304 research outputs found
QES-Fire: A dynamically coupled fast-response wildfire model
A microscale wildfire model, QES-Fire, that dynamically couples the fire front to microscale winds was developed using a simplified physics rate of spread (ROS) model, a kinematic plume-rise model and a mass-consistent wind solver. The model is three-dimensional and couples fire heat fluxes to the wind field while being more computationally efficient than other coupled models. The plume-rise model calculates a potential velocity field scaled by the ROS model\u27s fire heat flux. Distinct plumes are merged using a multiscale plume-merging methodology that can efficiently represent complex fire fronts. The plume velocity is then superimposed on the ambient winds and the wind solver enforces conservation of mass on the combined field, which is then fed into the ROS model and iterated on until convergence. QES-Fire\u27s ability to represent plume rise is evaluated by comparing its results with those from an atmospheric large-eddy simulation (LES) model. Additionally, the model is compared with data from the FireFlux II field experiment. QES-Fire agrees well with both the LES and field experiment data, with domain-integrated buoyancy fluxes differing by less than 17% between LES and QES-Fire and less than a 10% difference in the ROS between QES-Fire and FireFlux II data
Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity
Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML
Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.
Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015
WHAT GOOD IS WEALTH WITHOUT HEALTH? THE EFFECT OF HEALTH ON THE MARGINAL UTILITY OF CONSUMPTION
We estimate how the marginal utility of consumption varies with health. To do so, we develop a simple model in which the impact of health on the marginal utility of consumption can be estimated from data on permanent income, health, and utility proxies. We estimate the model using the Health and Retirement Study's panel data on the elderly and near-elderly, and proxy for utility with measures of subjective well-being. Across a wide range of alternative specifications and assumptions, we find that the marginal utility of consumption declines as health deteriorates, and we are able to clearly reject the null of no state dependence. Our point estimates indicate that a one-standard-deviation increase in the number of chronic diseases is associated with a 10%–25% decline in the marginal utility of consumption relative to this marginal utility when the individual has no chronic diseases. We present some simple, illustrative calibration results that suggest that state dependence of the magnitude we estimate can have a substantial effect on important economic problems such as the optimal level of health insurance benefits and the optimal level of life-cycle savings.United States. Social Security Administration (National Bureau of Economic Research Grant 10-P-98363-1-05)National Institute on Aging (Grant T32-AG000186
2020 Collage Concert
An exciting highlight each season, Collage is the signature production of the School of Music and a major fundraising event for supporting scholarships for music students. This special performance features over 200 student and faculty performers and includes jazz, orchestra, choir, band, percussion, and opera selections for soloists, chamber groups, and ensembles. Special lighting effects and stage design combine with the diverse and exciting program presented as rapid-fire, flowing vignettes to create a truly unique performance.https://digitalcommons.kennesaw.edu/musicprograms/2295/thumbnail.jp
A detailed hierarchical model of psychopathology: From individual symptoms up to the general factor of psychopathology
Much of the knowledge about the relationships among domains of psychopathology is built on the diagnostic categories described in the Diagnostic and Statistical Manual of Mental Disorders (DSM), and relatively little research has examined the symptom-level structure of psychopathology. The aim of this study was to delineate a detailed hierarchical model of psychopathology—from individual symptoms up to a general factor of psychopathology—allowing both higher- and lower-order dimensions to depart from the structure of the DSM. We explored the hierarchical structure of hundreds of symptoms spanning 18 DSM disorders in two large samples—one from the general population in Australia (n = 3,175) and the other a treatment-seeking clinical sample from the United States (n = 1,775). There was marked convergence between the two samples, offering new perspectives on higher-order dimensions of psychopathology. We also found several noteworthy departures from the structure of the DSM in the symptom-level data.R. F. Krueger is supported in part by U.S. National Institute on Aging Grants R01-AG053217 and U19-AG05142
Maternal DNA Methylation Regulates Early Trophoblast Development
This work was funded by the BBSRC, Wellcome Trust, MRC, the EC Network of Excellence EpiGeneSys, the EC BLUEPRINT project, the Centre for Trophoblast Research, and CIHR (grant MOP-119357 to L.L.). M.R.B. is a Sir Henry Dale Fellow (101225/Z/13/Z), jointly funded by the Wellcome Trust and the Royal Society
Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants
Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size amp;gt;39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFkB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including T(H)0, T(H)1 and T(H)17). The identified loci explain similar to 28% of the genetic heritability and generate a discriminatory genetic risk score (AUC = 0.76 in our sample) that is significantly correlated with age at onset (p = 2 x 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.Funding Agencies|National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183]; Foundation for the National Institutes of Health; Dermatology Foundation; National Psoriasis Foundation; Arthritis National Research Foundation; Ann Arbor Veterans Affairs Hospital; Dawn and Dudley Holmes Foundation; Babcock Memorial Trust; Medical Research Council [MR/L011808/1]; German Ministry of Education and Research (BMBF); Doris Duke Foundation [2013106]; National Institute of Health [K08AR060802, R01AR06907]; Taubman Medical Research Institute; Department of Health via the NIHR comprehensive Biomedical Research Center; Kings College London; KCH NHS Foundation Trust; Barbara and Neal Henschel Charitable Foundation; Heinz Nixdorf Foundation; Estonian Ministry of Education and Research [IUT20-46]; Centre of Translational Genomics of University of Tartu (SP1GVARENG); European Regional Development Fund (Centre of Translational Medicine, University of Tartu); German Federal Ministry of Education and Research (BMBF); National Human Genome Research Institute of the National Institutes of Health [R44HG006981]; International Psoriasis Council</p
Should UI Eligibility Be Expanded to Low-Earning Workers? Evidence on Employment, Transfer Receipt, and Income from Administrative Data
Recent efforts to expand unemployment insurance (UI) eligibility are expected to increase low-earning workers’ access to UI. Although the expansion’s aim is to smooth the income and consumption of previously ineligible workers, it is possible that UI benefits simply displace other sources of income. Standard economic models predict that UI delays reemployment, thereby reducing wage income. Additionally, low-earning workers are often eligible for benefits from means-tested programs, which may decrease with UI benefits. In this paper, we estimate the impact of UI eligibility on employment, means-tested program participation, and income after job loss using a unique individual-level administrative data set from the state of Michigan. To identify a causal effect, we implement a fuzzy regression discontinuity design around the minimum earnings threshold for UI eligibility. Our main finding is that while UI eligibility increases jobless durations by up to 25 percent and temporarily lowers receipt of cash assistance (TANF) by 63 percent, the net impact on total income is still positive and large. In the quarter immediately following job loss, UI-eligible workers have 46-61 percent higher incomes than ineligibles
Think twice: A cognitive perspective of an antibiotic timeout intervention to improve antibiotic use
ObjectivesTo understand clinicians' impressions of and decision-making processes regarding an informatics-supported antibiotic timeout program to re-evaluate the appropriateness of continuing vancomycin and piperacillin/tazobactam.MethodsWe implemented a multi-pronged informatics intervention, based on Dual Process Theory, to prompt discontinuation of unwarranted vancomycin and piperacillin/tazobactam on or after day three in a large Veterans Affairs Medical Center. Two workflow changes were introduced to facilitate cognitive deliberation about continuing antibiotics at day three: (1) teams completed an electronic template note, and (2) a paper summary of clinical and antibiotic-related information was provided to clinical teams. Shortly after starting the intervention, six focus groups were conducted with users or potential users. Interviews were recorded and transcribed. Iterative thematic analysis identified recurrent themes from feedback.ResultsThemes that emerged are represented by the following quotations: (1) captures and controls attention ("it reminds us to think about it"), (2) enhances informed and deliberative reasoning ("it makes you think twice"), (3) redirects decision direction ("…because [there was no indication] I just [discontinued] it without even trying"), (4) fosters autonomy and improves team empowerment ("the template… forces the team to really discuss it"), and (5) limits use of emotion-based heuristics ("my clinical concern is high enough I think they need more aggressive therapy…").ConclusionsRequiring template completion to continue antibiotics nudged clinicians to re-assess the appropriateness of specified antibiotics. Antibiotic timeouts can encourage deliberation on overprescribed antibiotics without substantially curtailing autonomy. An effective nudge should take into account clinician's time, workflow, and thought processes
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