The Plant Ontology facilitates comparisons of plant development stages across species

The Plant Ontology (PO) is a community resource consisting of standardized terms, definitions, and logical relations describing plant structures and development stages, augmented by a large database of annotations from genomic and phenomic studies. This paper describes the structure of the ontology and the design principles we used in constructing PO terms for plant development stages. It also provides details of the methodology and rationale behind our revision and expansion of the PO to cover development stages for all plants, particularly the land plants (bryophytes through angiosperms). As a case study to illustrate the general approach, we examine variation in gene expression across embryo development stages in Arabidopsis and maize, demonstrating how the PO can be used to compare patterns of expression across stages and in developmentally different species. Although many genes appear to be active throughout embryo development, we identified a small set of uniquely expressed genes for each stage of embryo development and also between the two species. Evaluating the different sets of genes expressed during embryo development in Arabidopsis or maize may inform future studies of the divergent developmental pathways observed in monocotyledonous versus dicotyledonous species. The PO and its annotation databasemake plant data for any species more discoverable and accessible through common formats, thus providing support for applications in plant pathology, image analysis, and comparative development and evolution

Bone turnover and metabolite responses to exercise in people with and without long-duration type 1 diabetes: a case-control study

INTRODUCTION: Exercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and matched controls. RESEARCH DESIGN AND METHODS: Participants with type 1 diabetes (n=15; age: 38.7±13.3; glycosylated hemoglobin: 60.5±6.7 mmol/mol; diabetes duration: 19.3±11.4 years) and age-matched, fitness-matched, and body mass index-matched controls (n=15) completed 45 min of incline walking (60% peak oxygen uptake). Blood samples were collected at baseline and immediately, 30 min, and 60 min postexercise. Markers of bone resorption (β-C-terminal cross-linked telopeptide of type 1 collagen, β-CTx) and formation (procollagen type-1 amino-terminal propeptide, P1NP), parathyroid hormone (PTH), phosphate, and calcium (albumin-adjusted and ionized) were measured. Data (mean±SD) were analyzed by a mixed-model analysis of variance. RESULTS: Baseline concentrations of P1NP and β-CTx were comparable between participants with type 1 diabetes and controls. P1NP did not change with exercise (p=0.20) but β-CTx decreased (p0.39). Participants with type 1 diabetes had reduced albumin and ionized calcium at all sample points (p<0.01). CONCLUSIONS: Following exercise, participants with type 1 diabetes displayed similar time-course changes in markers of bone formation and associated metabolites, but an attenuated suppression in bone resorption. The reduced albumin and ionized calcium may have implications for future bone health. Further investigation of the interactions between type 1 diabetes, differing modalities and intensities of exercise, and bone health is warranted

A controlled trial of value-based insurance design – The MHealthy: Focus on Diabetes (FOD) trial

<p>Abstract</p> <p>Background</p> <p>Diabetes affects over 20 million Americans, resulting in substantial morbidity, mortality, and costs. While medications are the cornerstone of secondary prevention, many evidence-based therapies are underutilized, and patients often cite out-of-pocket costs as the reason. Value-based insurance design (VBID) is a 'clinically sensitive' refinement to benefit design which links patient cost-sharing to therapy value; the more clinically beneficial (and valuable) a therapy is for a patient, the lower that patient's cost-sharing should be. We describe the design and implementation of MHealthy: Focus on Diabetes (FOD), a prospective, controlled trial of targeted co-payment reductions for high value, underutilized therapies for individuals with diabetes.</p> <p>Methods</p> <p>The FOD trial includes 2,507 employees and dependents with diabetes insured by one large employer. Approximately 81% are enrolled in a single independent-practice association model health maintenance organization. The control group includes 8,637 patients with diabetes covered by other employers and enrolled in the same managed care organization. Both groups received written materials about the importance of adherence to secondary prevention therapies, while only the intervention group received targeted co-payment reductions for glycemic agents, antihypertensives, lipid-lowering agents, antidepressants, and diabetic eye exams. Primary outcomes include medication uptake and adherence. Secondary outcomes include health care utilization and expenditures. An interrupted time series, control group design will allow rigorous assessment of the intervention's impact, while controlling for unrelated temporal trends. Individual patient-level baseline data are presented.</p> <p>Discussion</p> <p>To our knowledge, this is the first prospective controlled trial of co-payment reductions targeted to high-value services for high-risk patients. It will provide important information on feasibility of implementation and effectiveness of VBID in a real-world setting. This program has the potential for broad dissemination to other employers and insurers wishing to improve the value of their health care spending.</p

Mean biases, variability, and trends in air–sea fluxes and sea surface temperature in the CCSM4

Author Posting. © American Meteorological Society, 2012. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 25 (2012): 7781–7801, doi:10.1175/JCLI-D-11-00442.1.Air–sea fluxes from the Community Climate System Model version 4 (CCSM4) are compared with the Coordinated Ocean-Ice Reference Experiment (CORE) dataset to assess present-day mean biases, variability errors, and late twentieth-century trend differences. CCSM4 is improved over the previous version, CCSM3, in both air–sea heat and freshwater fluxes in some regions; however, a large increase in net shortwave radiation into the ocean may contribute to an enhanced hydrological cycle. The authors provide a new baseline for assessment of flux variance at annual and interannual frequency bands in future model versions and contribute a new metric for assessing the coupling between the atmospheric and oceanic planetary boundary layer (PBL) schemes of any climate model. Maps of the ratio of CCSM4 variance to CORE reveal that variance on annual time scales has larger error than on interannual time scales and that different processes cause errors in mean, annual, and interannual frequency bands. Air temperature and specific humidity in the CCSM4 atmospheric boundary layer (ABL) follow the sea surface conditions much more closely than is found in CORE. Sensible and latent heat fluxes are less of a negative feedback to sea surface temperature warming in the CCSM4 than in the CORE data with the model’s PBL allowing for more heating of the ocean’s surface.The CESM project is supported by the National Science Foundation and the Office of Science (BER) of the U.S. Department of Energy. S. Stevensonwas supported byNASAGrantNNX09A020H and B. Fox-Kemper by Grants NSF 0934737 and NASA NNX09AF38G.2013-05-1

Typical 22q11.2 deletion syndrome appears to confer a reduced risk of schwannoma

Purpose: The LZTR1 gene has been associated with schwannomatosis tumor predisposition and is located in a region that is deleted in the great majority (89%) of patients with 22q11.2 deletion syndrome (22q11.2DS). Since it is known that approximately 1 in 500 people in the general population will develop a sporadic schwannoma and there are no reports of the occurrence of schwannoma in 22q11.2DS, we investigated whether whole-gene deletion of LZTR1 occurs in schwannomatosis and assessed the risk of schwannoma in 22q11.2DS. Methods: We assessed the genetic testing results for LZTR1-associated schwannomatosis and the clinical phenotypes of patients with 22q11.2DS. Results: There were no reports of schwannoma in over 1,500 patients with 22q11.2DS. In addition, no patients meeting clinical diagnostic criteria for schwannomatosis had a whole-gene deletion in LZTR1. Only 1 patient in 110 with an apparently sporadic vestibular schwannoma had a constitutional whole-gene deletion of LZTR1. Conclusion: People with a large 22q11.2 deletion may have a reduced risk of developing a schwannoma compared to the general population

Future global mortality from changes in air pollution attributable to climate change

Ground-level ozone and fine particulate matter (PM2.5) are associated with premature human mortality1-4; their future concentrations depend on changes in emissions, which dominate the near-term5, and on climate change6,7. Previous global studies of the air quality-related health effects of future climate change8,9 used single atmospheric models. However, in related studies, mortality results differ among models10-12. Here we use an ensemble of global chemistry-climate models13 to show that premature mortality from changes in air pollution attributable to climate change, under the high greenhouse gas scenario RCP8.514, is likely positive. We estimate 3,340 (-30,300 to 47,100) ozone-related deaths in 2030, relative to 2000 climate, and 43,600 (-195,000 to 237,000) in 2100 (14% of the increase in global ozone-related mortality). For PM2.5, we estimate 55,600 (-34,300 to 164,000) deaths in 2030 and 215,000 (-76,100 to 595,000) in 2100 (countering by 16% the global decrease in PM2.5-related mortality). Premature mortality attributable to climate change is estimated to be positive in all regions except Africa, and is greatest in India and East Asia. Most individual models yield increased mortality from climate change, but some yield decreases, suggesting caution in interpreting results from a single model. Climate change mitigation will likely reduce air pollution-related mortality

A Case for Humans-in-the-Loop: Decisions in the Presence of Erroneous Algorithmic Scores

The increased use of algorithmic predictions in sensitive domains has been accompanied by both enthusiasm and concern. To understand the opportunities and risks of these technologies, it is key to study how experts alter their decisions when using such tools. In this paper, we study the adoption of an algorithmic tool used to assist child maltreatment hotline screening decisions. We focus on the question: Are humans capable of identifying cases in which the machine is wrong, and of overriding those recommendations? We first show that humans do alter their behavior when the tool is deployed. Then, we show that humans are less likely to adhere to the machine's recommendation when the score displayed is an incorrect estimate of risk, even when overriding the recommendation requires supervisory approval. These results highlight the risks of full automation and the importance of designing decision pipelines that provide humans with autonomy.Comment: Accepted at ACM Conference on Human Factors in Computing Systems (ACM CHI), 202

Efficient clinical-grade γ-retroviral vector purification by high-speed centrifugation for CAR T cell manufacturing

γ-Retroviral vectors (γ-RV) are powerful tools for gene therapy applications. Current clinical vectors are produced from stable producer cell lines which require minimal further downstream processing, while purification schemes for γ-RV produced by transient transfection have not been thoroughly investigated. We aimed to develop a method to purify transiently produced γ-RV for early clinical studies. Here, we report a simple one-step purification method by high-speed centrifugation for γ-RV produced by transient transfection for clinical application. High-speed centrifugation enabled the concentration of viral titers in the range of 107-108 TU/mL with >80% overall recovery. Analysis of research-grade concentrated vector revealed sufficient reduction in product- and process-related impurities. Furthermore, product characterization of clinical-grade γ-RV by BioReliance demonstrated two-logs lower impurities per transducing unit compared with regulatory authority-approved stable producer cell line vector for clinical application. In terms of CAR T cell manufacturing, clinical-grade γ-RV produced by transient transfection and purified by high-speed centrifugation was similar to γ-RV produced from a clinical-grade stable producer cell line. This method will be of value for studies using γ-RV to bridge vector supply between early- and late-stage clinical trials