76 research outputs found

    U.S. Policymakers\u27 Perspectives Regarding the Causes of Terrorism and the Impact on U.S. Counterterrorism Policy

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    U.S. counterterrorism policy appears to be influenced by different perspectives, as evidenced by conflicting statements by U.S. presidents regarding the causes of terrorism. Academic theories are not always applied by U.S. government employees who develop, influence, and implement counterterrorism policy. The purpose of this qualitative phenomenological study was to understand U.S. government policymakers\u27 perspectives on the causes of terrorism, the influences on these views, and the impact on U.S. counterterrorism policy. Six theories regarding the causes of terrorism provided the theoretical framework. Additional theories related to individual and organizational impact on decision-making provided a broader conceptual framework. Data were collected from interviews and survey questionnaires from 31 participants. Data were coded and categorized for thematic analysis. Five key findings were observed: (a) Root causes theory was a predominant factor in participants\u27 understanding of the cause of terrorism, (b) personal experiences are a dominant influence on these views, (c) organizational influence on the views of terrorism varied by organization, (d) participants viewed their interagency colleagues as well informed regarding the causes of terrorism, and (e) individual views among U.S. policymakers have a minimal impact on U.S. counterterrorism policy. Findings may be used to influence U.S. counterterrorism policymakers\u27 views at the national policy level

    Trends in the medical management of patients with heart failure

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    BACKGROUND: Despite the availability of effective therapies, heart failure (HF) remains a highly prevalent disease and the leading cause of hospitalizations in the U.S. Few data are available, however, describing changing trends in the use of various cardiac medications to treat patients with HF and factors associated with treatment. The objectives of this population-based study were to examine decade-long trends (1995 - 2004) in the use of several cardiac medications in patients hospitalized with acute decompensated heart failure (ADHF) and factors associated with evidence-based treatment. METHODS: We reviewed the medical records of 9,748 residents of the Worcester, MA, metropolitan area who were hospitalized with ADHF at all 11 central Massachusetts medical centers in 1995, 2000, 2002, and 2004. RESULTS: Between 1995 and 2004, respectively, the prescription upon hospital discharge of beta-blockers (23%; 67%), angiotensin pathway inhibitors (47%; 55%), statins (5%; 43%), and aspirin (35%; 51%) increased markedly, while the use of digoxin (51%; 29%), nitrates (46%; 24%), and calcium channel blockers (33%; 22%) declined significantly; nearly all patients received diuretics. Patients in the earliest study year, those with a history of obstructive pulmonary disease or anemia, incident HF, non-specific symptoms, and women were less likely to receive beta blockers and angiotensin pathway inhibitors than respective comparison groups. In 2004, 82% of patients were discharged on at least one of these recommended agents; however, only 41% were discharged on medications from both recommended classes. CONCLUSIONS: Our data suggest that opportunities exist to further improve the use of HF therapeutics

    Speckle echocardiographic left atrial strain and stiffness index as predictors of maintenance of sinus rhythm after cardioversion for atrial fibrillation: a prospective study

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    BACKGROUND: Echocardiographic left atrial (LA) strain parameters have been associated with atrial fibrillation (AF) in prior studies. Our goal was to determine if strain measures [peak systolic longitudinal strain (LAS) and stiffness index (LASt)] changed after cardioversion (CV); and their relation to AF recurrence. METHODS AND RESULTS: 46 participants with persistent AF and 41 age-matched participants with no AF were recruited. LAS and LASt were measured before and immediately after CV using 2D speckle tracking imaging (2DSI). Maintenance of sinus rhythm was assessed over a 6-month follow up. Mean LAS was lower, and mean LASt higher, in participants with AF before CV as compared to control group (11.9 +/- 1.0 vs 35.7 +/- 1.7, p CONCLUSIONS: LAS and LASt differed between participants with and without AF, irrespective of the rhythm at the time of echocardiographic assessment. Baseline LAS and LASt were not associated with AF recurrence. However, change in LAS after CV may be a useful predictor of recurrent arrhythmia

    Comparison of On-Site Versus Remote Mobile Device Support in the Framingham Heart Study Using the Health eHeart Study for Digital Follow-up: Randomized Pilot Study Set Within an Observational Study Design

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    BACKGROUND: New electronic cohort (e-Cohort) study designs provide resource-effective methods for collecting participant data. It is unclear if implementing an e-Cohort study without direct, in-person participant contact can achieve successful participation rates. OBJECTIVE: The objective of this study was to compare 2 distinct enrollment methods for setting up mobile health (mHealth) devices and to assess the ongoing adherence to device use in an e-Cohort pilot study. METHODS: We coenrolled participants from the Framingham Heart Study (FHS) into the FHS-Health eHeart (HeH) pilot study, a digital cohort with infrastructure for collecting mHealth data. FHS participants who had an email address and smartphone were randomized to our FHS-HeH pilot study into 1 of 2 study arms: remote versus on-site support. We oversampled older adults (age \u3e /=65 years), with a target of enrolling 20% of our sample as older adults. In the remote arm, participants received an email containing a link to enrollment website and, upon enrollment, were sent 4 smartphone-connectable sensor devices. Participants in the on-site arm were invited to visit an in-person FHS facility and were provided in-person support for enrollment and connecting the devices. Device data were tracked for at least 5 months. RESULTS: Compared with the individuals who declined, individuals who consented to our pilot study (on-site, n=101; remote, n=93) were more likely to be women, highly educated, and younger. In the on-site arm, the connection and initial use of devices was \u3e /=20% higher than the remote arm (mean percent difference was 25% [95% CI 17-35] for activity monitor, 22% [95% CI 12-32] for blood pressure cuff, 20% [95% CI 10-30] for scale, and 43% [95% CI 30-55] for electrocardiogram), with device connection rates in the on-site arm of 99%, 95%, 95%, and 84%. Once connected, continued device use over the 5-month study period was similar between the study arms. CONCLUSIONS: Our pilot study demonstrated that the deployment of mobile devices among middle-aged and older adults in the context of an on-site clinic visit was associated with higher initial rates of device use as compared with offering only remote support. Once connected, the device use was similar in both groups

    Extended Sentinel Monitoring of Helicoverpa zea Resistance to Cry and Vip3Aa Toxins in Bt Sweet Corn: Assessing Changes in Phenotypic and Allele Frequencies of Resistance

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    Transgenic corn and cotton that produce Cry and Vip3Aa toxins derived from Bacillus thuringiensis (Bt) are widely planted in the United States to control lepidopteran pests. The sustainability of these Bt crops is threatened because the corn earworm/bollworm, Helicoverpa zea (Boddie), is evolving a resistance to these toxins. Using Bt sweet corn as a sentinel plant to monitor the evolution of resistance, collaborators established 146 trials in twenty-five states and five Canadian provinces during 2020–2022. The study evaluated overall changes in the phenotypic frequency of resistance (the ratio of larval densities in Bt ears relative to densities in non-Bt ears) in H. zea populations and the range of resistance allele frequencies for Cry1Ab and Vip3Aa. The results revealed a widespread resistance to Cry1Ab, Cry2Ab2, and Cry1A.105 Cry toxins, with higher numbers of larvae surviving in Bt ears than in non-Bt ears at many trial locations. Depending on assumptions about the inheritance of resistance, allele frequencies for Cry1Ab ranged from 0.465 (dominant resistance) to 0.995 (recessive resistance). Although Vip3Aa provided high control efficacy against H. zea, the results show a notable increase in ear damage and a number of surviving older larvae, particularly at southern locations. Assuming recessive resistance, the estimated resistance allele frequencies for Vip3Aa ranged from 0.115 in the Gulf states to 0.032 at more northern locations. These findings indicate that better resistance management practices are urgently needed to sustain efficacy the of corn and cotton that produce Vip3Aa

    The time scale of recombination rate evolution in great apes

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    We present three linkage-disequilibrium (LD)-based recombination maps generated using whole-genome sequence data from 10 Nigerian chimpanzees, 13 bonobos, and 15 western gorillas, collected as part of the Great Ape Genome Project (Prado-Martinez J, et al. 2013. Great ape genetic diversity and population history. Nature 499:471-475). We also identified species-specific recombination hotspots in each group using a modified LDhot framework, which greatly improves statistical power to detect hotspots at varying strengths. We show that fewer hotspots are shared among chimpanzee subspecies than within human populations, further narrowing the time scale of complete hotspot turnover. Further, using species-specific PRDM9 sequences to predict potential binding sites (PBS), we show higher predicted PRDM9 binding in recombination hotspots as compared to matched cold spot regions in multiple great ape species, including at least one chimpanzee subspecies. We found that correlations between broad-scale recombination rates decline more rapidly than nucleotide divergence between species. We also compared the skew of recombination rates at centromeres and telomeres between species and show a skew from chromosome means extending as far as 10-15Mb from chromosome ends. Further, we examined broad-scale recombination rate changes near a translocation in gorillas and found minimal differences as compared to other great ape species perhaps because the coordinates relative to the chromosome ends were unaffected. Finally, on the basis of multiple linear regression analysis, we found that various correlates of recombination rate persist throughout the African great apes including repeats, diversity, and divergence. Our study is the first to analyze within- And between-species genome-wide recombination rate variation in several close relatives

    AI is a viable alternative to high throughput screening: a 318-target study

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    : High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

    Determining crystal structures through crowdsourcing and coursework

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    We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality
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