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Ecological forecasting has vast potential to support environmental decision making with repeated, testable predictions across management-relevant timescales and locations. Yet resource managers rarely use co-designed forecasting systems or embed them in decision making. Although prediction of planned management outcomes is particularly important for biological invasions to optimize when and where resources should be allocated, spatial-temporal models of spread typically have not been openly shared, iteratively updated, or interactive to facilitate exploration of management actions. We describe a species-agnostic, open-source framework - called the Pest or Pathogen Spread (PoPS) Forecasting Platform - for co-designing near-term iterative forecasts of biological invasions. Two case studies are presented to demonstrate that iterative calibration yields higher forecast skill than using only the earliest-available data to predict future spread. The PoPS framework is a primary example of an ecological forecasting system that has been both scientifically improved and optimized for real-world decision making through sustained participation and use by management stakeholders.

Mucopolysaccharidosis (MPS) IIIB is a neuropathic lysosomal storage disease characterized by the deficient activity of a lysosomal enzyme obligate for the degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The pathogenesis of neurodegeneration in MPS IIIB is incompletely understood. Large animal models are attractive for pathogenesis and therapeutic studies due to their larger size, outbred genetics, longer lifespan, and naturally occurring MPS IIIB disease. However, the temporospatial development of neuropathologic changes has not been reported for canine MPS IIIB. Here we describe lesions in 8 brain regions, cervical spinal cord, and dorsal root ganglion (DRG) in a canine model of MPS IIIB that includes dogs aged from 2 to 26 months of age. Pathological changes in the brain included early microscopic vacuolation of glial cells initially observed at 2 months, and vacuolation of neurons initially observed at 10 months. Inclusions within affected cells variably stained positively with PAS and LFB stains. Quantitative immunohistochemistry demonstrated increased glial expression of GFAP and Iba1 in dogs with MPS IIIB compared to age-matched controls at all time points, suggesting neuroinflammation occurs early in disease. Loss of Purkinje cells was initially observed at 10 months and was pronounced in 18- and 26-month-old dogs with MPS IIIB. Our results support the dog as a replicative model of MPS IIIB neurologic lesions and detail the pathologic and neuroinflammatory changes in the spinal cord and DRG of MPS IIIB-affected dogs.

Ecological forecasts will be best suited to inform intervention strategies if they are accessible to a diversity of decision-makers. Researchers are developing intuitive forecasting interfaces to guide stakeholders through the development of intervention strategies and visualization of results. Yet, few studies to date have evaluated how user interface design facilitates the coordinated, cross-boundary management required for controlling biological invasions. We used a participatory approach to develop complementary tangible and online interfaces for collaboratively forecasting biological invasions and devising control strategies. A diverse group of stakeholders evaluated both systems in the real-world context of controlling sudden oak death, an emerging forest disease killing millions of trees in California and Oregon. Our findings suggest that while both interfaces encouraged adaptive experimentation, tangible interfaces are particularly well suited to support collaborative decision-making. Reflecting on the strengths of both systems, we suggest workbench-style interfaces that support simultaneous interactions and dynamic geospatial visualizations.

Coping Power (CP) is an evidence-based preventive intervention for youth with disruptive behavior problems. This study examined whether Mindful Coping Power (MCP), a novel adaptation which integrates mindfulness into CP, enhances program effects on children’s reactive aggression and self-regulation. A pilot randomized design was utilized to estimate the effect sizes for MCP versus CP in a sample of 102 child participants (fifth grade students, predominantly low-middle income, 87% Black). MCP produced significantly greater improvement in children’s self-reported dysregulation (emotional, behavioral, cognitive) than CP, including children’s perceived anger modulation. Small to moderate effects favoring MCP were also observed for improvements in child-reported inhibitory control and breath awareness and parent-reported child attentional capacity and social skills. MCP did not yield a differential effect on teacher-rated reactive aggression. CP produced a stronger effect than MCP on parent-reported externalizing behavior problems. Although MCP did not enhance program effects on children’s reactive aggression as expected, it did have enhancing effects on children’s internal, embodied experiences (self-regulation, anger modulation, breath awareness). Future studies are needed to compare MCP and CP in a large scale, controlled efficacy trial and to examine whether MCP-produced improvements in children’s internal experiences lead to improvements in their observable behavior over time.

Although cognitive-behavioral interventions have reduced the risk of substance use, little is known about moderating factors in children with disruptive behaviors. This study examined whether aggressive preadolescents’ inhibitory control and intervention engagement moderates the effect of group versus individual delivery on their substance use. Following screening for aggression in 4th grade, 360 children were randomly assigned to receive the Coping Power intervention in either group or individual formats. The sample was primarily African American (78%) and male (65%). Assessments were made of children’s self-reported substance use from preintervention through a six-year follow-up after intervention, parent-reported inhibitory control at preintervention, and observed behavioral engagement in the group intervention. Multilevel growth modeling found lower increases in substance use slopes for children with low inhibitory control receiving individual intervention, and for children with higher inhibitory control receiving group intervention. Children with low inhibitory control but who displayed more positive behavioral engagement in the group sessions had slower increases in their substance use than did similar children without positive engagement. Aggressive children’s level of inhibitory control can lead to tailoring of group versus individual delivery of intervention. Children’s positive behavioral engagement in group sessions is a protective factor for children with low inhibitory control.

We present evidence that variability in the STEREO‐A Heliospheric Imager (HI) data is correlated with in situ solar wind speed estimates from WIND, STEREO‐A, and STEREO‐B. For 2008–2012, we compute the variability in HI differenced images in a plane‐of‐sky shell between 20 to 22.5 solar radii and, for a range of position angles, compare daily means of HI variability and in situ solar wind speed estimates. We show that the HI variability data and in situ solar wind speeds have similar temporal autocorrelation functions. Carrington rotation periodicities are well documented for in situ solar wind speeds, but, to our knowledge, this is the first time they have been presented in statistics computed from HI images. In situ solar wind speeds from STEREO‐A, STEREO‐B, and WIND are all are correlated with the HI variability, with a lag that varies in a manner consistent with the longitudinal separation of the in situ monitor and the HI instrument. Unlike many approaches to processing HI observations, our method requires no manual feature tracking; it is automated, is quick to compute, and does not suffer the subjective biases associated with manual classifications. These results suggest we could possibly estimate solar wind speeds in the low heliosphere directly from HI observations. This motivates further investigation, as this could be a significant asset to the space weather forecasting community; it might provide an independent observational constraint on heliospheric solar wind forecasts, through, for example, data assimilation. Finally, these results are another argument for the potential utility of including a HI on an operational space weather mission.

Images of coronal mass ejections (CMEs) from the Heliospheric Imager (HI) instruments on board the STEREO spacecraft frequently contain rich structure. Here, we present analysis of the Earth-directed CME launched on 12 December 2008 in which we intepret the revealed structure as projections of separate discrete sections of the physical boundary of the CME. By comparing the relative position of the outer and inner 'ghost' fronts seen in the STEREO HI1 cameras with the positions of features determined from three CME models we show that the two fronts seen in the images correspond to the expected position of the flank and nose of the CME where the background solar wind is uniform. In contrast, the flank of the CME observed expanding into a structured background solar wind results in the elongation between the two fronts being greater than expected. This is consistent with the CME flank distorting in the presence of a high-speed solar wind stream. Further work is required to consolidate these results. The presence of a shock for this event was ruled out by consideration of the low CME speed and by studying in-situ spacecraft data. The CME flank crossing the Thomson sphere was also ruled out as a cause of the ghost fronts. Ghost fronts could provide information about the longitudinal shape of the CME independent of geometric models. This technique could subsequently be used to improve space weather forecast models through techniques such as data assimilation.

Models that are both spatially and temporally dynamic are needed to forecast where and when non-native pests and pathogens are likely to spread, to provide advance information for natural resource managers. The potential US range of the invasive spotted lanternfly (SLF, Lycorma delicatula) has been modeled, but until now, when it could reach the West Coast’s multi-billion-dollar fruit industry has been unknown. We used process-based modeling to forecast the spread of SLF assuming no treatments to control populations occur. We found that SLF has a low probability of first reaching the grape-producing counties of California by 2027 and a high probability by 2033. Our study demonstrates the importance of spatio-temporal modeling for predicting the spread of invasive species to serve as an early alert for growers and other decision makers to prepare for impending risks of SLF invasion. It also provides a baseline for comparing future control options.

We present a method for augmenting spacecraft measurements of thermospheric composition with quantitative estimates of daytime thermospheric composition below 200 km, inferred from ionospheric data, for which there is a global network of ground-based stations. Measurements of thermospheric composition via ground-based instrumentation are challenging to make, and so details about this important region of the upper atmosphere are currently sparse. The visibility of the F1 peak in ionospheric soundings from ground-based instrumentation is a sensitive function of thermospheric composition. The ionospheric profile in the transition region between F1 and F2 peaks can be expressed by the “G” factor, a function of ion production rate and loss rates via ion–atom interchange reactions and dissociative recombination of molecular ions. This in turn can be expressed as the square of the ratio of ions lost via these processes. We compare estimates of the G factor obtained from ionograms recorded at Kwajalein (9∘ N, 167.2∘ E) for 25 times during which the Thermosphere, Ionosphere, Mesosphere, Energetics and Dynamics (TIMED) spacecraft recorded approximately co-located measurements of the neutral thermosphere. We find a linear relationship between G and the molecular-to-atomic composition ratio, with a gradient of 2.55±0.40. Alternatively, using hmF1 values obtained by ionogram inversion, this gradient was found to be 4.75±0.4. Further, accounting for equal ionisation in molecular and atomic species yielded a gradient of 4.20±0.8. This relationship has potential for using ground-based ionospheric measurements to infer quantitative variations in the composition of the neutral thermosphere via a relatively simple model. This has applications in understanding long-term change and the efficacy of the upper atmosphere on satellite drag.

Background Anatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown. Objectives The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS. Methods In this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST. Results Between 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group. Conclusions The authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence.

Background: Myocardial infarction leads to a massive loss of cardiomyocytes (CM) and cardiac remodeling, which results in reduced cardiac function and, ultimately, heart failure. Adult mammalian CMs cannot spontenously proliferate, and thus repair the cardiac injury, however in our previous study we showed that simultaneous knock down of Rb1 and Meis2 induced CM cell cycle activation that resulted in improved cardiac function. Moreover, most significant cardioprotective effects were due to CM mediated paracrine mechanisms including angiogenesis and CM cell survival. Thus, this study aims to identify these indirect cardioprotective pathways dependent on CM cell cycle. Methods and Results: We utilized genetically modified FUCCI mice, which allows identifying the cycling vs. non-cycling CM for transcriptome analysis. Adult mouse CM was isolated through the Langendorff heart perfusion method, using our modified isolation protocol, and cultured in the modified DMEM media. Adult CMs were transfected with equimolar (50uM each) combination of siRb1 and siMeis2 (siRNA-cocktail), cel-miR-67 served as control. CMs were harvested, and RNA isolation was performed on day seven after transfection. Rb1 and Meis2 knock-down were validated through CM proliferation analysis and RT-PCR based expression profiling for selected markers of proliferation, angiogenesis, cell survival, and structural genes. Our analysis showed a significant down-regulation of Rb1 and Meis2 after siRNA treatment.Further, we observed an up-regulation of pro-angiogenic and pro-survival genes without any significant alteration in the structural genes. After validating our samples, we performed a whole-genome transcriptome analysis using a high-throughput Illumina NextSeq platform. Our RNAseq analysis revealed the activation of pathways, which may induce the CM rejuvenation. The identified potential targets will be further validated through in vivo experiments. Conclusions: Our results suggest the activation of CM rejuvenation after knocking-down Rb1 and Meis2 to improve the cardioprotection after injury.

The Heliospheric Imagers on board National Aeronautics and Space Administration (NASA)'s\ud twin STEREO spacecraft show that coronal mass ejections (CMEs) can be visually complex structures. To\ud explore this complexity, we created a citizen science project with the U.K. Science Museum, in which\ud participants were shown pairs of CME images and asked to decide which image in each pair appeared the\ud most “complicated.” A Bradley‐Terry model was then applied to these data to rank the CMEs by their\ud “complicatedness,” or “visual complexity.” This complexity ranking revealed that the annual average visual\ud complexity values follow the solar activity cycle, with a higher level of complexity being observed at the peak\ud of the cycle. The average complexity of CMEs observed by STEREO‐A was also found to be significantly\ud higher than those observed by STEREO‐B. Visual complexity was found to be associated with CME size and\ud brightness, but our results suggest that complexity may be influenced by the scale‐sizes of structure in the\ud CMEs.

The present study assessed whether tefillin use (tight, nonocclusive, wrapping of the arm) elicits a remote ischemic preconditioning (RIPC)-like effect in subjects with both acute and chronic use. RIPC, created by short bursts of ischemia-reperfusion, has not been successfully taken to the bedside. Several large population studies have found that Orthodox Jewish men (who wear tefillin almost daily) have decreased cardiovascular mortality compared with non-Orthodox counterparts. We hypothesized that tefillin use is a relevant component in triggering a preconditioning effect. Jewish men ( n = 20) were enrolled; 9 men were daily tefillin users (conditioned) and 11 men were nonusers of tefillin as controls (naïve). Subjects were evaluated for adherence to traditional Jewish practice, had vital signs measured, blood drawn for analysis of circulating cytokines and monocyte function, and underwent brachial flow-mediated dilation to evaluate vascular reactivity at baseline (basal) and after 30 min of using tefillin (acute treatment). Under basal conditions, both groups had similar peak systolic velocity (SV), diameter, and flow volume, although the conditioned group had higher SV at 120 s postdeflation ( P = 0.05). Acute tefillin use augmented artery diameter and flow volume in both groups, with conditioned subjects experiencing higher SV than control subjects at 90 and 120 s postdeflation ( P = 0.03 and P = 0.02, respectively). Conditioned subjects had decreased inflammation, monocyte migration and adhesion, and endothelial activation compared with control subjects at baseline. Acute use of tefillin did not significantly alter monocyte function in either group. In this pilot study, acute tefillin use improves vascular function, whereas chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype. NEW & NOTEWORTHY We hypothesized that tefillin use among Orthodox Jewish men (who practice a nonocclusive leather banding of their nondominant arm) will induce a remote ischemic preconditioning phenotype. Chronic use of tefillin in Orthodox Jewish men was associated with increased systolic velocity and attenuated inflammation and monocyte chemotaxis and adhesion versus Jewish men who do not wear tefillin. Acute use of tefillin in both populations augmented brachial artery diameter and blood flow but not inflammatory profiles compared with baseline.

In this work we have, for the first time, applied the interpretation of multiple “ghost-fronts” to two synthetic coronal mass ejections (CMEs) propagating within a structured solar wind using the Heliospheric Upwind eXtrapolation time (HUXt) solar wind model. The two CMEs occurred on 2012 June 13–14 showing multiple fronts in images from Solar Terrestrial Relations Observatory Heliospheric Imagers (HIs). The HUXt model is used to simulate the evolution of these CMEs across the inner heliosphere as they interacted with structured ambient solar wind. The simulations reveal that the evolution of CME shape is consistent with observations across a wide range of solar latitudes and that the manifestation of multiple “ghost-fronts” within HIs’ field of view is consistent with the positions of the nose and flank of the same CME structure. This provides further confirmation that the angular separation of these features provides information on the longitudinal extent of a CME. For one of the CMEs considered in this study, both simulations and observations show that a concave shape develops within the outer CME front. We conclude that this distortion results from a latitudinal structure in the ambient solar wind speed. The work emphasizes that the shape of the CME cannot be assumed to remain a coherent geometrical shape during its propagation in the heliosphere. Our analysis demonstrates that the presence of “ghost” CME fronts can be used to infer the distortion of CMEs by ambient solar wind structure as a function of both latitude and longitude. This information has the potential to improve the forecasting of space weather events at Earth.

This study describes the results from a feasibility study of an innovative indicated prevention intervention with hybrid face-to-face and web-based components for preadolescent youth. This intervention includes a considerably briefer set of face-to-face sessions from the evidence-based Coping Power program and a carefully integrated internet component with practice and teaching activities and cartoon videos for children and for parents. The Coping Power - Internet Enhanced (CP-IE) program introduces a set of cognitive-behavioral skills in 12 small group sessions for children delivered during the school day and 7 group sessions for parents. Eight elementary schools were randomly assigned to CP-IE or to Control, and six children at each school were identified each year based on 4th grade teacher ratings of aggressive behavior. Path analyses of teacher-rated disruptive behavior outcomes for 91 fifth grade children, across two annual cohorts, indicated Control children had significantly greater increases in conduct problem behaviors across the 5th grade year than did CP-IE children. This much briefer version of Coping Power provided beneficial preventive effects on children's behavior in the school setting similar to the effects of the longer version of Coping Power. The website materials appeared to successfully engage children, and parents' use of the website predicted children's changes in conduct problems across the year.

Cardiac fibrosis is a grim consequence for almost all myocardial injuries. In myocardial infarction (MI), what starts as a protective scarring process to prevent ventricular wall rupture becomes a pathological remodeling of the tissue with the accumulation of excess extracellular matrix (ECM) proteins. Eventually, this adaptation impedes the mechanical and electrical properties of the myocardium resulting in heart failure. Recently, we showed that periostin (Postn) expressing resident cardiac fibroblasts (CFs) are a potential therapeutic target since they differentiate into the scar associated, matrix-producing myofibroblasts (MFs) after injury. In fact, deletion of these cells after an acute injury eliminates interstitial fibrosis but results in ventricular rupture which is a hallmark outcome of impaired ECM deposition during the acute phase of MI. On the other hand, ablation of these cells during a chronic injury such as pressure overload-induced cardiac fibrosis model, we observe sustained perivascular fibrosis. Previous studies report heterogeneity of origin and function for ECM producing cells associated with different cardiac diseases. Here we utilized several novel mouse models that permit lineage tracing of all activated MFs as well as perivascular mural cells in the heart to elucidate the role and fate of these distinct cardiac interstitial cells during fibrogenesis. Cells were lineage traced with a tamoxifen-inducible cre recombinase cDNA knock-in alleles (PostnMCM and Gli1CreER) in combination with a Rosa26-eGFP cre-dependent reporter. Hearts subjected to MI, TAC or Angiotensin injury were processed for extensive histological and RNAseq analyses. Results show that interstitial fibrosis in acute MI injury is a result of Postn+ MFs activity, whereas a subset of Gli1+ mural cells are responsible for the perivascular fibrosis observed after pressure overload models. Therefore, we concluded that pathological ECM deposition resulting in fibrosis comes from disease-specific specialized sub-populations of interstitial cells of the heart with distinct gene expressions and require manipulation of alternative cell- and state-specific therapeutic targets.

RNA binding proteins represent an emerging class of proteins with a role in cardiac dysfunction. We show that activation of the RNA binding protein human antigen R (HuR) is increased in the failing human heart. To determine the functional role of HuR in pathological cardiac hypertrophy, we created an inducible cardiomyocyte-specific HuR-deletion mouse and showed that HuR deletion reduces left ventricular hypertrophy, dilation, and fibrosis while preserving cardiac function in a transverse aortic constriction (TAC) model of pressure overload-induced hypertrophy. Assessment of HuR-dependent changes in global gene expression suggests that the mechanistic basis for this protection occurs through a reduction in fibrotic signaling, specifically through a reduction in TGF-β (Tgfb) expression. Finally, pharmacological inhibition of HuR at a clinically relevant time point following the initial development of pathological hypertrophy after TAC also yielded a significant reduction in pathological progression, as marked by a reduction in hypertrophy, dilation, and fibrosis and preserved function. In summary, this study demonstrates a functional role for HuR in the progression of pressure overload-induced cardiac hypertrophy and establishes HuR inhibition as a viable therapeutic approach for pathological cardiac hypertrophy and heart failure.

We propose a reciprocal, self-propelled model swimmer at intermediate Reynolds numbers ($Re$). Our swimmer consists of two unequal spheres that oscillate in antiphase generating nonlinear steady streaming (SS) flows. We show computationally that the SS flows enable the swimmer to propel itself, and also switch direction as $Re$ increases. We quantify the transition in the swimming direction by collapsing our data on a critical $Re$ and show that the transition in swimming directions corresponds to the reversal of the SS flows. Based on our findings, we propose that SS can be an important physical mechanism for motility at intermediate $Re$., Comment: 6 pages, 3 figures

The smallest flying insects commonly possess wings with long bristles. Little quantitative information is available on the morphology of these bristles, and their functional importance remains a mystery. In this study, we (1) collected morphological data on the bristles of 23 species of Mymaridae by analyzing high-resolution photographs and (2) used the immersed boundary method to determine via numerical simulation whether bristled wings reduced the force required to fling the wings apart while still maintaining lift. The effects of Reynolds number, angle of attack, bristle spacing and wing–wing interactions were investigated. In the morphological study, we found that as the body length of Mymaridae decreases, the diameter and gap between bristles decreases and the percentage of the wing area covered by bristles increases. In the numerical study, we found that a bristled wing experiences less force than a solid wing. The decrease in force with increasing gap to diameter ratio is greater at higher angles of attack than at lower angles of attack, suggesting that bristled wings may act more like solid wings at lower angles of attack than they do at higher angles of attack. In wing–wing interactions, bristled wings significantly decrease the drag required to fling two wings apart compared with solid wings, especially at lower Reynolds numbers. These results support the idea that bristles may offer an aerodynamic benefit during clap and fling in tiny insects.

This study describes the nature, causes, and outcomes of steadfast, unquestioned “true” belief in later life (Hoffer, 1950). According to some theorists, such “true” belief develops from more childish, extrinsically-motivated, compartmentalized beliefs and behaviors to become more mature, intrinsically-motivated, comprehensive and integrated beliefs and behaviors (e.g., Allport, 1950). Research, however, is equivocal regarding the validity of this position. From “grounded-theory” analysis of a sample of 278 semi-structured interviews of older adults from six New England states and New York (aged 55-101 years-old.), we demonstrate the need for a more nuanced definition of a “true” belief as a form of religiousness without commitment to rigid orthodoxy. For example, a sizable segment of this sample changed religious denominations over the course of their lives without ever doubting the presence of a diety (i.e., a God, a Higher Power, etc.), but who dramatically changed the way they expressed this belief. This prompts a reconceptualization of “true” belief by Hoffer and a more nuanced understanding of religious development than implied by Allport, one that more adequately accounts for individual differences in life experiences, personality, religious upbringing, and religious cultural expectations. We discuss these findings in light of recent research by Wink and Dillon (2002, 2008).

The present study examines the impact of traumatic life events on religious complexity in later life. We anticipated that those older adults experiencing stressors that produce significant personal vulnerability (e.g., life threatening illnesses) demonstrate reduced complexity of belief and behavior (e.g., less belief with doubt). From a sample of 278 semi-structured interviews of older adults (aged 55-101 years-old.) from six New England and New York states, we analyzed 166 interviews using grounded theory (Strauss & Corbin, 1990). Individuals who experienced trauma related to war, close familial loss, and/or severe physical illness tended to be “true believers,” (i.e., adhere to rigid belief orthodoxy; Hoffer, 1950). By contrast, those who experienced less severe trauma (e.g., minor illness, job loss) were less apt to describe rigid belief. Temporal proximity of trauma was not consistently associated with greater complexity of belief and behavior, in the sense that with great distance from trauma, individuals were able to “work through” their experiences of trauma, and thereby increase complexity of belief and behavior. This is consistent with findings by Harris and Leak (2015), Krause and Hayward (2012), and Wong (2013) that suggest that trauma leading to personal vulnerability leads to long-term physical, mental, behavioral, and spiritual deficits that rigid religious belief and behavior help to offset. These findings are discussed in terms of psychological theories of grief resolution, personal coping, and terror management.

Lifespan extension under low temperature is well conserved across both endothermic and exothermic taxa, but the mechanism underlying this change in aging is poorly understood. Low temperature is thought to decrease metabolic rate, thus slowing the accumulation of cellular damage from reactive oxygen species, although recent evidence suggests involvement of specific cold-sensing biochemical pathways. We tested the effect of low temperature on aging in 11 strains of Brachionus rotifers, with the hypothesis that if the mechanism of lifespan extension is purely thermodynamic, all strains should have a similar increase in lifespan. We found differences in change in median lifespan ranging from a 6% decrease to a 100% increase, as well as differences in maximum and relative lifespan extension and in mortality rate. Low temperature delays reproductive senescence in most strains, suggesting an extension of healthspan, even in strains with little to no change in lifespan. The combination of low temperature and caloric restriction in one strain resulted in an additive lifespan increase, indicating these interventions may work via non- or partially-overlapping pathways. The known low temperature sensor TRPA1 is present in the rotifer genome, but chemical TRPA1 agonists did not affect lifespan, suggesting that this gene may be involved in low temperature sensation but not in chemoreception in rotifers. The congeneric variability in response to low temperature suggests that the mechanism of low temperature lifespan extension is an active genetic process rather than a passive thermodynamic one and is dependent upon genotype.

In contrast to larger species, little is known about the flight of the smallest flying insects, such as thrips and fairyflies. These tiny animals range from 300 to 1000 microns in length and fly at Reynolds numbers ranging from about 4 to 60. Previous work with numerical and physical models have shown that the aerodynamics of these diminutive insects is significantly different from that of larger animals, but most of these studies have relied on two-dimensional approximations. There can, however, be significant differences between two- and three-dimensional flows, as has been found for larger insects. To better understand the flight of the smallest insects, we have performed a systematic study of the forces and flow structures around a three-dimensional revolving elliptical wing. We used both a dynamically scaled physical model and a three-dimensional computational model at Reynolds numbers ranging from 1 to 130 and angles of attacks ranging from 0&deg, to 90&deg, The results of the physical and computational models were in good agreement and showed that dimensionless drag, aerodynamic efficiency, and spanwise flow all decrease with decreasing Reynolds number. In addition, both the leading and trailing edge vortices remain attached to the wing over the scales relevant to the smallest flying insects. Overall, these observations suggest that there are drastic differences in the aerodynamics of flight at the scale of the smallest flying animals.

Background: The gut microbiota is a metabolically active endocrine organ critical to the maintenance of cardiovascular health. Dietary sources of choline are metabolized by microbial enzymes to form trimethylamine (TMA). Metabolism by the host hepatic enzyme flavin-containing monooxygenase 3 (FMO3) converts TMA to the pro-inflammatory molecule trimethylamine N-oxide (TMAO). Human clinical trials have correlated high levels of circulating TMAO to an increased risk of cardiometabolic diseases. However, this meta-organismal pathway has not been evaluated in the context of abdominal aortic aneurysm (AAA). The objective of this study was to determine the effects of a high choline diet on the development of AAA. Methods: C57BL/6J male (n=20) and female (n=20) mice were fed either a standard chow control diet (n = 10 each sex) or a choline-rich diet (1%; n = 10 each sex) for 5 weeks. After 1 week of diet, basal abdominal ultrasounds were performed and angiotensin II (AngII; 1,000 ng/kg/min) was infused for 28 days via implantation of osmotic minipumps. Termination ultrasounds were performed on day 27 and mice were sacrificed on day 28. Aortas were harvested for evaluation of aneurysm progression and plasma was analyzed for the metabolites TMA, TMAO, and choline. To determine whether TMAO was elevated in human patients with AAA, plasma samples from participants with fast growing AAAs (n = 85), slow growing AAAs (n = 84), and normal (non-aneurysmal) aortas (n = 115) were analyzed for plasma TMAO levels via liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: Administration of a choline-rich diet augmented the incidence (P < 0.02) and aortic diameter (P < 0.001) of AAAs in both male and female mice versus placebo-fed mice. Plasma levels of TMA, TMAO, and choline were significantly elevated in choline-fed mice versus normal chow (P < 0.05). Importantly, circulating levels of plasma TMAO were significantly elevated in a step-wise fashion with the rate of aneurysm growth versus non-aneurysmal control patients (fast growing > slow growing > normal patients; P < 0.001). Conclusions: Our results indicate increases in circulating TMAO augments the growth status of aneurysms in human patients and the incidence of AAA in a low penetrant C57BL/6J mouse model.

Background: Fibrinogen and fibrin provide physical and biochemical support to a developing clot and is defined as one of the most crucial independent risk factors for cardiovascular diseases (CVDs). In addition to clot formation, fibrinogen promotes wound healing and powerful inflammatory and immune responses by engagement of leukocytes. Increased circulating fibrinogen and fibrin degradation products are correlated with increased diameter and progression of abdominal aortic aneurysm (AAA). However, a causal link between fibrinogen and AAA has not yet been established. The objective of this study was to determine the role of fibrinogen depletion in a mouse model of AAA. Methods and results: To determine whether aneurysm resulted in a procoagulant environment, we examined plasma levels of thrombin generation by calibrated automated thrombography (CAT), thrombin anti-thrombin (TAT), and fibrinogen in control and AAA plasma from mice and humans. Patients and mice with AAA had significant elevations in thrombin generation, TAT, and fibrinogen versus saline controls (mice) and control patients (human). To determine the effect of fibrinogen, in vivo, low density lipoprotein receptor deficient ( Ldlr -/- ) mice were injected with scrambled anti-sense oligonucleotide (ASO) or β-fibrinogen ASO (30 mg/kg) 3 weeks prior to experimentation and throughout the study. Fibrinogen ASO treatment achieved > 90% depletion of fibrinogen. After 3 weeks, mice were fed a fat and cholesterol enriched diet (42% milk fat; 0.2% cholesterol) 1 week prior to and throughout infusion with angiotensin II (AngII; 1,000 ng/kg/day) for 28 days. Fibrinogen ASO attenuated abdominal diameter (33% decrease; P = 0.001), and inflammatory cytokines (>75% decreased IL-1 and IL-6; P = 0.001) versus scrambled ASO control. Further, fibrinogen depletion significantly attenuated aneurysm incidence and rupture-induced death (P < 0.05). Conclusions: Our results demonstrate that AAAs augment procoagulant markers in both humans and mice. Importantly, fibrinogen depletion attenuates AAA incidence, diameter, rupture-induced death, and inflammation. Therefore, reduction of plasma fibrinogen may be a novel treatment strategy in patients with AAA.

Objective— PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. Approach and Results— PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice (8–12 weeks old) that were Par2 +/+ or Par2 −/− were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Conclusions— Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration.