigned to Web-based eDoctoring (n=48) or small-group Doctoring (n=71) curricula. Self-efficacy and knowledge improved equivalently between groups (e.g., prognosis self-efficacy, 19%; knowledge, 10%-42%). Student and faculty ratings of the Web-based eDoctoring curriculum and the small-group Doctoring curriculum were equivalent for most goals, and overall satisfaction was equivalent for each, with a trend toward decreased eDoctoring student satisfaction. CONCLUSIONS: Findings showed equivalent gains in self-efficacy and knowledge between students participating in a Web-based PEOL curriculum in comparison with students learning similar content in a small-group format. Web-based curricula can standardize content presentation when local teaching expertise is limited, but it may lead to decreased user satisfaction.