The Impact of Motivation on Continued VFR into IMC: Another Perspective to an On-Going Problem

Continued flight under visual flight rules into instrument meteorological conditions remains the predominant cause for fatal accidents by percentage for general aviation aircraft operations. There are gaps in the research in determining how motivation might influence the decision-making process. Therefore, the purpose of this study was to determine how motivation and meteorological conditions might affect a pilot’s willingness to persist in flight into meteorological conditions. Four hundred and fifty-four general aviation pilots participated in a mixed factorial experiment to assess their willingness to persist in varying weather conditions. Participants were randomly assigned into one of three motivation groups (intrinsic, extrinsic, or no motivation) and were subjected to all three meteorological conditions (visual, marginal, and instrument) that were randomized in order of appearance. They were then asked to indicate their willingness to persist in each condition via a slider scale, scaled from 0 to 100. The results indicated the main effect of meteorological condition has a significant effect on willingness to persist, while the main effect of motivation did not. The interaction between meteorological condition and motivation resulted in a significant effect, particularly in the marginal meteorological condition

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats

AbstractObjectivesp38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats.MethodsRats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2) the FR group (daily FR167653, 2 mg · kg−1 · d−1), (3) the MCT group (daily 0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the MCT+FR group (daily FR167653, 2 mg · kg−1 · d−1, the day after a single MCT dose). Body weight, pulmonary artery pressure, and morphometric changes of the pulmonary artery with the histopathologic method were observed weekly for 4 weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory cytokine expression in the lung were measured.ResultsFour weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group was lower than in the MCT group (MCT+FR vs MCT: 24.7 ± 1.9 vs 36.5 ± 2.1 mm Hg; P < .05). In morphometric analysis the percentage of medial wall thickness and the percentage of muscularization in the MCT+FR group were reduced compared with those in the MCT group after 4 weeks (P < .05); however, the number of macrophages was not significantly different. p38 mitogen-activated protein kinase activity was significantly attenuated in the MCT+FR group compared with in the MCT group (7.2 ± 0.52 vs 2.1 ± 0.23 fold-increase, P < .05, at 1 week). Although mRNA levels of tumor necrosis factor α and interleukin 1β were reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor α: 1.18 ± 0.36 vs 3.05 ± 1.12 fold-increase, P < .05, at 2 weeks; interleukin 1β: 2.2 ± 0.34 vs 4.4 ± 1.09 fold-increase, P < .05, at 1 week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA expression induced by monocrotaline (3.2 ± 0.62 vs 3.1 ± 0.42 fold-increase, at 1 week).ConclusionFR167653 significantly attenuates the expression of inflammatory cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38 mitogen-activated protein kinase might play a central role in the molecular events that underlie the development and progression of pulmonary hypertension

Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy

Purpose: To evaluate CD4+CD25+FOXP3+ T regulatory cells (TREG) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating TREG combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis. Design: Eighteen patients with mRCC and twelve volunteers (controls) were available for analysis. TREG phenotype was examined using flow cytometry (FCM). TREG were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the gene signatures were explored using pathway analysis. Results We observed higher numbers of TREG in pre-treatment PBL of mRCC patients compared to controls. A significant increase in TREG was detected in all mRCC patients after the two cycles of immunotherapy. The expansion of TREG was significantly higher in non-responders than in responding patients. Methylation specific PCR confirmed the FCM data and circumvented the variability and subjectivity of the FCM method. Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant enrichment of FOXP3 target genes, CTLA-4 and TGF-ß associated pathways in the patient cohort. Conclusion: Immune monitoring of the peripheral blood and tumor tissue is important for a wide range of diseases and treatment strategies. Adoption of methodology for quantifying TREG with the least variability and subjectivity will enhance the ability to compare and interpret findings across studies

The landscape of extreme genomic variation in the highly adaptable Atlantic killifish

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Genome Biology and Evolution 9 (2017): 659-676, doi:10.1093/gbe/evx023.Understanding and predicting the fate of populations in changing environments require knowledge about the mechanisms that support phenotypic plasticity and the adaptive value and evolutionary fate of genetic variation within populations. Atlantic killifish (Fundulus heteroclitus) exhibit extensive phenotypic plasticity that supports large population sizes in highly fluctuating estuarine environments. Populations have also evolved diverse local adaptations. To yield insights into the genomic variation that supports their adaptability, we sequenced a reference genome and 48 additional whole genomes from a wild population. Evolution of genes associated with cell cycle regulation and apoptosis is accelerated along the killifish lineage, which is likely tied to adaptations for life in highly variable estuarine environments. Genome-wide standing genetic variation, including nucleotide diversity and copy number variation, is extremely high. The highest diversity genes are those associated with immune function and olfaction, whereas genes under greatest evolutionary constraint are those associated with neurological, developmental, and cytoskeletal functions. Reduced genetic variation is detected for tight junction proteins, which in killifish regulate paracellular permeability that supports their extreme physiological flexibility. Low-diversity genes engage in more regulatory interactions than high-diversity genes, consistent with the influence of pleiotropic constraint on molecular evolution. High genetic variation is crucial for continued persistence of species given the pace of contemporary environmental change. Killifish populations harbor among the highest levels of nucleotide diversity yet reported for a vertebrate species, and thus may serve as a useful model system for studying evolutionary potential in variable and changing environments.This work was primarily supported by a grant from the National Science Foundation (collaborative research grants DEB-1265282, DEB-1120512, DEB-1120013, DEB-1120263, DEB-1120333, DEB-1120398 to J.K.C., D.L.C., M.E.H., S.I.K., M.F.O., J.R.S., W.W., and A.W.). Further support was provided by the National Institute of Environmental Health Sciences (1R01ES021934-01 to A.W., P42ES7373 to T.H.H., P42ES007381 to M.E.H., and R01ES019324 to J.R.S.), the National Institute of General Medical Sciences (P20GM103423 and P20GM104318 to B.L.K.), and the National Science Foundation (DBI-0640462 and XSEDE-MCB100147 to D.G.)

Food web de-synchronization in England's largest lake: an assessment based on multiple phenological metrics

Phenological changes have been observed globally for marine, freshwater and terrestrial species, and are an important element of the global biological ‘fingerprint’ of climate change. Differences in rates of change could desynchronize seasonal species interactions within a food web, threatening ecosystem functioning. Quantification of this risk is hampered by the rarity of long-term data for multiple interacting species from the same ecosystem and by the diversity of possible phenological metrics, which vary in their ecological relevance to food web interactions. We compare phenological change for phytoplankton (chlorophyll a), zooplankton (Daphnia) and fish (perch, Perca fluviatilis) in two basins of Windermere over 40 years and determine whether change has differed among trophic levels, while explicitly accounting for among-metric differences in rates of change. Though rates of change differed markedly among the nine metrics used, seasonal events shifted earlier for all metrics and trophic levels: zooplankton advanced most, and fish least, rapidly. Evidence of altered synchrony was found in both lake basins, when combining information from all phenological metrics. However, comparisons based on single metrics did not consistently detect this signal. A multimetric approach showed that across trophic levels, earlier phenological events have been associated with increasing water temperature. However, for phytoplankton and zooplankton, phenological change was also associated with changes in resource availability. Lower silicate, and higher phosphorus, concentrations were associated with earlier phytoplankton growth, and earlier phytoplankton growth was associated with earlier zooplankton growth. The developing trophic mismatch detected between the dominant fish species in Windermere and important zooplankton food resources may ultimately affect fish survival and portend significant impacts upon ecosystem functioning.We advocate that future studies on phenological synchrony combine data from multiple phenological metrics, to increase confidence in assessments of change and likely ecological consequences

Microfluidic Amperometric Sensor for Analysis of Nitric Oxide in Whole Blood

Standard photolithographic techniques and a nitric oxide (NO) selective xerogel polymer were utilized to fabricate an amperometric NO microfluidic sensor with low background noise and the ability to analyze NO levels in small sample volumes (~250 μL). The sensor exhibited excellent analytical performance in phosphate buffered saline, including a NO sensitivity of 1.4 pA nM−1, a limit of detection (LOD) of 840 pM, and selectivity over nitrite, ascorbic acid, acetaminophen, uric acid, hydrogen sulfide, ammonium, ammonia, and both protonated and deprotonated peroxynitrite (selectivity coefficients of −5.3, −4.2, −4.0, −5.0, −6.0, −5.8, −3.8, −1.5, and −4.0 respectively). To demonstrate the utility of the microfluidic NO sensor for biomedical analysis, the device was used to monitor changes in blood NO levels during the onset of sepsis in a murine pneumonia model

Multi-modality machine learning predicting Parkinson's disease

Personalized medicine promises individualized disease prediction and treatment. The convergence of machine learning (ML) and available multimodal data is key moving forward. We build upon previous work to deliver multimodal predictions of Parkinson's disease (PD) risk and systematically develop a model using GenoML, an automated ML package, to make improved multi-omic predictions of PD, validated in an external cohort. We investigated top features, constructed hypothesis-free disease-relevant networks, and investigated drug-gene interactions. We performed automated ML on multimodal data from the Parkinson's progression marker initiative (PPMI). After selecting the best performing algorithm, all PPMI data was used to tune the selected model. The model was validated in the Parkinson's Disease Biomarker Program (PDBP) dataset. Our initial model showed an area under the curve (AUC) of 89.72% for the diagnosis of PD. The tuned model was then tested for validation on external data (PDBP, AUC 85.03%). Optimizing thresholds for classification increased the diagnosis prediction accuracy and other metrics. Finally, networks were built to identify gene communities specific to PD. Combining data modalities outperforms the single biomarker paradigm. UPSIT and PRS contributed most to the predictive power of the model, but the accuracy of these are supplemented by many smaller effect transcripts and risk SNPs. Our model is best suited to identifying large groups of individuals to monitor within a health registry or biobank to prioritize for further testing. This approach allows complex predictive models to be reproducible and accessible to the community, with the package, code, and results publicly available

Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy

To evaluate CD4(+)CD25(+)FOXP3(+) T regulatory cells (T(REG)) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating T(REG) combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis

Effect of foot orthoses on lower extremity kinetics during running: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Throughout the period of one year, approximately 50% of recreational runners will sustain an injury that disrupts their training regimen. Foot orthoses have been shown to be clinically effective in the prevention and treatment of several running-related conditions, yet the physical effect of this intervention during running remains poorly understood. The aim of this literature review was therefore to evaluate the effect of foot orthoses on lower extremity forces and pressure (kinetics) during running.</p> <p>Methods</p> <p>A systematic search of electronic databases including Medline (1966-present), CINAHL, SportDiscus, and The Cochrane Library occurred on 7 May 2008. Eligible articles were selected according to pre-determined criteria. Methodological quality was evaluated by use of the Quality Index as described by Downs & Black, followed by critical analysis according to outcome variables.</p> <p>Results</p> <p>The most widely reported kinetic outcomes were loading rate and impact force, however the effect of foot orthoses on these variables remains unclear. In contrast, current evidence suggests that a reduction in the rearfoot inversion moment is the most consistent kinetic effect of foot orthoses during running.</p> <p>Conclusion</p> <p>The findings of this review demonstrate systematic effects that may inform the direction of future research, as further evidence is required to define the mechanism of action of foot orthoses during running. Continuation of research in this field will enable targeting of design parameters towards biomechanical variables that are supported by evidence, and may lead to advancements in clinical efficacy.</p