Prospective evaluation of multiplicative hybrid earthquake forecasting models in California

The Regional Earthquake Likelihood Models (RELM) experiment, conducted within the Collaboratory for the Study of Earthquake Predictability (CSEP), showed that the smoothed seismicity (HKJ) model by Helmstetter et al. was the most informative time-independent earthquake model in California during the 2006–2010 evaluation period. The diversity of competing forecast hypotheses and geophysical data sets used in RELM was suitable for combining multiple models that could provide more informative earthquake forecasts than HKJ. Thus, Rhoades et al. created multiplicative hybrid models that involve the HKJ model as a baseline and one or more conjugate models. In retrospective evaluations, some hybrid models showed significant information gains over the HKJ forecast. Here, we prospectively assess the predictive skills of 16 hybrids and 6 original RELM forecasts at a 0.05 significance level, using a suite of traditional and new CSEP tests that rely on a Poisson and a binary likelihood function. In addition, we include consistency test results at a Bonferroni-adjusted significance level of 0.025 to address the problem of multiple tests. Furthermore, we compare the performance of each forecast to that of HKJ. The evaluation data set contains 40 target events recorded within the CSEP California testing region from 2011 January 1 to 2020 December 31, including the 2016 Hawthorne earthquake swarm in southwestern Nevada and the 2019 Ridgecrest sequence. Consistency test results show that most forecasting models overestimate the number of earthquakes and struggle to explain the spatial distribution of epicenters, especially in the case of seismicity clusters. The binary likelihood function significantly reduces the sensitivity of spatial log-likelihood scores to clustering, however; most models still fail to adequately describe spatial earthquake patterns. Contrary to retrospective analyses, our prospective test results show that none of the models are significantly more informative than the HKJ benchmark forecast, which we interpret to be due to temporal instabilities in the fit that forms hybrids. These results suggest that smoothing high-resolution, small earthquake data remains a robust method for forecasting moderate-to-large earthquakes over a period of 5–15 yr in California.This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 821115, Real-time earthquake rIsk reduction for a reSilient Europe (RISE), http://www.rise-eu.org). Additionally, this research was supported by the Southern California Earthquake Center (contribution no. 11011). SCEC is funded by NSF Cooperative agreement EAR-1600087 and USGS Cooperative agreement G17AC00047

Pseudo-prospective Evaluation of UCERF3-ETAS Forecasts During the 2019 Ridgecrest Sequence

The 2019 Ridgecrest sequence provides the first opportunity to evaluate Uniform California Earthquake Rupture Forecast v.3 with epidemic‐type aftershock sequences (UCERF3‐ETAS) in a pseudoprospective sense. For comparison, we include a version of the model without explicit faults more closely mimicking traditional ETAS models (UCERF3‐NoFaults). We evaluate the forecasts with new metrics developed within the Collaboratory for the Study of Earthquake Predictability (CSEP). The metrics consider synthetic catalogs simulated by the models rather than synoptic probability maps, thereby relaxing the Poisson assumption of previous CSEP tests. Our approach compares statistics from the synthetic catalogs directly against observations, providing a flexible approach that can account for dependencies and uncertainties encoded in the models. We find that, to the first order, both UCERF3‐ETAS and UCERF3‐NoFaults approximately capture the spatiotemporal evolution of the Ridgecrest sequence, adding to the growing body of evidence that ETAS models can be informative forecasting tools. However, we also find that both models mildly overpredict the seismicity rate, on average, aggregated over the evaluation period. More severe testing indicates the overpredictions occur too often for observations to be statistically indistinguishable from the model. Magnitude tests indicate that the models do not include enough variability in forecasted magnitude‐number distributions to match the data. Spatial tests highlight discrepancies between the forecasts and observations, but the greatest differences between the two models appear when aftershocks occur on modeled UCERF3‐ETAS faults. Therefore, any predictability associated with embedding earthquake triggering on the (modeled) fault network may only crystalize during the presumably rare sequences with aftershocks on these faults. Accounting for uncertainty in the model parameters could improve test results during future experiments.Maximilian J. Werner and Warner Marzocchi received funding from the European Union's Horizon 2020 research and innovation program (Number 821115, RISE: Real‐Time Earthquake Risk Reduction for a Resilient Europe). This research was supported by the Southern California Earthquake Center (SCEC; Contribution Number 10082). SCEC is funded by National Science Foundation (NSF) Cooperative Agreement EAR‐1600087 and the U.S. Geological Survey (USGS) Cooperative Agreement G17AC00047

Adapting the AHA’s Blood Pressure and Nutrition Management Program into Digestible Teaching Plans for Low-Income Communities

Executive Summary: Adapting the AHA’s blood pressure and nutrition management program into digestible teaching plans for low-income communities According to the American Heart Association (AHA), 46% of American adults have high blood pressure (Whelton et al., 2017). High blood pressure, especially for those above the age of 50, is associated with a higher prevalence of heart disease and a shorter life expectancy. The AHA’s Check Change Control program (CCC), is an evidence based, self-directed blood pressure management guide (American Heart Association, 2021). The CCC program incorporates four lesson topics related to lifestyle changes to manage hypertension. The four topics are: self-monitoring of blood pressure, healthy eating and reducing sodium, exercise, and stress management. Our group’s mission focused on creating educational plans on the first two topics, self-monitoring of blood pressure and healthy eating. Our goal was to provide future educators at an independent senior living facility with a condensed framework of the CCC program that would be more easily understood for an older adult population. Background For our project, we worked alongside a nonprofit organization that provided sustainable housing and services for seniors and families. Our group consisted of eight quarter-five Seattle Pacific University (SPU) nursing students working with a representative from the AHA, our clinical instructor, and a representative from the site to create an educational plan based on a needs assessment of the community. Our primary community was an independent living facility for low-income older adults located south of Seattle, Washington. Based on prior assessments by the community management and AHA, they found a knowledge deficit in blood pressure management and understanding of nutrition. In our site assessments we validated these needs. Residents had limited knowledge of the importance of blood pressure management, had no way to self-monitor, and had limited access to healthy food options. Representatives of the food pantry reported that they had no consistent supplies, relying on internal donations. The pantry consisted primarily of high-sodium prepackaged foods like instant noodles and canned beans. A new addition to the community was a garden; but, for the autumn and winter, fresh vegetables were scarce. In our review of the AHA’s CCC program, we found barriers to its implementation. The document itself was wholly online and utilized many hyperlinks, PowerPoints, and videos. For low-income adults with limited knowledge or access to technology, this program was found to be hard to access by themselves. The complex modules the AHA had prepared were difficult for the residents of the community to use and understand due to the sheer size and depth of the content. For future SPU students who would be implementing the education, the length and depth of the program were also much larger than what was possible to cover within a regular ten-week school quarter. Our group worked to reduce these barriers by condensing the material into weekly teaching activities. Activities We generated a lesson outline to target two main areas of concern within the community as determined by site assessments: blood pressure management, and nutrition, for use by future SPU students. From the CCC program, we curated a five-week outline for nursing students or similar educators to implement over the course of a ten-week school quarter. The first two weeks we focused on blood pressure management, and the second two weeks on nutrition, with a flexible fifth week for review, open activity, or a separate teaching topic. The first week’s topic was blood pressure literacy, measurements, and tracking. This included a review of what blood pressure is, the importance of monitoring, an open discussion of barriers to monitoring, how to accurately check and analyze the readings, and physically getting their blood pressure taken by the educators. The second week’s topic was medications and adherence. The education plan included for students to have a brief check in and review of the content from the previous week, and hold information sessions on specific medications. These information sessions would be private and personalized by being held in a one-on-one manner. The education plan also focuses on identifying potential struggles, assessing a lack of education on their medications such as indications, symptoms, and management, as well as reinforcing adherence. The third week’s topic was nutritional literacy. The education plan includes having students assess the residents’ understanding of what a healthy diet consists of, and then they would provide education on sodium intake with a demonstration of serving sizes. The focus of the fourth week was healthy nutrition options. The education plan included having residents create meals with provided food pages and discuss their choices. The fifth week’s topic would be a flex week, where students and/or residents would pick a topic based on their own community needs assessments. The activities in the education plan include different styles of engagement, including lecture, presentations, PowerPoints, videos, hands-on activities, games, surveys, one-on-one sessions and open discussions, and distribution of educational materials and resources to monitor health effectively. We also have incorporated a weekly survey to assess the effectiveness of our project goals. Outcomes Our project was based on goals and topics organized by facility leadership in collaboration with the AHA. We were tasked with creating teaching materials and educational plans for future SPU Nursing Students to teach the residents during their clinicals. Our lesson outline was provided to agency staff in order to ensure the success of the project goals. Evaluation surveys was provided to the students in the implementation document to allow the students to have sources to use to assess the effectiveness of the teaching plan, activities, and resources. Based on survey responses, adjustments, a weekly focus could be made. Further evaluation of the effectiveness of our plan would be overseen by the AHA representative. For this project we have created a lesson outline at the request of the community manager, using AHA resources along with the assessments by the site management and by our group. This was done in order to aid future SPU Nursing Students in the implementation of our lesson plans for the community. Future nursing students will continue to gather and add information based on their own observations and experiences to ensure the continuity of this project and the health outcomes of the focused community. References American Heart Association (2021) Check. Change. Control. check-change-control-implementation-guide.pdf (heart.org) Whelton, P. K., Carey, R.M., Aronow, W.S., Casey, D.E., Jr., Collins, K.J., Himmelfarb Dennison, C., DePalma, S.M., Gidding, S., Jamerson, K.A., Jones, D.W., MacLaughlin, E.J., Muntner, P., Ovbiagele, B., Smith, S.C., Jr., Spencer, C.C., Stafford, R.S., Taler, S.J., Thomas, R.J., Williams, K.A., Sr., … Wright, J.T., Jr. (2017). ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension, 71(6), e13-e115. https://doi.org/10.1161/HYP.000000000000006

Depressive Symptom Trajectories Among Girls in the Juvenile Justice System: Findings from an RCT of Multidimensional Treatment Foster Care

Youth depression is a significant and growing international public health problem. Youth who engage in high levels of delinquency are at particularly high risk for developing problems with depression. The present study examined the impact of a behavioral intervention designed to reduce delinquency (Multidimensional Treatment Foster Care; MTFC) compared to a group care intervention (GC; i.e., services as usual) on trajectories of depressive symptoms among adolescent girls in the juvenile justice system. MTFC has documented effects on preventing girls’ recidivism, but its effects on preventing the normative rise in girls’ depressive symptoms across adolescence have not been examined. This indicated prevention sample included 166 girls (13–17 years at T1) who had at least one criminal referral in the past 12 months and who were mandated to out-of-home care; girls were randomized to MTFC or GC. Intent-to-treat analyses examined the main effects of MTFC on depression symptoms and clinical cut-offs, and whether benefits were greatest for girls most at risk. Depressive symptom trajectories were specified in hierarchical linear growth models over a two year period using five waves of data at six month intervals. Depression clinical cut-off scores were specified as nonlinear probability growth models. Results showed significantly greater rates of deceleration for girls in MTFC versus GC for depressive symptoms and for clinical cut-off scores. The MTFC intervention also showed greater benefits for girls with higher levels of initial depressive symptoms. Possible mechanisms of effect are discussed, given MTFC’s effectiveness on targeted and nontargeted outcomes.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Springer and can be found at: http://link.springer.com/journal/11121.Keywords: randomized controlled trial, juvenile justice, maltreatment, MTFC (Multidimensional Treatment Foster Care), girls, depressio

Highlights from the first ten years of the New Zealand earthquake forecast testing center

We present highlights from the first decade of operation of the New Zealand Earthquake Forecast Testing Center of the Collaboratory for the Study of Earthquake Predictability (CSEP). Most results are based on reprocessing using the best available catalog, because the testing center did not consistently capture the complete real-time catalog. Tests of models with daily updating show that aftershock models incorporating Omori- Utsu decay can outperform long-term smoothed seismicity models with probability gains up to 1000 during major aftershock sequences. Tests of models with 3-month updating show that several models with every earthquake a precursor according to scale (EEPAS) model, incorporating the precursory scale increase phenomenon and without Omori-Utsu decay, and the double-branching model, with both Omori-Utsu and exponential decay in time, outperformed a regularly updated smoothed seismicity model. In tests of 5-yr models over 10 yrs without updating, a smoothed seismicity model outperformed the earthquake source model of the New Zealand National Seismic Hazard Model. The performance of 3-month and 5-yr models was strongly affected by the Canterbury earthquake sequence, which occurred in a region of previously low seismicity. Smoothed seismicity models were shown to perform better with more frequent updating. CSEP models were a useful resource for the development of hybrid time-varying models for practical forecasting after major earthquakes in the Canterbury and Kaikoura regions. © 2018 Seismological Society of America. All rights reserved

Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases.

Trehalose 6,6′-dimycolate (TDM) is a cell wall glycolipid and an important virulence factor of mycobacteria. In order to study the role of TDM in the innate immune response to Mycobacterium tuberculosis, microarray analysis was used to examine gene regulation in murine bone marrow-derived macrophages in response to 90-μm-diameter polystyrene microspheres coated with TDM. A large number of genes, particularly those involved in the immune response and macrophage function, were up- or downregulated in response to these TDM-coated beads compared to control beads. Genes involved in the immune response were specifically upregulated in a myeloid differentiation primary response gene 88 (MyD88)-dependent manner. The complexity of the transcriptional response also increased greatly between 2 and 24 h. Matrix metalloproteinases (MMPs) were significantly upregulated at both time points, and this was confirmed by quantitative real-time reverse transcription-PCR (RT-PCR). Using an in vivo Matrigel granuloma model, the presence and activity of MMP-9 were examined by immunohistochemistry and in situ zymography (ISZ), respectively. We found that TDM-coated beads induced MMP-9 expression and activity in Matrigel granulomas. Macrophages were primarily responsible for MMP-9 expression, as granulomas from neutrophil-depleted mice showed staining patterns similar to that for wild-type mice. The relevance of these observations to human disease is supported by the similar induction of MMP-9 in human caseous tuberculosis (TB) granulomas. Given that MMPs likely play an important role in both the construction and breakdown of tuberculous granulomas, our results suggest that TDM may drive MMP expression during TB pathogenesis

Mammalian microRNAs predominantly act to decrease target mRNA levels

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.National Institutes of Health (U.S.