Interventions to Decrease Mortality Among Patients with Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a severe complication which affects thousands of patients every year and is associated with high mortality rates and increased healthcare costs. A systematic review was conducted to determine the efficacy of various interventions used to decrease the staggering mortality rate of ARDS. The interventions studied were extracorporeal membrane oxygenation (ECMO), prone positioning, and neuromuscular blockade. Data bases searched were Google Scholar, PubMed, Cochrane library, and the CINAHL databases to find relevant research articles and a literature review conducted. A total of 21 articles were considered and screened for inclusion/exclusion criteria, ultimately yielding five articles included in this systematic review. To guide this major project, the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and flow diagram were utilized. To further assess the quality of reach study, the Critical Appraisal Skills Programme (CASP) checklist was used. A cross study analysis was performed to compare identified outcomes. This systematic review determined one study to be underpowered, one study demonstrated a decrease in mortality in the intervention group but was not statistically significant, and two studies were stopped for futility. One study was adequately powered and displayed a significant decrease in mortality rate. The results of this systematic review indicates further research is needed on the efficacy of interventions to decrease ARDS-related mortality and guide advanced practice nurse decision-making

Visual and linguistic narrative comprehension in autism spectrum disorders:Neural evidence for modality-independent impairments

Individuals with autism spectrum disorders (ASD) have notable language difficulties, including with understanding narratives. However, most narrative comprehension studies have used written or spoken narratives, making it unclear whether narrative difficulties stem from language impairments or more global impairments in the kinds of general cognitive processes (such as understanding meaning and structural sequencing) that are involved in narrative comprehension. Using event-related potentials (ERPs), we directly compared semantic comprehension of linguistic narratives (short sentences) and visual narratives (comic panels) in adults with ASD and typically-developing (TD) adults. Compared to the TD group, the ASD group showed reduced N400 effects for both linguistic and visual narratives, suggesting comprehension impairments for both types of narratives and thereby implicating a more domain-general impairment. Based on these results, we propose that individuals with ASD use a more bottom-up style of processing during narrative comprehension

Western Spruce Budworm and Wildfire: Is There a Connection?

In the interior Pacific Northwest, extensive defoliation of mixed conifer forests during outbreaks of western spruce budworm (WSB) may leave the visual impression of a tinderbox with trees primed to burst into flame. But is this the case? We addressed this question with funding from the USDA/U.S. Department of the Interior Joint Fire Science Program (project 09– 1–06–5). Here we summarize our three recent publications exploring the potential relationship between WSB outbreaks and fire. We used a multimethod approach to explore potential disturbance interactions that might cause one disturbance to change the occurrence or severity of the other. We used tree-ring records to see whether WSB and fire are related in time and computer modeling to see how defoliation could affect crown fire behavior

Rounding frequency and hospital length of stay for children with respiratory illnesses: A simulation study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102158/1/jhm2097.pd

Actinin BioID reveals sarcomere crosstalk with oxidative metabolism through interactions with IGF2BP2.

Actinins are strain-sensing actin cross-linkers that are ubiquitously expressed and harbor mutations in human diseases. We utilize CRISPR, pluripotent stem cells, and BioID to study actinin interactomes in human cardiomyocytes. We identify 324 actinin proximity partners, including those that are dependent on sarcomere assembly. We confirm 19 known interactors and identify a network of RNA-binding proteins, including those with RNA localization functions. In vivo and biochemical interaction studies support that IGF2BP2 localizes electron transport chain transcripts to actinin neighborhoods through interactions between its K homology (KH) domain and actinin\u27s rod domain. We combine alanine scanning mutagenesis and metabolic assays to disrupt and functionally interrogate actinin-IGF2BP2 interactions, which reveal an essential role in metabolic responses to pathological sarcomere activation using a hypertrophic cardiomyopathy model. This study expands our functional knowledge of actinin, uncovers sarcomere interaction partners, and reveals sarcomere crosstalk with IGF2BP2 for metabolic adaptation relevant to human disease

A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.

Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-binding protein C3 mutations, and studied iPSC-derived cardiomyocytes in cardiac microtissue assays that resemble cardiac architecture and biomechanics. All HCM mutations resulted in hypercontractility with prolonged relaxation kinetics in proportion to mutation pathogenicity, but not changes in calcium handling. RNA sequencing and expression studies of HCM models identified p53 activation, oxidative stress, and cytotoxicity induced by metabolic stress that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as a direct consequence of thick-filament mutations, irrespective of mutation localization, and the p53 pathway as a molecular marker of contraction stress and candidate therapeutic target for HCM patients

Western Spruce Budworm Outbreaks Did Not Increase Fire Risk over the Last Three Centuries: A Dendrochronological Analysis of Inter-Disturbance Synergism

Insect outbreaks are often assumed to increase the severity or probability of fire occurrence through increased fuel availability, while fires may in turn alter susceptibility of forests to subsequent insect outbreaks through changes in the spatial distribution of suitable host trees. However, little is actually known about the potential synergisms between these natural disturbances. Assessing interdisturbance synergism is challenging due to the short length of historical records and the confounding influences of land use and climate changes on natural disturbance dynamics. We used dendrochronological methods to reconstruct defoliator outbreaks and fire occurrence at ten sites along a longitudinal transect running from central Oregon to western Montana. We assessed synergism between disturbance types, analyzed long-term changes in disturbance dynamics, and compared these disturbance histories with dendroclimatological moisture availability records to quantify the influence of moisture availability on disturbances. After approximately 1890, fires were largely absent and defoliator outbreaks became longer-lasting, more frequent, and more synchronous at our sites. Fires were more likely to occur during warm-dry years, while outbreaks were most likely to begin near the end of warm-dry periods. Our results show no discernible impact of defoliation events on subsequent fire risk. Any effect from the addition of fuels during defoliation events appears to be too small to detect given the overriding influence of climatic variability. We therefore propose that if there is any relationship between the two disturbances, it is a subtle synergistic relationship wherein climate determines the probability of occurrence of each disturbance type, and each disturbance type damps the severity, but does not alter the probability of occurrence, of the other disturbance type over long time scales. Although both disturbance types may increase in frequency or extent in response to future warming, our records show no precedent that western spruce budworm outbreaks will increase future fire risk

Interactions of Insects, Fire and Climate on Fuel Loads and Fire Behavior in Mixed Conifer Forest

Mixed-conifer forests in the interior Pacific Northwest are subject to sporadic outbreaks of the western spruce budworm, the most destructive defoliator in western North America. Such outbreaks usually occur synchronously over broad regions and lead to widespread decreases in growth rates and low to moderate levels of mortality. In the last century, changing land use and fire suppression have led to an increase in the amount and density of host tree species, and changed fire regimes. This has altered the severity and frequency of both fire and western spruce budworm. In spite of the ecological and economic significance of these disturbances, their interactions with each other and with climate are not fully understood. We used two approaches to examine these interactions across a range of temporal and spatial scales. First, we used dendrochronological methods to examine the climatic drivers of budworm outbreaks and fires and to assess the association of fire and budworm over three centuries in 13 stands across Oregon, Idaho, and Montana. Second, we used a mechanistic fire behavior model, the Wildland-urban interface Fire Dynamics Simulator (WFDS) to examine the sensitivity of crown fire to multiple aspects of defoliated crown fuels, including changing crown bulk density and branchwood moisture. The dendrochronological reconstructions revealed repeated western spruce budworm outbreaks and fires over the past several centuries, with different climate events associated with each disturbance. Outbreaks sometimes persisted more than a decade and were often synchronous among sites. An average of 12 outbreaks occurred at each site, each lasting an average of 12 years in length, with an average of 15 years between outbreaks. Outbreak initiation was often regionally synchronous. Synchrony was higher in the second half of the record (since 1900), possibly due to increased abundance and continuity of host trees during the fire suppression era. Outbreak duration and frequency were also somewhat higher after approximately 1890. We found that warm-dry conditions occurred one to three years preceding outbreak initiation, suggesting that drought-stressed trees permit population growth to a level at which predators no longer strongly limit the budworm population. The mean fire return interval in these mixed-conifer stands was 34 years (range: 16 – 53 years). Fires tended to occur during warm-dry years. We found no evidence of a consistent relationship between the timing of fires and western spruce budworm outbreaks. Western spruce budworm is associated with the ends of droughts and fire is simply associated with single drought years. The simulation study found that defoliation reduces both torching and crowning potential, requiring greater surface fire intensity for crown ignition than undefoliated tree crowns with the same crown base height. Single, highly defoliated trees (80%) experienced little or no torching, and moderately defoliated trees (50%) required about twice the surface fire intensity of undefoliated trees to produce the same heat output. For example, at a surface fire intensity of 700 kW/m2 , 99% of the canopy fuel from the undefoliated tree was consumed, leaving 2 kg of foliage on the tree, compared to 81% consumption of a moderately (50%) defoliated tree, leaving 15 kg of foliage. The effects of defoliation were somewhat mitigated by canopy fuel heterogeneity and potential branchwood drying, but these effects were less pronounced than defolation itself. Our study suggests that areas heavily defoliated by western spruce budworm may inhibit crown fire spread and may thus promote non-lethal surface fires

Reaching within a dynamic virtual environment

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