Intra-city Differences in Cardiac Expression of Inflammatory Genes and Inflammasomes in Young Urbanites: A Pilot Study.

PubMed

Villarreal-Calderon, Rodolfo; Dale, Gary; Delgado-Chávez, Ricardo; Torres-Jardón, Ricardo; Zhu, Hongtu; Herritt, Lou; Gónzalez-Maciel, Angelica; Reynoso-Robles, Rafael; Yuan, Ying; Wang, Jiaping; Solorio-López, Edelmira; Medina-Cortina, Humberto; Calderón-Garcidueñas, Lilian

2012-06-01

Southwest Mexico City (SWMC) air pollution is characterized by high concentrations of ozone and particulate matter < 10 μm (PM(10)) containing lipopolysaccharides while in the North PM(2.5) is high. These intra-city differences are likely accounting for higher CD14 and IL-1β in SWMC v NMC mice myocardial expression. This pilot study was designed to investigate whether similar intra-city differences exist in the levels of myocardial inflammatory genes in young people. Inflammatory mediator genes and inflammasome arrays were measured in right and left autopsy ventricles of 6 southwest/15 north (18.5 ± 2.6 years) MC residents after fatal sudden accidental deaths. There was a significant S v N right ventricle up-regulation of IL-1β (p=0.008), TNF-α (p=0.001), IL-10 (p=0.001), and CD14 (p=0.002), and a left ventricle difference in TNF-α (p=0.007), and IL-10 (p=0.02). SW right ventricles had significant up-regulation of NLRC1, NLRP3 and of 29/84 inflammasome genes, including NOD factors and caspases. There was significant degranulation of mast cells both in myocardium and epicardial nerve fibers. Differential expression of key inflammatory myocardial genes and inflammasomes are influenced by the location of residence. Myocardial inflammation and inflammasome activation in young hearts is a plausible pathway of heart injury in urbanites and adverse effects on the cardiovascular system are expected.

Pilot study: do California highways act as barriers to gene flow for ground-dwelling mammals? A National Center for Sustainable Transportation research report.

DOT National Transportation Integrated Search

2015-12-01

Roads have the potential to fragment wildlife populations, leading to genetic diversity loss, : inbreeding, and increased extinction risk for small, isolated populations. In this study, we used : coyote as a model to investigate how four Northern Cal...

Mechanistic Indicators of Childhood Asthma (MICA): piloting an integrative design for evaluating environmental health

EPA Science Inventory

Background: Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma; however appropriately designed studies are critical for these methods to...

Multiplex transcriptional analysis of paraffin-embedded liver needle biopsy from patients with liver fibrosis

PubMed Central

2012-01-01

Background The possibility of extracting RNA and measuring RNA expression from paraffin sections can allow extensive investigations on stored paraffin samples obtained from diseased livers and could help with studies of the natural history of liver fibrosis and inflammation, and in particular, correlate basic mechanisms to clinical outcomes. Results To address this issue, a pilot study of multiplex gene expression using branched-chain DNA technology was conducted to directly measure mRNA expression in formalin-fixed paraffin-embedded needle biopsy samples of human liver. Twenty-five genes were selected for evaluation based on evidence obtained from human fibrotic liver, a rat BDL model and in vitro cultures of immortalized human hepatic stellate cells. The expression levels of these 25 genes were then correlated with liver fibrosis and inflammation activity scores. Statistical analysis revealed that three genes (COL3A1, KRT18, and TUBB) could separate fibrotic from non-fibrotic samples and that the expression of ten genes (ANXA2, TIMP1, CTGF, COL4A1, KRT18, COL1A1, COL3A1, ACTA2, TGFB1, LOXL2) were positively correlated with the level of liver inflammation activity. Conclusion This is the first report describing this multiplex technique for liver fibrosis and has provided the proof of concept of the suitability of RNA extracted from paraffin sections for investigating the modulation of a panel of proinflammatory and profibrogenic genes. This pilot study suggests that this technique will allow extensive investigations on paraffin samples from diseased livers and possibly from any other tissue. Using identical or other genes, this multiplex expression technique could be applied to samples obtained from extensive patient cohorts with stored paraffin samples in order to correlate gene expression with valuable clinically relevant information. This method could be used to provide a better understanding of the mechanisms of liver fibrosis and inflammation, its progression, and help development of new therapeutic approaches for this indication. PMID:23270325

Pregnancy-induced gene expression changes in vivo among women with rheumatoid arthritis: a pilot study.

PubMed

Goin, Dana E; Smed, Mette Kiel; Pachter, Lior; Purdom, Elizabeth; Nelson, J Lee; Kjærgaard, Hanne; Olsen, Jørn; Hetland, Merete Lund; Zoffmann, Vibeke; Ottesen, Bent; Jawaheer, Damini

2017-05-25

Little is known about gene expression changes induced by pregnancy in women with rheumatoid arthritis (RA) and healthy women because the few studies previously conducted did not have pre-pregnancy samples available as baseline. We have established a cohort of women with RA and healthy women followed prospectively from a pre-pregnancy baseline. In this study, we tested the hypothesis that pregnancy-induced changes in gene expression among women with RA who improve during pregnancy (pregDAS improved ) overlap substantially with changes observed among healthy women and differ from changes observed among women with RA who worsen during pregnancy (pregDAS worse ). Global gene expression profiles were generated by RNA sequencing (RNA-seq) from 11 women with RA and 5 healthy women before pregnancy (T0) and at the third trimester (T3). Among the women with RA, eight showed an improvement in disease activity by T3, whereas three worsened. Differential expression analysis was used to identify genes demonstrating significant changes in expression within each of the RA and healthy groups (T3 vs T0), as well as between the groups at each time point. Gene set enrichment was assessed in terms of Gene Ontology processes and protein networks. A total of 1296 genes were differentially expressed between T3 and T0 among the 8 pregDAS improved women, with 161 genes showing at least two-fold change (FC) in expression by T3. The majority (108 of 161 genes) were also differentially expressed among healthy women (q<0.05, FC≥2). Additionally, a small cluster of genes demonstrated contrasting changes in expression between the pregDAS improved and pregDAS worse groups, all of which were inducible by type I interferon (IFN). These IFN-inducible genes were over-expressed at T3 compared to the T0 baseline among the pregDAS improved women. In our pilot RNA-seq dataset, increased pregnancy-induced expression of type I IFN-inducible genes was observed among women with RA who improved during pregnancy, but not among women who worsened. These findings warrant further investigation into expression of these genes in RA pregnancy and their potential role in modulation of disease activity. These results are nevertheless preliminary and should be interpreted with caution until replicated in a larger sample.

Gene expression analysis identify a metabolic and cell function alterations as a hallmark of obesity without metabolic syndrome in peripheral blood, a pilot study.

PubMed

de Luis, Daniel Antonio; Almansa, Raquel; Aller, Rocío; Izaola, Olatz; Romero, E

2017-06-10

Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. The purpose of our pilot study was to evaluate the gene expression profiles in the peripheral blood of obese patients without other metabolic complications. A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way. Following 'One-Color Microarray-Based Gene Expression Analysis' protocol Version 5.7 (Agilent p/n 4140-90040), cRNA was hybridized with Whole Human Genome Oligo Microarray Kit (Agilent p/n G2519F-014850) containing 41,000+ unique human genes and transcripts. The average age of the study group was 43.6 ± 19.7 years with a sex distribution of 64.7% females and 35.3% males. No statistical differences were detected with healthy controls 41.9 ± 12.3 years with a sex distribution of 70% females and 30% males. Obese patients showed 1436 genes that were differentially expressed compared to control group. Ingenuity Pathway Analysis showed that these genes participated in 13 different categories related to metabolism and cellular functions. In the gene set of cellular function, the most important genes were C-terminal region of Nel-like molecule 1 protein (NELL1) and Pigment epithelium-derived factor (SPEDF), both genes were over-expressed. In the gene set of metabolism, insulin growth factor type 1 (IGF1), ApoA5 (apolipoprotein subtype 5), Foxo4 (Forkhead transcription factor 4), ADIPOR1 (receptor of adiponectin type 1) and AQP7 (aquaporin channel proteins7) were over expressed. Moreover, PIKFYVE (PtdIns(3) P 5-kinase), and ROCK-2 (rho-kinase II) were under expressed. We showed that PBMCs from obese subjects presented significant changes in gene expression, exhibiting 1436 differentially expressed genes compared to PBMCs from non-obese subjects. Furthermore, our data showed a number of genes involved in relevant processes implicated in metabolism, with genes presenting high fold-change values (up-regulation and down regulation) associated with lipid, carbohydrate and protein metabolism. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Circadian gene variants and susceptibility to type 2 diabetes: a pilot study.

PubMed

Kelly, M Ann; Rees, Simon D; Hydrie, M Zafar I; Shera, A Samad; Bellary, Srikanth; O'Hare, J Paul; Kumar, Sudhesh; Taheri, Shahrad; Basit, Abdul; Barnett, Anthony H

2012-01-01

Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18 × 10(-5)), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively). None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.

Attachment style and oxytocin receptor gene variation interact in influencing social anxiety.

PubMed

Notzon, S; Domschke, K; Holitschke, K; Ziegler, C; Arolt, V; Pauli, P; Reif, A; Deckert, J; Zwanzger, P

2016-01-01

Social anxiety has been suggested to be promoted by an insecure attachment style. Oxytocin is discussed as a mediator of trust and social bonding as well as a modulator of social anxiety. Applying a gene-environment (G × E) interaction approach, in the present pilot study the main and interactive effects of attachment styles and oxytocin receptor (OXTR) gene variation were probed in a combined risk factor model of social anxiety in healthy probands. Participants (N = 388; 219 females, 169 males; age 24.7 ± 4.7 years) were assessed for anxiety in social situations (Social Phobia and Anxiety Inventory) depending on attachment style (Adult Attachment Scale, AAS) and OXTR rs53576 A/G genotype. A less secure attachment style was significantly associated with higher social anxiety. This association was partly modulated by OXTR genotype, with a stronger negative influence of a less secure attachment style on social anxiety in A allele carriers as compared to GG homozygotes. The present pilot data point to a strong association of less secure attachment and social anxiety as well as to a gene-environment interaction effect of OXTR rs53576 genotype and attachment style on social anxiety possibly constituting a targetable combined risk marker of social anxiety disorder.

Occurrence of potentially pathogenic nontuberculous mycobacteria in Mexican household potable water: a pilot study.

PubMed

Perez-Martinez, Iza; Aguilar-Ayala, Diana A; Fernandez-Rendon, Elizabeth; Carrillo-Sanchez, Alma K; Helguera-Repetto, Addy C; Rivera-Gutierrez, Sandra; Estrada-Garcia, Teresa; Cerna-Cortes, Jorge F; Gonzalez-Y-Merchand, Jorge A

2013-12-11

Nontuberculous mycobacteria (NTM) are environmental opportunistic pathogens found in natural and human-engineered waters, including drinking water distribution systems and household plumbing. This pilot study examined the frequency of occurrence of NTM in household potable water samples in Mexico City. Potable water samples were collected from the "main house faucet" and kitchen faucet. The presence of aerobic-mesophilic bacteria (AMB), total coliforms (TC), fecal coliforms (FC) and NTM species were determined. Mycobacteria species were identified by PCR restriction enzyme pattern analysis (PRA) of the 65-kDa heat shock protein gene (hsp65) and sequencing of the hypervariable region 2 (V2) of the 16S rRNA gene and of the rpoB gene. AMB (<100 CFU/ml) were present in 118 out of 120 samples; only two samples were outside guidelines ranges (>100 CFU/ml). TC and FC were detected in four and one samples, respectively. NTM species were recovered from 16% samples (19/120) and included M. mucogenicum (nine), M. porcinum (three), M. avium (three), M. gordonae (one), M. cosmeticum (one), M. fortuitum (one), and Mycobacterium sp (one). All household water samples that contained NTM complied with the standards required to grade the water as "good quality" potable water. Household potable water may be a potential source of NTM infection in Mexico City.

Succession of microbial functional communities in response to a pilot-scale ethanol-blended fuel release throughout the plume life cycle.

PubMed

Ma, Jie; Deng, Ye; Yuan, Tong; Zhou, Jizhong; Alvarez, Pedro J J

2015-03-01

GeoChip, a comprehensive gene microarray, was used to examine changes in microbial functional gene structure throughout the 4-year life cycle of a pilot-scale ethanol blend plume, including 2-year continuous released followed by plume disappearance after source removal. Canonical correlation analysis (CCA) and Mantel tests showed that dissolved O2 (which was depleted within 5 days of initiating the release and rebounded 194 days after source removal) was the most influential environmental factor on community structure. Initially, the abundance of anaerobic BTEX degradation genes increased significantly while that of aerobic BTEX degradation genes decreased. Gene abundance for N fixation, nitrification, P utilization, sulfate reduction and S oxidation also increased, potentially changing associated biogeochemical cycle dynamics. After plume disappearance, most genes returned to pre-release abundance levels, but the final functional structure significantly differed from pre-release conditions. Overall, observed successions of functional structure reflected adaptive responses that were conducive to biodegradation of ethanol-blend releases. Copyright © 2015. Published by Elsevier Ltd.

A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women.

PubMed

Wee, Bryan A; Thomas, Mark; Sweeney, Emma Louise; Frentiu, Francesca D; Samios, Melanie; Ravel, Jacques; Gajer, Pawel; Myers, Garry; Timms, Peter; Allan, John A; Huston, Wilhelmina M

2018-06-01

We know very little about the microbiota inhabiting the upper female reproductive tract and how it impacts on fertility. This pilot study aimed to examine the vaginal, cervical and endometrial microbiota for women with a history of infertility compared to women with a history of fertility. Using a retrospective case-control study design, women were recruited for collection of vaginal, cervical and endometrial samples. The microbiota composition was analysed by 16S ribosomal RNA (rRNA) gene amplification and endometrial expression of selected human genes by quantitative reverse transcription polymerase chain reaction. Sixty-five specimens from the reproductive tract of 31 women were successfully analysed using 16S rRNA gene amplicon sequencing (16 controls and 15 cases). The dominant microbial community members were consistent in the vagina and cervix, and generally consistent with the endometrium although the relative proportions varied. We detected three major microbiota clusters that did not group by tissue location or case-control status. There was a trend that infertile women more often had Ureaplasma in the vagina and Gardnerella in the cervix. Testing for the expression of selected genes in the endometrium did not show evidence of correlation with case-control status, or with microbial community composition, although Tenascin-C expression correlated with a history of miscarriage. There is a need for further exploration of the endometrial microbiota, and how the microbiota members or profile interplays with fertility or assisted reproductive technologies. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Gene-Culture Coevolution in a Social Cetacean: Integrating Acoustic and Genetic Data to Understand Population Structure in the Short-Finned Pilot Whale (Globicephala macrorhynchus)

NASA Astrophysics Data System (ADS)

Van Cise, Amy

The evolutionary ecology of a species is driven by a combination of random events, ecological and environmental mechanisms, and social behavior. Gene-culture coevolutionary theory attempts to understand the evolutionary trajectory of a species by examining the interactions between these potential drivers. Further, our choice of data type will affect the patterns we observe, therefore by integrating several types of data we achieve a holistic understanding of the various aspects of evolutionary ecology within a species. In order to understand population structure in short-finned pilot whales, I use a combination of genetic and acoustic data to examine structure on evolutionary (genetic) and cultural (acoustic) timescales. I first examine structure among geographic populations in the Pacific Ocean. Using genetic sequences from the mitochondrial control region, I show that two genetically and morphologically distinct types of short-finned pilot whale, described off the coast of Japan, have non-overlapping distributions throughout their range in the Pacific Ocean. Analysis of the acoustic features of their social calls indicates that they are acoustically differentiated, possibly due to limited communication between the two types. This evidence supports the hypothesis that the two types may be separate species or subspecies. Next, I examine structure among island communities and social groups within the Hawaiian Island population of short-finned pilot whales. Using a combination of mitochondrial and nuclear DNA, I showed that the hierarchical social structure in Hawaiian pilot whales is driven by genetic relatedness; individuals remain in groups with their immediate family members, and preferentially associate with relatives. Similarly, social structure affects genetic differentiation, likely by restricting access to mates. Acoustic differentiation among social groups indicates that social structure may also restrict the flow of cultural information, such as vocal repertoire or dialect. The qualitative correlation between social structure, cultural information transfer, and genetic structure suggest that gene-culture coevolution may be an important mechanism to the evolutionary ecology of short-finned pilot whales. Further research may reveal a similar structure in the transmission of ecological behaviors, such as diet preference, habitat use, or movements. The results of this research underscore the applicability of gene-culture coevolutionary theory to non-human taxa.

Toxicity of Doxorubicin on Pig Liver After Chemoembolization with Doxorubicin-loaded Microspheres: A Pilot DNA-microarrays and Histology Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verret, Valentin, E-mail: valentin.verret@archimmed.com; Namur, Julien; Ghegediban, Saieda Homayra

The potential mechanisms accounting for the hepatotoxicity of doxorubicin-loaded microspheres in chemoembolization were examined by combining histology and DNA-microarray techniques.The left hepatic arteries of two pigs were embolized with 1 mL of doxorubicin-loaded (25 mg; (DoxMS)) or non-loaded (BlandMS) microspheres. The histopathological effects of the embolization were analyzed at 1 week. RNAs extracted from both the embolized and control liver areas were hybridized onto Agilent porcine microarrays. Genes showing significantly different expression (p < 0.01; fold-change > 2) between two groups were classified by biological process. At 1 week after embolization, DoxMS caused arterial and parenchymal necrosis in 51 andmore » 38 % of embolized vessels, respectively. By contrast, BlandMS did not cause any tissue damage. Up-regulated genes following embolization with DoxMS (vs. BlandMS, n = 353) were mainly involved in cell death, apoptosis, and metabolism of doxorubicin. Down-regulated genes (n = 120) were mainly related to hepatic functions, including enzymes of lipid and carbohydrate metabolisms. Up-regulated genes included genes related to cell proliferation (growth factors and transcription factors), tissue remodeling (MMPs and several collagen types), inflammatory reaction (interleukins and chemokines), and angiogenesis (angiogenic factors and HIF1a pathway), all of which play an important role in liver healing and regeneration. DoxMS caused lesions to the liver, provoked cell death, and disturbed liver metabolism. An inflammatory repair process with cell proliferation, tissue remodeling, and angiogenesis was rapidly initiated during the first week after chemoembolization. This pilot study provides a comprehensive method to compare different types of DoxMS in healthy animals or tumor models.« less

Circadian Gene Variants and Susceptibility to Type 2 Diabetes: A Pilot Study

PubMed Central

Kelly, M. Ann; Rees, Simon D.; Hydrie, M. Zafar I.; Shera, A. Samad; Bellary, Srikanth; O’Hare, J. Paul; Kumar, Sudhesh; Taheri, Shahrad; Basit, Abdul; Barnett, Anthony H.

2012-01-01

Background Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. Methodology/Principal Findings The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66–0.86], p = 3.18×10−5), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07–1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01–1.08], p = 0.008 and OR = 0.95 [0.91–0.99], p = 0.015 respectively). Conclusions/significance None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility. PMID:22485135

The role of gut microbiota in fetal methylmercury exposure: Insights from a pilot study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothenberg, Sarah E.; Keiser, Sharon; Ajami, Nadim J.

The mechanisms by which gut microbiota contribute to methylmercury metabolism remain unclear. Among a cohort of pregnant mothers, the main objectives of our pilot study were to determine 1) associations between gut microbiota and mercury concentrations in biomarkers (stool, hair and cord blood) and 2) the contributions of gut microbial mercury methylation/demethylation to stool methylmercury. Moreover, for pregnant women (36-39 weeks gestation, n=17) donated hair and stool specimens, and cord blood was collected for a subset (n=7). The diversity of gut microbiota was determined using 16S rRNA gene profiling (n=17). For 6 stool samples with highest/lowest methylmercury concentrations, metagenomic wholemore » genome shotgun sequencing was employed to search for one mercury methylation gene (hgcA), and two mer operon genes involved in methylmercury detoxification (merA and merB). There were seventeen bacterial genera that were significantly correlated (increasing or decreasing) with stool methylmercury, stool inorganic mercury, or hair total mercury; however, aside from one genus, there was no overlap between biomarkers. No definitive matches for hgcA or merB, while merA were detected at low concentrations in all six samples. Proportional differences in stool methylmercury were not likely attributed to gut microbiota through methylation/demethylation. Gut microbiota potentially altered methylmercury metabolism using indirect pathways.« less

Occurrence of potentially pathogenic nontuberculous mycobacteria in Mexican household potable water: a pilot study

PubMed Central

2013-01-01

Background Nontuberculous mycobacteria (NTM) are environmental opportunistic pathogens found in natural and human-engineered waters, including drinking water distribution systems and household plumbing. This pilot study examined the frequency of occurrence of NTM in household potable water samples in Mexico City. Potable water samples were collected from the “main house faucet” and kitchen faucet. The presence of aerobic-mesophilic bacteria (AMB), total coliforms (TC), fecal coliforms (FC) and NTM species were determined. Mycobacteria species were identified by PCR restriction enzyme pattern analysis (PRA) of the 65-kDa heat shock protein gene (hsp65) and sequencing of the hypervariable region 2 (V2) of the 16S rRNA gene and of the rpoB gene. Results AMB (<100 CFU/ml) were present in 118 out of 120 samples; only two samples were outside guidelines ranges (>100 CFU/ml). TC and FC were detected in four and one samples, respectively. NTM species were recovered from 16% samples (19/120) and included M. mucogenicum (nine), M. porcinum (three), M. avium (three), M. gordonae (one), M. cosmeticum (one), M. fortuitum (one), and Mycobacterium sp (one). All household water samples that contained NTM complied with the standards required to grade the water as “good quality” potable water. Conclusion Household potable water may be a potential source of NTM infection in Mexico City. PMID:24330835

The role of gut microbiota in fetal methylmercury exposure: Insights from a pilot study

DOE PAGES

Rothenberg, Sarah E.; Keiser, Sharon; Ajami, Nadim J.; ...

2016-02-01

The mechanisms by which gut microbiota contribute to methylmercury metabolism remain unclear. Among a cohort of pregnant mothers, the main objectives of our pilot study were to determine 1) associations between gut microbiota and mercury concentrations in biomarkers (stool, hair and cord blood) and 2) the contributions of gut microbial mercury methylation/demethylation to stool methylmercury. Moreover, for pregnant women (36-39 weeks gestation, n=17) donated hair and stool specimens, and cord blood was collected for a subset (n=7). The diversity of gut microbiota was determined using 16S rRNA gene profiling (n=17). For 6 stool samples with highest/lowest methylmercury concentrations, metagenomic wholemore » genome shotgun sequencing was employed to search for one mercury methylation gene (hgcA), and two mer operon genes involved in methylmercury detoxification (merA and merB). There were seventeen bacterial genera that were significantly correlated (increasing or decreasing) with stool methylmercury, stool inorganic mercury, or hair total mercury; however, aside from one genus, there was no overlap between biomarkers. No definitive matches for hgcA or merB, while merA were detected at low concentrations in all six samples. Proportional differences in stool methylmercury were not likely attributed to gut microbiota through methylation/demethylation. Gut microbiota potentially altered methylmercury metabolism using indirect pathways.« less

Identification of a single nucleotide polymorphism indicative of high risk in acute myocardial infarction

PubMed Central

Shalia, Kavita; Saranath, Dhananjaya; Rayar, Jaipreet; Shah, Vinod K.; Mashru, Manoj R.; Soneji, Surendra L.

2017-01-01

Background & objectives: Acute myocardial infarction (AMI) is a major health concern in India. The aim of the study was to identify single nucleotide polymorphisms (SNPs) associated with AMI in patients using dedicated chip and validating the identified SNPs on custom-designed chips using high-throughput microarray analysis. Methods: In pilot phase, 48 AMI patients and 48 healthy controls were screened for SNPs using human CVD55K BeadChip with 48,472 SNP probes on Illumina high-throughput microarray platform. The identified SNPs were validated by genotyping additional 160 patients and 179 controls using custom-made Illumina VeraCode GoldenGate Genotyping Assay. Analysis was carried out using PLINK software. Results: From the pilot phase, 98 SNPs present on 94 genes were identified with increased risk of AMI (odds ratio of 1.84-8.85, P=0.04861-0.003337). Five of these SNPs demonstrated association with AMI in the validation phase (P<0.05). Among these, one SNP rs9978223 on interferon gamma receptor 2 [IFNGR2, interferon (IFN)-gamma transducer 1] gene showed a significant association (P=0.00021) with AMI below Bonferroni corrected P value (P=0.00061). IFNGR2 is the second subunit of the receptor for IFN-gamma, an important cytokine in inflammatory reactions. Interpretation & conclusions: The study identified an SNP rs9978223 on IFNGR2 gene, associated with increased risk in AMI patient from India. PMID:29434065

A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with O6-methylguanine DNA methyltransferase.

PubMed

Cornetta, K; Croop, J; Dropcho, E; Abonour, R; Kieran, M W; Kreissman, S; Reeves, L; Erickson, L C; Williams, D A

2006-09-01

Administration of chemotherapy is often limited by myelosuppression. Expression of drug-resistance genes in hematopoietic cells has been proposed as a means to decrease the toxicity of cytotoxic agents. In this pilot study, we utilized a retroviral vector expressing methylguanine DNA methyltransferase (MGMT) to transduce hematopoietic progenitors, which were subsequently used in the setting of alkylator therapy (procarbazine, CCNU, vincristine (PCV)) for poor prognosis brain tumors. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells were collected by apheresis and enriched for CD34+ expression. Nine subjects were infused with CD34+-enriched cells treated in a transduction procedure involving a 4-day exposure to cytokines with vector exposure on days 3 and 4. No major adverse event was related to the gene therapy procedure. Importantly, the engraftment kinetics of the treated product was similar to unmanipulated peripheral blood stem cells, suggesting that the ex vivo manipulation did not significantly reduce engrafting progenitor cell function. Gene-transduced cells were detected in all subjects. Although the level and duration was limited, patients receiving cells transduced using fibronectin 'preloaded' with virus supernatant appeared to show improved in vivo marking frequency. These findings demonstrate the feasibility and safety of utilizing MGMT-transduced CD34+ peripheral blood progenitor cells in the setting of chemotherapy.

Gene-activated fat grafts for the repair of spinal cord injury: a pilot study.

PubMed

Betz, Volker M; Sitoci-Ficici, K Hakan; Uckermann, Ortrud; Leipnitz, Elke; Iltzsche, Anne; Thirion, Christian; Salomon, Michael; Zwipp, Hans; Schackert, Gabriele; Betz, Oliver B; Kirsch, Matthias

2016-02-01

Spinal cord injury (SCI) is a complex disease requiring a concerted multi-target approach. The most appropriate combination of therapeutic gene, cellular vehicle, and space filling scaffold still has to be determined. We present an approach that employs syngeneic adipose tissue serving as a three-dimensional biological implant, source of progenitor cells, and delivery system for therapeutic genes. In this pilot experiment, we evaluated the feasibility and short-term effects using gene-activated autologous fat grafts after SCI. An experimental SCI model was established in syngeneic Fischer 344 rats by a T9-T10 hemimyelonectomy. Fat tissue was harvested from two donor rats. Animals were divided into four groups and treated with either (i) fat grafts activated by an adenoviral vector carrying the human NT-3 cDNA, (ii) or BDNF, (iii) or with untreated fat grafts or (iv) remained untreated. Animals were euthanized either 7 or 21 days after surgery, and spinal cord tissue was investigated by histological and immunohistochemical methods. NT-3 and BDNF were produced by gene-activated fat grafts for at least 21 days in vitro and in vivo. Fat tissue grafts remained stable at the site of implantation at 7 days and at 21 days. Neither BDNF-activated nor NT-3-activated fat graft had a detectable limiting effect on the neuronal degeneration. BDNF recruited microglia to perilesional site and attenuated their inflammatory response. Gene-activated syngeneic fat tissue serves as a three-dimensional biological material delivering therapeutic molecules to the site of SCI over an extended period of time. The BDNF-fat graft attenuated the inflammatory response. Whether these findings translate into functional recovery will require extended observation times.

Gene expression of inflammation and bone healing in peri-implant crevicular fluid after placement and loading of dental implants. A kinetic clinical pilot study using quantitative real-time PCR.

PubMed

Slotte, Christer; Lennerås, Maria; Göthberg, Catharina; Suska, Felicia; Zoric, Neven; Thomsen, Peter; Nannmark, Ulf

2012-10-01

Early detection of healing complications after placement of dental implants is a pressing but elusive goal. This paper proposes a non-invasive diagnostic tool for monitoring healing- and peri-implant disease specific genes, complementary to clinical evaluations. Eighteen partially edentulous patients were recruited to this pilot study. Three Brånemark TiUnite® implants/patient (Nobel Biocare) were placed in a one-stage procedure. Abutments with smooth or rough (TiUnite®) surface were placed. The test group (n = 9) received fixed bridges (immediate loading), whereas the control group (n = 9) implants were loaded 3 months after surgery. In addition to clinical measurements, crevicular fluid was collected using paper strips at the implant abutments 2, 14, 28, and 90 days postoperative. mRNA was extracted, purified, and converted to cDNA. Quantitative PCR assays for IL-1β, TNF-α, Osteocalcin (OC), Alkaline Phosphatase (ALP), Cathepsin K, Tartrate Resistant Acid Phosphatase, and 18S ribosomal RNA were designed and validated. Relative gene expression levels were calculated. One implant was lost in the control group and three in the test group. In one test patient, one implant showed lowered stability after 2 to 4 weeks and was unloaded. Later implant stability improved which allowed for loading after 3 to 4 months. TNF-α and ALP most commonly showed correlation with clinical parameters followed by IL-1β and OC. The strongest correlation was found for TNF-α with clinical complications at 2 and 14 days (p = .01/r = -048, and p = .0004/r = -0.56, respectively; test and control groups together). In some cases, gene expression predicted clinical complications (TNF-α, ALP, CK). This study is based on samples from few individuals; still, some genes showed correlation with clinical findings. Further studies are needed to refine and optimize the sampling process, to find the appropriate panel, and to validate gene expression for monitoring implant healing. © 2010 Wiley Periodicals, Inc.

High early growth response 1 (EGR1) expression correlates with resistance to anti-EGFR treatment in vitro and with poorer outcome in metastatic colorectal cancer patients treated with cetuximab.

PubMed

Kumar, S S; Tomita, Y; Wrin, J; Bruhn, M; Swalling, A; Mohammed, M; Price, T J; Hardingham, J E

2017-06-01

Biomarkers, such as mutant RAS, predict resistance to anti-EGFR therapy in only a proportion of patients, and hence, other predictive biomarkers are needed. The aims were to identify candidate genes upregulated in colorectal cancer cell lines resistant to anti-EGFR monoclonal antibody treatment, to knockdown (KD) these genes in the resistant cell lines to determine if sensitivity to anti-EGFR antibody was restored, and finally to perform a pilot correlative study of EGR1 expression and outcomes in a cohort of metastatic colorectal cancer (mCRC) patients given cetuximab therapy. Comparative expression array analysis of resistant cell lines (SW48, COLO-320DM, and SNU-C1) vs sensitive cell lines (LIM1215, CaCo2, and SW948) was performed. The highest up-regulated gene in each resistant cell line was knocked down (KD) using RNA interference, and effect on proliferation was assessed with and without anti-EGFR treatment. Expression of the candidate genes in patients' tumours treated with cetuximab was assessed by immunohistochemistry; survival analyses were performed comparing high vs low expression. Genes significantly upregulated in resistant cell lines were EGR1 (early growth response protein 1), HBEGF (heparin-binding epidermal growth factor-like growth factor), and AKT3 (AKT serine/threonine kinase 3). KD of each gene resulted in the respective cells being more sensitive to anti-EGFR treatment, suggesting that the resistant phenotype was reversed. In the pilot study of mCRC patients treated with cetuximab, both median PFS (1.38 months vs 6.79 months; HR 2.77 95% CI 1.2-19.4) and median OS (2.59 months vs 9.82 months; HR 3.0 95% CI 1.3-23.2) were significantly worse for those patients with high EGR1 expression. High EGR1 expression may be a candidate biomarker of resistance to anti-EGFR therapy.

Analysis of common transforming growth factor beta-1 gene polymorphisms in gastric and duodenal ulcer disease: pilot study.

PubMed

Polonikov, Alexey V; Ivanov, Vladimir P; Belugin, Dmitry A; Khoroshaya, Irina V; Kolchanova, Inessa O; Solodilova, Mariya A; Tutochkina, Margarita P; Stepchenko, Alexander A

2007-04-01

Transforming growth factor-beta1 (TGF-beta1) has been shown to be an important cytokine that plays a role in cell proliferation, differentiation, tissue injury repair and ulcer healing. The purpose of this pilot study was to investigate if common polymorphisms Leu10Pro, Arg25Pro and C-509T within the TGF-beta1 gene are associated with susceptibility to gastric and duodenal ulcer disease in Russians. Blood samples from 377 unrelated patients with gastric and duodenal ulcer disease and 226 sex- and age-matched healthy controls were used to determine TGF-beta1 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Leu10Pro substitution in the signal peptide of TGF-beta1 has been found to be associated with susceptibility to gastric ulcer (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.12-2.77). A genotype combination of 10Leu/Leu x 25Arg/Arg x -509C/C was also associated with susceptibility to gastric ulcer disease (OR 1.81, P = 0.01). In addition, the frequency of a combination of genotypes 10Pro/Pro x 25Arg/Pro x -509C/T was statistically lower in patients with duodenal ulcer than in controls (OR 0.42, P = 0.05). A significant difference (P = 0.04) in the distribution of rare haplotypes of the TGF-beta1 gene between patients with duodenal ulcer and healthy controls has been found. Polymorphism Leu10Pro was in positive linkage disequilibrium with C-509T polymorphism (coefficient D = 0.191; P < 0.0001). These findings indicate that the Leu10Pro and C-509T polymorphisms may be involved in the modulation of expression of the TGF-beta1 gene, and therefore a predisposition to peptic ulcer disease could be linked to particular alleles of this gene. In particular, a possible role of TGF-beta1 in the pathogenesis of gastric ulcer disease is discussed.

Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study

PubMed Central

Trotta, Antonella; Iyegbe, Conrad; Di Forti, Marta; Sham, Pak C.; Campbell, Desmond D.; Cherny, Stacey S.; Mondelli, Valeria; Aitchison, Katherine J.; Murray, Robin M.

2016-01-01

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis. PMID:27648571

From Genomes to Protein Models and Back

NASA Astrophysics Data System (ADS)

Tramontano, Anna; Giorgetti, Alejandro; Orsini, Massimiliano; Raimondo, Domenico

2007-12-01

The alternative splicing mechanism allows genes to generate more than one product. When the splicing events occur within protein coding regions they can modify the biological function of the protein. Alternative splicing has been suggested as one way for explaining the discrepancy between the number of human genes and functional complexity. We analysed the putative structure of the alternatively spliced gene products annotated in the ENCODE pilot project and discovered that many of the potential alternative gene products will be unlikely to produce stable functional proteins.

Adipose Gene Expression Profile Changes With Lung Allograft Reperfusion.

PubMed

Diamond, Joshua M; Arcasoy, Selim; McDonnough, Jamiela A; Sonett, Joshua R; Bacchetta, Matthew; D'Ovidio, Frank; Cantu, Edward; Bermudez, Christian A; McBurnie, Amika; Rushefski, Melanie; Kalman, Laurel H; Oyster, Michelle; D'Errico, Carly; Suzuki, Yoshikazu; Giles, Jon T; Ferrante, Anthony; Lippel, Matthew; Singh, Gopal; Lederer, David J; Christie, Jason D

2017-01-01

Obesity is a risk factor for primary graft dysfunction (PGD), a form of lung injury resulting from ischemia-reperfusion after lung transplantation, but the impact of ischemia-reperfusion on adipose tissue is unknown. We evaluated differential gene expression in thoracic visceral adipose tissue (VAT) before and after lung reperfusion. Total RNA was isolated from thoracic VAT sampled from six subjects enrolled in the Lung Transplant Body Composition study before and after allograft reperfusion and quantified using the Human Gene 2.0 ST array. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment for genes involved in complement and coagulation cascades and Jak-STAT signaling pathways. Overall, 72 genes were upregulated and 56 genes were downregulated in the postreperfusion time compared with baseline. Long pentraxin-3, a gene and plasma protein previously associated with PGD, was the most upregulated gene (19.5-fold increase, p = 0.04). Fibronectin leucine-rich transmembrane protein-3, a gene associated with cell adhesion and receptor signaling, was the most downregulated gene (4.3-fold decrease, p = 0.04). Ischemia-reperfusion has a demonstrable impact on gene expression in visceral adipose tissue in our pilot study of nonobese, non-PGD lung transplant recipients. Future evaluation will focus on differential adipose tissue gene expression and the development of PGD after transplant. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Lessons learned from additional research analyses of unsolved clinical exome cases.

PubMed

Eldomery, Mohammad K; Coban-Akdemir, Zeynep; Harel, Tamar; Rosenfeld, Jill A; Gambin, Tomasz; Stray-Pedersen, Asbjørg; Küry, Sébastien; Mercier, Sandra; Lessel, Davor; Denecke, Jonas; Wiszniewski, Wojciech; Penney, Samantha; Liu, Pengfei; Bi, Weimin; Lalani, Seema R; Schaaf, Christian P; Wangler, Michael F; Bacino, Carlos A; Lewis, Richard Alan; Potocki, Lorraine; Graham, Brett H; Belmont, John W; Scaglia, Fernando; Orange, Jordan S; Jhangiani, Shalini N; Chiang, Theodore; Doddapaneni, Harsha; Hu, Jianhong; Muzny, Donna M; Xia, Fan; Beaudet, Arthur L; Boerwinkle, Eric; Eng, Christine M; Plon, Sharon E; Sutton, V Reid; Gibbs, Richard A; Posey, Jennifer E; Yang, Yaping; Lupski, James R

2017-03-21

Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts.

Functional Mu Opioid Receptor Polymorphism (OPRM1 A118G) Associated With Heroin Use Outcomes in Caucasian Males: A Pilot Study

PubMed Central

Woodcock, Eric A.; Lundahl, Leslie H.; Burmeister, Margit; Greenwald, Mark K.

2017-01-01

Background Heroin’s analgesic, euphoric and dependence-producing effects are primarily mediated by the mu opioid receptor (MOR). A single gene, OPRM1, encodes the MOR. The functional polymorphism A118G, located in exon 1 of the OPRM1 gene, results in anatomically-specific reductions in MOR expression, which may alter an individual’s response to heroin. In prior studies 118G (rare allele) carriers demonstrated significantly greater opioid tolerance, overdose vulnerability, and pain sensitivity than 118AA homozygotes. Those findings suggest OPRM1 genotype may impact characteristics of heroin use. Methods The present pilot study characterized the impact of OPRM1 genotype (rs1799971, 118G allele carriers vs. 118AA homozygotes) on heroin-use phenotypes associated with heroin dependence severity in a sample of male, Caucasian chronic heroin users (n = 86). Results Results indicate that 118G allele carriers reported significantly more heroin use-related consequences and heroin-quit attempts, and were more likely to have sought treatment for their heroin use than 118AA homozygotes. Conclusions These preliminary findings, consistent with extant data, illustrate a role for OPRM1 allelic variation on heroin use characteristics, and provide support for considering genotype in heroin treatment and relapse prevention. PMID:25911999

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer

PubMed Central

Santa-Maria, Cesar August; Kato, Taigo; Park, Jae-Hyun; Kiyotani, Kazuma; Rademaker, Alfred; Shah, Ami N.; Gross, Leeaht; Blanco, Luis Z.; Jain, Sarika; Flaum, Lisa; Tellez, Claudia; Stein, Regina; Uthe, Regina; Gradishar, William J.; Cristofanilli, Massimo; Nakamura, Yusuke; Giles, Francis J.

2018-01-01

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of CD8, granzyme A, and perforin 1 gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, p = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy. PMID:29721177

Antimicrobial peptide gene expression in periodontitis patients: A pilot study.

PubMed

Jourdain, Marie-Laure; Pierrard, Loïc; Kanagaratnam, Lukshe; Velard, Frédéric; Sergheraert, Johan; Lefèvre, Benoît; Gangloff, Sophie C; Braux, Julien

2018-05-01

Antimicrobial peptides (AMPs) are one of the most active components of innate immunity and have characteristics that could place them at the heart of the pathogenesis of periodontal disease. This study investigated differences in the expression of AMP coding genes obtained using a simple harvesting technique, gingival smear, between two groups of patients: chronic periodontitis subjects versus healthy ones. Twenty-three patients were enrolled in two groups: 12 were diagnosed with moderate or severe generalized chronic periodontitis, and 11 were diagnosed as clinically healthy. Gingival smears were retrieved and studied using reverse transcription-quantitative PCR (RT-qPCR) after mRNA purification. Fifteen gene expressions were obtained using real-time RT-qPCR. Three AMP genes, histatin 3 (HTN3), α-defensin 4 (DEFA4) and lysozyme C (LYZ), presented different expression levels in periodontitis patients compared with healthy subjects. The relative expression level of DEFA4 appeared to be a protective factor against periodontitis. Gingival smears studied by RT-qPCR may be used to assess the expression of AMPs coding genes. A lack of expression of DEFA4 could be a potential indicator of periodontitis status. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Statistical aspects of quantitative real-time PCR experiment design.

PubMed

Kitchen, Robert R; Kubista, Mikael; Tichopad, Ales

2010-04-01

Experiments using quantitative real-time PCR to test hypotheses are limited by technical and biological variability; we seek to minimise sources of confounding variability through optimum use of biological and technical replicates. The quality of an experiment design is commonly assessed by calculating its prospective power. Such calculations rely on knowledge of the expected variances of the measurements of each group of samples and the magnitude of the treatment effect; the estimation of which is often uninformed and unreliable. Here we introduce a method that exploits a small pilot study to estimate the biological and technical variances in order to improve the design of a subsequent large experiment. We measure the variance contributions at several 'levels' of the experiment design and provide a means of using this information to predict both the total variance and the prospective power of the assay. A validation of the method is provided through a variance analysis of representative genes in several bovine tissue-types. We also discuss the effect of normalisation to a reference gene in terms of the measured variance components of the gene of interest. Finally, we describe a software implementation of these methods, powerNest, that gives the user the opportunity to input data from a pilot study and interactively modify the design of the assay. The software automatically calculates expected variances, statistical power, and optimal design of the larger experiment. powerNest enables the researcher to minimise the total confounding variance and maximise prospective power for a specified maximum cost for the large study. Copyright 2010 Elsevier Inc. All rights reserved.

Accurate and fast multiple-testing correction in eQTL studies.

PubMed

Sul, Jae Hoon; Raj, Towfique; de Jong, Simone; de Bakker, Paul I W; Raychaudhuri, Soumya; Ophoff, Roel A; Stranger, Barbara E; Eskin, Eleazar; Han, Buhm

2015-06-04

In studies of expression quantitative trait loci (eQTLs), it is of increasing interest to identify eGenes, the genes whose expression levels are associated with variation at a particular genetic variant. Detecting eGenes is important for follow-up analyses and prioritization because genes are the main entities in biological processes. To detect eGenes, one typically focuses on the genetic variant with the minimum p value among all variants in cis with a gene and corrects for multiple testing to obtain a gene-level p value. For performing multiple-testing correction, a permutation test is widely used. Because of growing sample sizes of eQTL studies, however, the permutation test has become a computational bottleneck in eQTL studies. In this paper, we propose an efficient approach for correcting for multiple testing and assess eGene p values by utilizing a multivariate normal distribution. Our approach properly takes into account the linkage-disequilibrium structure among variants, and its time complexity is independent of sample size. By applying our small-sample correction techniques, our method achieves high accuracy in both small and large studies. We have shown that our method consistently produces extremely accurate p values (accuracy > 98%) for three human eQTL datasets with different sample sizes and SNP densities: the Genotype-Tissue Expression pilot dataset, the multi-region brain dataset, and the HapMap 3 dataset. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A pilot-scale study on PVA gel beads based integrated fixed film activated sludge (IFAS) plant for municipal wastewater treatment.

PubMed

Kumar Singh, Nitin; Singh, Jasdeep; Bhatia, Aakansha; Kazmi, A A

2016-01-01

In the present study, a pilot-scale reactor incorporating polyvinyl alcohol gel beads as biomass carrier and operating in biological activated sludge mode (a combination of moving bed biofilm reactor (MBBR) and activated sludge) was investigated for the treatment of actual municipal wastewater. The results, during a monitoring period of 4 months, showed effective removal of chemical oxygen demand (COD), biological oxygen demand (BOD) and NH3-N at optimum conditions with 91%, ∼92% and ∼90% removal efficiencies, respectively. Sludge volume index (SVI) values of activated sludge varied in the range of 25-72 mL/g, indicating appreciable settling characteristics. Furthermore, soluble COD and BOD in the effluent of the pilot plant were reduced to levels well below discharge limits of the Punjab Pollution Control Board, India. A culture dependent method was used to enrich and isolate abundant heterotrophic bacteria in activated sludge. In addition to this, 16S rRNA genes analysis was performed to identify diverse dominant bacterial species in suspended and attached biomass. Results revealed that Escherichia coli, Pseudomonas sp. and Nitrosomonas communis played a significant role in biomass carrier, while Acinetobactor sp. were dominant in activated sludge of the pilot plant. Identification of ciliated protozoa populations rendered six species of ciliates in the plant, among which Vorticella was the most dominant.

Experience of targeted Usher exome sequencing as a clinical test

PubMed Central

Besnard, Thomas; García-García, Gema; Baux, David; Vaché, Christel; Faugère, Valérie; Larrieu, Lise; Léonard, Susana; Millan, Jose M; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

2014-01-01

We show that massively parallel targeted sequencing of 19 genes provides a new and reliable strategy for molecular diagnosis of Usher syndrome (USH) and nonsyndromic deafness, particularly appropriate for these disorders characterized by a high clinical and genetic heterogeneity and a complex structure of several of the genes involved. A series of 71 patients including Usher patients previously screened by Sanger sequencing plus newly referred patients was studied. Ninety-eight percent of the variants previously identified by Sanger sequencing were found by next-generation sequencing (NGS). NGS proved to be efficient as it offers analysis of all relevant genes which is laborious to reach with Sanger sequencing. Among the 13 newly referred Usher patients, both mutations in the same gene were identified in 77% of cases (10 patients) and one candidate pathogenic variant in two additional patients. This work can be considered as pilot for implementing NGS for genetically heterogeneous diseases in clinical service. PMID:24498627

[Advance of genetics and genomics in neurology].

PubMed

Ginter, E K; Illarioshkin, S N

2012-01-01

Studies of genomic background of neurological disorders are very actual in view of their high population prevalence, severe course, serious impact on patients' disability and progressive mental and physical de-adaptation. In the paper, problems of genetic heterogeneity of hereditary neurological disorders and character of the respective genetic burden in the regions of Russian Federation are discussed in detail, a 'dynamic' type of mutations (increase in number of microsatellite repeats copies) attributable to many neurodegenerative diseases is analyzed, and achievements of Russian researchers in the identification of genes for hereditary neurological disorders and in the realization of pilot protocols of gene therapy are presented. Problems related to studies of genetic predisposition to common multifactorial diseases of the nervous system are discussed.

Elastin: a possible genetic biomarker for more severe ligament injuries in elite soccer. A pilot study

PubMed Central

Artells, Rosa; Pruna, Ricard; Dellal, Alexandre; Maffulli, Nicola

2016-01-01

Summary Background The study of new genetic biomarkers in genes related to connective tissue repair and regeneration may help to identify individuals with greater predisposition to injury, who may benefit from targeted preventive measures, and those who require longer recovery time following a muscle, ligament or tendon injury. The present study investigated whether single nucleotide polymorphisms of the Elastin gene could be related to MCL injury. Methods 60 top class football players were studied to identify single nucleotide polymorphisms for the Elastin (ELN) gene using Allelic Discrimination analysis. Each player was followed for 7 seasons, and each MCL injury was noted. Results Ligament injury rate, severity and recovery time are related to specific genotypes observed in the elastin gene, especially the ELN-AA (16 MCL) and the ELN-AG (3 MCL). Players with the ELN-GG genotype sustained no MCL injury during the 7 seasons of the study. Conclusions The identification of polymorphisms in the ELN gene may be used as a novel tool to better define an athlete’s genotype, and help to plan training and rehabilitation programmes to prevent or minimize MCL ligament injuries, and optimize the therapeutic and rehabilitation process after soft tissue injuries, and manage the workloads during trainings and matches. PMID:27900291

Responses of microbial community functional structures to pilot-scale uranium in situ bioremediation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, M.; Wu, W.-M.; Wu, L.

2010-02-15

A pilot-scale field test system with an inner loop nested within an outer loop was constructed for in situ U(VI) bioremediation at a US Department of Energy site, Oak Ridge, TN. The outer loop was used for hydrological protection of the inner loop where ethanol was injected for biostimulation of microorganisms for U(VI) reduction/immobilization. After 2 years of biostimulation with ethanol, U(VI) levels were reduced to below drinking water standard (<30 {micro}gl{sup -1}) in the inner loop monitoring wells. To elucidate the microbial community structure and functions under in situ uranium bioremediation conditions, we used a comprehensive functional gene arraymore » (GeoChip) to examine the microbial functional gene composition of the sediment samples collected from both inner and outer loop wells. Our study results showed that distinct microbial communities were established in the inner loop wells. Also, higher microbial functional gene number, diversity and abundance were observed in the inner loop wells than the outer loop wells. In addition, metal-reducing bacteria, such as Desulfovibrio, Geobacter, Anaeromyxobacter and Shewanella, and other bacteria, for example, Rhodopseudomonas and Pseudomonas, are highly abundant in the inner loop wells. Finally, the richness and abundance of microbial functional genes were highly correlated with the mean travel time of groundwater from the inner loop injection well, pH and sulfate concentration in groundwater. These results suggest that the indigenous microbial communities can be successfully stimulated for U bioremediation in the groundwater ecosystem, and their structure and performance can be manipulated or optimized by adjusting geochemical and hydrological conditions.« less

Oxidative stress and inflammation in retained placenta: a pilot study of protein and gene expression of GPX1 and NFκB.

PubMed

Endler, Margit; Saltvedt, Sissel; Eweida, Mohamed; Åkerud, Helena

2016-12-06

Retained placenta is associated with severe postpartum hemorrhage. Its etiology is unknown and its biochemistry has not been studied. We aimed to assess whether levels of the antioxidative enzyme Glutathione Peroxidase 1 (GPX1) and the transcription factor Nuclear Factor κβ (NFκβ), as markers of oxidative stress and inflammation, were affected in retained placentas compared to spontaneously released placentas from otherwise normal full term pregnancies. In a pilot study we assessed concentrations of GPX1 by ELISA and gene (mRNA) expression of GPX1, NFκβ and its inhibitor Iκβα, by quantitative real-time-PCR in periumbilical and peripheral samples from retained (n = 29) and non-retained (n = 31) placental tissue. Median periumbilical GPX1 concentrations were 13.32 ng/ml in retained placentas and 17.96 ng/ml in non-retained placentas (p = 0.22), peripheral concentrations were 13.27 ng/ml and 19.09 ng/ml (p = 0.08). Retained placental tissue was more likely to have a low GPX1 protein concentration (OR 3.82, p = 0.02 for periumbilical and OR 3.95, p = 0.02 for peripheral samples). Median periumbilical GPX1 gene expressions were 1.13 for retained placentas and 0.88 for non-retained placentas (p = 0.08), peripheral expression was 1.32 and 1.18 (p = 0.46). Gene expressions of NFκβ and Iκβα were not significantly different between retained and non-retained placental tissue. Women with retained placenta were more likely to have a low level of GPX1 protein concentration in placental tissue compared to women without retained placenta and retained placental tissue showed a tendency of lower median concentrations of GPX1 protein expression. This may indicate decreased antioxidative capacity as a component in this disorder but requires a larger sample to corroborate results.

Knowledge-driven genomic interactions: an application in ovarian cancer.

PubMed

Kim, Dokyoon; Li, Ruowang; Dudek, Scott M; Frase, Alex T; Pendergrass, Sarah A; Ritchie, Marylyn D

2014-01-01

Effective cancer clinical outcome prediction for understanding of the mechanism of various types of cancer has been pursued using molecular-based data such as gene expression profiles, an approach that has promise for providing better diagnostics and supporting further therapies. However, clinical outcome prediction based on gene expression profiles varies between independent data sets. Further, single-gene expression outcome prediction is limited for cancer evaluation since genes do not act in isolation, but rather interact with other genes in complex signaling or regulatory networks. In addition, since pathways are more likely to co-operate together, it would be desirable to incorporate expert knowledge to combine pathways in a useful and informative manner. Thus, we propose a novel approach for identifying knowledge-driven genomic interactions and applying it to discover models associated with cancer clinical phenotypes using grammatical evolution neural networks (GENN). In order to demonstrate the utility of the proposed approach, an ovarian cancer data from the Cancer Genome Atlas (TCGA) was used for predicting clinical stage as a pilot project. We identified knowledge-driven genomic interactions associated with cancer stage from single knowledge bases such as sources of pathway-pathway interaction, but also knowledge-driven genomic interactions across different sets of knowledge bases such as pathway-protein family interactions by integrating different types of information. Notably, an integration model from different sources of biological knowledge achieved 78.82% balanced accuracy and outperformed the top models with gene expression or single knowledge-based data types alone. Furthermore, the results from the models are more interpretable because they are framed in the context of specific biological pathways or other expert knowledge. The success of the pilot study we have presented herein will allow us to pursue further identification of models predictive of clinical cancer survival and recurrence. Understanding the underlying tumorigenesis and progression in ovarian cancer through the global view of interactions within/between different biological knowledge sources has the potential for providing more effective screening strategies and therapeutic targets for many types of cancer.

In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: pilot results from the Aragon Workers Health Study.

PubMed

Riffo-Campos, Angela L; Fuentes-Trillo, Azahara; Tang, Wan Y; Soriano, Zoraida; De Marco, Griselda; Rentero-Garrido, Pilar; Adam-Felici, Victoria; Lendinez-Tortajada, Veronica; Francesconi, Kevin; Goessler, Walter; Ladd-Acosta, Christine; Leon-Latre, Montse; Casasnovas, Jose A; Chaves, F Javier; Navas-Acien, Ana; Guallar, Eliseo; Tellez-Plaza, Maria

2018-06-05

We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010-2013 (follow-up visit). The median metal levels were 7.36 µg g -1 , 0.33 µg g -1 , 0.11 µg g -1 and 0.07 µg g -1 , for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson's r = 0.27; p = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes ( p < 0.001). Pathway enrichment analysis of atherosclerosis-DMR genes showed a role in inflammatory, metabolic and transport pathways. In in silico protein-to-protein interaction networks among proteins encoded by 162 and 108 genes attributed to atherosclerosis- and metal-DMRs, respectively, with proteins known to have a role in atherosclerosis pathways, we observed hub proteins in the network associated with both atherosclerosis and metal-DMRs (e.g. SMAD3 and NOP56 ), and also hub proteins associated with metal-DMRs only but with relevant connections with atherosclerosis effectors (e.g. SSTR5 , HDAC4 , AP2A2 , CXCL12 and SSTR4 ). Our integrative in silico analysis demonstrates the feasibility of identifying epigenomic regions linked to environmental exposures and potentially involved in relevant pathways for human diseases. While our results support the hypothesis that metal exposures can influence health due to epigenetic changes, larger studies are needed to confirm our pilot results.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'. © 2018 The Author(s).

Association between the Peroxisome proliferator-activated receptor-gamma Pro12Ala Variant and Haplotype and Pancreatic Cancer in a High-Risk Cohort of Smokers: A Pilot Study

PubMed Central

Fesinmeyer, Megan Dann; Stanford, Janet L.; Brentnall, Teresa A.; Mandelson, Margaret T.; Farin, Federico M.; Srinouanprachanh, Sengkeo; Afsharinejad, Zahra; Goodman, Gary E.; Barnett, Matt J.; Austin, Melissa A.

2010-01-01

Objectives The Pro12Ala variant in the proliferator-activated receptor-gamma (PPARG) gene has been associated with diabetes and several cancers. This pilot study tested for the association between Pro12Ala and pancreatic cancer risk in a high-risk sample of smokers. Methods A nested case-control study was conducted in 83 incident cases of pancreatic cancer and 166 matched controls originally recruited into a cohort chemoprevention study of lung cancer. Associations between Pro12Ala and pancreatic cancer risk were measured using conditional logistic regression. Results Carriers of the G allele (Ala) of the Pro12Ala variant had a borderline increased relative risk of pancreatic cancer compared to homozygous carriers of the C allele (Pro), with an odds ratio (OR) of 1.79 (95% confidence interval (CI): 0.96–3.33, p-value: 0.06). Among subjects randomized to high-dose vitamin A, the OR was 2.80 (95: CI: 1.16–6.74, p-value 0.02) versus 1.20 (95% CI: 0.45–3.23, p-value 0.71) in the placebo group. A haplotype including Pro12Ala was also significantly associated with pancreatic cancer risk in all subjects and in subjects randomized to vitamin A. Conclusions This analysis presents the first evidence that PPARG may be associated with pancreatic cancer risk, and this candidate gene should be investigated in future, larger studies. PMID:19436234

Underbody Blast Models of TBI Caused by Hyper-Acceleration and Secondary Head Impact

DTIC Science & Technology

2016-02-01

discovery rate (FDR), which controls for the expected proportion of false rejected hypotheses. ANOVA was performed to evaluate the significance in gene...acceleration/deceleration11,27 and blast4,13 have also been designed for the purpose of evaluating coup-contrecoup and blast wave energies potentially... evaluation of different angles/ locations of the projectile impact to the surface of the rat head. Finally, pilot studies were conducted to provide further

Behavior of tetracycline and sulfamethazine with corresponding resistance genes from swine wastewater in pilot-scale constructed wetlands.

PubMed

Liu, Lin; Liu, Yu-Hong; Wang, Zhen; Liu, Chao-Xiang; Huang, Xu; Zhu, Ge-Fu

2014-08-15

Four pilot-scale constructed wetlands (free water surface, SF; horizontal subsurface flow, HSF; vertical subsurface flows with different water level, VSF-L and VSF-H) were operated to assess their ability to remove sulfamethazine (SMZ) and tetracycline (TC) from wastewaters, and to investigate the abundance level of corresponding resistance genes (sulI, sulII, tetM, tetW and tetO) in the CWs. The results indicated that CWs could significantly reduce the concentration of antibiotics in wastewater, and the mass removal rate range of SMZ and TC were respectively 11%-95% and 85%-95% in the four systems on the basis of hydraulic equilibrium; further relatively high removal rate was observed in VSF with low water level. Seasonal condition had a significant effect on SMZ removal in the CWs (especially SMZ in SF), but TC removal in VSFs were not considered to have statistically significant differences in winter and summer. At the end period, the relative abundances of target genes in the CWs showed obvious increases compared to initial levels, ranging from 2.98 × 10(-5) to 1.27 × 10(-1) for sul genes and 4.68 × 10(-6) to 1.54 × 10(-1) for tet genes after treatment, and those abundances showed close relation to both characteristic of wastewater and configuration of CWs. Copyright © 2014 Elsevier B.V. All rights reserved.

Lymphotoxin-Alpha Gene Polymorphism +252A/G (rs909253, A/G) Is Associated with Susceptibility to Chronic Periodontitis: A Pilot Study

PubMed Central

Vasconcelos, Daniel Fernando Pereira; da Silva, Marco Antônio Dias; Marques, Marcelo Rocha; de Brito Júnior, Rui Barbosa; Vasconcelos, Any Carolina Cardoso Guimarães; Barros, Silvana Pereira

2012-01-01

Background. Periodontal disease leading to clinical findings such as increased periodontal probing depth involves a complex interaction between invading pathogenic microorganisms and the patient's immune system. Lymphotoxin alpha (LT-α) is a potent multifunctional immune modulator that contributes toward susceptibility to immune regulation disorders, including periodontal disease. Objective. In this study, we tested the hypothesis that chronic periodontitis (CP) is associated with polymorphisms of the LT-α gene. Materials and Methods. A total of 126 subjects, 44 healthy subjects, and 82 subjects with CP, were evaluated for periodontal disease by measuring clinical attachment loss and separation. Samples of epithelial cells were obtained for DNA analysis by scraping of the buccal mucosa. The LT-α gene was analyzed by polymerase chain reaction followed by endonuclease digestion with NcoI to analyze restriction fragment length polymorphisms. Results. The LT-α gene (+252A/G) polymorphism was associated with CP. LT-α allele frequencies were significantly different (P = 0.0019) between patients with CP and healthy individuals, with an odds ratio of 2.67 for patients with CP with the G allele. Conclusions. These findings suggest the LT-α gene genotype is a risk indicator for susceptibility to chronic periodontal disease in the Brazilian population studied. PMID:23050158

Gene expression analysis of whole blood, peripheral blood mononuclear cells, and lymphoblastoid cell lines from the Framingham Heart Study

PubMed Central

Joehanes, Roby; Johnson, Andrew D.; Barb, Jennifer J.; Raghavachari, Nalini; Liu, Poching; Woodhouse, Kimberly A.; O'Donnell, Christopher J.; Munson, Peter J.

2012-01-01

Despite a growing number of reports of gene expression analysis from blood-derived RNA sources, there have been few systematic comparisons of various RNA sources in transcriptomic analysis or for biomarker discovery in the context of cardiovascular disease (CVD). As a pilot study of the Systems Approach to Biomarker Research (SABRe) in CVD Initiative, this investigation used Affymetrix Exon arrays to characterize gene expression of three blood-derived RNA sources: lymphoblastoid cell lines (LCL), whole blood using PAXgene tubes (PAX), and peripheral blood mononuclear cells (PBMC). Their performance was compared in relation to identifying transcript associations with sex and CVD risk factors, such as age, high-density lipoprotein, and smoking status, and the differential blood cell count. We also identified a set of exons that vary substantially between participants, but consistently in each RNA source. Such exons are thus stable phenotypes of the participant and may potentially become useful fingerprinting biomarkers. In agreement with previous studies, we found that each of the RNA sources is distinct. Unlike PAX and PBMC, LCL gene expression showed little association with the differential blood count. LCL, however, was able to detect two genes related to smoking status. PAX and PBMC identified Y-chromosome probe sets similarly and slightly better than LCL. PMID:22045913

Smoking, but not malnutrition, influences promoter-specific DNA methylation of the proopiomelanocortin gene in patients with and without anorexia nervosa.

PubMed

Ehrlich, Stefan; Walton, Esther; Roffman, Joshua L; Weiss, Deike; Puls, Imke; Doehler, Nico; Burghardt, Roland; Lehmkuhl, Ulrike; Hillemacher, Thomas; Muschler, Marc; Frieling, Helge

2012-03-01

Our pilot study evaluates the impact of environmental factors, such as nutrition and smoking status, on epigenetic patterns in a disease-associated gene. We measured the effects of malnutrition and cigarette smoking on proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients with and without anorexia nervosa (AN). POMC and its derived peptides (alpha melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in stress and feeding response. Promoter-specific DNA methylation of the POMC gene was determined in peripheral blood mononuclear cells of 54 healthy female control subjects, 40 underweight patients with AN, and 21 weight-restored patients with AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin. POMC promoter-specific DNA methylation was not affected by diagnosis or nutritional status but significantly negatively associated with cigarette smoking. Although malnutrition may be expected to reduce DNA methylation through its effects on one-carbon metabolism, our negative results are in line with several in vitro and clinical studies that did not show a direct relation between gene-specific DNA methylation and folate levels. In contrast, smoking has been repeatedly reported to alter DNA methylation of specific genes and should be controlled for in future epigenetic studies.

Functional Study of Genes Essential for Autogamy and Nuclear Reorganization in Paramecium▿§

PubMed Central

Nowak, Jacek K.; Gromadka, Robert; Juszczuk, Marek; Jerka-Dziadosz, Maria; Maliszewska, Kamila; Mucchielli, Marie-Hélène; Gout, Jean-François; Arnaiz, Olivier; Agier, Nicolas; Tang, Thomas; Aggerbeck, Lawrence P.; Cohen, Jean; Delacroix, Hervé; Sperling, Linda; Herbert, Christopher J.; Zagulski, Marek; Bétermier, Mireille

2011-01-01

Like all ciliates, Paramecium tetraurelia is a unicellular eukaryote that harbors two kinds of nuclei within its cytoplasm. At each sexual cycle, a new somatic macronucleus (MAC) develops from the germ line micronucleus (MIC) through a sequence of complex events, which includes meiosis, karyogamy, and assembly of the MAC genome from MIC sequences. The latter process involves developmentally programmed genome rearrangements controlled by noncoding RNAs and a specialized RNA interference machinery. We describe our first attempts to identify genes and biological processes that contribute to the progression of the sexual cycle. Given the high percentage of unknown genes annotated in the P. tetraurelia genome, we applied a global strategy to monitor gene expression profiles during autogamy, a self-fertilization process. We focused this pilot study on the genes carried by the largest somatic chromosome and designed dedicated DNA arrays covering 484 genes from this chromosome (1.2% of all genes annotated in the genome). Transcriptome analysis revealed four major patterns of gene expression, including two successive waves of gene induction. Functional analysis of 15 upregulated genes revealed four that are essential for vegetative growth, one of which is involved in the maintenance of MAC integrity and another in cell division or membrane trafficking. Two additional genes, encoding a MIC-specific protein and a putative RNA helicase localizing to the old and then to the new MAC, are specifically required during sexual processes. Our work provides a proof of principle that genes essential for meiosis and nuclear reorganization can be uncovered following genome-wide transcriptome analysis. PMID:21257794

Effects of Lifestyle Modification on Telomerase Gene Expression in Hypertensive Patients: A Pilot Trial of Stress Reduction and Health Education Programs in African Americans.

PubMed

Duraimani, Shanthi; Schneider, Robert H; Randall, Otelio S; Nidich, Sanford I; Xu, Shichen; Ketete, Muluemebet; Rainforth, Maxwell A; Gaylord-King, Carolyn; Salerno, John W; Fagan, John

2015-01-01

African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans. Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes. Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors. In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP observed in this high-risk population suggest hypotheses that telomerase gene expression may either be a biomarker for reduced BP or a mechanism by which stress reduction and lifestyle modification reduces BP. ClinicalTrials.gov NCT00681200.

Effects of Lifestyle Modification on Telomerase Gene Expression in Hypertensive Patients: A Pilot Trial of Stress Reduction and Health Education Programs in African Americans

PubMed Central

Duraimani, Shanthi; Schneider, Robert H.; Randall, Otelio S.; Nidich, Sanford I.; Xu, Shichen; Ketete, Muluemebet; Rainforth, Maxwell A.; Gaylord-King, Carolyn; Salerno, John W.; Fagan, John

2015-01-01

Background African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans. Methods Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes. Results Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors. Conclusion In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP observed in this high-risk population suggest hypotheses that telomerase gene expression may either be a biomarker for reduced BP or a mechanism by which stress reduction and lifestyle modification reduces BP. Trial Registration ClinicalTrials.gov NCT00681200 PMID:26571023

Results of a pilot study using self-collected mid-turbinate nasal swabs for detection of influenza virus infection among pregnant women.

PubMed

Thompson, Mark G; Ferber, Jeannette R; Odouli, Roxana; David, Donna; Shifflett, Pat; Meece, Jennifer K; Naleway, Allison L; Bozeman, Sam; Spencer, Sarah M; Fry, Alicia M; Li, De-Kun

2015-05-01

We evaluated the feasibility of asking pregnant women to self-collect and ship respiratory specimens. In a preliminary laboratory study, we compared the RT-PCR cycle threshold (CT) values of influenza A and B viruses incubated at 4 storage temperatures (from 4 to 35°C) for 6 time periods (8, 24, 48, 72, and 168 hours and 30 days), resulting in 24 conditions that were compared to an aliquot tested after standard freezing (-20°C) (baseline condition). In a subsequent pilot study, during January-February, 2014, we delivered respiratory specimen collection kits to 53 pregnant women with a medically attended acute respiratory illness using three delivery methods. CT values were stable after storage at temperatures <27°C for up to 72 hours for influenza A viruses and 48 hours for influenza B viruses. Of 53 women who received kits during the pilot, 89% collected and shipped nasal swabs as requested. However, 30% (14/47) of the women took over 2 days to collect and ship their specimen. The human control gene, ribonuclease P (RNase P), was detected in 100% of nasal swab specimens. However, the mean CT values for RNase P (26.5, 95% confidence interval [CI] = 26.0-27.1) and for the 8 influenza A virus positives in our pilot (32.2, 95% CI = 28.9-35.5) were significantly higher than the CTs observed in our 2010-2012 study using staff-collected nasal pharyngeal swabs (P-values < 0.01). Self-collection of respiratory specimens is a promising research method, but further research is needed to quantify the sensitivity and specificity of the approach. © 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Spaceflight modulates gene expression in the whole blood of astronauts.

PubMed

Barrila, Jennifer; Ott, C Mark; LeBlanc, Carly; Mehta, Satish K; Crabbé, Aurélie; Stafford, Phillip; Pierson, Duane L; Nickerson, Cheryl A

2016-01-01

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1 , HSP27 , GPX1 , XRCC1 , BAG-1 , HHR23A , FAP48 , and C-FOS . No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

Spaceflight modulates gene expression in the whole blood of astronauts

PubMed Central

Barrila, Jennifer; Ott, C Mark; LeBlanc, Carly; Mehta, Satish K; Crabbé, Aurélie; Stafford, Phillip; Pierson, Duane L; Nickerson, Cheryl A

2016-01-01

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight. PMID:28725744

Fatigue-Related Gene Networks Identified in CD14+ Cells Isolated From HIV-Infected Patients—Part I: Research Findings

PubMed Central

Voss, Joachim G.; Dobra, Adrian; Morse, Caryn; Kovacs, Joseph A.; Danner, Robert L.; Munson, Peter J.; Logan, Carolea; Rangel, Zoila; Adelsberger, Joseph W.; McLaughlin, Mary; Adams, Larry D.; Raju, Raghavan; Dalakas, Marinos C.

2016-01-01

Purpose Human immunodeficiency virus (HIV)–related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). Methodology The authors compared gene expression profiles of CD14+ cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. Relevance for nursing practice Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14+ cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients. Implication for Practice The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction. PMID:23324479

Influence of Serotonin Transporter SLC6A4 Genotype on the Effect of Psychosocial Stress on Cognitive Performance: An Exploratory Pilot Study.

PubMed

Beversdorf, David Q; Carpenter, Allen L; Alexander, Jessica K; Jenkins, Neil T; Tilley, Michael R; White, Catherine A; Hillier, Ashleigh J; Smith, Ryan M; Gu, Howard H

2018-06-01

Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams. In this exploratory pilot study, 28 healthy young adults were genotyped for long (L)-allele versus S-allele promoter region polymorphism of the 5-HTT gene, SLC6A4. Participants solved anagrams during the Trier Social Stress Test, which included public speaking and mental arithmetic stressors. We compared the participants' cognitive response to stress across genotypes. A Gene×Stress interaction effect was observed in this small sample. Comparisons revealed that participants with at least one S-allele performed worse during the Stress condition. Genetic susceptibility to stress conferred by SLC6A4 appeared to modulate unconstrained cognitive flexibility during psychosocial stress in this exploratory sample. If confirmed, this finding may have implications for conditions associated with increased stress response, including performance anxiety and cocaine withdrawal. Future work is needed both to confirm our findings with a larger sample and to explore the mechanisms of this proposed effect.

Association of ACE, VEGF and CCL2 gene polymorphisms with Henoch-Schönlein purpura and an evaluation of the possible interaction effects of these loci in HSP patients.

PubMed

Mohammadian, Tahereh; Bonyadi, Mortaza; Nabat, Elahe; Rafeey, Mandana

2017-07-01

Henoch-Schönlein purpura (HSP) is a multisystem, small vessel, leucocytoclastic vasculitis. It is predominantly a childhood vasculitis, rarely reported in adults. Studies have shown that several different genetic factors such as genes involved in inflammatory system and renin-angiotensin system (RAS) are important in the pathogenesis of Henoch-Schönlein purpura. The purpose of this study was to evaluate the independent effect of 3 gene polymorphisms including CCL2-2518 C/T, VEGF-634G/C and ACE(I/D) with HSP disease and their possible joint interactions in developing the disease. In this case-control study 47 HSP cases and 74 unrelated healthy controls were enrolled for evaluation. All individuals were genotyped for CCL2-2518C/T, VEGF-634G/C and ACE(I/D) gene polymorphisms. The possible association of these polymorphisms with susceptibility to develop HSP disease independently and in different joint combinations was evaluated. The frequencies of TT genotype and T allele of CCL2-2518C/T gene polymorphism and CC genotype and C allele of VEGF-634G/C gene polymorphism were significantly high in HSP children (p-values = 0.005 and = 0.007 respectively). Interestingly, studying the joint interaction of these 2 genotypes (CC genotype of VEGF G-634C and TT genotype of CCL2 C-2518T) in this cohort showed a more significant effect in the development of the disease (p < 0.000, OR = 6.009). The frequency of TT genotype of CCL2 gene when combined with II genotype of ACE gene in HSP children was significantly higher (p < 0.000, OR = 4.213). The results of this pilot study provide evidence of the possible gene-gene interaction effects of CCL2, VEGF and ACE genes in developing HSP disease.

Toward an Understanding of Changes in Diversity Associated with Fecal Microbiome Transplantation Based on 16S rRNA Gene Deep Sequencing

PubMed Central

Shahinas, Dea; Silverman, Michael; Sittler, Taylor; Chiu, Charles; Kim, Peter; Allen-Vercoe, Emma; Weese, Scott; Wong, Andrew; Low, Donald E.; Pillai, Dylan R.

2012-01-01

ABSTRACT Fecal microbiome transplantation by low-volume enema is an effective, safe, and inexpensive alternative to antibiotic therapy for patients with chronic relapsing Clostridium difficile infection (CDI). We explored the microbial diversity of pre- and posttransplant stool specimens from CDI patients (n = 6) using deep sequencing of the 16S rRNA gene. While interindividual variability in microbiota change occurs with fecal transplantation and vancomycin exposure, in this pilot study we note that clinical cure of CDI is associated with an increase in diversity and richness. Genus- and species-level analysis may reveal a cocktail of microorganisms or products thereof that will ultimately be used as a probiotic to treat CDI. PMID:23093385

Analysis of host response to bacterial infection using error model based gene expression microarray experiments

PubMed Central

Stekel, Dov J.; Sarti, Donatella; Trevino, Victor; Zhang, Lihong; Salmon, Mike; Buckley, Chris D.; Stevens, Mark; Pallen, Mark J.; Penn, Charles; Falciani, Francesco

2005-01-01

A key step in the analysis of microarray data is the selection of genes that are differentially expressed. Ideally, such experiments should be properly replicated in order to infer both technical and biological variability, and the data should be subjected to rigorous hypothesis tests to identify the differentially expressed genes. However, in microarray experiments involving the analysis of very large numbers of biological samples, replication is not always practical. Therefore, there is a need for a method to select differentially expressed genes in a rational way from insufficiently replicated data. In this paper, we describe a simple method that uses bootstrapping to generate an error model from a replicated pilot study that can be used to identify differentially expressed genes in subsequent large-scale studies on the same platform, but in which there may be no replicated arrays. The method builds a stratified error model that includes array-to-array variability, feature-to-feature variability and the dependence of error on signal intensity. We apply this model to the characterization of the host response in a model of bacterial infection of human intestinal epithelial cells. We demonstrate the effectiveness of error model based microarray experiments and propose this as a general strategy for a microarray-based screening of large collections of biological samples. PMID:15800204

Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy.

PubMed

Michel, S; Busato, F; Genuneit, J; Pekkanen, J; Dalphin, J-C; Riedler, J; Mazaleyrat, N; Weber, J; Karvonen, A M; Hirvonen, M-R; Braun-Fahrländer, C; Lauener, R; von Mutius, E; Kabesch, M; Tost, J

2013-03-01

Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases. We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3, and RUNX3) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon-Mann-Whitney tests. In cord blood, regions in ORMDL1 and STAT6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD50 and IL13 were hypermethylated (lowest P-value (STAT6) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P-value (IL13) = 1.57*10(-8)). Interestingly, these differences clustered in the genes highly associated with asthma (ORMDL family) and IgE regulation (RAD50, IL13, and IL4), but not in the T-regulatory genes (FOXP3, RUNX3). In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma- and allergy-related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Development of a Web-based Family Intervention for BRCA Carriers and Their Biological Relatives: Acceptability, Feasibility, and Usability Study.

PubMed

Katapodi, Maria C; Jung, Miyeon; Schafenacker, Ann M; Milliron, Kara J; Mendelsohn-Victor, Kari E; Merajver, Sofia D; Northouse, Laurel L

2018-04-13

Carriers of breast cancer gene (BRCA) mutations are asked to communicate genetic test results to their biological relatives to increase awareness of cancer risk and promote use of genetic services. This process is highly variable from family to family. Interventions that support communication of genetic test results, coping, and offer decision support in families harboring a pathogenic variant may contribute to effective management of hereditary cancer. The aim of this paper was to describe the development of the Family Gene Toolkit, a Web-based intervention targeting BRCA carriers and untested blood relatives, designed to enhance coping, family communication, and decision making. We present findings from focus groups regarding intervention acceptability and participant satisfaction and from a pre-post pilot study with random allocation to a wait-listed control group regarding intervention feasibility and usability. The Family Gene Toolkit was developed by a multidisciplinary team as a psycho-educational and skills-building intervention. It includes two live webinar sessions and a follow-up phone call guided by a certified genetic counselor and a master's prepared oncology nurse. Each live webinar includes two modules (total four modules) presenting information about BRCA mutations, a decision aid for genetic testing, and two skill-building modules for effective coping and family communication. Participants in focus groups (n=11) were highly satisfied with the intervention, reporting it to be useful and describing clearly the important issues. From the 12 dyads recruited in the pre-post pilot study (response rate 12/52, 23%), completion rate was 71% (10/14) for intervention and 40% (4/10) for wait-listed control groups. Acceptability and satisfaction with the Family Gene Toolkit is high. On the basis of the findings from usability and feasibility testing, modifications on timing, delivery mode, and recruitment methods have been implemented. ClinicalTrials.gov NCT02154633; https://clinicaltrials.gov/ct2/show/NCT02154633 (Archived by WebCite at http://www.webcitation.org/6yYNvLPjv). ©Maria C Katapodi, Miyeon Jung, Ann M Schafenacker, Kara J Milliron, Kari E Mendelsohn-Victor, Sofia D Merajver, Laurel L Northouse. Originally published in JMIR Cancer (http://cancer.jmir.org), 13.04.2018.

Rejuvenation of Gene Expression Pattern of Aged Human Skin by Broadband Light Treatment: A Pilot Study

PubMed Central

Chang, Anne Lynn S; Bitter, Patrick H; Qu, Kun; Lin, Meihong; Rapicavoli, Nicole A; Chang, Howard Y

2013-01-01

Studies in model organisms suggest that aged cells can be functionally rejuvenated, but whether this concept applies to human skin is unclear. Here we apply 3′-end sequencing for expression quantification (“3-seq”) to discover the gene expression program associated with human photoaging and intrinsic skin aging (collectively termed “skin aging”), and the impact of broadband light (BBL) treatment. We find that skin aging was associated with a significantly altered expression level of 2,265 coding and noncoding RNAs, of which 1,293 became “rejuvenated” after BBL treatment; i.e., they became more similar to their expression level in youthful skin. Rejuvenated genes (RGs) included several known key regulators of organismal longevity and their proximal long noncoding RNAs. Skin aging is not associated with systematic changes in 3′-end mRNA processing. Hence, BBL treatment can restore gene expression pattern of photoaged and intrinsically aged human skin to resemble young skin. In addition, our data reveal, to our knowledge, a previously unreported set of targets that may lead to new insights into the human skin aging process. PMID:22931923

Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer’s Disease patients: A pilot study

PubMed Central

González-Castañeda, Rocío E.; Sánchez-González, Víctor J.; Flores-Soto, Mario; Vázquez-Camacho, Gonzalo; Macías-Islas, Miguel A.; Ortiz, Genaro G.

2013-01-01

Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer’s Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels. PMID:23569405

Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome.

PubMed

Massingham, Lauren J; Johnson, Kirby L; Scholl, Thomas M; Slonim, Donna K; Wick, Heather C; Bianchi, Diana W

2014-09-01

Turner syndrome is a sex chromosome aneuploidy with characteristic malformations. Amniotic fluid, a complex biological material, could contribute to the understanding of Turner syndrome pathogenesis. In this pilot study, global gene expression analysis of cell-free RNA in amniotic fluid supernatant was utilized to identify specific genes/organ systems that may play a role in Turner syndrome pathophysiology. Cell-free RNA from amniotic fluid of five mid-trimester Turner syndrome fetuses and five euploid female fetuses matched for gestational age was extracted, amplified, and hybridized onto Affymetrix(®) U133 Plus 2.0 arrays. Significantly differentially regulated genes were identified using paired t tests. Biological interpretation was performed using Ingenuity Pathway Analysis and BioGPS gene expression atlas. There were 470 statistically significantly differentially expressed genes identified. They were widely distributed across the genome. XIST was significantly down-regulated (p < 0.0001); SHOX was not differentially expressed. One of the most highly represented organ systems was the hematologic/immune system, distinguishing the Turner syndrome transcriptome from other aneuploidies we previously studied. Manual curation of the differentially expressed gene list identified genes of possible pathologic significance, including NFATC3, IGFBP5, and LDLR. Transcriptomic differences in the amniotic fluid of Turner syndrome fetuses are due to genome-wide dysregulation. The hematologic/immune system differences may play a role in early-onset autoimmune dysfunction. Other genes identified with possible pathologic significance are associated with cardiac and skeletal systems, which are known to be affected in females with Turner syndrome. The discovery-driven approach described here may be useful in elucidating novel mechanisms of disease in Turner syndrome.

Novel approaches to global mining of aberrantly methylated promoter sites in squamous head and neck cancer.

PubMed

Worsham, Maria J; Chen, Kang Mei; Stephen, Josena K; Havard, Shaleta; Benninger, Michael S

2010-07-01

Promoter hypermethylation is emerging as a promising molecular strategy for early detection of cancer. We examined promoter methylation status of 1143 cancer-associated genes to perform a global but unbiased inspection of methylated regions in head and neck squamous cell carcinoma (HNSCC). Laboratory-based study. Integrated health care system. Five samples, two frozen primary HNSCC biopsies and three HNSCC cell lines, were examined. Whole genomic DNA was interrogated using a combination of DNA immunoprecipitation (IP) and Affymetrix whole-genome tiling arrays. Of the 1143 unique cancer genes on the array, 265 were recorded across five samples. Of the 265 genes, 55 were present in all five samples, and 36 were common to four of five samples, 46 to three of five, 56 to two of five, and 72 to one of five samples. Hypermethylated genes in the five samples were cross-examined against those in PubMeth, a cancer methylation database combining text mining and expert annotation (http://www.pubmeth.org). Of the 441 genes in PubMeth, only 33 are referenced to HNSCC. We matched 34 genes in our samples to the 441 genes in the PubMeth database. Of the 34 genes, eight are reported in PubMeth as HNSCC associated. This pilot study examined the contribution of global DNA hypermethylation to the pathogenesis of HNSCC. The whole-genome methylation approach indicated 231 new genes with methylated promoter regions not yet reported in HNSCC. Examination of this comprehensive gene panel in a larger HNSCC cohort should advance selection of HNSCC-specific candidate genes for further validation as biomarkers in HNSCC. 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Modification of the association between early adversity and obsessive-compulsive disorder by polymorphisms in the MAOA, MAOB and COMT genes.

PubMed

McGregor, N W; Hemmings, S M J; Erdman, L; Calmarza-Font, I; Stein, D J; Lochner, C

2016-12-30

The monoamine oxidases (MAOA/B) and catechol-O-methyltransferase (COMT) enzymes break down regulatory components within serotonin and dopamine pathways, and polymorphisms within these genes are candidates for OCD susceptibility. Childhood trauma has been linked OCD psychopathology, but little attention has been paid to the interactions between genes and environment in OCD aetiology. This pilot study investigated gene-by-environment interactions between childhood trauma and polymorphisms in the MAOA, MAOB and COMT genes in OCD. Ten polymorphisms (MAOA: 3 variants, MAOB: 4 variants, COMT: 3 variants) were genotyped in a cohort of OCD patients and controls. Early-life trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Gene-by-gene (GxG) and gene-by-environment interactions (GxE) of the variants and childhood trauma were assessed using logistic regression models. Significant GxG interactions were found between rs362204 (COMT) and two independent polymorphisms in the MAOB gene (rs1799836 and rs6651806). Haplotype associations for OCD susceptibility were found for MAOB. Investigation of GxE interactions indicated that the sexual abuse sub-category was significantly associated with all three genes in haplotype x environment interaction analyses. Preliminary findings indicate that polymorphisms within the MAOB and COMT genes interact resulting in risk for OCD. Childhood trauma interacts with haplotypes in COMT, MAOA and MAOB, increasing risk for OCD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

SHOX gene is expressed in vertebral body growth plates in idiopathic and congenital scoliosis: implications for the etiology of scoliosis in Turner syndrome.

PubMed

Day, Gregory; Szvetko, Attila; Griffiths, Lyn; McPhee, I Bruce; Tuffley, John; LaBrom, Robert; Askin, Geoffrey; Woodland, Peter; McClosky, Eamonn; Torode, Ian; Tomlinson, Francis

2009-06-01

Reduced SHOX gene expression has been demonstrated to be associated with all skeletal abnormalities in Turner syndrome, other than scoliosis (and kyphosis). There is evidence to suggest that Turner syndrome scoliosis is clinically and radiologically similar to idiopathic scoliosis, although the phenotypes are dissimilar. This pilot gene expression study used relative quantitative real-time PCR (qRT-PCR) of the SHOX (short stature on X) gene to determine whether it is expressed in vertebral body growth plates in idiopathic and congenital scoliosis. After vertebral growth plate dissection, tissue was examined histologically and RNA was extracted and its integrity was assessed using a Bio-Spec Mini, NanoDrop ND-1000 spectrophotometer and standard denaturing gel electrophoresis. Following cDNA synthesis, gene-specific optimization in a Corbett RotorGene 6000 real-time cycler was followed by qRT-PCR of vertebral tissue. Histological examination of vertebral samples confirmed that only growth plate was analyzed for gene expression. Cycling and melt curves were resolved in triplicate for all samples. SHOX abundance was demonstrated in congenital and idiopathic scoliosis vertebral body growth plates. SHOX expression was 11-fold greater in idiopathic compared to congenital (n = 3) scoliosis (p = 0.027). This study confirmed that SHOX was expressed in vertebral body growth plates, which implies that its expression may also be associated with the scoliosis (and kyphosis) of Turner syndrome. SHOX expression is reduced in Turner syndrome (short stature). In this study, increased SHOX expression was demonstrated in idiopathic scoliosis (tall stature) and congenital scoliosis. Copyright 2008 Orthopaedic Research Society

Preemptive Pharmacogenomic Testing for Precision Medicine

PubMed Central

Ji, Yuan; Skierka, Jennifer M.; Blommel, Joseph H.; Moore, Brenda E.; VanCuyk, Douglas L.; Bruflat, Jamie K.; Peterson, Lisa M.; Veldhuizen, Tamra L.; Fadra, Numrah; Peterson, Sandra E.; Lagerstedt, Susan A.; Train, Laura J.; Baudhuin, Linnea M.; Klee, Eric W.; Ferber, Matthew J.; Bielinski, Suzette J.; Caraballo, Pedro J.; Weinshilboum, Richard M.; Black, John L.

2017-01-01

Significant barriers, such as lack of professional guidelines, specialized training for interpretation of pharmacogenomics (PGx) data, and insufficient evidence to support clinical utility, prevent preemptive PGx testing from being widely clinically implemented. The current study, as a pilot project for the Right Drug, Right Dose, Right Time–Using Genomic Data to Individualize Treatment Protocol, was designed to evaluate the impact of preemptive PGx and to optimize the workflow in the clinic setting. We used an 84-gene next-generation sequencing panel that included SLCO1B1, CYP2C19, CYP2C9, and VKORC1 together with a custom-designed CYP2D6 testing cascade to genotype the 1013 subjects in laboratories approved by the Clinical Laboratory Improvement Act. Actionable PGx variants were placed in patient's electronic medical records where integrated clinical decision support rules alert providers when a relevant medication is ordered. The fraction of this cohort carrying actionable PGx variant(s) in individual genes ranged from 30% (SLCO1B1) to 79% (CYP2D6). When considering all five genes together, 99% of the subjects carried an actionable PGx variant(s) in at least one gene. Our study provides evidence in favor of preemptive PGx testing by identifying the risk of a variant being present in the population we studied. PMID:26947514

Trial to assess the utility of genetic sequencing to improve patient outcomes

Cancer.gov

A pilot trial to assess whether assigning treatment based on specific gene mutations can provide benefit to patients with metastatic solid tumors is being launched this month by the NCI. The Molecular Profiling based Assignment of Cancer Therapeutics, or

Genome-wide QTL analysis for anxiety trait in bipolar disorder type I.

PubMed

Contreras, J; Hare, E; Chavarría-Soley, G; Raventós, H

2018-07-01

Genetic studies have been consistent that bipolar disorder type I (BPI) runs in families and that this familial aggregation is strongly influenced by genes. In a preliminary study, we proved that anxiety trait meets endophenotype criteria for BPI. We assessed 619 individuals from the Central Valley of Costa Rica (CVCR) who have received evaluation for anxiety following the same methodological procedure used for the initial pilot study. Our goal was to conduct a multipoint quantitative trait linkage analysis to identify quantitative trait loci (QTLs) related to anxiety trait in subjects with BPI. We conducted the statistical analyses using Quantitative Trait Loci method (Variance-components models), implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR), using 5606 single nucleotide polymorphism (SNPs). We identified a suggestive linkage signal with a LOD score of 2.01 at chromosome 2 (2q13-q14). Since confounding factors such as substance abuse, medical illness and medication history were not assessed in our study, these conclusions should be taken as preliminary. We conclude that region 2q13-q14 may harbor a candidate gene(s) with an important role in the pathophysiology of BPI and anxiety. Published by Elsevier B.V.

Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study.

PubMed

Gunes, S; Agarwal, A; Henkel, R; Mahmutoglu, A M; Sharma, R; Esteves, S C; Aljowair, A; Emirzeoglu, D; Alkhani, A; Pelegrini, L; Joumah, A; Sabanegh, E

2018-04-01

MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation. © 2017 Blackwell Verlag GmbH.

Modulation of Genetic and Epigenetic Biomarkers of Colorectal Cancer in Humans by Black Raspberries: A Phase I Pilot Study

PubMed Central

Wang, Li-Shu; Arnold, Mark; Huang, Yi-Wen; Sardo, Christine; Seguin, Claire; Martin, Edward; Huang, Tim H.-M.; Riedl, Ken; Schwartz, Steven; Frankel, Wendy; Pearl, Dennis; Xu, Yiqing; Winston, John; Yang, Guang-Yu; Stoner, Gary

2010-01-01

Purpose This study evaluated the effects of black raspberries (BRBs) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes, cell proliferation, apoptosis, angiogenesis and expression of Wnt pathway genes. Experimental Design Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder (60g/day) for 1-to-9 wks. Methylation status of promoter regions of five tumor suppressor genes was quantified. Protein expression of DNA methyltransferase 1 (DNMT1) and genes associated with cell proliferation, apoptosis, angiogenesis, and Wnt signaling were measured. Results The methylation of three Wnt inhibitors, SFRP2, SFRP5, and WIF1, upstream genes in Wnt pathway, and PAX6a, a developmental regulator, was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received an average of 4 wks of BRB treatment, but not in all 20 patients with 1-to-9 wks of BRB treatment. This was associated with decreased expression of DNMT1. BRBs modulated expression of genes associated with Wnt pathway, proliferation, apoptosis and angiogenesis in a protective direction. Conclusions These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum. While demethylation of genes did not occur in colorectal tissues from all treated patients, the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted. PMID:21123457

Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles.

PubMed

Levine, Morgan E; Crimmins, Eileen M; Weir, David R; Cole, Steve W

2017-09-01

Environmental or social challenges can stimulate a cascade of coordinated physiological changes in stress response systems. Unfortunately, chronic activation of these adaptations under conditions such as low socioeconomic status (SES) can have negative consequences for long-term health. While there is substantial evidence tying low SES to increased disease risk and reduced life expectancy, the underlying biology remains poorly understood. Using pilot data on 120 older adults from the Health and Retirement Study (United States, 2002-2010), we examined the associations between SES and gene expression levels in adulthood, with particular focus on a gene expression program known as the conserved transcriptional response to adversity. We also used a bioinformatics-based approach to assess the activity of specific gene regulation pathways involved in inflammation, antiviral responses, and stress-related neuroendocrine signaling. We found that low SES was related to increased expression of conserved transcriptional response to adversity genes and distinct patterns of proinflammatory, antiviral, and stress signaling (e.g., sympathetic nervous system and hypothalamic-pituitary-adrenal axis) transcription factor activation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Single Nucleotide Polymorphisms in IL8 and TLR4 Genes as Candidates for Digital Dermatitis Resistance/Susceptibility in Holstein Cattle.

PubMed

El-Shafaey, El-Sayed; Ateya, Ahmed; Ramadan, Hazem; Saleh, Rasha; Elseady, Yousef; Abo El Fadl, Eman; El-Khodery, Sabry

2017-04-03

Relatedness between single nucleotide polymorphisms in IL8 and TLR4 genes and digital dermatitis resistance/susceptibility was investigated in seventy Holstein dairy cows. Animals were assigned into two groups, affected group (n = 35) and resistant group (n = 35) based on clinical signs and previous history of farm clinical records. Blood samples were collected for DNA extraction to ampliy fragments of 267-bp and 382-bp for IL8 and TLR4 genes, respectively. PCR-DNA sequencing revealed three SNPs in each of IL8 and TLR4 genes. The identified SNPs associated with digital dermatitis resistance were C94T, A220G, and T262A for IL8 and C118T for TLR4. However, the G349C and C355A SNPs in TLR4 gene were associated with digital dermatitis susceptibility. Chi-square analysis for comparison the distribution of all identified SNPs in both IL8 and TLR4 genes between resistant and affected animals showed no significant variation among the identified SNPs in IL8 gene. Meanwhile, there was a significant variation in case of TLR4 gene. As a pilot study, the present results revealed that identified SNPs in IL8 and TLR4 genes can be used as a genetic marker and predisposing factor for resistance/susceptibility to digital dermatitis in dairy cows. However, TLR4 gene may be a potential candidate for such disease.

Single-cell genomic profiling of acute myeloid leukemia for clinical use: A pilot study

PubMed Central

Yan, Benedict; Hu, Yongli; Ban, Kenneth H.K.; Tiang, Zenia; Ng, Christopher; Lee, Joanne; Tan, Wilson; Chiu, Lily; Tan, Tin Wee; Seah, Elaine; Ng, Chin Hin; Chng, Wee-Joo; Foo, Roger

2017-01-01

Although bulk high-throughput genomic profiling studies have led to a significant increase in the understanding of cancer biology, there is increasing awareness that bulk profiling approaches do not completely elucidate tumor heterogeneity. Single-cell genomic profiling enables the distinction of tumor heterogeneity, and may improve clinical diagnosis through the identification and characterization of putative subclonal populations. In the present study, the challenges associated with a single-cell genomics profiling workflow for clinical diagnostics were investigated. Single-cell RNA-sequencing (RNA-seq) was performed on 20 cells from an acute myeloid leukemia bone marrow sample. Putative blasts were identified based on their gene expression profiles and principal component analysis was performed to identify outlier cells. Variant calling was performed on the single-cell RNA-seq data. The present pilot study demonstrates a proof of concept for clinical single-cell genomic profiling. The recognized limitations include significant stochastic RNA loss and the relatively low throughput of the current proposed platform. Although the results of the present study are promising, further technological advances and protocol optimization are necessary for single-cell genomic profiling to be clinically viable. PMID:28454300

STS-119 crew visit

NASA Image and Video Library

2009-05-05

Stennis Space Center Director Gene Goldman (r to l) presents a commemorative photo of a space shuttle main engine test firing to STS-119 Mission Commander Lee Archambault, Pilot Tony Antonelli and Mission Specialists Steve Swanson and Richard Arnold during the crew's May 5 visit to the facility.

[Mutation in the beta3-adrenergic receptor gene (Trp64Arg) does not influence insulin resistence, energy metabolism, fat distribution and lipid spectrum in young people. Pilot study].

PubMed

Bendlová, B; Mazura, I; Vcelák, J; Pelikánová, T; Kunesová, M; Hainer, V; Obenberger, J; Palyzová, D

1999-05-01

A missence mutation Trp64Arg in the beta3-adrenergic receptor gene is associated with obesity, insulin resistance, a lower metabolic rate and the earlier onset of NIDDM but the published results are controversial. We investigated the effect of this mutation on insulin resistance (euglycemic hyperinsulinemic clamp), on fat mass and fat distribution (anthropometry, bioimpedance, CT) and resting metabolic rate (indirect calorimetry), lipid spectrum and other metabolic disturbances in Czech juveniles recruited from juvenile hypertensives (H, n = 68) and controls (C, n = 81). The frequency of this mutation (determined by digestion of 210 bp PCR product with MvaI) was double in H than in C (14.7%, vs. 7.4%) and the carriers of Arg64 allele had sig. higher fasting glucose (H: p = 0.002. C: p = 0.025). Four Trp64/Arg64 and six Trp64/Trp64 men (age 23 +/- 4.2, vs. 22.5 +/- 1.9 y, BMI 26 +/- 5.5, vs. 22.9 +/- 5.1 kg/m2) took part in a detailed pilot study. But no signif. differences (Horn's method) in fasting glucose (4.6 +/- 0.6, vs. 4.9 +/- 0.4 mmol/l), in parameters of insulin resistance (M-value150-180 min. 9.1 +/- 1.1, vs. 8.9 +/- 1.5 mg glucose/kg.min(-1)), resting metabolic rate/lean body mass (RMR/kg LBM: 78.6 +/- 4.6, vs. 85.6 +/- 23.2 kJ/kg), lipid spectrum and other screened parameters were found. The lowest resting metabolic rate (RMR/kg LBM 55.4; 62.6 kJ/kg) was found in brothers (both C, Trp64/Trp64) who highly differ in body constitution (BMI 19.0 resp. 32.4 kg/m2). We suppose that in this case the energy metabolism is probably determined by other genetic loci and does not correlate with body fat mass. Our pilot study does not confirm the influence of Trp64Arg mutation in heterozygous carriers on insulin resistance, energy metabolism and lipid spectrum.

Interspecific Hybridization in Pilot Whales and Asymmetric Genetic Introgression in Northern Globicephala melas under the Scenario of Global Warming.

PubMed

Miralles, Laura; Oremus, Marc; Silva, Mónica A; Planes, Serge; Garcia-Vazquez, Eva

2016-01-01

Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus) whose distributions are correlated with water temperature and partially overlap in some areas like the North Atlantic Ocean. In the context of global warming, distribution range shifts are expected to occur in species affected by temperature. Consequently, a northward displacement of the tropical pilot whale G. macrorynchus is expected, eventually leading to increased secondary contact areas and opportunities for interspecific hybridization. Here, we describe genetic evidences of recurrent hybridization between pilot whales in northeast Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci, asymmetric introgression of G. macrorhynchus genes into G. melas was observed. For the latter species, a significant correlation was found between historical population growth rate estimates and paleotemperature oscillations. Introgressive hybridization, current temperature increases and lower genetic variation in G. melas suggest that this species could be at risk in its northern range. Under increasing environmental and human-mediated stressors in the North Atlantic Ocean, it seems recommendable to develop a conservation program for G. melas.

Interspecific Hybridization in Pilot Whales and Asymmetric Genetic Introgression in Northern Globicephala melas under the Scenario of Global Warming

PubMed Central

Miralles, Laura; Oremus, Marc; Silva, Mónica A.; Planes, Serge; Garcia-Vazquez, Eva

2016-01-01

Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus) whose distributions are correlated with water temperature and partially overlap in some areas like the North Atlantic Ocean. In the context of global warming, distribution range shifts are expected to occur in species affected by temperature. Consequently, a northward displacement of the tropical pilot whale G. macrorynchus is expected, eventually leading to increased secondary contact areas and opportunities for interspecific hybridization. Here, we describe genetic evidences of recurrent hybridization between pilot whales in northeast Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci, asymmetric introgression of G. macrorhynchus genes into G. melas was observed. For the latter species, a significant correlation was found between historical population growth rate estimates and paleotemperature oscillations. Introgressive hybridization, current temperature increases and lower genetic variation in G. melas suggest that this species could be at risk in its northern range. Under increasing environmental and human-mediated stressors in the North Atlantic Ocean, it seems recommendable to develop a conservation program for G. melas. PMID:27508496

Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study.

PubMed

Bowen, J M; White, I; Smith, L; Tsykin, A; Kristaly, K; Thompson, S K; Karapetis, C S; Tan, H; Game, P A; Irvine, T; Hussey, D J; Watson, D I; Keefe, D M K

2015-11-01

Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

PubMed

Adole, Prashant S; Kharbanda, Parampreet S; Sharma, Sadhna

2016-05-01

Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

PubMed Central

Adole, Prashant S.; Kharbanda, Parampreet S.; Sharma, Sadhna

2016-01-01

Background & objectives: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Methods: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. Results: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Interpretation & conclusions: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures. PMID:27488001

EvoCor: a platform for predicting functionally related genes using phylogenetic and expression profiles.

PubMed

Dittmar, W James; McIver, Lauren; Michalak, Pawel; Garner, Harold R; Valdez, Gregorio

2014-07-01

The wealth of publicly available gene expression and genomic data provides unique opportunities for computational inference to discover groups of genes that function to control specific cellular processes. Such genes are likely to have co-evolved and be expressed in the same tissues and cells. Unfortunately, the expertise and computational resources required to compare tens of genomes and gene expression data sets make this type of analysis difficult for the average end-user. Here, we describe the implementation of a web server that predicts genes involved in affecting specific cellular processes together with a gene of interest. We termed the server 'EvoCor', to denote that it detects functional relationships among genes through evolutionary analysis and gene expression correlation. This web server integrates profiles of sequence divergence derived by a Hidden Markov Model (HMM) and tissue-wide gene expression patterns to determine putative functional linkages between pairs of genes. This server is easy to use and freely available at http://pilot-hmm.vbi.vt.edu/. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Characterization of the quality of imbibed soybean at an early stage of pre-germination for the development of a new protein food item.

PubMed

Tamura, Tomoko; Kamei, Asuka; Ueda, Reiko; Arai, Soichi; Mura, Kiyoshi

2014-01-01

This was a pilot study carried out to develop a new protein food item from imbibed soybean before germination. It identified the significance of a short stage after imbibition and before germination, and that vitamin C production was activated in as little as 16 h from the start of imbibition, without any influence on the soy protein quality or sensory acceptability, while longer imbibition caused the imbibed soybean to activate its phytophysiological metabolism for germination. DNA microarray analysis indicated that the genes for carbohydrate metabolism were up-regulated prior to 16 h, and that the expression rates of genes responsible for environmental factors were down-regulated. Thereafter, the expression rates of the genes associated with lipid metabolism and secondary metabolite production were changed. This information should contribute to a better understanding of how to develop a new soy protein item in pre-germination before active physiological processes begin.

Saliva Microbiota Carry Caries-Specific Functional Gene Signatures

PubMed Central

Chang, Xingzhi; Yuan, Xiao; Tu, Qichao; Yuan, Tong; Deng, Ye; Hemme, Christopher L.; Van Nostrand, Joy; Cui, Xinping; He, Zhili; Chen, Zhenggang; Guo, Dawei; Yu, Jiangbo; Zhang, Yue; Zhou, Jizhong; Xu, Jian

2014-01-01

Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis. PMID:24533043

Saliva microbiota carry caries-specific functional gene signatures.

PubMed

Yang, Fang; Ning, Kang; Chang, Xingzhi; Yuan, Xiao; Tu, Qichao; Yuan, Tong; Deng, Ye; Hemme, Christopher L; Van Nostrand, Joy; Cui, Xinping; He, Zhili; Chen, Zhenggang; Guo, Dawei; Yu, Jiangbo; Zhang, Yue; Zhou, Jizhong; Xu, Jian

2014-01-01

Human saliva microbiota is phylogenetically divergent among host individuals yet their roles in health and disease are poorly appreciated. We employed a microbial functional gene microarray, HuMiChip 1.0, to reconstruct the global functional profiles of human saliva microbiota from ten healthy and ten caries-active adults. Saliva microbiota in the pilot population featured a vast diversity of functional genes. No significant distinction in gene number or diversity indices was observed between healthy and caries-active microbiota. However, co-presence network analysis of functional genes revealed that caries-active microbiota was more divergent in non-core genes than healthy microbiota, despite both groups exhibited a similar degree of conservation at their respective core genes. Furthermore, functional gene structure of saliva microbiota could potentially distinguish caries-active patients from healthy hosts. Microbial functions such as Diaminopimelate epimerase, Prephenate dehydrogenase, Pyruvate-formate lyase and N-acetylmuramoyl-L-alanine amidase were significantly linked to caries. Therefore, saliva microbiota carried disease-associated functional signatures, which could be potentially exploited for caries diagnosis.

CNVs affecting cancer predisposing genes (CPGs) detected as incidental findings in routine germline diagnostic chromosomal microarray (CMA) testing.

PubMed

Innes, Josie; Reali, Lisa; Clayton-Smith, Jill; Hall, Georgina; Lim, Derek Hk; Burghel, George J; French, Kim; Khan, Unzela; Walker, Daniel; Lalloo, Fiona; Evans, D Gareth R; McMullan, Dominic; Maher, Eamonn R; Woodward, Emma R

2018-02-01

Identification of CNVs through chromosomal microarray (CMA) testing is the first-line investigation in individuals with learning difficulties/congenital abnormalities. Although recognised that CMA testing may identify CNVs encompassing a cancer predisposition gene (CPG), limited information is available on the frequency and nature of such results. We investigated CNV gains and losses affecting 39 CPGs in 3366 pilot index case individuals undergoing CMA testing, and then studied an extended cohort (n=10 454) for CNV losses at 105 CPGs and CNV gains at 9 proto-oncogenes implicated in inherited cancer susceptibility. In the pilot cohort, 31/3366 (0.92%) individuals had a CNV involving one or more of 16/39 CPGs. 30/31 CNVs involved a tumour suppressor gene (TSG), and 1/30 a proto-oncogene (gain of MET ). BMPR1A , TSC2 and TMEM127 were affected in multiple cases. In the second stage analysis, 49/10 454 (0.47%) individuals in the extended cohort had 50 CNVs involving 24/105 CPGs. 43/50 CNVs involved a TSG and 7/50 a proto-oncogene (4 gains, 3 deletions). The most frequently involved genes, FLCN (n=10) and SDHA (n=7), map to the Smith-Magenis and cri-du-chat regions, respectively. Incidental identification of a CNV involving a CPG is not rare and poses challenges for future cancer risk estimation. Prospective data collection from CPG-CNV cohorts ascertained incidentally and through syndromic presentations is required to determine the risks posed by specific CNVs. In particular, ascertainment and investigation of adults with CPG-CNVs and adults with learning disability and cancer, could provide important information to guide clinical management and surveillance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prediction of Response to Therapy and Clinical Outcome through a Pilot Study of Complete Genetic Assessment of Ovarian Cancer

DTIC Science & Technology

2015-12-01

Oncology program supported by this grant consented patients to 11-104. OncoPanel is a cancer genomic assay that detects somatic mutations, copy number...KMT2D, EP300, FANCD2 Sertoli Leydig cell DICER1 Copy number variants: In addition, 219 patients were analyzed for copy-number variations ( CNV ) in...OncoPanel genes. >12,000 total CNV were reported in the cohort (Figure 2). Single- copy deletions (n=5558) and copy-number gains (low amplification) (n

Neonatal C57BL/6J and parkin mice respond differently following developmental manganese exposure: Result of a high dose pilot study.

PubMed

Foster, Melanie L; Bartnikas, Thomas B; Maresca-Fichter, Hailey C; Mercadante, Courtney; Dash, Miriam; Miller, Chelsea; Dorman, David C

2018-01-01

It has been suggested that childhood exposure to neurotoxicants may increase the risk of Parkinson's disease (PD) or other neurodegenerative disease in adults. Some recessive forms of PD have been linked to loss-of-function mutations in the Park2 gene that encodes for parkin. The purpose of this pilot study was to evaluate whether responses to neonatal manganese (Mn) exposure differ in mice with a Park2 gene defect (parkin mice) when compared with a wildtype strain (C57BL/6J). Neonatal parkin and C57BL/6J littermates were randomly assigned to 0, 11, or 25mg Mn/kg-day dose groups with oral exposures occurring from postnatal day (PND) 1 through PND 28. Motor activity was measured on PND 19-22 and 29-32. Tissue Mn concentrations were measured in liver, femur, olfactory bulb, frontal cortex, and striatum on PND 29. Hepatic and frontal cortex gene expression of Slc11a2, Slc40a1, Slc30a10, Hamp (liver only), and Park2 were also measured on PND 29. Some strain differences were seen. As expected, decreased hepatic and frontal cortex Park2 expression was seen in the parkin mice when compared with C57BL/6J mice. Untreated parkin mice also had higher liver and femur Mn concentrations when compared with the C57BL/6J mice. Exposure to≥11mg Mn/kg-day was associated with increased brain Mn concentrations in all mice, no strain difference was observed. Manganese exposure in C57Bl6, but not parkin mice, was associated with a negative correlation between striatal Mn concentration and motor activity. Manganese exposure was not associated with changes in frontal cortex gene expression. Decreased hepatic Slc30a10, Slc40a1, and Hamp expression were seen in PND 29 C57BL/6J mice given 25mg Mn/kg-day. In contrast, Mn exposure was only associated with decreased Hamp expression in the parkin mice. Our results suggest that the Parkin gene defect did not increase the susceptibility of neonatal mice to adverse health effects associated with high-dose Mn exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Are There Genetic Paths Common to Obesity, Cardiovascular Disease Outcomes, and Cardiovascular Risk Factors?

PubMed Central

Rankinen, Tuomo; Sarzynski, Mark A.; Ghosh, Sujoy; Bouchard, Claude

2015-01-01

Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets. PMID:25722444

Genetic Predictors of Susceptibility to Cutaneous Fungal Infections: a pilot Genome Wide Association Study to Refine a Candidate Gene Search

PubMed Central

Abdel-Rahman, Susan M.; Preuett, Barry L.

2012-01-01

Background Trichophyton tonsurans is the foremost fungal pathogen of minority children in the U.S. Despite overwhelming infection rates, it does not appear that this fungus infects children in a non-specific manner. Objective This study was designed to identify genes that may predispose or protect a child from T. tonsurans infection. Methods Children participating in an earlier longitudinal study wherein infection rates could be reliably determined were eligible for inclusion. DNA from a subset (n=40) of these children at the population extremes underwent whole genome genotyping (WGG). Allele frequencies between cases and controls were examined and significant SNPs were used to develop a candidate gene list for which the remainder of the cohort (n=115) were genotyped. Cumulative infection rate was examined by genotype and the ability of selected genotypes to predict the likelihood of infection explored by multivariable analysis. Results 23 genes with a putative mechanistic role in cutaneous infection were selected for evaluation. Of these, 21 demonstrated significant differences in infection rate between genotypes. A risk index assigned to genotypes in the 21 genes accounted for over 60% of the variability observed in infection rate (adjusted r2=0.665, p<0.001). Among these, 8 appeared to account for the majority of variability that was observed (r2=0.603, p<0.001). These included genes involved in: leukocyte activation and migration, extracellular matrix integrity and remodeling, epidermal maintenance and wound repair, and cutaneous permeability. Conclusions Applying WGG to individuals at the extremes of phenotype can help to guide the selection of candidate genes in populations of small cohorts where disease etiology is likely polygenic in nature. PMID:22704677

Identification of Unique Blood and Urine Biomarkers in Influenza Virus and Staphylococcus aureus Co-infection: A Preliminary Study.

PubMed

Prescott, Meagan A; Pastey, Manoj K

2010-12-05

Each year, there are estimated to be approximately 200,000 hospitalizations and 36,000 deaths due to influenza in the United States. Reports have indicated that most deaths are not directly due to influenza virus, but to secondary bacterial pneumonia, predominantly staphylococcal in origin. Here we identify the presence of candidate blood and urine biomarkers in mice with Staphyococcus aureus and influenza virus co-infection. In this pilot study, mice were grouped into four treatments: co-infected with influenza virus and S. aureus, singly infected with influenza virus or S. aureus, and a control group of uninfected mice (PBS treated). Gene expression changes were identified by DNA-microarrays from blood samples taken at day five post infection. Proteomic changes were obtained from urine samples collected at three and five days post infection using 2-D DIGE followed by protein ID by mass spectrometry. Differentially expressed genes and/or proteins were identified as candidate biomarkers for future validation in larger studies.

STS-124 crew visits Stennis

NASA Image and Video Library

2008-07-23

NASA's John C. Stennis Space Center Deputy Director Gene Goldman (center) welcomed members of the STS-124 Discovery space shuttle crew during their July 23 visit to the center. Crew members who visited Stennis were (l to r) Pilot Ken Ham, Mission Specialist Karen Nyberg, Kelly, and Mission Specialists Ron Garan and Mike Fossum.

A reduced transcriptome approach to assess environmental toxicants using zebrafish embryo tests

EPA Science Inventory

This paper reports on the pilot testing of a new bioassay platform that monitors expression of 1600 genes in zebrafish embryos exposed to either single chemicals or complex water samples. The method provides a more cost effective, high throughput means to broadly evaluate the pot...

Gene expression profile of blood cells for the prediction of delayed cerebral ischemia after intracranial aneurysm rupture: a pilot study in humans.

PubMed

Baumann, Antoine; Devaux, Yvan; Audibert, Gérard; Zhang, Lu; Bracard, Serge; Colnat-Coulbois, Sophie; Klein, Olivier; Zannad, Faiez; Charpentier, Claire; Longrois, Dan; Mertes, Paul-Michel

2013-01-01

Delayed cerebral ischemia (DCI) is a potentially devastating complication after intracranial aneurysm rupture and its mechanisms remain poorly elucidated. Early identification of the patients prone to developing DCI after rupture may represent a major breakthrough in its prevention and treatment. The single gene approach of DCI has demonstrated interest in humans. We hypothesized that whole genome expression profile of blood cells may be useful for better comprehension and prediction of aneurysmal DCI. Over a 35-month period, 218 patients with aneurysm rupture were included in this study. DCI was defined as the occurrence of a new delayed neurological deficit occurring within 2 weeks after aneurysm rupture with evidence of ischemia either on perfusion-diffusion MRI, CT angiography or CT perfusion imaging, or with cerebral angiography. DCI patients were matched against controls based on 4 out of 5 criteria (age, sex, Fisher grade, aneurysm location and smoking status). Genome-wide expression analysis of blood cells obtained at admission was performed by microarrays. Transcriptomic analysis was performed using long oligonucleotide microarrays representing 25,000 genes. Quantitative PCR: 1 µg of total RNA extracted was reverse-transcribed, and the resulting cDNA was diluted 10-fold before performing quantitative PCR. Microarray data were first analyzed by 'Significance Analysis of Microarrays' software which includes the Benjamini correction for multiple testing. In a second step, microarray data fold change was compared using a two-tailed, paired t test. Analysis of receiver-operating characteristic (ROC) curves and the area under the ROC curves were used for prediction analysis. Logistic regression models were used to investigate the additive value of multiple biomarkers. A total of 16 patients demonstrated DCI. Significance Analysis of Microarrays software failed to retrieve significant genes, most probably because of the heterogeneity of the patients included in the microarray experiments and the small size of the DCI population sample. Standard two-tailed paired t test and C-statistic revealed significant associations between gene expression and the occurrence of DCI: in particular, the expression of neuroregulin 1 was 1.6-fold upregulated in patients with DCI (p = 0.01) and predicted DCI with an area under the ROC curve of 0.96. Logistic regression analyses revealed a significant association between neuroregulin 1 and DCI (odds ratio 1.46, 95% confidence interval 1.02-2.09, p = 0.02). This pilot study suggests that blood cells may be a reservoir of prognostic biomarkers of DCI in patients with intracranial aneurysm rupture. Despite an evident lack of power, this study elicited neuroregulin 1, a vasoreactivity-, inflammation- and angiogenesis-related gene, as a possible candidate predictor of DCI. Larger cohort studies are needed but genome-wide microarray-based studies are promising research tools for the understanding of DCI after intracranial aneurysm rupture. © 2013 S. Karger AG, Basel.

Evaluation of inflammation-related genes polymorphisms in Mexican with Alzheimer’s disease: a pilot study

PubMed Central

Toral-Rios, Danira; Franco-Bocanegra, Diana; Rosas-Carrasco, Oscar; Mena-Barranco, Francisco; Carvajal-García, Rosa; Meraz-Ríos, Marco Antonio; Campos-Peña, Victoria

2015-01-01

Amyloid peptide is able to promote the activation of microglia and astrocytes in Alzheimer’s disease (AD), and this stimulates the production of pro-inflammatory cytokines. Inflammation contributes to the process of neurodegeneration and therefore is a key factor in the development of AD. Some of the most important proteins involved in AD inflammation are: clusterin (CLU), complement receptor 1 (CR1), C reactive protein (CRP), tumor necrosis factor α (TNF-α), the interleukins 1α (IL-1α), 6 (IL-6), 10 (IL-10) and cyclooxygenase 2 (COX-2). In particular, COX-2 is encoded by the prostaglandin-endoperoxide synthase 2 gene (PTGS2). Since variations in the genes that encode these proteins may modify gene expression or function, it is important to investigate whether these variations may change the developing AD. The aim of this study was to determine whether the presence of polymorphisms in the genes encoding the aforementioned proteins is associated in Mexican patients with AD. Fourteen polymorphisms were genotyped in 96 subjects with AD and 100 controls; the differences in allele, genotype and haplotype frequencies were analyzed. Additionally, an ancestry analysis was conducted to exclude differences in genetic ancestry among groups as a confounding factor in the study. Significant differences in frequencies between AD and controls were found for the single-nucleotide polymorphism (SNP) rs20417 within the PTGS2 gene. Ancestry analysis revealed no significant differences in the ancestry of the compared groups, and the association was significant even after adjustment for ancestry and correction for multiple testing, which strengthens the validity of the results. We conclude that this polymorphism plays an important role in the development of the AD pathology and further studies are required, including their proteins. PMID:26041990

A tutorial on pilot studies: the what, why and how

PubMed Central

2010-01-01

Pilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format. PMID:20053272

Functional Genomics in the Study of Mind-Body Therapies

PubMed Central

Niles, Halsey; Mehta, Darshan H.; Corrigan, Alexandra A.; Bhasin, Manoj K.; Denninger, John W.

2014-01-01

Background Mind-body therapies (MBTs) are used throughout the world in treatment, disease prevention, and health promotion. However, the mechanisms by which MBTs exert their positive effects are not well understood. Investigations into MBTs using functional genomics have revolutionized the understanding of MBT mechanisms and their effects on human physiology. Methods We searched the literature for the effects of MBTs on functional genomics determinants using MEDLINE, supplemented by a manual search of additional journals and a reference list review. Results We reviewed 15 trials that measured global or targeted transcriptomic, epigenomic, or proteomic changes in peripheral blood. Sample sizes ranged from small pilot studies (n=2) to large trials (n=500). While the reliability of individual genes from trial to trial was often inconsistent, genes related to inflammatory response, particularly those involved in the nuclear factor-kappa B (NF-κB) pathway, were consistently downregulated across most studies. Conclusion In general, existing trials focusing on gene expression changes brought about by MBTs have revealed intriguing connections to the immune system through the NF-κB cascade, to telomere maintenance, and to apoptotic regulation. However, these findings are limited to a small number of trials and relatively small sample sizes. More rigorous randomized controlled trials of healthy subjects and specific disease states are warranted. Future research should investigate functional genomics areas both upstream and downstream of MBT-related gene expression changes—from epigenomics to proteomics and metabolomics. PMID:25598735

Childhood and later life stressors and increased inflammatory gene expression at older ages.

PubMed

Levine, M E; Cole, S W; Weir, D R; Crimmins, E M

2015-04-01

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists. Copyright © 2015. Published by Elsevier Ltd.

Functional genomics in the study of mind-body therapies.

PubMed

Niles, Halsey; Mehta, Darshan H; Corrigan, Alexandra A; Bhasin, Manoj K; Denninger, John W

2014-01-01

Mind-body therapies (MBTs) are used throughout the world in treatment, disease prevention, and health promotion. However, the mechanisms by which MBTs exert their positive effects are not well understood. Investigations into MBTs using functional genomics have revolutionized the understanding of MBT mechanisms and their effects on human physiology. We searched the literature for the effects of MBTs on functional genomics determinants using MEDLINE, supplemented by a manual search of additional journals and a reference list review. We reviewed 15 trials that measured global or targeted transcriptomic, epigenomic, or proteomic changes in peripheral blood. Sample sizes ranged from small pilot studies (n=2) to large trials (n=500). While the reliability of individual genes from trial to trial was often inconsistent, genes related to inflammatory response, particularly those involved in the nuclear factor-kappa B (NF-κB) pathway, were consistently downregulated across most studies. In general, existing trials focusing on gene expression changes brought about by MBTs have revealed intriguing connections to the immune system through the NF-κB cascade, to telomere maintenance, and to apoptotic regulation. However, these findings are limited to a small number of trials and relatively small sample sizes. More rigorous randomized controlled trials of healthy subjects and specific disease states are warranted. Future research should investigate functional genomics areas both upstream and downstream of MBT-related gene expression changes-from epigenomics to proteomics and metabolomics.

Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study.

PubMed

Kanazawa, H; Hirata, K; Yoshikawa, J

2003-07-01

We have previously shown that angiotensin converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). A pilot study was designed to examine the effects of captopril on these exercise related variables in COPD patients categorised according to ACE gene polymorphisms. Thirty six patients with COPD (II=13, ID=11, DD=12) received oral captopril (25 mg) or placebo in a randomised, double blind, crossover manner and underwent right heart catheterisation with exercise. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and lactate concentration after exercise with both placebo and captopril were higher in patients with the DD genotype than in those with the II or ID genotypes. In contrast, mixed venous oxygen tension (PvO(2)) was lower in patients with the DD genotype than in those with the other genotypes. Moreover, mPAP, PVR, and lactate concentration after exercise were lower in the captopril group than in the placebo group in patients with the II or ID genotype, but not in those with the DD genotype. PvO(2) after exercise was higher with captopril than with placebo in patients with the II genotype, but not in those with the other genotypes. These findings suggest that pulmonary haemodynamic variables and state of tissue oxygenation during exercise are dependent on ACE genotypes, and that captopril administration effectively influences these exercise related variables. Although the sample size in this pilot study was limited, it is likely that the improvement in exercise related variables in COPD patients with the II genotype is relatively sensitive to captopril.

Why undertake a pilot in a qualitative PhD study? Lessons learned to promote success.

PubMed

Wray, Jane; Archibong, Uduak; Walton, Sean

2017-01-23

Background Pilot studies can play an important role in qualitative studies. Methodological and practical issues can be shaped and refined by undertaking pilots. Personal development and researchers' competence are enhanced and lessons learned can inform the development and quality of the main study. However, pilot studies are rarely published, despite their potential to improve knowledge and understanding of the research. Aim To present the main lessons learned from undertaking a pilot in a qualitative PhD study. Discussion This paper draws together lessons learned when undertaking a pilot as part of a qualitative research project. Important methodological and practical issues identified during the pilot study are discussed including access, recruitment, data collection and the personal development of the researcher. The resulting changes to the final study are also highlighted. Conclusion Sharing experiences of and lessons learned in a pilot study enhances personal development, improves researchers' confidence and competence, and contributes to the understanding of research. Implications for practice Pilots can be used effectively in qualitative studies to refine the final design, and provide the researcher with practical experience to enhance confidence and competence.

Arsenic Methylation and its Relationship to Abundance and Diversity of arsM Genes in Composting Manure

NASA Astrophysics Data System (ADS)

Zhai, Weiwei; Wong, Mabel T.; Luo, Fei; Hashmi, Muhammad Z.; Liu, Xingmei; Edwards, Elizabeth A.; Tang, Xianjin; Xu, Jianming

2017-03-01

Although methylation is regarded as one of the main detoxification pathways for arsenic (As), current knowledge about this process during manure composting remains limited. In this study, two pilot-scale compost piles were established to treat manure contaminated with As. An overall accumulation of methylated As occurred during 60 day-composting time. The concentration of monomethylarsonic acid (MMA) increased from 6 to 190 μg kg-1 within 15 days and decreased to 35 μg kg-1 at the end of the maturing phase; while the concentration of dimethylarsinic acid (DMA) continuously increased from 33 to 595 μg kg-1 over the composting time. The arsM gene copies increased gradually from 0.08 × 109 to 6.82 × 109 copies g-1 dry mass over time and correlated positively to the concentrations of methylated As. 16S rRNA gene sequencing and arsM clone library analysis confirmed the high abundance and diversity of arsM genes. Many of these genes were related to those from known As-methylating microbes, including Streptomyces sp., Amycolatopsis mediterranei and Sphaerobacter thermophiles. These results demonstrated that As methylation during manure composting is significant and, for the first time, established a linkage between As biomethylation and the abundance and diversity of the arsM functional genes in composting manure.

Arsenic Methylation and its Relationship to Abundance and Diversity of arsM Genes in Composting Manure

PubMed Central

Zhai, Weiwei; Wong, Mabel T.; Luo, Fei; Hashmi, Muhammad Z.; Liu, Xingmei; Edwards, Elizabeth A.; Tang, Xianjin; Xu, Jianming

2017-01-01

Although methylation is regarded as one of the main detoxification pathways for arsenic (As), current knowledge about this process during manure composting remains limited. In this study, two pilot-scale compost piles were established to treat manure contaminated with As. An overall accumulation of methylated As occurred during 60 day-composting time. The concentration of monomethylarsonic acid (MMA) increased from 6 to 190 μg kg−1 within 15 days and decreased to 35 μg kg−1 at the end of the maturing phase; while the concentration of dimethylarsinic acid (DMA) continuously increased from 33 to 595 μg kg−1 over the composting time. The arsM gene copies increased gradually from 0.08 × 109 to 6.82 × 109 copies g−1 dry mass over time and correlated positively to the concentrations of methylated As. 16S rRNA gene sequencing and arsM clone library analysis confirmed the high abundance and diversity of arsM genes. Many of these genes were related to those from known As-methylating microbes, including Streptomyces sp., Amycolatopsis mediterranei and Sphaerobacter thermophiles. These results demonstrated that As methylation during manure composting is significant and, for the first time, established a linkage between As biomethylation and the abundance and diversity of the arsM functional genes in composting manure. PMID:28266584

Prevalence and distribution of Chlamydia trachomatis genovars in Indian infertile patients: a pilot study.

PubMed

Rawre, Jyoti; Dhawan, Benu; Malhotra, Neena; Sreenivas, Vishnubhatla; Broor, Shobha; Chaudhry, Rama

2016-12-01

To determine the prevalence and distribution of Chlamydia trachomatis genovars in patients with infertility by PCR-RFLP and ompA gene sequencing. Prevalence of other etiological agents (viz., Ureaplasma spp. and Mycoplasma hominis) were also assessed. Endocervical swabs were collected from 477 women and urine was collected from 151 men attending the Infertility Clinic. The samples were screened for C. trachomatis by cryptic plasmid, ompA gene and nested ompA gene PCR. Genotyping was performed by PCR-RFLP and sequencing. Samples were screened for Ureaplasma spp. and M. hominis. The prevalence of C. trachomatis in infertile women and their male partners were 15.7% (75 of 477) and 10.0% (15 of 151) respectively. Secondary infertility was significantly associated with chlamydial infection. Genovar E was the most prevalent followed by genovar D and F. Twenty-four C. trachomatis strains were selected for ompA gene sequencing. No mixed infection was picked. Variability in ompA sequences was seen in 50.0%. Both PCR-RFLP and ompA gene sequencing showed concordant results. High prevalence of C. trachomatis in infertile couples warrants routine screening for C. trachomatis infection in all infertile couples. Genotyping of the ompA gene of C. trachomatis may be a valuable tool in understanding the natural history of C. trachomatis infection. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Light, Brain, and Action: An Introductory, Interdisciplinary Course on Optogenetics for Undergraduate Students

ERIC Educational Resources Information Center

Kouh, Minjoon; Merz, River

2013-01-01

We piloted a semester-long, interdisciplinary, introductory science course using recently developed optogenetic technique as a main context. In neuroscience application, this technique introduces the gene of light-sensitive membrane protein into a targeted class of neurons, whose activity then can be modulated with a laser of specific wavelength.…

Tumour necrosis factor (TNF)-α-308 gene polymorphism in Indian patients with Takayasu's arteritis - a pilot study.

PubMed

Sandhya, P; Danda, Sumita; Danda, Debashish; Lonarkar, Shraddha; Luke, Shana S; Sinha, Shanta; Joseph, George

2013-04-01

Tumour necrosis factor-alpha (TNF-α)- 308 promoter gene polymorphism has been shown to be associated with several autoimmune disorders and infections such as tuberculosis. There is no study on TNF-α gene polymorphism in Takayasu's arteritis (TA) till date. We aimed to study this polymorphism in TA, a granulomatous vasculitis, probably triggered by Mycobacterium tuberculosis. TNF-α - 308 gene polymorphism was studied in 34 patients with TA and 39 healthy controls recruited from Christian Medical College, India. PCR was done followed by enzyme digestion. G and A polymorphisms were analysed. Occurrence of alleles in the disease group was compared with controls as well as with historical controls. GG allele was most frequent in TA and in controls. GA allele was detected in four controls but only in one patient who was the oldest in the study group. AA polymorphism was detected in one control but not in TA. When compared with controls from other populations, it was found that our allelic frequency was similar to that in Japan as well as from USA with mixed population. However, predominantly Caucasian population studied from Netherlands, Germany and England, where TA is rare, had a higher frequency of A allele as compared to our controls. Our preliminary results indicated that G allele at TNF-α - 308 was more common in TA patients and controls similar to that in other Indian as well as Japanese population. Compared to the western population, A allele was relatively less common in our study subjects.

The Effects of Longitudinal Control-System Dynamics on Pilot Opinion and Response Characteristics as Determined from Flight Tests and from Ground Simulator Studies

NASA Technical Reports Server (NTRS)

Sadoff, Melvin

1958-01-01

The results of a fixed-base simulator study of the effects of variable longitudinal control-system dynamics on pilot opinion are presented and compared with flight-test data. The control-system variables considered in this investigation included stick force per g, time constant, and dead-band, or stabilizer breakout force. In general, the fairly good correlation between flight and simulator results for two pilots demonstrates the validity of fixed-base simulator studies which are designed to complement and supplement flight studies and serve as a guide in control-system preliminary design. However, in the investigation of certain problem areas (e.g., sensitive control-system configurations associated with pilot- induced oscillations in flight), fixed-base simulator results did not predict the occurrence of an instability, although the pilots noted the system was extremely sensitive and unsatisfactory. If it is desired to predict pilot-induced-oscillation tendencies, tests in moving-base simulators may be required. It was found possible to represent the human pilot by a linear pilot analog for the tracking task assumed in the present study. The criterion used to adjust the pilot analog was the root-mean-square tracking error of one of the human pilots on the fixed-base simulator. Matching the tracking error of the pilot analog to that of the human pilot gave an approximation to the variation of human-pilot behavior over a range of control-system dynamics. Results of the pilot-analog study indicated that both for optimized control-system dynamics (for poor airplane dynamics) and for a region of good airplane dynamics, the pilot response characteristics are approximately the same.

76 FR 70152 - Pilot Program for Early Feasibility Study Investigational Device Exemption Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-10

...] Pilot Program for Early Feasibility Study Investigational Device Exemption Applications AGENCY: Food and... feasibility study investigational device exemption (IDE) applications. The pilot program will conform to the... Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies.'' Under the pilot...

Selenium regulation of selenoprotein enzyme activity and transcripts in a pilot study with Founder strains from the Collaborative Cross

PubMed Central

2018-01-01

Rodents and humans have 24–25 selenoproteins, and these proteins contain the 21st amino acid, selenocysteine, incorporated co-translationally into the peptide backbone in a series of reactions dependent on at least 6 unique gene products. In selenium (Se) deficiency, there is differential regulation of selenoprotein expression, whereby levels of some selenoproteins and their transcripts decrease dramatically in Se deficiency, but other selenoprotein transcripts are spared this decrease; the underlying mechanism, however, is not fully understood. To begin explore the genetic basis for this variation in regulation by Se status in a pilot study, we fed Se-deficient or Se-adequate diets (0.005 or 0.2 μg Se/g, respectively) for eight weeks to the eight Founder strains of the Collaborative Cross. We found rather uniform expression of selenoenzyme activity for glutathione peroxidase (Gpx) 3 in plasma, Gpx1 in red blood cells, and Gpx1, Gpx4, and thioredoxin reductase in liver. In Founder mice, Se deficiency decreased each of these activities to a similar extent. Regulation of selenoprotein transcript expression by Se status was also globally retained intact, with dramatic down-regulation of Gpx1, Selenow, and Selenoh transcripts in all 8 strains of Founder mice. These results indicate that differential regulation of selenoprotein expression by Se status is an essential aspect of Se metabolism and selenoprotein function. A few lone differences in Se regulation were observed for individual selenoproteins in this pilot study, but these differences did not single-out one strain or one selenoprotein that consistently had unique Se regulation of selenoprotein expression. These differences should be affirmed in larger studies; use of the Diversity Outbred and Collaborative Cross strains may help to better define the functions of these selenoproteins. PMID:29338053

The Subgingival Microbiome of Periodontal Pockets With Different Probing Depths in Chronic and Aggressive Periodontitis: A Pilot Study.

PubMed

Shi, Meng; Wei, Yiping; Hu, Wenjie; Nie, Yong; Wu, Xiaolei; Lu, Ruifang

2018-01-01

Periodontitis is a kind of infectious disease initiated by colonization of subgingival periodontal pathogens, which cause destruction of tooth-supporting tissues, and is a predominant threat to oral health as the most common cause of loss of teeth. The aim of this pilot study was to characterize the subgingival bacterial biodiversity of periodontal pockets with different probing depths in patients with different forms of periodontitis. Twenty-one subgingival plaque samples were collected from three patients with chronic periodontitis (ChP), three patients with aggressive periodontitis (AgP) and three periodontally healthy subjects (PH). Each patient with periodontitis was sampled at three sites, at different probing depths (PDs, one each at 4 mm, 5-6 mm, and ≥ 7 mm). Using 16S rRNA gene high-throughput sequencing and bioinformatic analysis, we found that subgingival communities in health and periodontitis samples largely differed. Meanwhile, Acholeplasma, Fretibacterium, Porphyromonas, Peptococcus, Treponema_2, Defluviitaleaceae_UCG_011, Filifactor , and Mycoplasma increased with the deepening of the pockets in ChP, whilst only Corynebacterium was negatively associated with PD. In AgP, Corynebacterium and Klebsiella were positively associated with PD, while Serratia, Pseudoramibacter, Defluviitaleaceae_UCG_011 , and Desulfobulbus were negatively associated with PD. And among these two groups, Corynebacterium shifted differently. Moreover, in subgingival plaque, the unweighted UniFrac distances between samples from pockets with different PD in the same patients were significantly lower than those from pockets within the same PD category from different patients. This study demonstrated the shift of the subgingival microbiome in individual teeth sites during disease development. Within the limitation of the relative small sample size, this pilot study shed new light on the dynamic relationship between the extent of periodontal destruction and the subgingival microbiome.

Using laser capture microdissection to study fiber specific signaling in locomotor muscle in COPD: A pilot study.

PubMed

Mohan, Divya; Lewis, Amy; Patel, Mehul S; Curtis, Katrina J; Lee, Jen Y; Hopkinson, Nicholas S; Wilkinson, Ian B; Kemp, Paul R; Polkey, Michael I

2017-06-01

Quadriceps dysfunction is important in chronic obstructive pulmonary disease (COPD), with an associated increased proportion of type II fibers. Investigation of protein synthesis and degradation has yielded conflicting results, possibly due to study of whole biopsy samples, whereas signaling may be fiber-specific. Our objective was to develop a method for fiber-specific gene expression analysis. 12 COPD and 6 healthy subjects underwent quadriceps biopsy. Cryosections were immunostained for type II fibers, which were separated using laser capture microdissection (LCM). Whole muscle and different fiber populations were subject to quantitative polymerase chain reaction. Levels of muscle-RING-finger-protein-1 and Atrogin-1 were lower in type II fibers of COPD versus healthy subjects (P = 0.02 and P = 0.03, respectively), but differences were not apparent in whole muscle or type I fibers. We describe a novel method for studying fiber-specific gene expression in optimum cutting temperature compound-embedded muscle specimens. LCM offers a more sensitive way to identify molecular changes in COPD muscle. Muscle Nerve 55: 902-912, 2017. © 2016 Wiley Periodicals, Inc.

A Study of the Characteristics of Human-Pilot Control Response to Simulated Aircraft Lateral Motions

NASA Technical Reports Server (NTRS)

Cheatham, Donald C

1954-01-01

Report presents the results of studies made in an attempt to provide information on the control operations of the human pilot. These studies included an investigation of the ability of pilots to control simulated unstable yawing oscillations, a study of the basic characteristics of human-pilot control response, and a study to determine whether and to what extent pilot control response can be represented in an analytical form.

Dynamic Succession of Groundwater Functional Microbial Communities in Response to Emulsified Vegetable Oil Amendment during Sustained In Situ U(VI) Reduction.

PubMed

Zhang, Ping; Wu, Wei-Min; Van Nostrand, Joy D; Deng, Ye; He, Zhili; Gihring, Thomas; Zhang, Gengxin; Schadt, Chris W; Watson, David; Jardine, Phil; Criddle, Craig S; Brooks, Scott; Marsh, Terence L; Tiedje, James M; Arkin, Adam P; Zhou, Jizhong

2015-06-15

A pilot-scale field experiment demonstrated that a one-time amendment of emulsified vegetable oil (EVO) reduced groundwater U(VI) concentrations for 1 year in a fast-flowing aquifer. However, little is known about how EVO amendment stimulates the functional gene composition, structure, and dynamics of groundwater microbial communities toward prolonged U(VI) reduction. In this study, we hypothesized that EVO amendment would shift the functional gene composition and structure of groundwater microbial communities and stimulate key functional genes/groups involved in EVO biodegradation and reduction of electron acceptors in the aquifer. To test these hypotheses, groundwater microbial communities after EVO amendment were analyzed using a comprehensive functional gene microarray. Our results showed that EVO amendment stimulated sequential shifts in the functional composition and structure of groundwater microbial communities. Particularly, the relative abundance of key functional genes/groups involved in EVO biodegradation and the reduction of NO3 (-), Mn(IV), Fe(III), U(VI), and SO4 (2-) significantly increased, especially during the active U(VI) reduction period. The relative abundance for some of these key functional genes/groups remained elevated over 9 months. Montel tests suggested that the dynamics in the abundance, composition, and structure of these key functional genes/groups were significantly correlated with groundwater concentrations of acetate, NO3 (-), Mn(II), Fe(II), U(VI), and SO4 (2-). Our results suggest that EVO amendment stimulated dynamic succession of key functional microbial communities. This study improves our understanding of the composition, structure, and function changes needed for groundwater microbial communities to sustain a long-term U(VI) reduction. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Dynamic Succession of Groundwater Functional Microbial Communities in Response to Emulsified Vegetable Oil Amendment during Sustained In Situ U(VI) Reduction

PubMed Central

Zhang, Ping; Wu, Wei-Min; Van Nostrand, Joy D.; Deng, Ye; He, Zhili; Gihring, Thomas; Zhang, Gengxin; Schadt, Chris W.; Watson, David; Jardine, Phil; Criddle, Craig S.; Brooks, Scott; Marsh, Terence L.; Tiedje, James M.; Arkin, Adam P.

2015-01-01

A pilot-scale field experiment demonstrated that a one-time amendment of emulsified vegetable oil (EVO) reduced groundwater U(VI) concentrations for 1 year in a fast-flowing aquifer. However, little is known about how EVO amendment stimulates the functional gene composition, structure, and dynamics of groundwater microbial communities toward prolonged U(VI) reduction. In this study, we hypothesized that EVO amendment would shift the functional gene composition and structure of groundwater microbial communities and stimulate key functional genes/groups involved in EVO biodegradation and reduction of electron acceptors in the aquifer. To test these hypotheses, groundwater microbial communities after EVO amendment were analyzed using a comprehensive functional gene microarray. Our results showed that EVO amendment stimulated sequential shifts in the functional composition and structure of groundwater microbial communities. Particularly, the relative abundance of key functional genes/groups involved in EVO biodegradation and the reduction of NO3−, Mn(IV), Fe(III), U(VI), and SO42− significantly increased, especially during the active U(VI) reduction period. The relative abundance for some of these key functional genes/groups remained elevated over 9 months. Montel tests suggested that the dynamics in the abundance, composition, and structure of these key functional genes/groups were significantly correlated with groundwater concentrations of acetate, NO3−, Mn(II), Fe(II), U(VI), and SO42−. Our results suggest that EVO amendment stimulated dynamic succession of key functional microbial communities. This study improves our understanding of the composition, structure, and function changes needed for groundwater microbial communities to sustain a long-term U(VI) reduction. PMID:25862231

Good Laboratory Practice Preclinical Safety Studies for GSK2696273 (MLV Vector-Based Ex Vivo Gene Therapy for Adenosine Deaminase Deficiency Severe Combined Immunodeficiency) in NSG Mice.

PubMed

Carriglio, Nicola; Klapwijk, Jan; Hernandez, Raisa Jofra; Vezzoli, Michela; Chanut, Franck; Lowe, Rhiannon; Draghici, Elena; Nord, Melanie; Albertini, Paola; Cristofori, Patrizia; Richards, Jane; Staton, Hazel; Appleby, Jonathan; Aiuti, Alessandro; Sauer, Aisha V

2017-03-01

GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients. Ex vivo gene therapy of patient bone-marrow CD34+ cells is an alternative treatment. In order to prepare for a marketing authorization application in the European Union, preclinical safety studies in mice were requested by the European Medicines Agency (EMA). A pilot study and a main biodistribution study were performed according to Good Laboratory Practice (GLP) at the San Raffaele Telethon Institute for Gene Therapy test facility. In the main study, human umbilical cord blood (UCB)-derived CD34+ cells were transduced with gamma-retroviral vector used in the production of GSK2696273. Groups of 10 male and 10 female NOD-SCID gamma (NSG) mice were injected intravenously with a single dose of transduced- or mock-transduced UCB CD34+ cells, and they were observed for 4 months. Engraftment and multilineage differentiation of blood cells was observed in the majority of animals in both groups. There was no significant difference in the level of chimerism between the two groups. In the gene therapy group, vector was detectable in lymphohemopoietic and nonlymphohemopoietic tissues, consistent with the presence of gene-modified human hematopoietic donor cells. Given the absence of relevant safety concerns in the data, the nonclinical studies and the clinical experience with GSK2696273 supported a successful application for market authorization in the European Union for the treatment of ADA-SCID patients, for whom no suitable human leukocyte antigen-matched related donor is available.

A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism.

PubMed

Baca-García, Enrique; Salgado, Beatríz Rodríguez; Segal, Helen Dolengevich; Lorenzo, Concepción Vaquero; Acosta, Mercedes Navio; Romero, Manuel Arrojo; Hernández, Montserrat Díaz; Saiz-Ruiz, Jeronimo; Fernandez Piqueras, Jose; de Leon, Jose

2005-06-01

According to some authors the obsessive-compulsive (OC) spectrum includes on one extreme, the Obsessive-Compulsive Disorder (OCD) and on the other extreme the most impulsive behaviors. This is a controversial idea and other authors define the OC spectrum in different ways. The serotonin transporter (5-HTT) gene is one of the main genes that control serotonergic function. A polymorphism in the promoter area of this gene classifies subjects with low expression as S individuals (s/s or s/l) and subjects with high expression as L individuals (l/l). This polymorphism was studied in female OCD patients (n = 24), non-impulsive controls (n = 112) and impulsive suicidal patients (n = 118) to support the OC spectrum hypothesis from a genetic perspective. A linear association exists among the serotonin transporter promoter functional genotypes (S versus L individuals) (chi2 linear by linear association = 8.9; df = 1; p = 0.003). The frequency of S individuals (s/l or s/s) was lowest in OCD (54%, 13/24); intermediate in non-impulsive controls (71%, 80/112) and highest in impulsive suicide attempters (82%, 96/117). More importantly, future studies need to consider that genetics may be related to behavioral dimensions (compulsivity to impulsivity) instead of to specific psychiatric disorders defined in clinical terms.

Remediation of petroleum hydrocarbon-contaminated sites by DNA diagnosis-based bioslurping technology.

PubMed

Kim, Seungjin; Krajmalnik-Brown, Rosa; Kim, Jong-Oh; Chung, Jinwook

2014-11-01

The application of effective remediation technologies can benefit from adequate preliminary testing, such as in lab-scale and Pilot-scale systems. Bioremediation technologies have demonstrated tremendous potential with regards to cost, but they cannot be used for all contaminated sites due to limitations in biological activity. The purpose of this study was to develop a DNA diagnostic method that reduces the time to select contaminated sites that are good candidates for bioremediation. We applied an oligonucleotide microarray method to detect and monitor genes that lead to aliphatic and aromatic degradation. Further, the bioremediation of a contaminated site, selected based on the results of the genetic diagnostic method, was achieved successfully by applying bioslurping in field tests. This gene-based diagnostic technique is a powerful tool to evaluate the potential for bioremediation in petroleum hydrocarbon contaminated soil. Copyright © 2014 Elsevier B.V. All rights reserved.

Pilot Certification, Age of Pilot, and Drug Use in Fatal Civil Aviation Accidents.

PubMed

Akparibo, Issaka Y; Stolfi, Adrienne

2017-10-01

This study examined the association between mean age of pilot, pilot license, pilot medical certificate and drug use trends in pilots fatally injured in aircraft accidents. The prevalence of prescription drugs, OTC drugs, controlled drugs and drugs that may be potentially impairing was also examined. This study was a descriptive observational study in which the NTSB Aviation Accident Database was searched from the period beginning January 1, 2012 to December 31, 2014. During the study period a total of 706 accidents involving 711 fatalities were investigated by the NTSB. This study included 633 of these accidents, involving 646 fatalities. Of these pilots, 42.1% had drugs in their biological samples. The prevalence of prescription drugs, controlled drugs, OTC drugs, opioids, and potentially impairing drugs in the fatally injured pilot population over the study period was 28.9%, 15.0%, 20.1%, 5.1%, and 25.5%, respectively. Pilots with any drugs in their samples were significantly older than those without drugs. Medical certificate held was associated with drug use; pilots who held third class certificates had the highest prevalence at 54.1%. Pilot license was not associated with drug use. In 3.8% of the accidents, drugs were a contributing factor in the cause. Despite current FAA medical regulations, potentially impairing drugs are frequently found in biological samples of fatally injured pilots in the U.S. More education of airmen by aviation medical examiners is needed on the safety of drug use.Akparibo IY, Stolfi A. Pilot certification, age of pilot, and drug use in fatal civil aviation accidents. Aerosp Med Hum Perform. 2017; 88(10):931-936.

Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study.

PubMed

Kim, Youl-Ri; Kim, Jeong-Hyun; Kim, Mi Jeong; Treasure, Janet

2014-01-01

Recent studies in patients with anorexia nervosa suggest that oxytocin may be involved in the pathophysiology of anorexia nervosa. We examined whether there was evidence of variation in methylation status of the oxytocin receptor (OXTR) gene in patients with anorexia nervosa that might account for these findings. We analyzed the methylation status of the CpG sites in a region from the exon 1 to the MT2 regions of the OXTR gene in buccal cells from 15 patients and 36 healthy women using bisulfite sequencing. We further examined whether methylation status was associated with markers of illness severity or form. We identified six CpG sites with significant differences in average methylation levels between the patient and control groups. Among the six differentially methylated CpG sites, five showed higher than average methylation levels in patients than those in the control group (64.9-88.8% vs. 6.6-45.0%). The methylation levels of these five CpG sites were negatively associated with body mass index (BMI). BMI, eating disorders psychopathology, and anxiety were identified in a regression analysis as factors affecting the methylation levels of these CpG sites with more variation accounted for by BMI. Epigenetic misregulation of the OXTR gene may be implicated in anorexia nervosa, which may either be a mechanism linking environmental adversity to risk or may be a secondary consequence of the illness.

Enhanced treatment of Fischer-Tropsch wastewater using up-flow anaerobic sludge blanket system coupled with micro-electrolysis cell: A pilot scale study.

PubMed

Wang, Dexin; Han, Yuxing; Han, Hongjun; Li, Kun; Xu, Chunyan

2017-08-01

The coupling of micro-electrolysis cell (MEC) with an up-flow anaerobic sludge blanket (UASB) system in pilot scale was established for enhanced treatment of Fischer-Tropsch (F-T) wastewater. The lowest influent pH (4.99±0.10) and reduced alkali addition were accomplished under the assistance of anaerobic effluent recycling of 200% (stage 5). Simultaneously, the optimum COD removal efficiency (93.5±1.6%) and methane production (2.01±0.13m 3 /m 3 ·d) at the lower hydraulic retention time (HRT) were achieved in this stage. In addition, the dissolved iron from MEC could significantly increase the protein content of tightly bound extracellular polymeric substances (TB-EPS), which was beneficial to formation of stable granules. Furthermore, the high-throughput 16S rRNA gene pyrosequencing in this study further confirmed that Geobacter species could utilize iron oxides particles as electron conduit to perform the direct interspecies electron transfer (DIET) with Methanothrix, finally facilitating the syntrophic degradation of propionic acid and butyric acid and contributing completely methane production. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genenames.org: the HGNC and VGNC resources in 2017.

PubMed

Yates, Bethan; Braschi, Bryony; Gray, Kristian A; Seal, Ruth L; Tweedie, Susan; Bruford, Elspeth A

2017-01-04

The HUGO Gene Nomenclature Committee (HGNC) based at the European Bioinformatics Institute (EMBL-EBI) assigns unique symbols and names to human genes. Currently the HGNC database contains almost 40 000 approved gene symbols, over 19 000 of which represent protein-coding genes. In addition to naming genomic loci we manually curate genes into family sets based on shared characteristics such as homology, function or phenotype. We have recently updated our gene family resources and introduced new improved visualizations which can be seen alongside our gene symbol reports on our primary website http://www.genenames.org In 2016 we expanded our remit and formed the Vertebrate Gene Nomenclature Committee (VGNC) which is responsible for assigning names to vertebrate species lacking a dedicated nomenclature group. Using the chimpanzee genome as a pilot project we have approved symbols and names for over 14 500 protein-coding genes in chimpanzee, and have developed a new website http://vertebrate.genenames.org to distribute these data. Here, we review our online data and resources, focusing particularly on the improvements and new developments made during the last two years. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound

PubMed Central

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-01-01

Background Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era where tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesize that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Study Design Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (Arm 1) versus SLNB (Arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Results 68 subjects were enrolled in the pilot phase of the trial (34 subjects in Arm 1, no further staging; 32 subjects in Arm 2, SLNB, and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40-80) in Arm 1 and 59 years (range 31-81) in Arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1-32). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (> 2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Conclusions Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. PMID:27212005

Pilot-model analysis and simulation study of effect of control task desired control response

NASA Technical Reports Server (NTRS)

Adams, J. J.; Gera, J.; Jaudon, J. B.

1978-01-01

A pilot model analysis was performed that relates pilot control compensation, pilot aircraft system response, and aircraft response characteristics for longitudinal control. The results show that a higher aircraft short period frequency is required to achieve superior pilot aircraft system response in an altitude control task than is required in an attitude control task. These results were confirmed by a simulation study of target tracking. It was concluded that the pilot model analysis provides a theoretical basis for determining the effect of control task on pilot opinions.

Soil mesocosm studies on atrazine bioremediation.

PubMed

Sagarkar, Sneha; Nousiainen, Aura; Shaligram, Shraddha; Björklöf, Katarina; Lindström, Kristina; Jørgensen, Kirsten S; Kapley, Atya

2014-06-15

Accumulation of pesticides in the environment causes serious issues of contamination and toxicity. Bioremediation is an ecologically sound method to manage soil pollution, but the bottleneck here, is the successful scale-up of lab-scale experiments to field applications. This study demonstrates pilot-scale bioremediation in tropical soil using atrazine as model pollutant. Mimicking field conditions, three different bioremediation strategies for atrazine degradation were explored. 100 kg soil mesocosms were set-up, with or without atrazine application history. Natural attenuation and enhanced bioremediation were tested, where augmentation with an atrazine degrading consortium demonstrated best pollutant removal. 90% atrazine degradation was observed in six days in soil previously exposed to atrazine, while soil without history of atrazine use, needed 15 days to remove the same amount of amended atrazine. The bacterial consortium comprised of 3 novel bacterial strains with different genetic atrazine degrading potential. The progress of bioremediation was monitored by measuring the levels of atrazine and its intermediate, cyanuric acid. Genes from the atrazine degradation pathway, namely, atzA, atzB, atzD, trzN and trzD were quantified in all mesocosms for 60 days. The highest abundance of all target genes was observed on the 6th day of treatment. trzD was observed in the bioaugmented mesocosms only. The bacterial community profile in all mesocosms was monitored by LH-PCR over a period of two months. Results indicate that the communities changed rapidly after inoculation, but there was no drastic change in microbial community profile after 1 month. Results indicated that efficient bioremediation of atrazine using a microbial consortium could be successfully up-scaled to pilot scale. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of tobacco smoke and electronic cigarette vapor exposure on the oral and gut microbiota in humans: a pilot study.

PubMed

Stewart, Christopher J; Auchtung, Thomas A; Ajami, Nadim J; Velasquez, Kenia; Smith, Daniel P; De La Garza, Richard; Salas, Ramiro; Petrosino, Joseph F

2018-01-01

The use of electronic cigarettes (ECs) has increased drastically over the past five years, primarily as an alternative to smoking tobacco cigarettes. However, the adverse effects of acute and long-term use of ECs on the microbiota have not been explored. In this pilot study, we sought to determine if ECs or tobacco smoking alter the oral and gut microbiota in comparison to non-smoking controls. We examined a human cohort consisting of 30 individuals: 10 EC users, 10 tobacco smokers, and 10 controls. We collected cross-sectional fecal, buccal swabs, and saliva samples from each participant. All samples underwent V4 16S rRNA gene sequencing. Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella ( P = 0.006) and decreased Bacteroides ( P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced ( P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls. From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted.

SUPERFUND TREATABILITY CLEARINGHOUSE: SOIL STABILIZATION PILOT STUDY, UNITED CHROME NPL SITE PILOT STUDY AND HEALTH AND SAFETY PROGRAM, UNITED CHROME NPL SITE PILOT STUDY

EPA Science Inventory

This document is a project plan for a pilot study at the United Chrome NPL site, Corvallis, Oregon and includes the health and safety and quality assurance/quality control plans. The plan reports results of a bench-scale study of the treatment process as iieasured by the ...

Sphingosine-1-Phosphate Signaling and Metabolism Gene Signature in Pediatric Inflammatory Bowel Disease: A Matched-case Control Pilot Study

PubMed Central

Suh, Jung H.; Degagné, Émilie; Gleghorn, Elizabeth E.; Setty, Mala; Rodriguez, Alexis; Park, K. T.; Verstraete, Sofia G.; Heyman, Melvin B.; Patel, Ashish S.; Irek, Melissa; Gildengorin, Ginny L.; Hubbard, Neil E.; Borowsky, Alexander D.; Saba, Julie D.

2018-01-01

Goal The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population. Background IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals. Clinical IBD trials now underway target S1PR1, a receptor for the pro-inflammatory sphingolipid S1P. However, circulating and tissue sphingolipid levels and S1P-related gene expression have not been characterized in pediatric IBD. Methods Pediatric IBD patients and controls were recruited in a four-site study. Patients received a clinical score using PUCAI or PCDAI evaluation. Colon biopsies were collected during endoscopy. Gene expression was measured by qRT-PCR. Plasma and gut tissue sphingolipids were measured by LC-MS/MS. Results Genes of S1P synthesis (SPHK1, SPHK2), degradation (SGPL1), and signaling (S1PR1, S1PR2, and S1PR4) were significantly upregulated in colon biopsies of IBD patients with moderate/severe symptoms compared with controls or patients in remission. Tissue ceramide, dihydroceramide, and ceramide-1-phosphate (C1P) levels were significantly elevated in IBD patients compared with controls. Conclusions A signature of elevated S1P-related gene expression in colon tissues of pediatric IBD patients correlates with active disease and normalizes in remission. Biopsied gut tissue from symptomatic IBD patients contains high levels of pro-apoptotic and pro-inflammatory sphingolipids. A combined analysis of gut tissue sphingolipid profiles with this S1P-related gene signature may be useful for monitoring response to conventional therapy. PMID:29788359

Influence of allelic variations in relation to norepinephrine and mineralocorticoid receptors on psychopathic traits: a pilot study

PubMed Central

2018-01-01

Background Past findings support a relationship between abnormalities in the amygdala and the presence of psychopathic traits. Among other genes and biomarkers relevant to the amygdala, norepinephrine and mineralocorticoid receptors might both play a role in psychopathy due to their association with traits peripheral to psychopathy. The purpose is to examine if allelic variations in single nucleotide polymorphisms related to norepinephrine and mineralocorticoid receptors play a role in the display of psychopathic traits and executive functions. Methods Fifty-seven healthy participants from the community provided a saliva sample for SNP sampling of rs5522 and rs5569. Participants then completed the Psychopathic Personality Inventory–Short Form (PPI-SF) and the Tower of Hanoi. Results Allelic variations of both rs5522 and rs5569 were significant when compared to PPI-SF total score and the fearless dominance component of the PPI-SF. A significant result was also obtained between rs5522 and the number of moves needed to complete the 5-disk Tower of Hanoi. Conclusion This pilot study offers preliminary results regarding the effect of allelic variations in SNPs related to norepinephrine and mineralocorticoid receptors on the presence of psychopathic traits. Suggestions are provided to enhance the reliability and validity of a larger-scale study. PMID:29576985

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer.

PubMed

Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

2017-09-01

We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa -high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa -low PSA and non PCa -high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa.

A pilot study assessing the association between paraoxonase 1 gene polymorphism and prostate cancer

PubMed Central

Uluocak, Nihat; Atılgan, Doğan; Parlaktaş, Bekir Süha; Erdemir, Fikret; Ateş, Ömer

2017-01-01

Objective We aimed to show the relationship between paraoxonase 1 (PON1) gene polymorphism and the development of prostate cancer (PCa). Material and methods We investigated the association of single nuclotide polymorphisms of PON1 enzyme with the development of PCa risk. A total of 147 male patients were divided into PCa, and control groups. The control group was also divided into two subgroups according to serum prostate specific antigen (PSA) levels as non PCa-high PSA (>4 ng/mL) and non PCa-low PSA (≤4 ng/mL) groups. Results The mean ages of the patients were 64.81 years, 63.27 years and 64.22 years in PCa group, non PCa-low PSA and non PCa –high PSA groups, respectively. The mean PSA levels were 10.9 ng/mL, 1.16 ng/mL and 6.63 ng/mL for PCa group, non PCa –low PSA and non PCa –high PSA groups, respectively. In terms of PON1 polymorphisms and allele frequencies, there were no statistically significant differences between PCa and control groups. There was not a statistically significant difference between PCa and non PCa-high PSA groups as for genotypic and allelic frequencies. As a result of this small sample sized hypothetical study of polymorphism, a relationship could not be detected between PCa development and PON1 gene polymorphism. Conclusion According to the results of this preliminary study, it is thought that more comprehensive future studies are necessary to clarify the possible role of PON1 gene polymorphism in the etiology of PCa. PMID:28861298

Targeted and genome-scale methylomics reveals gene body signatures in human cell lines

PubMed Central

Ball, Madeleine Price; Li, Jin Billy; Gao, Yuan; Lee, Je-Hyuk; LeProust, Emily; Park, In-Hyun; Xie, Bin; Daley, George Q.; Church, George M.

2012-01-01

Cytosine methylation, an epigenetic modification of DNA, is a target of growing interest for developing high throughput profiling technologies. Here we introduce two new, complementary techniques for cytosine methylation profiling utilizing next generation sequencing technology: bisulfite padlock probes (BSPPs) and methyl sensitive cut counting (MSCC). In the first method, we designed a set of ~10,000 BSPPs distributed over the ENCODE pilot project regions to take advantage of existing expression and chromatin immunoprecipitation data. We observed a pattern of low promoter methylation coupled with high gene body methylation in highly expressed genes. Using the second method, MSCC, we gathered genome-scale data for 1.4 million HpaII sites and confirmed that gene body methylation in highly expressed genes is a consistent phenomenon over the entire genome. Our observations highlight the usefulness of techniques which are not inherently or intentionally biased in favor of only profiling particular subsets like CpG islands or promoter regions. PMID:19329998

Pilot study of small bowel mucosal gene expression in patients with irritable bowel syndrome with diarrhea.

PubMed

Camilleri, Michael; Carlson, Paula; Valentin, Nelson; Acosta, Andres; O'Neill, Jessica; Eckert, Deborah; Dyer, Roy; Na, Jie; Klee, Eric W; Murray, Joseph A

2016-09-01

Prior studies in with irritable bowel syndrome with diarrhea (IBS-D) patients showed immune activation, secretion, and barrier dysfunction in jejunal or colorectal mucosa. We measured mRNA expression by RT-PCR of 91 genes reflecting tight junction proteins, chemokines, innate immunity, ion channels, transmitters, housekeeping genes, and controls for DNA contamination and PCR efficiency in small intestinal mucosa from 15 IBS-D and 7 controls (biopsies negative for celiac disease). Fold change was calculated using 2((-ΔΔCT)) formula. Nominal P values (P < 0.05) were interpreted with false detection rate (FDR) correction (q value). Cluster analysis with Lens for Enrichment and Network Studies (LENS) explored connectivity of mechanisms. Upregulated genes (uncorrected P < 0.05) were related to ion transport (INADL, MAGI1, and SONS1), barrier (TJP1, 2, and 3 and CLDN) or immune functions (TLR3, IL15, and MAPKAPK5), or histamine metabolism (HNMT); downregulated genes were related to immune function (IL-1β, TGF-β1, and CCL20) or antigen detection (TLR1 and 8). The following genes were significantly upregulated (q < 0.05) in IBS-D: INADL, MAGI1, PPP2R5C, MAPKAPK5, TLR3, and IL-15. Among the 14 nominally upregulated genes, there was clustering of barrier and PDZ domains (TJP1, TJP2, TJP3, CLDN4, INADL, and MAGI1) and clustering of downregulated genes (CCL20, TLR1, IL1B, and TLR8). Protein expression of PPP2R5C in nuclear lysates was greater in patients with IBS-D and controls. There was increase in INADL protein (median 9.4 ng/ml) in patients with IBS-D relative to controls (median 5.8 ng/ml, P > 0.05). In conclusion, altered transcriptome (and to lesser extent protein) expression of ion transport, barrier, immune, and mast cell mechanisms in small bowel may reflect different alterations in function and deserves further study in IBS-D. Copyright © 2016 the American Physiological Society.

Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma

PubMed Central

Abdelaziz, Mohamed; Sherif, Lotfy; ElKhiary, Mostafa; Nair, Sanjeeta; Shalaby, Shahinaz; Mohamed, Sara; Eziba, Noura; El-Lakany, Mohamed; Curiel, David; Ismail, Nahed; Diamond, Michael P.; Al-Hendy, Ayman

2016-01-01

Background: Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. Study design: An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. Materials and methods: Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad-TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR. Results: In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P < 0.05), reduced expression of proliferation marker (PCNA) (P < 0.05), induced expression of apoptotic protein, c-PARP-1, (P < 0.05) and inhibited expression of extracellular matrix-related genes (TGF beta 3) and angiogenesis-related genes (VEGF & IGF-1) (P < 0.01). There were no detectable adenovirus in tested tissues other than leiomyoma lesions with both targeted and untargeted adenovirus. Conclusion: Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. PMID:26884457

Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study.

PubMed

Salas, Antonio; Pardo-Seco, Jacobo; Barral-Arca, Ruth; Cebey-López, Miriam; Gómez-Carballa, Alberto; Rivero-Calle, Irene; Pischedda, Sara; Currás-Tuala, María-José; Amigo, Jorge; Gómez-Rial, José; Martinón-Torres, Federico

2018-05-03

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene MEIS1 ; chromosome 2; p -value IBS = 3.71 × 10 -13 ) and rs576099063 (gene TSPAN15 ; chromosome 10; p -value IBS = 2.36 × 10 -8 ) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, OR9G9 , MUC6 , MUC3A and APOB , which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of MEIS1, TSPAN15 and APOBR (encoding the receptor of the APOB protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene OR9G9 has recently been related to some viral infectious diseases, while the role of mucin genes ( MUC6 and MUC3A ), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases.

Whole Exome Sequencing Identifies New Host Genomic Susceptibility Factors in Empyema Caused by Streptococcus pneumoniae in Children: A Pilot Study

PubMed Central

Salas, Antonio; Barral-Arca, Ruth; Cebey-López, Miriam; Pischedda, Sara; Currás-Tuala, María-José; Gómez-Rial, José

2018-01-01

Pneumonia is the leading cause of death amongst infectious diseases. Streptococcus pneumoniae is responsible for about 25% of pneumonia cases worldwide, and it is a major cause of childhood mortality. We carried out a whole exome sequencing (WES) study in eight patients with complicated cases of pneumococcal pneumonia (empyema). An initial assessment of statistical association of WES variation with pneumonia was carried out using data from the 1000 Genomes Project (1000G) for the Iberian Peninsula (IBS) as reference controls. Pseudo-replication statistical analyses were carried out using different European control groups. Association tests pointed to single nucleotide polymorphism (SNP) rs201967957 (gene MEIS1; chromosome 2; p-valueIBS = 3.71 × 10−13) and rs576099063 (gene TSPAN15; chromosome 10; p-valueIBS = 2.36 × 10−8) as the best candidate variants associated to pneumococcal pneumonia. A burden gene test of pathogenicity signaled four genes, namely, OR9G9, MUC6, MUC3A and APOB, which carry significantly increased pathogenic variation when compared to controls. By analyzing various transcriptomic data repositories, we found strong supportive evidence for the role of MEIS1, TSPAN15 and APOBR (encoding the receptor of the APOB protein) in pneumonia in mouse and human models. Furthermore, the association of the olfactory receptor gene OR9G9 has recently been related to some viral infectious diseases, while the role of mucin genes (MUC6 and MUC3A), encoding mucin glycoproteins, are well-known factors related to chronic obstructive airway disease. WES emerges as a promising technique to disentangle the genetic basis of host genome susceptibility to infectious respiratory diseases. PMID:29751582

SUPERFUND TREATABILITY CLEARINGHOUSE: PILOT STUDY OF ENCLOSED THERMAL SOIL AERATION FOR REMOVAL OF VOLATILE ORGANIC CONTAMINATION AT THE MCKIN SUPERFUND SITE

EPA Science Inventory

This paper reports on the results of a pilot study that treated vadose zone soil contaminated with VOCs in an enclosed thermal aeration system. The McKin site, an NPL site in Grey, Maine, was the location of the pilot study. The pilot study was chosen to demonstrate the viabili...

Patent foramen ovale and asymptomatic brain lesions in military fighter pilots.

PubMed

Kang, Kyung Wook; Kim, Joon-Tae; Choi, Won-Ho; Park, Won-Ju; Shin, Young Ho; Choi, Kang-Ho

2014-10-01

Previous studies have reported higher incidence of white matter lesions (WMLs) in military pilots. The anti-gravity straining maneuver, which fighter military pilots perform numerously during a flight is identical to the valsalva maneuver. We sought to investigate the prevalence of right-to-left shunt (RLS) associated with WMLs in military pilots. A prospective study was performed involving military pilots who visited the Airomedical Center. The pilots underwent brain magnetic resonance imaging (MRI) scan and transcranial Doppler (TCD) with intravenous injection of agitated saline solution for the detection of RLS. Periventricular WMLs (PVWMLs) on MRI were graded using Fazeka's scale, and deep WMLs (DWMLs) were graded using Scheltens's scale. This study included 81 military pilots. RLS on TCD was observed less frequently in non-fighter pilots than in fighter pilots (35.5% vs. 64.5%, p=0.011). Fighter pilot was an independently associated factor with RLS on the TCD. DWMLs were independently associated with RLSs through a patent foramen ovale (PFO) (OR 3.507, 95% CI 1.223-10.055, p=0.02). The results suggest that DWMLs in military pilots may significantly be associated with RLS via PFO. Additional investigations are warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

[Salivary microbiome in people with obesity: a pilot study].

PubMed

Wu, Y J; Chi, X P; Chen, F; Deng, X L

2018-02-18

To investigate the characterization of the salivary microbiome in people with obesity and the differences in microbial composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight controls. The study was carried out in people with obesity and age- and sex-matched normal weight controls. None of these selected participants had the systemic disease, oral mucosal disease or periodontal disease. Unstimulated saliva samples were collected and oral examination was conducted. DNAs from saliva samples were extracted and sequenced in an Illumina NextSeq 500 platform. Community composition, linear discriminant analysis of taxonomic differences,gene prediction, gene set construction and annotation of gene function were performed. The classified bacterial reads of the samples were 2 630 428 for each sample. A total of 11 phyla, 19 classes, 26 orders, 41 families, 62 genera and 164 species were detected ultimately. All samples had the same predominant phyla (Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria). There were statistical differences between the groups at the class, order, family, genus and species levels. At the class level, Negativicutes and Erysipelotrichia were more abundant in the obesity group, while Flavobacteriia and Bateroidetes dominated in normal weight group (P<0.05). At the species level, 16 showed significant differences in relative abundance among the groups, in which Prevotella melaninogenica,Prevotella salivae,Solobacterium moorei and Atopobium parvulum ware more abundant in the obesity group, whereas Streptococcus sanguinis dominated in normal weight group (P<0.05). The people with obesity had a higher number of salivary microbial genes (P<0.05). We produced statistics on gene prediction and found salivary microbiome of obesity group had a higher number of genes (P < 0.05). Genes associated with the pathways of metabolism and environmental information processing and human diseases were significantly enriched in the saliva samples of people with obesity (P < 0.01). Significant differences were seen in composition, gene function and metabolic pathways of salivary microbiome between people with obesity and normal weight people. We hope to go on further study with larger sample size in the near future.

Expertise and responsibility effects on pilots' reactions to flight deck alerts in a simulator.

PubMed

Zheng, Yiyuan; Lu, Yanyu; Yang, Zheng; Fu, Shan

2014-11-01

Flight deck alerts provide system malfunction information designed to lead corresponding pilot reactions aimed at guaranteeing flight safety. This study examined the roles of expertise and flight responsibility and their relationship to pilots' reactions to flight deck alerts. There were 17 pilots composing 12 flight crews that were assigned into pairs according to flight hours and responsibilities. The experiment included 9 flight scenarios and was carried out in a CRJ-200 flight simulator. Pilot performance was recorded by a wide angle video camera, and four kinds of reactions to alerts were defined for analysis. Pilots tended to have immediate reactions to uninterrupted cautions, with a turning off rate as high as 75%. However, this rate decreased sharply when pilots encountered interrupted cautions and warnings; they also exhibited many wrong reactions to warnings. Pilots with more expertise had more reactions to uninterrupted cautions than those with less expertise, both as pilot flying and pilot monitoring. Meanwhile, the pilot monitoring, regardless of level of expertise, exhibited more reactions than the pilot flying. In addition, more experienced pilots were more likely to have wrong reactions to warnings while acting as the monitoring pilot. These results suggest that both expertise and flight responsibility influence pilots' reactions to alerts. Considering crew pairing strategy, when a pilot flying is a less experienced pilot, a more experience pilot is suggested to be the monitoring pilot. The results of this study have implications for understanding pilots' behaviors to flight deck alerts, calling for specialized training and design of approach alarms on the flight deck.

Human factors in aviation crashes involving older pilots.

PubMed

Li, Guohua; Baker, Susan P; Lamb, Margaret W; Grabowski, Jurek G; Rebok, George W

2002-02-01

Pilot errors are recognized as a contributing factor in as many as 80% of aviation crashes. Experimental studies using flight simulators indicate that due to decreased working memory capacity, older pilots are outperformed by their younger counterparts in communication tasks and flight summary scores. This study examines age-related differences in crash circumstances and pilot errors in a sample of pilots who flew commuter aircraft or air taxis and who were involved in airplane or helicopter crashes. A historical cohort of 3306 pilots who in 1987 flew commuter aircraft or air taxis and were 45-54 yr of age was constructed using the Federal Aviation Administration's airmen information system. Crash records of the study subjects for the years 1983-1997 were obtained from the National Transportation Safety Board (NTSB) by matching name and date of birth. NTSB's investigation reports were reviewed to identify pilot errors and other contributing factors. Comparisons of crash circumstances and human factors were made between pilots aged 40-49 yr and pilots aged 50-63 yr. A total of 165 crash records were studied, with 52% of these crashes involving pilots aged 50-63 yr. Crash circumstances, such as time and location of crash, type and phase of flight, and weather conditions, were similar between the two age groups. Pilot error was a contributing factor in 73% of the crashes involving younger pilots and in 69% of the crashes involving older pilots (p = 0.50). Age-related differences in the pattern of pilot errors were statistically insignificant. Overall, 23% of pilot errors were attributable to inattentiveness, 20% to flawed decisions, 18% to mishandled aircraft kinetics, and 18% to mishandled wind/runway conditions. Neither crash circumstances nor the prevalence and patterns of pilot errors appear to change significantly as age increases from the 40s to the 50s and early 60s.

Partnering for functional genomics research conference: Abstracts of poster presentations

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-06-01

This reports contains abstracts of poster presentations presented at the Functional Genomics Research Conference held April 16--17, 1998 in Oak Ridge, Tennessee. Attention is focused on the following areas: mouse mutagenesis and genomics; phenotype screening; gene expression analysis; DNA analysis technology development; bioinformatics; comparative analyses of mouse, human, and yeast sequences; and pilot projects to evaluate methodologies.

Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

PubMed

Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2014-01-01

Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

PubMed Central

Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2015-01-01

Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

Randomized pilot trial of gene expression profiling versus heart biopsy in the first year after heart transplant: early invasive monitoring attenuation through gene expression trial.

PubMed

Kobashigawa, Jon; Patel, Jignesh; Azarbal, Babak; Kittleson, Michelle; Chang, David; Czer, Lawrence; Daun, Tiffany; Luu, Minh; Trento, Alfredo; Cheng, Richard; Esmailian, Fardad

2015-05-01

The endomyocardial biopsy (EMB) is considered the gold standard in rejection surveillance post cardiac transplant, but is invasive, with risk of complications. A previous trial suggested that the gene expression profiling (GEP) blood test was noninferior to EMB between 6 and 60 months post transplant. As most rejections occur in the first 6 months, we conducted a single-center randomized trial of GEP versus EMB starting at 55 days post transplant (when GEP is valid). Sixty heart transplant patients meeting inclusion criteria were randomized beginning at 55 days post transplant to either GEP or EMB arms. A positive GEP ≥30 between 2 and 6 months, or ≥34 after 6 months, prompted a follow-up biopsy. The primary end point included a composite of death/retransplant, rejection with hemodynamic compromise or graft dysfunction at 18 months post transplant. A coprimary end point included change in first-year maximal intimal thickness by intravascular ultrasound, a recognized surrogate for long-term outcome. Corticosteroid weaning was assessed in both the groups. The composite end point was similar between the GEP and EMB groups (10% versus 17%; log-rank P=0.44). The coprimary end point of first-year intravascular ultrasound change demonstrated no difference in mean maximal intimal thickness (0.35±0.36 versus 0.36±0.26 mm; P=0.944). Steroid weaning was successful in both the groups (91% versus 95%). In this pilot study, GEP starting at 55 days post transplant seems comparable with EMB for rejection surveillance in selected heart transplant patients and does not result in increased adverse outcomes. GEP also seems useful to guide corticosteroid weaning. Larger randomized trials are required to confirm these findings. URL: http://www.clinicaltrials.gov. Unique identifier: NCT014182482377. © 2015 American Heart Association, Inc.

Genome-wide gene–environment interaction analysis for asbestos exposure in lung cancer susceptibility

PubMed Central

Wei, Qingyi Wei

2012-01-01

Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene–environment interactions. To determine gene–asbestos interactions in lung cancer risk, we conducted genome-wide gene–environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10–6, which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10–5). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene–asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk. Abbreviations:CIconfidence intervalEenvironmentFDRfalse discovery rateGgeneGSEAgene-set-enrichment analysisGWASgenome-wide association studiesi-GSEAimproved gene-set-enrichment analysis approachORodds ratioSNPsingle nucleotide polymorphism PMID:22637743

Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

PubMed Central

Miller-Delaney, Suzanne F.C.; Bryan, Kenneth; Das, Sudipto; McKiernan, Ross C.; Bray, Isabella M.; Reynolds, James P.; Gwinn, Ryder; Stallings, Raymond L.

2015-01-01

Temporal lobe epilepsy is associated with large-scale, wide-ranging changes in gene expression in the hippocampus. Epigenetic changes to DNA are attractive mechanisms to explain the sustained hyperexcitability of chronic epilepsy. Here, through methylation analysis of all annotated C-phosphate-G islands and promoter regions in the human genome, we report a pilot study of the methylation profiles of temporal lobe epilepsy with or without hippocampal sclerosis. Furthermore, by comparative analysis of expression and promoter methylation, we identify methylation sensitive non-coding RNA in human temporal lobe epilepsy. A total of 146 protein-coding genes exhibited altered DNA methylation in temporal lobe epilepsy hippocampus (n = 9) when compared to control (n = 5), with 81.5% of the promoters of these genes displaying hypermethylation. Unique methylation profiles were evident in temporal lobe epilepsy with or without hippocampal sclerosis, in addition to a common methylation profile regardless of pathology grade. Gene ontology terms associated with development, neuron remodelling and neuron maturation were over-represented in the methylation profile of Watson Grade 1 samples (mild hippocampal sclerosis). In addition to genes associated with neuronal, neurotransmitter/synaptic transmission and cell death functions, differential hypermethylation of genes associated with transcriptional regulation was evident in temporal lobe epilepsy, but overall few genes previously associated with epilepsy were among the differentially methylated. Finally, a panel of 13, methylation-sensitive microRNA were identified in temporal lobe epilepsy including MIR27A, miR-193a-5p (MIR193A) and miR-876-3p (MIR876), and the differential methylation of long non-coding RNA documented for the first time. The present study therefore reports select, genome-wide DNA methylation changes in human temporal lobe epilepsy that may contribute to the molecular architecture of the epileptic brain. PMID:25552301

DHPLC technology for high-throughput detection of mutations in a durum wheat TILLING population.

PubMed

Colasuonno, Pasqualina; Incerti, Ornella; Lozito, Maria Luisa; Simeone, Rosanna; Gadaleta, Agata; Blanco, Antonio

2016-02-17

Durum wheat (Triticum turgidum L.) is a cereal crop widely grown in the Mediterranean regions; the amber grain is mainly used for the production of pasta, couscous and typical breads. Single nucleotide polymorphism (SNP) detection technologies and high-throughput mutation induction represent a new challenge in wheat breeding to identify allelic variation in large populations. The TILLING strategy makes use of traditional chemical mutagenesis followed by screening for single base mismatches to identify novel mutant loci. Although TILLING has been combined to several sensitive pre-screening methods for SNP analysis, most rely on expensive equipment. Recently, a new low cost and time saving DHPLC protocol has been used in molecular human diagnostic to detect unknown mutations. In this work, we developed a new durum wheat TILLING population (cv. Marco Aurelio) using 0.70-0.85% ethyl methane sulfonate (EMS). To investigate the efficiency of the mutagenic treatments, a pilot screening was carried out on 1,140 mutant lines focusing on two target genes (Lycopene epsilon-cyclase, ε-LCY, and Lycopene beta-cyclase, β-LCY) involved in carotenoid metabolism in wheat grains. We simplify the heteroduplex detection by two low cost methods: the enzymatic cleavage (CelI)/agarose gel technique and the denaturing high-performance liquid chromatography (DHPLC). The CelI/agarose gel approach allowed us to identify 31 mutations, whereas the DHPLC procedure detected a total of 46 mutations for both genes. All detected mutations were confirmed by direct sequencing. The estimated overall mutation frequency for the pilot assay by the DHPLC methodology resulted to be of 1/77 kb, representing a high probability to detect interesting mutations in the target genes. We demonstrated the applicability and efficiency of a new strategy for the detection of induced variability. We produced and characterized a new durum wheat TILLING population useful for a better understanding of key gene functions. The availability of this tool together with TILLING technique will expand the polymorphisms in candidate genes of agronomically important traits in wheat.

Rapid Gynogenetic Mapping of Xenopus tropicalis Mutations to Chromosomes

PubMed Central

Khokha, Mustafa K.; Krylov, Vladimir; Reilly, Michael J.; Gall, Joseph G.; Bhattacharya, Dipankan; Cheung, Chung Yan J.; Kaufman, Sarah; Lam, Dang Khoa; Macha, Jaroslav; Ngo, Catherine; Prakash, Neha; Schmidt, Philip; Tlapakova, Tereza; Trivedi, Toral; Tumova, Lucie; Abu-Daya, Anita; Geach, Timothy; Vendrell, Elisenda; Ironfield, Holly; Sinzelle, Ludivine; Sater, Amy K.; Wells, Dan E.; Harland, Richard M.; Zimmerman, Lyle B.

2010-01-01

Pilot forward genetic screens in Xenopus tropicalis have isolated over 60 recessive mutations (Grammer et al., 2005; Noramly et al., 2005; Goda et al., 2006). Here we present a simple method for mapping mutations to chromosomes using gynogenesis and centromeric markers. When coupled with available genomic resources, gross mapping facilitates evaluation of candidate genes as well as higher resolution linkage studies. Using gynogenesis, we have mapped the genetic locations of the 10 X. tropicalis centromeres, and performed Fluorescence In Situ Hybridization to validate these locations cytologically. We demonstrate the use of this very small set of centromeric markers to map mutations efficiently to specific chromosomes. PMID:19441086

The psychophysiological assessment method for pilot's professional reliability.

PubMed

Zhang, L M; Yu, L S; Wang, K N; Jing, B S; Fang, C

1997-05-01

Previous research has shown that a pilot's professional reliability depends on two relative factors: the pilot's functional state and the demands of task workload. The Psychophysiological Reserve Capacity (PRC) is defined as a pilot's ability to accomplish additive tasks without reducing the performance of the primary task (flight task). We hypothesized that the PRC was a mirror of the pilot's functional state. The purpose of this study was to probe the psychophysiological method for evaluating a pilot's professional reliability on a simulator. The PRC Comprehensive Evaluating System (PRCCES) which was used in the experiment included four subsystems: a) quantitative evaluation system for pilot's performance on simulator; b) secondary task display and quantitative estimating system; c) multiphysiological data monitoring and statistical system; and d) comprehensive evaluation system for pilot PRC. Two studies were performed. In study one, 63 healthy and 13 hospitalized pilots participated. Each pilot performed a double 180 degrees circuit flight program with and without secondary task (three digit operation). The operator performance, score of secondary task and cost of physiological effort were measured and compared by PRCCES in the two conditions. Then, each pilot's flight skill in training was subjectively scored by instructor pilot ratings. In study two, 7 healthy pilots volunteered to take part in the experiment on the effects of sleep deprivation on pilot's PRC. Each participant had PRC tested pre- and post-8 h sleep deprivation. The results show that the PRC values of a healthy pilot was positively correlated with abilities of flexibility, operating and correcting deviation, attention distribution, and accuracy of instrument flight in the air (r = 0.27-0.40, p < 0.05), and negatively correlated with emotional anxiety in flight (r = -0.40, p < 0.05). The values of PRC in healthy pilots (0.61 +/- 0.17) were significantly higher than that of hospitalized pilots (0.43 +/- 0.15) (p < 0.05). The PRC value after 8 h sleep loss (0.50 +/- 0.17) was significantly lower than those before sleep loss (0.70 +/- 0.15) (p < 0.05). We conclude that a pilot's PRC, which was closely related to flight ability and functional state, could partly represent the pilot's professional reliability. It is worthwhile to further research using a pilot's PRC as a predictor of mental workload in aircraft design.

Potential diagnostic biomarkers for chronic kidney disease of unknown etiology (CKDu) in Sri Lanka: a pilot study.

PubMed

Sayanthooran, Saravanabavan; Magana-Arachchi, Dhammika N; Gunerathne, Lishanthe; Abeysekera, Tilak

2017-01-19

In Sri Lanka, there exists chronic kidney disease of both known (CKD) and unknown etiologies (CKDu). Identification of novel biomarkers that are customized to the specific causative factors would lead to early diagnosis and clearer prognosis of the diseases. This study aimed to find genetic biomarkers in blood to distinguish and identify CKDu from CKD as well as healthy populations from CKDu endemic and non-endemic areas of Sri Lanka. The expression patterns of a selected panel of 12 potential genetic biomarkers were analyzed in blood using RT-qPCR. Fold changes of gene expressions in early and late stages of CKD and CKDu patients, and an apparently healthy population of a CKDu endemic area, Girandurukotte (GH) were calculated relative to apparently healthy volunteers from a CKDu non-endemic area, Kandy (KH) of Sri Lanka, using the comparative CT method. Significant differences were observed between KH and early stage CKDu for both the insulin-like growth factor binding protein 1 (IGFBP1; p = 0.012) and kidney injury molecule-1 (KIM1; p = 0.003) genes, and KH and late stage CKD and CKDu for the glutathione-S-transferase mu 1 (GSTM1; p < 0.05) gene. IGFBP1 and KIM1 genes showed significant difference between the early and late stage CKDu (p < 0.01). The glutamate cysteine ligase catalytic subunit (GCLC) gene had significantly different expression between KH and all the other study groups (p < 0.01). The GH group was significantly different from the KH group for the oxidative stress related genes, G6PD, GCLC and GSTM1 (p < 0.01), and also the KIM1 gene (p = 0.003). IGFBP1, insulin-like growth factor binding protein 3 (IGFBP3), fibronectin 1 (FN1) and KIM1 showed significant correlations with serum creatinine, and IGFBP1, KIM1 and kallikrein 1 (KLK1) with eGFR (p < 0.05). A panel consisting of IGFBP1, KIM1, GCLC and GSTM1 genes could be used in combination for early screening of CKDu, whereas these genes in addition with FN1, IGFBP3 and KLK1 could be used to monitor progression of CKDu. The regulation of these genes has to be studied on larger populations to validate their efficiency for further clinical use.

Arab-American adolescent tobacco use: four pilot studies.

PubMed

Rice, Virginia Hill; Templin, Thomas; Kulwicki, Anahid

2003-11-01

Four pilot studies were conducted to determine the (1) current tobacco use patterns and predictors among 14- to 18-year-old Arab-American youths; (2) psychometric properties of study measures (English and Arabic); (3) cultural appropriateness of Project Toward No Tobacco (TNT) for intervention; (4) accessible population for a longitudinal study. Three studies were descriptive and one used a pretest-posttest design. From four Pilot Focus groups (N = 28 smokers) key tobacco use themes emerged along with information on study measures and the Project TNT intervention; Pilot Intervention tested the tailored Project TNT intervention with 9 Arab-American teens; Pilot Clinic (N = 44) determined the characteristics of the accessible teen health clinic population; and Pilot School (N = 119) obtained tobacco use data only. From Pilot Focus seven themes (being cool, "nshar ma'a al shabab" [hanging out with the guys], present [time] orientation, smoking feels and tastes good, keeps your mind off trouble, easy to get, and (many) "barriers to quitting") emerged from the data. In the Pilot Intervention a 37.5% cessation rate was found. In the Pilot Clinic study, 24% males and 17% females smoked. The current smoking rate in the Pilot School (N = 119) sample was 17%; 34% admitted to having ever smoked (even a puff). Significant predictors for current tobacco use included poor grades, stress, having many family members and peers who smoke, being exposed to many hours of smoking each day, receiving offers of tobacco products, advertising and mail, and believing that tobacco can help one to make friends. The four pilots contributed unique and essential knowledge for designing a longitudinal clinical trial on tobacco use by Arab-American adolescents.

Epigenetics insights into chronic pain: DNA hypomethylation in fibromyalgia-a controlled pilot-study.

PubMed

Ciampi de Andrade, Daniel; Maschietto, Mariana; Galhardoni, Ricardo; Gouveia, Gisele; Chile, Thais; Victorino Krepischi, Ana C; Dale, Camila S; Brunoni, André R; Parravano, Daniella C; Cueva Moscoso, Ana S; Raicher, Irina; Kaziyama, Helena H S; Teixeira, Manoel J; Brentani, Helena P

2017-08-01

To evaluate changes in DNA methylation profiles in patients with fibromyalgia (FM) compared to matched healthy controls (HCs). All individuals underwent full clinical and neurophysiological assessment by cortical excitability (CE) parameters measured by transcranial magnetic stimulation. DNA from the peripheral blood of patients with FM (n = 24) and HC (n = 24) were assessed using the Illumina-HumanMethylation450 BeadChips. We identified 1610 differentially methylated positions (DMPs) in patients with FM displaying a nonrandom distribution in regions of the genome. Sixty-nine percent of DMP in FM were hypomethylated compared to HC. Differentially methylated positions were enriched in 5 genomic regions (1p34; 6p21; 10q26; 17q25; 19q13). The functional characterization of 960 genes related to DMPs revealed an enrichment for MAPK signaling pathway (n = 18 genes), regulation of actin cytoskeleton (n = 15 genes), and focal adhesion (n = 13 genes). A gene-gene interaction network enrichment analysis revealed the participation of DNA repair pathways, mitochondria-related processes, and synaptic signaling. Even though DNA was extracted from peripheral blood, this set of genes was enriched for disorders such as schizophrenia, mood disorders, bulimia, hyperphagia, and obesity. Remarkably, the hierarchical clusterization based on the methylation levels of the 1610 DMPs showed an association with neurophysiological measurements of CE in FM and HC. Fibromyalgia has a hypomethylation DNA pattern, which is enriched in genes implicated in stress response and DNA repair/free radical clearance. These changes occurred parallel to changes in CE parameters. New epigenetic insights into the pathophysiology of FM may provide the basis for the development of biomarkers of this disorder.

Nitrogen cycling processes and microbial community composition in bed sediments in the Yukon River at Pilot Station

USGS Publications Warehouse

Repert, Deborah A.; Underwood, Jennifer C.; Smith, Richard L.; Song, Bongkeun

2014-01-01

Information on the contribution of nitrogen (N)-cycling processes in bed sediments to river nutrient fluxes in large northern latitude river systems is limited. This study examined the relationship between N-cycling processes in bed sediments and N speciation and loading in the Yukon River near its mouth at the Bering Sea. We conducted laboratory bioassays to measure N-cycling processes in sediment samples collected over distinct water cycle seasons. In conjunction, the microbial community composition in the bed sediments using genes involved in N-cycling (narG, napA, nosZ, and amoA) and 16S rRNA gene pyrosequences was examined. Temporal variation was observed in net N mineralization, nitrate uptake, and denitrification rate potentials and correlated strongly with sediment carbon (C) and extractable N content and microbial community composition rather than with river water nutrient concentrations. The C content of the bed sediment was notably impacted by the spring flood, ranging from 1.1% in the midst of an ice-jam to 0.1% immediately after ice-out, suggesting a buildup of organic material (OM) prior to scouring of the bed sediments during ice break up. The dominant members of the microbial community that explained differences in N-processing rates belonged to the genera Crenothrix,Flavobacterium, and the family of Comamonadaceae. Our results suggest that biogeochemical processing rates in the bed sediments appear to be more coupled to hydrology, nutrient availability in the sediments, and microbial community composition rather than river nutrient concentrations at Pilot Station.

Genetic (In)stability of 2,6-Dichlorobenzamide Catabolism in Aminobacter sp. Strain MSH1 Biofilms under Carbon Starvation Conditions

PubMed Central

Raes, Bart; Brocatus, Hannelore; T'Syen, Jeroen; Rombouts, Caroline; Vanhaecke, Lynn; Hofkens, Johan; Springael, Dirk

2017-01-01

ABSTRACT Aminobacter sp. strain MSH1 grows on and mineralizes the groundwater micropollutant 2,6-dichlorobenzamide (BAM) and is of interest for BAM removal in drinking water treatment plants (DWTPs). The BAM-catabolic genes in MSH1 are located on plasmid pBAM1, carrying bbdA, which encodes the conversion of BAM to 2,6-dichlorobenzoic acid (2,6-DCBA) (BbdA+ phenotype), and plasmid pBAM2, carrying gene clusters encoding the conversion of 2,6-DCBA to tricarboxylic acid (TCA) cycle intermediates (Dcba+ phenotype). There are indications that MSH1 easily loses its BAM-catabolic phenotype. We obtained evidence that MSH1 rapidly develops a population that lacks the ability to mineralize BAM when grown on nonselective (R2B medium) and semiselective (R2B medium with BAM) media. Lack of mineralization was explained by loss of the Dcba+ phenotype and corresponding genes. The ecological significance of this instability for the use of MSH1 for BAM removal in the oligotrophic environment of DWTPs was explored in lab and pilot systems. A higher incidence of BbdA+ Dcba− MSH1 cells was also observed when MSH1 was grown as a biofilm in flow chambers under C and N starvation conditions due to growth on nonselective residual assimilable organic carbon. Similar observations were made in experiments with a pilot sand filter reactor bioaugmented with MSH1. BAM conversion to 2,6-DCBA was not affected by loss of the DCBA-catabolic genes. Our results show that MSH1 is prone to BAM-catabolic instability under the conditions occurring in a DWTP. While conversion of BAM to 2,6-DCBA remains unaffected, BAM mineralization activity is at risk, and monitoring of metabolites is warranted. IMPORTANCE Bioaugmentation of dedicated biofiltration units with bacterial strains that grow on and mineralize micropollutants was suggested as an alternative for treating micropollutant-contaminated water in drinking water treatment plants (DWTPs). Organic-pollutant-catabolic genes in bacteria are often easily lost, especially under nonselective conditions, which affects the bioaugmentation success. In this study, we provide evidence that Aminobacter sp. strain MSH1, which uses the common groundwater micropollutant 2,6-dichlorobenzamide (BAM) as a C source, shows a high frequency of loss of its BAM-mineralizing phenotype due to the loss of genes that convert 2,6-DCBA to Krebs cycle intermediates when nonselective conditions occur. Moreover, we show that catabolic-gene loss also occurs in the oligotrophic environment of DWTPs, where growth of MSH1 depends mainly on the high fluxes of low concentrations of assimilable organic carbon, and hence show the ecological relevance of catabolic instability for using strain MSH1 for BAM removal in DWTPs. PMID:28363960

78 FR 23941 - Pilot Program for Early Feasibility Study Investigational Device Exemption Applications...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

...] Pilot Program for Early Feasibility Study Investigational Device Exemption Applications; Extending the... 13343), FDA terminated the acceptance of applications into the program and extended the pilot program for the nine accepted sponsors until May 8, 2013. The pilot program will be further extended for the...

Molecular genetics external quality assessment pilot scheme for KRAS analysis in metastatic colorectal cancer.

PubMed

Deans, Zandra C; Tull, Justyna; Beighton, Gemma; Abbs, Stephen; Robinson, David O; Butler, Rachel

2011-11-01

Laboratories are increasingly required to perform molecular tests for the detection of mutations in the KRAS gene in metastatic colorectal cancers to allow better clinical management and more effective treatment for these patients. KRAS mutation status predicts a patient's likely response to the monoclonal antibody cetuximab. To provide a high standard of service, these laboratories require external quality assessment (EQA) to monitor the level of laboratory output and measure the performance of the laboratory against other service providers. National External Quality Assurance Services for Molecular Genetics provided a pilot EQA scheme for KRAS molecular analysis in metastatic colorectal cancers during 2009. Very few genotyping errors were reported by participating laboratories; however, the reporting nomenclature of the genotyping results varied considerably between laboratories. The pilot EQA scheme highlighted the need for continuing EQA in this field which will assess the laboratories' ability not only to obtain accurate, reliable results but also to interpret them safely and correctly ensuring that the referring clinician has the correct information to make the best clinical therapeutic decision for their patient.

Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study.

PubMed

Nishikawa, Saori; Toshima, Tamotsu; Kobayashi, Masao

2015-01-01

This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy) during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age = 24.05 years old) provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing]), and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task), and a gene × environment (G × E) interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links.

Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study

PubMed Central

Nishikawa, Saori

2015-01-01

This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy) during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age = 24.05 years old) provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing]), and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task), and a gene × environment (G×E) interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links. PMID:26418317

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

PubMed

Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M

2016-01-01

We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof of principle study with colorectal cancer

PubMed Central

Tang, Jie; Li, Yaping; Lyon, Kenneth; Camps, Jordi; Dalton, Stephen; Ried, Thomas; Zhao, Shaying

2014-01-01

Herein we report a proof of principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver–passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human- and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, while PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A, and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals. PMID:23416983

Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer.

PubMed

Tang, J; Li, Y; Lyon, K; Camps, J; Dalton, S; Ried, T; Zhao, S

2014-02-13

Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species, and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, although PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.

Similar Response Patterns to 5%Topical Minoxidil Foam in Frontal and Vertex Scalp of Men with Androgenetic Alopecia: A Microarray Analysis

PubMed Central

Mirmirani, P.; Consolo, M.; Oyetakin-White, P.; Baron, E.; Leahy, P.; Karnik, P.

2014-01-01

Summary Background There are regional variations in scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions are less well studied. Methods A placebo controlled double-blinded prospective pilot study of minoxidil topical foam 5% (MTF) vs placebo was conducted in sixteen healthy men ages 18-49 with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for eight weeks. Stereotactic scalp photographs were taken at the baseline and final visits to monitor global hair growth. Scalp biopsies were done at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo and microarray analysis was done using the Affymetrix GeneChip HG U133 Plus 2.0. Results Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of AGA patients. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin associated genes and decreased the expression of epidermal differentiation complex (EDC) and inflammatory genes in both scalp regions. Conclusions These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of AGA patients. PMID:25204361

Downregulation of mucosal mast cell activation and immune response in diarrhoea-irritable bowel syndrome by oral disodium cromoglycate: A pilot study

PubMed Central

Lobo, Beatriz; Ramos, Laura; Martínez, Cristina; Guilarte, Mar; González-Castro, Ana M; Alonso-Cotoner, Carmen; Pigrau, Marc; de Torres, Inés; Rodiño-Janeiro, Bruno K; Salvo-Romero, Eloisa; Fortea, Marina; Pardo-Camacho, Cristina; Guagnozzi, Danila; Azpiroz, Fernando

2017-01-01

Background and goal Diarrhoea-predominant irritable bowel syndrome (IBS-D) exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC stabilisers have been shown to improve IBS symptoms but the mechanism is unclear. Our primary aim was to investigate the effect of oral disodium cromoglycate (DSCG) on jejunal MC activation and specific innate immune signalling pathways in IBS-D, and secondarily, its potential clinical benefit. Study Mucosal MC activation (by ultrastructural changes, tryptase release and gene expression) and innate immune signalling (by protein and gene expression) were quantified in jejunal biopsies from healthy (HS; n = 16) and IBS-D subjects after six months of either treatment with DSCG (600 mg/day, IBS-D-DSCG group; n = 18) or without treatment (IBS-D-NT group; n = 25). All IBS-D patients recorded abdominal pain and bowel habits at baseline and in the last 10 days prior to jejunal sampling. Results IBS-D-NT exhibited significant MC activation and over-expression of immune-related genes as compared to HS, whereas in IBS-D-DSCG MC activity and gene expression were similar to HS. Furthermore, DSCG significantly reduced abdominal pain and improved stool consistency. Conclusion Oral DSCG modulates mucosal immune activity and improves gut symptoms in IBS-D patients. Future placebo-controlled clinical trials are needed for confirmation of clinical benefit of DSCG for IBS-D. PMID:29026603

Study to determine the IFR operational profile and problems of the general aviation single pilot

NASA Technical Reports Server (NTRS)

Weislogel, G. S.

1983-01-01

General aviation single pilot operating under instrument flight rules (GA SPIFR) was studied. The objectives of the study were to (1) develop a GA SPIFR operational profile, (2) identify problems experienced by the GA SPIFR pilot, and (3) identify research tasks which have the potential for eliminating or reducing the severity of the problems. To obtain the information necessary to accomplish these objectives, a mail questionnaire survey of instrument rated pilots was conducted. The general aviation IFR single pilot operational profile and selected data analysis examples are presented.

Piloted studies of Enhanced or Synthetic Vision display parameters

NASA Technical Reports Server (NTRS)

Harris, Randall L., Sr.; Parrish, Russell V.

1992-01-01

This paper summarizes the results of several studies conducted at Langley Research Center over the past few years. The purposes of these studies were to investigate parameters of pictorial displays and imaging sensors that affect pilot approach and landing performance. Pictorial displays have demonstrated exceptional tracking performance and improved the pilots' spatial awareness. Stereopsis cueing improved pilot flight performance and reduced pilot stress. Sensor image parameters such as increased field-of-view. faster image update rate, and aiding symbology improved flare initiation. Finer image resolution and magnification improved attitude control performance parameters.

Altered DNA Methylation Patterns Associated With Clinically Relevant Increases in PTSD Symptoms and PTSD Symptom Profiles in Military Personnel.

PubMed

Martin, Christiana; Cho, Young-Eun; Kim, Hyungsuk; Yun, Sijung; Kanefsky, Rebekah; Lee, Hyunhwa; Mysliwiec, Vincent; Cashion, Ann; Gill, Jessica

2018-05-01

Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD severity is not yet clearly understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms and investigate DNA methylation changes related to increases in the severity of PTSD in military personnel. In this pilot study, a cross-sectional comparison was made between military personnel with PTSD (n = 8) and combat-matched controls without PTSD (n = 6). Symptom measures were obtained, and genome-wide DNA methylation was measured using methylated DNA immunoprecipitation (MeDIP-seq) from whole blood samples at baseline and 3 months later. A longitudinal comparison measured DNA methylation changes in military personnel with clinically relevant increases in PTSD symptoms between time points (PTSD onset) and compared methylation patterns to controls with no clinical changes in PTSD. In military personnel with elevated PTSD symptoms 3 months following baseline, 119 genes exhibited reduced methylation and 8 genes exhibited increased methylation. Genes with reduced methylation in the PTSD-onset group relate to the canonical pathways of netrin signaling, Wnt/Ca + pathway, and axonal guidance signaling. These gene pathways relate to neurological disorders, and the current findings suggest that these epigenetic changes potentially relate to PTSD symptomology. This study provides some novel insights into the role of epigenetic changes in PTSD symptoms and the progression of PTSD symptoms in military personnel.

PILOT STUDY: THE TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

EPA Science Inventory

The Tampa Asthmatic Children's Study (TACS) was a pilot research study that focused on developing and evaluating air pollution exposure assessment methods and participant recruiting tools for children in the age range of 1-5 years old. The pilot study focused on (a) simple, cost-...

Field-Scale Evaluation of Monitored Natural Attenuation for Dissolved Chlorinated Solvent Plumes

DTIC Science & Technology

2009-04-01

biological in-situ treatment, an air sparging pilot study, and a phytoremediation study. The innovative technology studies were conducted within the source... phytoremediation (June to September 1997), reductive anaerobic biological in-situ treatment technology (RABITT; 1998), and groundwater recirculation wells...u g / L ) Measured Concentrations in 1381MWS09 Air Sparge Pilot Test (1996/1997) Phytoremediation Pilot Test (1997) RABITT Pilot Test (1998

The Necessity of ASEAN Community in Producing Pilots

ERIC Educational Resources Information Center

Saowaros, Thanoo; Puncreobutr, Vichian

2016-01-01

The main objectives of this study are to identify the reasons for the shortage of pilots; the necessity of producing Pilots and the obstacles and problems faced by ASEAN Community in producing pilots. The study is conducted by official documents, observations, in-depth interview from personnel who are working for Airports Authority of Thailand,…

SPEEDIER Project. Preliminary Report on Social Studies Pilot Projects.

ERIC Educational Resources Information Center

Myers, Charles B.; And Others

This preliminary report describes five social studies pilot programs in the counties of Dauphin, Lancaster, Lebanon, and York, Pennsylvania. It is expected that these pilot endeavors will affect educators in the counties served by SPEEDIER as follows: 1) increase understanding of the newer content, ideas, and strategies in the pilot programs; 2)…

Pilot Study: Foam Wedge Chin Support Static Tolerance Testing

DTIC Science & Technology

2017-10-24

AFRL-SA-WP-SR-2017-0026 Pilot Study : Foam Wedge Chin Support Static Tolerance Testing Austin M. Fischer, BS1; William W...COVERED (From – To) April – October 2017 4. TITLE AND SUBTITLE Pilot Study : Foam Wedge Chin Support Static Tolerance Testing 5a. CONTRACT NUMBER...prototype to mitigate the increase in helmet weight and forward center of gravity. The purpose of this pilot study was to determine the feasibility and

An analytical study of aircraft lateral-directional handling qualities using pilot models

NASA Technical Reports Server (NTRS)

Adams, J. J.; Moore, F. L.

1976-01-01

A procedure for predicting lateral-directional pilot ratings on the basis of the characteristics of the pilot model and the closed-loop system characteristics is demonstrated. A correlation is shown to exist between experimentally obtained pilot ratings and the computed pilot ratings.

Dynamic Tunnel Usability Study: Format Recommendations for Synthetic Vision System Primary Flight Displays

NASA Technical Reports Server (NTRS)

Arthur, Jarvis J., III; Prinzel, Lawrence J., III; Kramer, Lynda J.; Bailey, Randall E.

2006-01-01

A usability study evaluating dynamic tunnel concepts has been completed under the Aviation Safety and Security Program, Synthetic Vision Systems Project. The usability study was conducted in the Visual Imaging Simulator for Transport Aircraft Systems (VISTAS) III simulator in the form of questionnaires and pilot-in-the-loop simulation sessions. Twelve commercial pilots participated in the study to determine their preferences via paired comparisons and subjective rankings regarding the color, line thickness and sensitivity of the dynamic tunnel. The results of the study showed that color was not significant in pilot preference paired comparisons or in pilot rankings. Line thickness was significant for both pilot preference paired comparisons and in pilot rankings. The preferred line/halo thickness combination was a line width of 3 pixels and a halo of 4 pixels. Finally, pilots were asked their preference for the current dynamic tunnel compared to a less sensitive dynamic tunnel. The current dynamic tunnel constantly gives feedback to the pilot with regard to path error while the less sensitive tunnel only changes as the path error approaches the edges of the tunnel. The tunnel sensitivity comparison results were not statistically significant.

Effects of alcohol on pilot performance in simulated flight

NASA Technical Reports Server (NTRS)

Billings, C. E.; Demosthenes, T.; White, T. R.; O'Hara, D. B.

1991-01-01

Ethyl alcohol's known ability to produce reliable decrements in pilot performance was used in a study designed to evaluate objective methods for assessing pilot performance. Four air carrier pilot volunteers were studied during eight simulated flights in a B727 simulator. Total errors increased linearly and significantly with increasing blood alcohol. Planning and performance errors, procedural errors and failures of vigilance each increased significantly in one or more pilots and in the group as a whole.

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria

PubMed Central

Qu, Ying; Rolicka, Anna; Sirima, Sodiomon B; O'Connell, Mary A; Lennartsson, Andreas; Troye-Blomberg, Marita; Nebie, Issa

2017-01-01

The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria, as reflected by fewer symptomatic cases of malaria, lower infection rates, and lower parasite densities compared to sympatric ethnic groups. However, the basis for this lower susceptibility to malaria by the Fulani is unknown. The incidence of classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations, and targeted SNP analyses of other candidate genes involved in the immune response to malaria have not been able to account for the observed difference in the Fulani susceptibility to P.falciparum. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani to elucidate the mechanisms that confer the lower susceptibility to P.falciparum malaria. When we compared uninfected and infected Fulani individuals, in contrast to uninfected and infected individuals from the sympatric ethnic group Mossi, we observed a key difference: a strong transcriptional response was only detected in the monocyte fraction of the Fulani, where over 1000 genes were significantly differentially expressed upon P.falciparum infection. PMID:28923166

Copy Number Variation in the Horse Genome

PubMed Central

Ghosh, Sharmila; Qu, Zhipeng; Das, Pranab J.; Fang, Erica; Juras, Rytis; Cothran, E. Gus; McDonell, Sue; Kenney, Daniel G.; Lear, Teri L.; Adelson, David L.; Chowdhary, Bhanu P.; Raudsepp, Terje

2014-01-01

We constructed a 400K WG tiling oligoarray for the horse and applied it for the discovery of copy number variations (CNVs) in 38 normal horses of 16 diverse breeds, and the Przewalski horse. Probes on the array represented 18,763 autosomal and X-linked genes, and intergenic, sub-telomeric and chrY sequences. We identified 258 CNV regions (CNVRs) across all autosomes, chrX and chrUn, but not in chrY. CNVs comprised 1.3% of the horse genome with chr12 being most enriched. American Miniature horses had the highest and American Quarter Horses the lowest number of CNVs in relation to Thoroughbred reference. The Przewalski horse was similar to native ponies and draft breeds. The majority of CNVRs involved genes, while 20% were located in intergenic regions. Similar to previous studies in horses and other mammals, molecular functions of CNV-associated genes were predominantly in sensory perception, immunity and reproduction. The findings were integrated with previous studies to generate a composite genome-wide dataset of 1476 CNVRs. Of these, 301 CNVRs were shared between studies, while 1174 were novel and require further validation. Integrated data revealed that to date, 41 out of over 400 breeds of the domestic horse have been analyzed for CNVs, of which 11 new breeds were added in this study. Finally, the composite CNV dataset was applied in a pilot study for the discovery of CNVs in 6 horses with XY disorders of sexual development. A homozygous deletion involving AKR1C gene cluster in chr29 in two affected horses was considered possibly causative because of the known role of AKR1C genes in testicular androgen synthesis and sexual development. While the findings improve and integrate the knowledge of CNVs in horses, they also show that for effective discovery of variants of biomedical importance, more breeds and individuals need to be analyzed using comparable methodological approaches. PMID:25340504

An experimental study of the effect of a pilot flame on technically pre-mixed, self-excited combustion instabilities

NASA Astrophysics Data System (ADS)

O'Meara, Bridget C.

Combustion instabilities are a problem facing the gas turbine industry in the operation of lean, pre-mixed combustors. Secondary flames known as "pilot flames" are a common passive control strategy for eliminating combustion instabilities in industrial gas turbines, but the underlying mechanisms responsible for the pilot flame's stabilizing effect are not well understood. This dissertation presents an experimental study of a pilot flame in a single-nozzle, swirl-stabilized, variable length atmospheric combustion test facility and the effect of the pilot on combustion instabilities. A variable length combustor tuned the acoustics of the system to excite instabilities over a range of operating conditions without a pilot flame. The inlet velocity was varied from 25 -- 50 m/s and the equivalence ratio was varied from 0.525 -- 0.65. This range of operating conditions was determined by the operating range of the combustion test facility. Stability at each operating condition and combustor length was characterized by measurements of pressure oscillations in the combustor. The effect of the pilot flame on the magnitude and frequency of combustor stability was then investigated. The mechanisms responsible for the pilot flame effect were studied using chemiluminescence flame images of both stable and unstable flames. Stable flame structure was investigated using stable flame images of CH* chemiluminescence emission. The effect of the pilot on stable flame metrics such as flame length, flame angle, and flame width was investigated. In addition, a new flame metric, flame base distance, was defined to characterize the effect of the pilot flame on stable flame anchoring of the flame base to the centerbody. The effect of the pilot flame on flame base anchoring was investigated because the improved stability with a pilot flame is usually attributed to improved flame anchoring through the recirculation of hot products from the pilot to the main flame base. Chemiluminescence images of unstable flames were used to identify several instability mechanisms and infer how these mechanisms are affected by the pilot flame. Flame images of cases in which the pilot flame did not eliminate the instability were investigated to understand why the pilot flame is not effective in certain cases. The phase of unstable pilot flame oscillations was investigated to determine how the phase of pilot flame oscillations may affect its ability to interfere with instability mechanisms in the main flame. A forced flame response study was conducted to determine the effect of inlet velocity oscillation amplitude on the pilot flame. The flame response was characterized by measurements of velocity oscillations in the injector and chemiluminescence intensity oscillations determined from flame images. As the forcing amplitude increases, the pilot flame's effect on the flame transfer function magnitude becomes weaker. Flame images show that as the forcing amplitude increases, the pilot flame oscillations increase, leading to an ineffective pilot. The results of the flame response portion of this study highlight the effect of instability amplitude on the ability of a pilot flame to eliminate a combustion instability.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

PubMed

Braga, D; Barcella, M; D'Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, M H; DeLano, F A; Baselli, G; Schmid-Schönbein, G W; Kistler, E B; Aletti, F; Barlassina, C

2017-08-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Effects of tobacco smoke and electronic cigarette vapor exposure on the oral and gut microbiota in humans: a pilot study

PubMed Central

Auchtung, Thomas A.; Ajami, Nadim J.; Velasquez, Kenia; De La Garza, Richard; Petrosino, Joseph F.

2018-01-01

Background The use of electronic cigarettes (ECs) has increased drastically over the past five years, primarily as an alternative to smoking tobacco cigarettes. However, the adverse effects of acute and long-term use of ECs on the microbiota have not been explored. In this pilot study, we sought to determine if ECs or tobacco smoking alter the oral and gut microbiota in comparison to non-smoking controls. Methods We examined a human cohort consisting of 30 individuals: 10 EC users, 10 tobacco smokers, and 10 controls. We collected cross-sectional fecal, buccal swabs, and saliva samples from each participant. All samples underwent V4 16S rRNA gene sequencing. Results Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella (P = 0.006) and decreased Bacteroides (P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced (P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls. Discussion From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted. PMID:29736335

Controlling road rage : a literature review and pilot study

DOT National Transportation Integrated Search

1999-06-01

This report discusses results of a literature review and pilot study on how to prevent aggressive driving and road rage. The study "Controlling Road Rage: A Literature Review and Pilot Study" defines road rage as "an incident in which an angry or imp...

Physiological studies on air tanker pilots flying forest fire retardant missions.

DOT National Transportation Integrated Search

1968-10-01

Pre-flight and post-flight studies were carried out on five air tanker pilots; in-flight studies were carried out on four of these five pilots. Pre- and post-flight studies consisted of a questionnaire and determinations of blood pressure, psychomoto...

Enumeration and Characterization of Acidophilic Microorganisms Isolated from a Pilot Plant Stirred-Tank Bioleaching Operation

PubMed Central

Okibe, Naoko; Gericke, Mariekie; Hallberg, Kevin B.; Johnson, D. Barrie

2003-01-01

Microorganisms were enumerated and isolated on selective solid media from a pilot-scale stirred-tank bioleaching operation in which a polymetallic sulfide concentrate was subjected to biologically accelerated oxidation at 45°C. Four distinct prokaryotes were isolated: three bacteria (an Acidithiobacillus caldus-like organism, a thermophilic Leptospirillum sp., and a Sulfobacillus sp.) and one archaeon (a Ferroplasma-like isolate). The relative numbers of these prokaryotes changed in the three reactors sampled, and the Ferroplasma isolate became increasingly dominant as mineral oxidation progressed, eventually accounting for >99% of plate isolates in the third of three in-line reactors. The identities of the isolates were confirmed by analyses of their 16S rRNA genes, and some key physiological traits (e.g., oxidation of iron and/or sulfur and autotrophy or heterotrophy) were examined. More detailed studies were carried out with the Leptospirillum and Ferroplasma isolates. The data presented here represent the first quantitative study of the microorganisms in a metal leaching situation and confirm that mixed cultures of iron- and sulfur-oxidizing prokaryotic acidophiles catalyze the accelerated dissolution of sulfidic minerals in industrial tank bioleaching operations. The results show that indigenous acidophilic microbial populations change as mineral dissolution becomes more extensive. PMID:12676667

Lessons from a One-to-One Laptop Pilot

ERIC Educational Resources Information Center

Peterson, Lana; Scharber, Cassandra

2017-01-01

The purpose of this study was to document the process one district used to design, develop, and implement a one-to-one pilot at its high school as part of its broader commitment to contemporary learning. Specifically, this qualitative case study (a) outlines the process of the laptop pilot, (b) describes the pilot implementation experience for…

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus.

PubMed

Vernon, Suzanne D; Whistler, Toni; Cameron, Barbara; Hickie, Ian B; Reeves, William C; Lloyd, Andrew

2006-01-31

Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection. We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.

Developing and applying a gene functional association network for anti-angiogenic kinase inhibitor activity assessment in an angiogenesis co-culture model

PubMed Central

Chen, Yuefeng; Wei, Tao; Yan, Lei; Lawrence, Frank; Qian, Hui-Rong; Burkholder, Timothy P; Starling, James J; Yingling, Jonathan M; Shou, Jianyong

2008-01-01

Background Tumor angiogenesis is a highly regulated process involving intercellular communication as well as the interactions of multiple downstream signal transduction pathways. Disrupting one or even a few angiogenesis pathways is often insufficient to achieve sustained therapeutic benefits due to the complexity of angiogenesis. Targeting multiple angiogenic pathways has been increasingly recognized as a viable strategy. However, translation of the polypharmacology of a given compound to its antiangiogenic efficacy remains a major technical challenge. Developing a global functional association network among angiogenesis-related genes is much needed to facilitate holistic understanding of angiogenesis and to aid the development of more effective anti-angiogenesis therapeutics. Results We constructed a comprehensive gene functional association network or interactome by transcript profiling an in vitro angiogenesis model, in which human umbilical vein endothelial cells (HUVECs) formed capillary structures when co-cultured with normal human dermal fibroblasts (NHDFs). HUVEC competence and NHDF supportiveness of cord formation were found to be highly cell-passage dependent. An enrichment test of Biological Processes (BP) of differentially expressed genes (DEG) revealed that angiogenesis related BP categories significantly changed with cell passages. Built upon 2012 DEGs identified from two microarray studies, the resulting interactome captured 17226 functional gene associations and displayed characteristics of a scale-free network. The interactome includes the involvement of oncogenes and tumor suppressor genes in angiogenesis. We developed a network walking algorithm to extract connectivity information from the interactome and applied it to simulate the level of network perturbation by three multi-targeted anti-angiogenic kinase inhibitors. Simulated network perturbation correlated with observed anti-angiogenesis activity in a cord formation bioassay. Conclusion We established a comprehensive gene functional association network to model in vitro angiogenesis regulation. The present study provided a proof-of-concept pilot of applying network perturbation analysis to drug phenotypic activity assessment. PMID:18518970

Pilot Non-Conformance to Alerting System Commands

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Hansman, R. John

1997-01-01

Instances of pilot non-conformance to alerting system commands have been identified in previous studies. Pilot non-conformance changes the final behavior of the system, and therefore may reduce actual performance from that anticipated. A simulator study has examined pilot non-conformance, using the task of collision avoidance during closely spaced parallel approaches as a case study. Consonance between the display and the alerting system was found to significantly improve subject agreement with automatic alerts. Based on these results, a more general discussion of the factors involved in pilot conformance is given, and design guidelines for alerting systems are given.

Pilot error in air carrier accidents: does age matter?

PubMed

Li, Guohua; Grabowski, Jurek G; Baker, Susan P; Rebok, George W

2006-07-01

The relationship between pilot age and safety performance has been the subject of research and controversy since the "Age 60 Rule" became effective in 1960. This study aimed to examine age-related differences in the prevalence and patterns of pilot error in air carrier accidents. Investigation reports from the National Transportation Safety Board for accidents involving Part 121 operations in the United States between 1983 and 2002 were reviewed to identify pilot error and other contributing factors. Accident circumstances and the presence and type of pilot error were analyzed in relation to pilot age using Chi-square tests. Of the 558 air carrier accidents studied, 25% resulted from turbulence, 21% from mechanical failure, 16% from taxiing events, 13% from loss of control at landing or takeoff, and 25% from other causes. Accidents involving older pilots were more likely to be caused by turbulence, whereas accidents involving younger pilots were more likely to be taxiing events. Pilot error was a contributing factor in 34%, 38%, 35%, and 34% of the accidents involving pilots ages 25-34 yr, 35-44 yr, 45-54 yr, and 55-59 yr, respectively (p = 0.87). The patterns of pilot error were similar across age groups. Overall, 26% of the pilot errors identified were inattentiveness, 22% flawed decisions, 22% mishandled aircraft kinetics, and 11% poor crew interactions. The prevalence and patterns of pilot error in air carrier accidents do not seem to change with pilot age. The lack of association between pilot age and error may be due to the "safe worker effect" resulting from the rigorous selection processes and certification standards for professional pilots.

77 FR 13343 - Pilot Program for Early Feasibility Study Investigational Device Exemption Applications...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

...] Pilot Program for Early Feasibility Study Investigational Device Exemption Applications; Termination of... acceptance of nominations for the Early Feasibility Study Investigational Device Exemption (IDE) Applications... technologies to participate in a pilot program for early feasibility study IDE applications. FDA is also...

Levetiracetam attenuates hippocampal expression of synaptic plasticity-related immediate early and late response genes in amygdala-kindled rats

PubMed Central

2010-01-01

Background The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined. Results Cyclooxygenase-2 (Cox-2), Protocadherin-8 (Pcdh8) and TGF-beta-inducible early response gene-1 (TIEG1) were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-α, RGS2, Egr2/krox-20 and β-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs) as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD) duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration. Conclusions The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus. PMID:20105316

Dynamic Succession of Groundwater Functional Microbial Communities in Response to Emulsified Vegetable Oil Amendment during Sustained In Situ U(VI) Reduction

DOE PAGES

Zhang, Ping; Wu, Wei-Min; Van Nostrand, Joy D.; ...

2015-04-10

A pilot-scale field experiment demonstrated that a one-time amendment of emulsified vegetable oil (EVO) reduced groundwater U(VI) concentrations for 1 year in a fast-flowing aquifer. However, little is known about how EVO amendment stimulates the functional gene composition, structure, and dynamics of groundwater microbial communities toward prolonged U(VI) reduction. In this paper, we hypothesized that EVO amendment would shift the functional gene composition and structure of groundwater microbial communities and stimulate key functional genes/groups involved in EVO biodegradation and reduction of electron acceptors in the aquifer. To test these hypotheses, groundwater microbial communities after EVO amendment were analyzed using amore » comprehensive functional gene microarray. Our results showed that EVO amendment stimulated sequential shifts in the functional composition and structure of groundwater microbial communities. Particularly, the relative abundance of key functional genes/groups involved in EVO biodegradation and the reduction of NO 3 -, Mn(IV), Fe(III), U(VI), and SO 4 2- significantly increased, especially during the active U(VI) reduction period. The relative abundance for some of these key functional genes/groups remained elevated over 9 months. Montel tests suggested that the dynamics in the abundance, composition, and structure of these key functional genes/groups were significantly correlated with groundwater concentrations of acetate, NO 3 -, Mn(II), Fe(II), U(VI), and SO 4 2-. Our results suggest that EVO amendment stimulated dynamic succession of key functional microbial communities. Finally, this study improves our understanding of the composition, structure, and function changes needed for groundwater microbial communities to sustain a long-term U(VI) reduction.« less

Dynamic Succession of Groundwater Functional Microbial Communities in Response to Emulsified Vegetable Oil Amendment during Sustained In Situ U(VI) Reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ping; Wu, Wei-Min; Van Nostrand, Joy D.

A pilot-scale field experiment demonstrated that a one-time amendment of emulsified vegetable oil (EVO) reduced groundwater U(VI) concentrations for 1 year in a fast-flowing aquifer. However, little is known about how EVO amendment stimulates the functional gene composition, structure, and dynamics of groundwater microbial communities toward prolonged U(VI) reduction. In this paper, we hypothesized that EVO amendment would shift the functional gene composition and structure of groundwater microbial communities and stimulate key functional genes/groups involved in EVO biodegradation and reduction of electron acceptors in the aquifer. To test these hypotheses, groundwater microbial communities after EVO amendment were analyzed using amore » comprehensive functional gene microarray. Our results showed that EVO amendment stimulated sequential shifts in the functional composition and structure of groundwater microbial communities. Particularly, the relative abundance of key functional genes/groups involved in EVO biodegradation and the reduction of NO 3 -, Mn(IV), Fe(III), U(VI), and SO 4 2- significantly increased, especially during the active U(VI) reduction period. The relative abundance for some of these key functional genes/groups remained elevated over 9 months. Montel tests suggested that the dynamics in the abundance, composition, and structure of these key functional genes/groups were significantly correlated with groundwater concentrations of acetate, NO 3 -, Mn(II), Fe(II), U(VI), and SO 4 2-. Our results suggest that EVO amendment stimulated dynamic succession of key functional microbial communities. Finally, this study improves our understanding of the composition, structure, and function changes needed for groundwater microbial communities to sustain a long-term U(VI) reduction.« less

Cigarette smoke induces methylation of the tumor suppressor gene NISCH

PubMed Central

Ostrow, Kimberly Laskie; Michalidi, Christina; Guerrero-Preston, Rafael; Hoque, Mohammad O.; Greenberg, Alissa; Rom, William; Sidransky, David

2013-01-01

We have previously identified a putative tumor suppressor gene, NISCH, whose promoter is methylated in lung tumor tissue as well as in plasma obtained from lung cancer patients. NISCH was observed to be more frequently methylated in smoker lung cancer patients than in non-smoker lung cancer patients. Here, we investigated the effect of tobacco smoke exposure on methylation of the NISCH gene. We tested methylation of NISCH after oral keratinocytes were exposed to mainstream and side stream cigarette smoke extract in culture. Methylation of the promoter region of the NISCH gene was also evaluated in plasma obtained from lifetime non-smokers and light smokers (< 20 pack/year), with and without lung tumors, and heavy smokers (20+ pack/year) without disease. Promoter methylation of NISCH was tested by quantitative fluorogenic real-time PCR in all samples. Promoter methylation of NISCH occurred after exposure to mainstream tobacco smoke as well as to side stream tobacco smoke in normal oral keratinocyte cell lines. NISCH methylation was also detected in 68% of high-risk, heavy smokers without detectable tumors. Interestingly, in light smokers, NISCH methylation was present in 69% of patients with lung cancer and absent in those without disease. Our pilot study indicates that tobacco smoke induces methylation changes in the NISCH gene promoter before any detectable cancer. Methylation of the NISCH gene was also found in lung cancer patients’ plasma samples. After confirming these findings in longitudinally collected plasma samples from high-risk populations (such as heavy smokers), examining patients for hypermethylation of the NISCH gene may aid in identifying those who should undergo additional screening for lung cancer. PMID:23503203

Simulation and estimation of gene number in a biological pathway using almost complete saturation mutagenesis screening of haploid mouse cells.

PubMed

Tokunaga, Masahiro; Kokubu, Chikara; Maeda, Yusuke; Sese, Jun; Horie, Kyoji; Sugimoto, Nakaba; Kinoshita, Taroh; Yusa, Kosuke; Takeda, Junji

2014-11-24

Genome-wide saturation mutagenesis and subsequent phenotype-driven screening has been central to a comprehensive understanding of complex biological processes in classical model organisms such as flies, nematodes, and plants. The degree of "saturation" (i.e., the fraction of possible target genes identified) has been shown to be a critical parameter in determining all relevant genes involved in a biological function, without prior knowledge of their products. In mammalian model systems, however, the relatively large scale and labor intensity of experiments have hampered the achievement of actual saturation mutagenesis, especially for recessive traits that require biallelic mutations to manifest detectable phenotypes. By exploiting the recently established haploid mouse embryonic stem cells (ESCs), we present an implementation of almost complete saturation mutagenesis in a mammalian system. The haploid ESCs were mutagenized with the chemical mutagen N-ethyl-N-nitrosourea (ENU) and processed for the screening of mutants defective in various steps of the glycosylphosphatidylinositol-anchor biosynthetic pathway. The resulting 114 independent mutant clones were characterized by a functional complementation assay, and were shown to be defective in any of 20 genes among all 22 known genes essential for this well-characterized pathway. Ten mutants were further validated by whole-exome sequencing. The predominant generation of single-nucleotide substitutions by ENU resulted in a gene mutation rate proportional to the length of the coding sequence, which facilitated the experimental design of saturation mutagenesis screening with the aid of computational simulation. Our study enables mammalian saturation mutagenesis to become a realistic proposition. Computational simulation, combined with a pilot mutagenesis experiment, could serve as a tool for the estimation of the number of genes essential for biological processes such as drug target pathways when a positive selection of mutants is available.

Autogenic Feedback Training Exercise and pilot performance: enhanced functioning under search-and-rescue flying conditions.

PubMed

Cowings, P S; Kellar, M A; Folen, R A; Toscano, W B; Burge, J D

2001-01-01

Studies have shown that autonomous mode behavior is one cause of aircraft fatalities due to pilot error. In such cases, the pilot is in a high state of psychological and physiological arousal and tends to focus on one problem, while ignoring more critical information. This study examined the effect of training in physiological self-recognition and regulation, as a means of improving crew cockpit performance. Seventeen pilots were assigned to the treatment and control groups matched for accumulated flight hours. The treatment group contained 4 pilots from HC-130 Hercules aircraft and 4 HH-65 Dolphin helicopter pilots; the control group contained 3 pilots of HC-130s and 6 helicopter pilots. During an initial flight, physiological data were recorded on each crewmember and an instructor pilot rated individual crew performance. Eight crewmembers were then taught to regulate their own physiological response levels using Autogenic-Feedback Training Exercise (AFTE). The remaining participants received no training. During a second flight, treatment participants showed significant improvement in performance (rated by the same instructor pilot as in pretests) while controls did not improve. The results indicate that AFTE management of high states of physiological arousal may improve pilot performance during emergency flying conditions.

Autogenic Feedback Training Exercise and pilot performance: enhanced functioning under search-and-rescue flying conditions

NASA Technical Reports Server (NTRS)

Cowings, P. S.; Kellar, M. A.; Folen, R. A.; Toscano, W. B.; Burge, J. D.

2001-01-01

Studies have shown that autonomous mode behavior is one cause of aircraft fatalities due to pilot error. In such cases, the pilot is in a high state of psychological and physiological arousal and tends to focus on one problem, while ignoring more critical information. This study examined the effect of training in physiological self-recognition and regulation, as a means of improving crew cockpit performance. Seventeen pilots were assigned to the treatment and control groups matched for accumulated flight hours. The treatment group contained 4 pilots from HC-130 Hercules aircraft and 4 HH-65 Dolphin helicopter pilots; the control group contained 3 pilots of HC-130s and 6 helicopter pilots. During an initial flight, physiological data were recorded on each crewmember and an instructor pilot rated individual crew performance. Eight crewmembers were then taught to regulate their own physiological response levels using Autogenic-Feedback Training Exercise (AFTE). The remaining participants received no training. During a second flight, treatment participants showed significant improvement in performance (rated by the same instructor pilot as in pretests) while controls did not improve. The results indicate that AFTE management of high states of physiological arousal may improve pilot performance during emergency flying conditions.

EXPOSURE ASSESSMENT METHODS DEVELOPMENT PILOTS FOR THE NATIONAL CHILDREN'S STUDY

EPA Science Inventory

Accurate exposure classification tools are needed to link exposure with health effects. EPA began methods development pilot studies in 2000 to address general questions about exposures and outcome measures. Selected pilot studies are highlighted in this poster. The “Literature Re...

Prevalence of fatigue in a group of airline pilots.

PubMed

Reis, Cátia; Mestre, Catarina; Canhão, Helena

2013-08-01

Fatigue is a common phenomenon in airline pilots that can impair alertness and ability of crewmembers to safely operate an aircraft and perform safety related tasks. Fatigue can increase the risk of an incident or even an accident. This study provides the first prevalence values for clinically significant fatigue in Portuguese airline pilots. The hypothesis that medium/short-haul pilots may currently present different levels of fatigue than long-haul pilots was also tested. A survey was conducted by requesting Portuguese airline pilots to complete questionnaires placed in the pilots' personal lockers from 1 April until 15 May 2012. The questionnaire included the self-response Fatigue Severity Scale (FSS) to measure subjective fatigue and some additional questions concerning perception of fatigue by pilots. The prevalence values for total and mental fatigue achieved in the Portuguese airline pilots were: 89.3% (FSS > or = 4) and 94.1% (FSS > or = 4) when splitting the sample in two subsamples, long- and medium/short-haul pilots. Levels of total and mental fatigue were higher for medium/short-haul pilots. The analysis of fatigue levels in each type of aviator showed that medium/short-haul pilots presented the highest levels of total and mental fatigue. This study produced the first prevalence values of total and mental fatigue among Portuguese airline pilots, which represents a great step to understanding and addressing this critical phenomenon.

76 FR 12367 - Proposed Information Collection; Visibility Valuation Survey Pilot Study

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

... Survey Pilot Study AGENCY: National Park Service, U.S. Department of the Interior. ACTION: Notice... Code of Federal Regulations). Updated estimates of visibility benefits are required because the studies... a pilot study to test the survey instrument and implementation procedures prior to the full survey...

Pre-Study Walkthrough with a Commercial Pilot for a Preliminary Single Pilot Operations Experiment

NASA Technical Reports Server (NTRS)

O'Connor-Dreher, Ryan; Roberts, Z.; Ziccardi, J.; Vu, K-P. L.; Strybel, T.; Koteskey, Robert William; Lachter, Joel B.; Vi Dao, Quang; Johnson, Walter W.; Battiste, V.

2013-01-01

The number of crew members in commercial flights has decreased to two members, down from the five-member crew required 50 years ago. One question of interest is whether the crew should be reduced to one pilot. In order to determine the critical factors involved in safely transitioning to a single pilot, research must examine whether any performance deficits arise with the loss of a crew member. With a concrete understanding of the cognitive and behavioral role of a co-pilot, aeronautical technologies and procedures can be developed that make up for the removal of the second aircrew member. The current project describes a pre-study walkthrough process that can be used to help in the development of scenarios for testing future concepts and technologies for single pilot operations. Qualitative information regarding the tasks performed by the pilots can be extracted with this technique and adapted for future investigations of single pilot operations.

Whole-genome resequencing of honeybee drones to detect genomic selection in a population managed for royal jelly.

PubMed

Wragg, David; Marti-Marimon, Maria; Basso, Benjamin; Bidanel, Jean-Pierre; Labarthe, Emmanuelle; Bouchez, Olivier; Le Conte, Yves; Vignal, Alain

2016-06-03

Four main evolutionary lineages of A. mellifera have been described including eastern Europe (C) and western and northern Europe (M). Many apiculturists prefer bees from the C lineage due to their docility and high productivity. In France, the routine importation of bees from the C lineage has resulted in the widespread admixture of bees from the M lineage. The haplodiploid nature of the honeybee Apis mellifera, and its small genome size, permits affordable and extensive genomics studies. As a pilot study of a larger project to characterise French honeybee populations, we sequenced 60 drones sampled from two commercial populations managed for the production of honey and royal jelly. Results indicate a C lineage origin, whilst mitochondrial analysis suggests two drones originated from the O lineage. Analysis of heterozygous SNPs identified potential copy number variants near to genes encoding odorant binding proteins and several cytochrome P450 genes. Signatures of selection were detected using the hapFLK haplotype-based method, revealing several regions under putative selection for royal jelly production. The framework developed during this study will be applied to a broader sampling regime, allowing the genetic diversity of French honeybees to be characterised in detail.

Whole-genome resequencing of honeybee drones to detect genomic selection in a population managed for royal jelly

PubMed Central

Wragg, David; Marti-Marimon, Maria; Basso, Benjamin; Bidanel, Jean-Pierre; Labarthe, Emmanuelle; Bouchez, Olivier; Le Conte, Yves; Vignal, Alain

2016-01-01

Four main evolutionary lineages of A. mellifera have been described including eastern Europe (C) and western and northern Europe (M). Many apiculturists prefer bees from the C lineage due to their docility and high productivity. In France, the routine importation of bees from the C lineage has resulted in the widespread admixture of bees from the M lineage. The haplodiploid nature of the honeybee Apis mellifera, and its small genome size, permits affordable and extensive genomics studies. As a pilot study of a larger project to characterise French honeybee populations, we sequenced 60 drones sampled from two commercial populations managed for the production of honey and royal jelly. Results indicate a C lineage origin, whilst mitochondrial analysis suggests two drones originated from the O lineage. Analysis of heterozygous SNPs identified potential copy number variants near to genes encoding odorant binding proteins and several cytochrome P450 genes. Signatures of selection were detected using the hapFLK haplotype-based method, revealing several regions under putative selection for royal jelly production. The framework developed during this study will be applied to a broader sampling regime, allowing the genetic diversity of French honeybees to be characterised in detail. PMID:27255426

Mechanistic Indicators of Childhood Asthma (MICA): piloting ...

EPA Pesticide Factsheets

Background: Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma; however appropriately designed studies are critical for these methods to reach their full potential. Objective: We used a case-control study to investigate whether genomic data (blood gene expression), viewed together with a spectrum of exposure effects and susceptibility markers (blood, urine and nail), can provide a mechanistic explanation for the increased susceptibility of asthmatics to ambient air pollutants. Methods: We studied 205 non-asthmatic and asthmatic children, (9-12 years of age) who participated in a clinical study in Detroit, Michigan. The study combines a traditional epidemiological design with an integrative approach to investigate the environmental exposure of children to indoor-outdoor air. The study includes measurements of internal dose (metals, allergen specific IgE, PAH and VOC metabolites) and clinical measures of health outcome (immunological, cardiovascular and respiratory). Results: Expected immunological indications of asthma have been obtained. In addition, initial results from our analyses point to the complex nature of childhood health and risk factors linked to metabolic syndrome (obesity, blood pressure and dyslipidemia). For example, 31% and 34% of the asthmatic MICA subjects were either overweight (BMI > 25) o

Dysregulation of apoptosis and autophagy gene expression in PBMCs of efficiently treated HIV-infected patients.

PubMed

Serrano, Amandine; El Haddad, Saïd; Moal, Frédéric; Prazuck, Thierry; Legac, Eric; Robin, Chloé; Brule, Fabienne; Charpentier, Stéphane; Normand, Thierry; Legrand, Alain; Hocqueloux, Laurent; Mollet, Lucile

2018-05-03

We measure the transcript levels of the pro-apoptotic GALIG, anti-apoptotic MCL1 genes and those of the autophagy genes BECN1, MAP1LC3B, ATG9a, P62/SQSTM1, GABARAP, GABARAPL1 and GABARAPL2 to define if mRNA alteration can characterize HIV infected patients effectively treated with combined antiretroviral therapy (cART). Monocentric pilot study conducted on PBMC of 40 uninfected donors and 27 HIV positive patients effectively treated by cART for at least 8.4 years. Transcripts of the various genes were quantified by RT-qPCR and RT- droplet digital PCR, and compared using the standard statistical Mann-Whitney U test and machine learning algorithms. A concomitant overexpression of GALIG and MCL1 is detected in PBMC of effectively cART-treated patients. Overexpression of MAP1LC3B and GABARAPL1 is also measured while BECN1 is under-expressed. Finally, accurate classification (94.5%) of our PBMC samples as HIV negative donors or HIV positive cART-treated is obtained in 3 separate machine-learning algorithms with GABARAPL1 and ATG9a as input variables. cART-treated HIV patients display altered transcript levels for 3 genes of basal autophagy. Some of these alterations may appear contradictory: BECN1 and ATG9a, both key actors in the formation of mammalian autophagosome, exhibit decreased amount of transcripts while mRNA from the ATG8 family increase. Given the known role of impaired basal autophagy in immune senescence and chronic inflammation, the functional significance of our findings should be explored in larger studies.

Similar response patterns to topical minoxidil foam 5% in frontal and vertex scalp of men with androgenetic alopecia: a microarray analysis.

PubMed

Mirmirani, P; Consolo, M; Oyetakin-White, P; Baron, E; Leahy, P; Karnik, P

2015-06-01

There are regional variations in the scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions have been less well studied. To determine whether scalp biopsies from men with AGA show variable gene expression before and after 8 weeks of treatment with minoxidil topical foam 5% (MTF) vs. placebo. A placebo-controlled double-blinded prospective pilot study of MTF vs. placebo was conducted in 16 healthy men aged 18-49 years with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for 8 weeks. Stereotactic scalp photographs were taken at the baseline and final visits, to monitor global hair growth. Scalp biopsies were taken at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo, and microarray analysis was performed using the Affymetrix GeneChip HG U133 Plus 2.0. Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of patients with AGA. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin-associated genes and decreased the expression of epidermal differentiation complex and inflammatory genes in both scalp regions. These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of patients with AGA. © 2014 British Association of Dermatologists.

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Daily Intake of Protein from Cod Residual Material Lowers Serum Concentrations of Nonesterified Fatty Acids in Overweight Healthy Adults: A Randomized Double-Blind Pilot Study.

PubMed

Vildmyren, Iselin; Cao, Huy John Vu; Haug, Lina Bowitz; Valand, Ida Ulrikke; Eng, Øyvin; Oterhals, Åge; Austgulen, Maren Hoff; Halstensen, Alfred; Mellgren, Gunnar; Gudbrandsen, Oddrun A

2018-06-05

Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails) and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized to three experimental groups consuming tablets corresponding to 6 g/day of proteins from cod residuals as presscake meal (Cod-PC), presscake and stickwater meal (Cod-PCW), or placebo tablets (control) for eight weeks. The primary outcome of this study was changes in metabolites related to glucose regulation in overweight or obese healthy adults after intake of proteins from cod residuals. Cod-PC supplementation decreased postprandial serum nonesterified fatty acids (NEFA) concentration and increased gene expressions of diglyceride acyltransferase 1 and 2 in subcutaneous adipose tissue compared with controls. Fasting insulin increased while fasting NEFA and 120-min postprandial glucose decreased within the Cod-PC group, but these changes did not differ from the other groups. In conclusion, supplementation with Cod-PC beneficially affected postprandial serum NEFA concentration compared with the other groups in overweight or obese adults. Supplementation with Cod-PCW, which contains a higher fraction of water-soluble protein compared to Cod-PC, did not affect serum markers of glucose regulation.

Improving FHWA's Ability to Assess Highway Infrastructure Health : Pilot Study Report

DOT National Transportation Integrated Search

2012-07-01

This report documents the results of a pilot study conducted as part of a project on improving FHWAs ability to assess highway infrastructure health. As part of the pilot study, a section of Interstate 90 through South Dakota, Minnesota, and Wisco...

Recommendations for Planning Pilot Studies in Clinical and Translational Research

PubMed Central

Moore, Charity G.; Carter, Rickey E.; Nietert, Paul J.; Stewart, Paul W.

2011-01-01

Abstract  Advances in clinical and translation science are facilitated by building on prior knowledge gained through experimentation and observation. In the context of drug development, preclinical studies are followed by a progression of phase I through phase IV clinical trials. At each step, the study design and statistical strategies are framed around research questions that are prerequisites for the next phase. In other types of biomedical research, pilot studies are used for gathering preliminary support for the next research step. However, the phrase “pilot study” is liberally applied to projects with little or no funding, characteristic of studies with poorly developed research proposals, and usually conducted with no detailed thought of the subsequent study. In this article, we present a rigorous definition of a pilot study, offer recommendations for the design, analysis and sample size justification of pilot studies in clinical and translational research, and emphasize the important role that well‐designed pilot studies play in the advancement of science and scientific careers. Clin Trans Sci 2011; Volume 4: 332–337 PMID:22029804

Development and pilot evaluation of novel genetic educational materials designed for an underserved patient population.

PubMed

Lubitz, Rebecca Jean; Komaromy, Miriam; Crawford, Beth; Beattie, Mary; Lee, Robin; Luce, Judith; Ziegler, John

2007-01-01

Genetic counseling for BRCA1 and BRCA2 mutations involves teaching about hereditary cancer, genetics and risk, subjects that are difficult to grasp and are routinely misunderstood. Supported by a grant from the Avon Foundation, the UCSF Cancer Risk Program started the first genetic testing and counseling service for a population of traditionally underserved women of varied ethnic and social backgrounds at the San Francisco General Hospital (SFGH). Informed by educational theory and clinical experience, we devised and piloted two simplified explanations of heredity and genetic risk, with the aim of uncovering how to best communicate genetics and risk to this underserved population. A "conventional" version comprised pictures of genes, pedigrees, and quantitative representations of risk. A "colloquial" pictorial version used an analogy of the "information book" of genes, family stories and vignettes, and visual representations of risk, without using scientific words such as genes or chromosomes. A verbal narrative accompanied each picture. We presented these modules to four focus groups of five to eight women recruited from the SFGH Family Practice Clinic. Overall, women preferred a picture-based approach and commented that additional text would have been distracting. The majority of women preferred the colloquial version because it was easier to understand and better conveyed a sense of comfort and hope. We conclude that simplicity, analogies, and familiarity support comprehension while vignettes, family stories, and photos of real people provide comfort and hope. These elements may promote understanding of complex scientific topics in healthcare, particularly when communicating with patients who come from disadvantaged backgrounds.

[Identification of candidate genes and expression profiles, as doping biomarkers].

PubMed

Paparini, A; Impagnatiello, F; Pistilli, A; Rinaldi, M; Gianfranceschi, G; Signori, E; Stabile, A M; Fazio, V; Rende, M; Romano Spica, V

2007-01-01

Administration of prohibited substances to enhance athletic performance represents an emerging medical, social, ethical and legal issue. Traditional controls are based on direct detection of substances or their catabolites. However out-of-competition doping may not be easily revealed by standard analytical methods. Alternative indirect control strategies are based on the evaluation of mid- and long-term effects of doping in tissues. Drug-induced long-lasting changes of gene expression may be taken as effective indicators of doping exposure. To validate this approach, we used real-time PCR to monitor the expression pattern of selected genes in human haematopoietic cells exposed to nandrolone, insulin-like growth factor I (IGF-I) or growth hormone (GH). Some candidate genes were found significantly and consistently modulated by treatments. Nandrolone up-regulated AR, ESR2 and PGR in K562 cells, and SRD5A1, PPARA and JAK2 in Jurkat cells; IGF-I up-regulated EPOR and PGR in HL60 cells, and SRD5A1 in Jurkat; GH up-regulated SRD5A1 and GHR in K562. GATA1 expression was down-regulated in IGF-1-treated HL60, ESR2 was down-regulated in nandrolone-treated Jurkat, and AR and PGR were down-regulated in GH-treated Jurkat. This pilot study shows the potential of molecular biology-based strategies in anti-doping controls.

Piloted simulation study of an ILS approach of a twin-pusher business/commuter turboprop aircraft configuration

NASA Technical Reports Server (NTRS)

Riley, Donald R.; Brandon, Jay M.; Glaab, Louis J.

1994-01-01

A six-degree-of-freedom nonlinear simulation of a twin-pusher, turboprop business/commuter aircraft configuration representative of the Cessna ATPTB (Advanced turboprop test bed) was developed for use in piloted studies with the Langley General Aviation Simulator. The math models developed are provided, simulation predictions are compared with with Cessna flight-test data for validation purposes, and results of a handling quality study during simulated ILS (instrument landing system) approaches and missed approaches are presented. Simulated flight trajectories, task performance measures, and pilot evaluations are presented for the ILS approach and missed-approach tasks conducted with the vehicle in the presence of moderate turbulence, varying horizontal winds and engine-out conditions. Six test subjects consisting of two research pilots, a Cessna test pilot, and three general aviation pilots participated in the study. This effort was undertaken in cooperation with the Cessna Aircraft Company.

Study to determine the IFR operational profile and problems to the general aviation pilot

NASA Technical Reports Server (NTRS)

Weislogel, S.

1983-01-01

A study of the general aviation single pilot operating under instrument flight rules (GA SPIFR) has been conducted for NASA Langley Research Center. The objectives of the study were to (1) develop a GA SPIFR operational profile, (2) identify problems experienced by the GA SPIFR pilot, and (3) identify research tasks which have the potential for eliminating or reducing the severity of the problems. To obtain the information necessary to accomplish these objectives, a mail questionnaire survey of instrument rated pilots was conducted. Complete questionnaire data is reported in NASA CR-165805, "Statistical Summary: Study to Determine the IFR Operational Profile and Problems of the General Aviation Single Pilot'-Based upon the results of the GA SPIFR survey, this final report presents the general aviation IFR single pilot operational profile, illustrates selected data analysis, examples, identifies the problems which he is experiencing, and recommends further research.

Performance of a pilot-scale submerged membrane bioreactor (MBR) in treating bathing wastewater.

PubMed

Xia, Siqing; Guo, Jifeng; Wang, Rongchang

2008-10-01

Bathing wastewater was treated by a pilot-scale submerged membrane bioreactor (MBR) for more than 60 days. The results showed that the removal rates of main pollutants of wastewater such as COD(Cr), LAS, NH(4)(+)-N and total nitrogen (TN) were above 93%, 99%, 99%, and 90%, respectively. The results of denaturing gel gradient electrophoresis (DGGE) and fluorescent in situ hybridization (FISH) indicated that the bacteria were stable. The abundant nitrobacteria intercepted by the membrane led to the high removal rate of ammonia and TN. FISH and 16S rDNA gene sequence analysis revealed that some specific phylogenetic group of bacteria, the Pseudomonas sp. Ochrobactrum anthropi sp. and Enterobacter sp. probably played a major role in the development of the mature biofilms, which led to the severe irreversible membrane biofouling.

KSC-2011-1308

NASA Image and Video Library

2011-01-29

CAPE CANAVERAL, Fla. -- Lunar module pilot of Apollo 10 and commander of Apollo 17 Gene Cernan talks to attendees of the Apollo 14 Anniversary Soirée at the Kennedy Space Center Visitor Complex's Saturn V Center. The celebration was hosted by the Astronaut Scholarship Foundation. Apollo 14 landed on the lunar surface 40 years ago on Feb. 5, 1971. Cernan was the backup commander for the Apollo 14 mission. Photo credit: NASA/Kim Shiflett

Reflecting on the Germanwings Disaster: A Systematic Review of Depression and Suicide in Commercial Airline Pilots.

PubMed

Pasha, Terouz; Stokes, Paul R A

2018-01-01

The 2015 Germanwings Flight 9525 disaster, in which 150 people were killed after the co-pilot may have intentionally crashed the plane in a suicide attempt, highlights the importance of better understanding the mental health of commercial airline pilots. However, there have been few systematic reviews investigating the topic of mental health in commercial aviation. This systematic review aims to identify the types and prevalence of mental health disorders that commercial airline pilots experience with a focus on mood disorders and suicide risk. A systematic literature search was performed using PubMed, EMBASE, and PsycINFO databases. Eligible studies were assessed and data was extracted and analyzed. 20 studies were identified. The prevalence of depression experienced by commercial airline pilots in this review ranged from 1.9% to 12.6%. Factors that negatively impacted the mental health of pilots included substance abuse, experiencing verbal or sexual abuse, disruption in sleep circadian rhythms and fatigue. This systematic review identifies that commercial airline pilots may experience depression at least as frequently as the general population. Commercial airline pilots experience occupational stressors, such as disrupted circadian rhythms and fatigue which may increase risks of developing mood disorders. Most studies identified in this review were cross-sectional in nature with substantial limitations. There is a clear need for further higher quality longitudinal studies to better understand the mental health of commercial airline pilots.

A study on aircraft map display location and orientation. [effects of map display location on manual piloting performance

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T. E.; Huff, E. M.

1973-01-01

Six airline pilots participated in a fixed-base simulator study to determine the effects of two Horizontal Situation Display (HSD/map) panel locations relative to the Vertical Situation Display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions, and among pilots, but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

The roles of COMT val158met status and aviation expertise in flight simulator performance and cognitive ability.

PubMed

Kennedy, Q; Taylor, J L; Noda, A; Adamson, M; Murphy, G M; Zeitzer, J M; Yesavage, J A

2011-09-01

The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41-69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task.

The Roles of COMT val158met Status and Aviation Expertise in Flight Simulator Performance and Cognitive Ability

PubMed Central

Taylor, J. L.; Noda, A.; Adamson, M.; Murphy, G. M.; Zeitzer, J. M.; Yesavage, J. A.

2011-01-01

The polymorphic variation in the val158met position of the catechol-O-methyltransferase (COMT) gene is associated with differences in executive performance, processing speed, and attention. The purpose of this study is: (1) replicate previous COMT val158met findings on cognitive performance; (2) determine whether COMT val158met effects extend to a real-world task, aircraft navigation performance in a flight simulator; and (3) determine if aviation expertise moderates any effect of COMT val158met status on flight simulator performance. One hundred seventy two pilots aged 41–69 years, who varied in level of aviation training and experience, completed flight simulator, cognitive, and genetic assessments. Results indicate that although no COMT effect was found for an overall measure of flight performance, a positive effect of the met allele was detected for two aspects of cognitive ability: executive functioning and working memory performance. Pilots with the met/met genotype benefited more from increased levels of expertise than other participants on a traffic avoidance measure, which is a component of flight simulator performance. These preliminary results indicate that COMT val158met polymorphic variation can affect a real-world task. PMID:21193954

78 FR 48715 - Proposed Information Collection; Comment Request: NPS Study of Value of Natural Sounds: A Pilot...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-09

....NS0000] Proposed Information Collection; Comment Request: NPS Study of Value of Natural Sounds: A Pilot Study AGENCY: National Park Service, Interior. ACTION: Notice; request for comments. SUMMARY: We.... This is a new collection. Title: NPS Study of Value of Natural Sounds: A Pilot Study. Type of Request...

Successful Completion of the Pilot Phase of a Randomized Controlled Trial Comparing Sentinel Lymph Node Biopsy to No Further Axillary Staging in Patients with Clinical T1-T2 N0 Breast Cancer and Normal Axillary Ultrasound.

PubMed

Cyr, Amy E; Tucker, Natalia; Ademuyiwa, Foluso; Margenthaler, Julie A; Aft, Rebecca L; Eberlein, Timothy J; Appleton, Catherine M; Zoberi, Imran; Thomas, Maria A; Gao, Feng; Gillanders, William E

2016-08-01

Axillary surgery is not considered therapeutic in patients with clinical T1-T2 N0 breast cancer. The importance of axillary staging is eroding in an era in which tumor biology, as defined by biomarker and gene expression profile, is increasingly important in medical decision making. We hypothesized that axillary ultrasound (AUS) is a noninvasive alternative to sentinel lymph node biopsy (SLNB), and AUS could replace SLNB without compromising patient care. Patients with clinical T1-T2 N0 breast cancer and normal AUS were eligible for enrollment. Subjects were randomized to no further axillary staging (arm 1) vs SLNB (arm 2). Descriptive statistics were used to describe the results of the pilot phase of the randomized controlled trial. Sixty-eight subjects were enrolled in the pilot phase of the trial (34 subjects in arm 1, no further staging; 32 subjects in arm 2, SLNB; and 2 subjects voluntarily withdrew from the trial). The median age was 61 years (range 40 to 80 years) in arm 1 and 59 years (range 31 to 81 years) in arm 2, and there were no significant clinical or pathologic differences between the arms. Median follow-up was 17 months (range 1 to 32 months). The negative predictive value (NPV) of AUS for identification of clinically significant axillary disease (>2.0 mm) was 96.9%. No axillary recurrences have been observed in either arm. Successful completion of the pilot phase of the randomized controlled trial confirms the feasibility of the study design, and provides prospective evidence supporting the ability of AUS to exclude clinically significant disease in the axilla. The results provide strong support for a phase 2 randomized controlled trial. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Prediction of aircraft handling qualities using analytical models of the human pilot

NASA Technical Reports Server (NTRS)

Hess, R. A.

1982-01-01

The optimal control model (OCM) of the human pilot is applied to the study of aircraft handling qualities. Attention is focused primarily on longitudinal tasks. The modeling technique differs from previous applications of the OCM in that considerable effort is expended in simplifying the pilot/vehicle analysis. After briefly reviewing the OCM, a technique for modeling the pilot controlling higher order systems is introduced. Following this, a simple criterion for determining the susceptibility of an aircraft to pilot-induced oscillations (PIO) is formulated. Finally, a model-based metric for pilot rating prediction is discussed. The resulting modeling procedure provides a relatively simple, yet unified approach to the study of a variety of handling qualities problems.

Prediction of aircraft handling qualities using analytical models of the human pilot

NASA Technical Reports Server (NTRS)

Hess, R. A.

1982-01-01

The optimal control model (OCM) of the human pilot is applied to the study of aircraft handling qualities. Attention is focused primarily on longitudinal tasks. The modeling technique differs from previous applications of the OCM in that considerable effort is expended in simplifying the pilot/vehicle analysis. After briefly reviewing the OCM, a technique for modeling the pilot controlling higher order systems is introduced. Following this, a simple criterion for determining the susceptibility of an aircraft to pilot induced oscillations is formulated. Finally, a model based metric for pilot rating prediction is discussed. The resulting modeling procedure provides a relatively simple, yet unified approach to the study of a variety of handling qualities problems.

An analytical approach for predicting pilot induced oscillations

NASA Technical Reports Server (NTRS)

Hess, R. A.

1981-01-01

The optimal control model (OCM) of the human pilot is applied to the study of aircraft handling qualities. Attention is focused primarily on longitudinal tasks. The modeling technique differs from previous applications of the OCM in that considerable effort is expended in simplifying the pilot/vehicle analysis. After briefly reviewing the OCM, a technique for modeling the pilot controlling higher order systems is introduced. Following this, a simple criterion or determining the susceptability of an aircraft to pilot induced oscillations (PIO) is formulated. Finally, a model-based metric for pilot rating prediction is discussed. The resulting modeling procedure provides a relatively simple, yet unified approach to the study of a variety of handling qualities problems.

Genes involved in muscle contractility and nutrient signaling pathways within celiac disease risk loci show differential mRNA expression.

PubMed

Montén, Caroline; Gudjonsdottir, Audur H; Browaldh, Lars; Arnell, Henrik; Nilsson, Staffan; Agardh, Daniel; Naluai, Åsa Torinsson

2015-06-30

Risk gene variants for celiac disease, identified in genome-wide linkage and association studies, might influence molecular pathways important for disease development. The aim was to examine expression levels of potential risk genes close to these variants in the small intestine and peripheral blood and also to test if the non-coding variants affect nearby gene expression levels in children with celiac disease. Intestinal biopsy and peripheral blood RNA was isolated from 167 children with celiac disease, 61 with potential celiac disease and 174 disease controls. Transcript levels for 88 target genes, selected from celiac disease risk loci, were analyzed in biopsies of a smaller sample subset by qPCR. Differentially expressed genes (3 from the pilot and 8 previously identified) were further validated in the larger sample collection (n = 402) of both tissues and correlated to nearby celiac disease risk variants. All genes were significantly down- or up-regulated in the intestinal mucosa of celiac disease children, NTS being most down-regulated (Fold change 3.6, p < 0.001). In contrast, PPP1R12B isoform C was up-regulated in the celiac disease mucosa (Fold change 1.9, p < 0.001). Allele specific expression of GLS (rs6741418, p = 0.009), INSR (rs7254060, p = 0.003) and NCALD (rs652008, p = 0.005) was also detected in the biopsies. Two genes (APPL2 and NCALD) were differentially expressed in peripheral blood but no allele specific expression was observed in this tissue. The differential expression of NTS and PPP1R12B indicate a potential role for smooth muscle contractility and cell proliferation in celiac disease, whereas other genes like GLS, NCALD and INSR suggests involvement of nutrient signaling and energy homeostasis in celiac disease pathogenesis. A disturbance in any of these pathways might contribute to development of childhood celiac disease.

Numerical and flight simulator test of the flight deterioration concept

NASA Technical Reports Server (NTRS)

Mccarthy, J.; Norviel, V.

1982-01-01

Manned flight simulator response to theoretical wind shear profiles was studied in an effort to calibrate fixed-stick and pilot-in-the-loop numerical models of jet transport aircraft on approach to landing. Results of the study indicate that both fixed-stick and pilot-in-the-loop models overpredict the deleterious effects of aircraft approaches when compared to pilot performance in the manned simulator. Although the pilot-in-the-loop model does a better job than does the fixed-stick model, the study suggests that the pilot-in-the-loop model is suitable for use in meteorological predictions of adverse low-level wind shear along approach and departure courses to identify situations in which pilots may find difficulty. The model should not be used to predict the success or failure of a specific aircraft. It is suggested that the pilot model be used as part of a ground-based Doppler radar low-level wind shear detection and warning system.

Mandibular position influence on pilots' postural balance analyzed under dynamic conditions.

PubMed

Baldini, Alberto; Nota, Alessandro; Cioffi, Clementina; Ballanti, Fabiana; Tecco, Simona

2017-11-01

The aim of this study is to evaluate the influence of the mandibular position on the postural stability in a sample of civilian and military pilots. Twenty military pilots (males, mean age 35.15 ± 3.14 years) and 17 civilian pilots (males, mean 34.91 ± 2.15 years) were enrolled in this study and underwent a Sensory Organization Test (SOT) using the EquiTest® (NeuroCom International Inc., Clackamas, OR, USA) computerized dynamic posturography. The composite parameter was recorded and analyzed. The equilibrium score (ES) recorded in centric occlusion is slightly higher than the ES recorded in mandibular rest position; civilian pilots showed ESs slightly higher than military pilots. The two-way ANOVA analysis shows these differences are not statistically significant. The findings of this study seem to suggest that the composite parameter of the SOT is not sensitive in analyzing the influence of the stomatognathic system on the postural balance of civilian and military pilots.

Human SLC26A1 gene variants: a pilot study.

PubMed

Dawson, Paul A; Sim, Pearl; Mudge, David W; Cowley, David

2013-01-01

Kidney stones are a global health problem, incurring massive health costs annually. Why stones recur in many patients remains unknown but likely involves environmental, physiological, and genetic factors. The solute linked carrier (SLC) 26A1 gene has previously been linked to kidney stones in mice. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) protein, and its loss in mice leads to hyperoxaluria and calcium oxalate renal stones. To investigate the possible involvement of SAT1 in human urolithiasis, we screened the SLC26A1 gene in a cohort of 13 individuals with recurrent calcium oxalate urolithiasis, which is the commonest type. DNA sequence analyses showed missense mutations in seven patients: one individual was heterozygous R372H; 4 individuals were heterozygous Q556R; one patient was homozygous Q556R; and one patient with severe nephrocalcinosis (requiring nephrectomy) was homozygous Q556R and heterozygous M132T. The M132 amino acid in human SAT1 is conserved with 15 other species and is located within the third transmembrane domain of the predicted SAT1 protein structure, suggesting that this amino acid may be important for SAT1 function. These initial findings demonstrate genetic variants in SLC26A1 of recurrent stone formers and warrant wider independent studies of SLC26A1 in humans with recurrent calcium oxalate stones.

Pilot age and error in air taxi crashes.

PubMed

Rebok, George W; Qiang, Yandong; Baker, Susan P; Li, Guohua

2009-07-01

The associations of pilot error with the type of flight operations and basic weather conditions are well documented. The correlation between pilot characteristics and error is less clear. This study aims to examine whether pilot age is associated with the prevalence and patterns of pilot error in air taxi crashes. Investigation reports from the National Transportation Safety Board for crashes involving non-scheduled Part 135 operations (i.e., air taxis) in the United States between 1983 and 2002 were reviewed to identify pilot error and other contributing factors. Crash circumstances and the presence and type of pilot error were analyzed in relation to pilot age using Chi-square tests. Of the 1751 air taxi crashes studied, 28% resulted from mechanical failure, 25% from loss of control at landing or takeoff, 7% from visual flight rule conditions into instrument meteorological conditions, 7% from fuel starvation, 5% from taxiing, and 28% from other causes. Crashes among older pilots were more likely to occur during the daytime rather than at night and off airport than on airport. The patterns of pilot error in air taxi crashes were similar across age groups. Of the errors identified, 27% were flawed decisions, 26% were inattentiveness, 23% mishandled aircraft kinetics, 15% mishandled wind and/or runway conditions, and 11% were others. Pilot age is associated with crash circumstances but not with the prevalence and patterns of pilot error in air taxi crashes. Lack of age-related differences in pilot error may be attributable to the "safe worker effect."

75 FR 80827 - Compliance Policy Guide; Radiofrequency Identification Feasibility Studies and Pilot Programs for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... Identification (RFID) Feasibility Studies and Pilot Programs for Drugs'' to December 31, 2012. FOR FURTHER... Sec. 400.210 entitled ``Radiofrequency Identification (RFID) Feasibility Studies and Pilot Programs... FR 65750, November 23, 2007; 73 FR 78371, December 22, 2008). FDA has identified RFID as a promising...

Autogenic-feedback training improves pilot performance during emergency flying conditions

NASA Technical Reports Server (NTRS)

Kellar, Michael A.; Folen, Raymond A.; Cowings, Patricia S.; Toscano, William B.; Hisert, Glen L.

1994-01-01

Studies have shown that autonomous mode behavior is one cause of aircraft fatalities due to pilot error. In such cases, the pilot is in a high state of psychological and physiological arousal and tends to focus on one problem, while ignoring more critical information. This study examined the effect of training in physiological self-recognition and regulation, as a means of improving crew cockpit performance. Seventeen pilots were assigned to the treatment and control groups matched for accumulated flight hours. The treatment group comprised three pilots of HC-130 Hercules aircraft and four HH-65 Dolphin helicopter pilots; the control group comprised three pilots of HC-130's and six Dolphin helicopter pilots. During an initial flight, physiological data were recorded for each crew member and individual crew performance was rated by an instructor pilot. Eight crewmembers were then taught to regulate their own physiological response levels using Autogenic-Feedback Training (AFT). The remaining subjects received no training. During a second flight, treatment subjects showed significant improvement in performance, while controls did not improve. The results indicate that AFT management of high states of physiological arousal may improve pilot performance during emergency flying conditions.

Using Motivational Enhancement Among OIF / OEF Veterans Returning to the Community

DTIC Science & Technology

2014-10-01

than veterans who receive treatment as usual. During this year the pilot study for the project was completed. The purpose of the pilot study group was...pilot group members could not be used. The veterans in the pilot study were notified of the lapse and were re-consented. During the year the team...Veterans must not be currently in counseling to participate in the project. To combat this, one idea proposed is to allow veterans who live outside of

Compensation for time delay in flight simulator visual-display systems

NASA Technical Reports Server (NTRS)

Crane, D. F.

1983-01-01

A piloted aircraft can be viewed as a closed-loop, man-machine control system. When a simulator pilot is performing a precision maneuver, a delay in the visual display of aircraft response to pilot-control input decreases the stability of the pilot-aircraft system. The less stable system is more difficult to control precisely. Pilot dynamic response and performance change as the pilot attempts to compensate for the decrease in system stability, and these changes bias the simulation results by influencing the pilot's rating of the handling qualities of the simulated aircraft. Delay compensation, designed to restore pilot-aircraft system stability, was evaluated in several studies which are reported here. The studies range from single-axis, tracking-task experiments (with sufficient subjects and trials to establish statistical significance of the results) to a brief evaluation of compensation of a computer-generated-imagery (CGI) visual display system in a full six-degree-of-freedom simulation. The compensation was effective - improvements in pilot performance and workload or aircraft handling-qualities rating (HQR) were observed. Results from recent aircraft handling-qualities research literature which support the compensation design approach are also reviewed.

NORTHWEST ORGEON PILOT STUDY AREA (USA): THE USE OF LANDSCAPE SCIENCE FOR ENVIRONMENTAL ASSESSMENT PILOT STUDY

EPA Science Inventory

The Northwest Oregon Pilot Study Area encompasses approximately 59,167 km2 and varies in elevation from sea level to 3,200 m. Annual precipitation varies with elevation and meridian and ranges from 25 - 460cm. The study area comprises a mixture of federal, state, and privately ow...

Exome Pool-Seq in neurodevelopmental disorders.

PubMed

Popp, Bernt; Ekici, Arif B; Thiel, Christian T; Hoyer, Juliane; Wiesener, Antje; Kraus, Cornelia; Reis, André; Zweier, Christiane

2017-12-01

High throughput sequencing has greatly advanced disease gene identification, especially in heterogeneous entities. Despite falling costs this is still an expensive and laborious technique, particularly when studying large cohorts. To address this problem we applied Exome Pool-Seq as an economic and fast screening technology in neurodevelopmental disorders (NDDs). Sequencing of 96 individuals can be performed in eight pools of 12 samples on less than one Illumina sequencer lane. In a pilot study with 96 cases we identified 27 variants, likely or possibly affecting function. Twenty five of these were identified in 923 established NDD genes (based on SysID database, status November 2016) (ACTB, AHDC1, ANKRD11, ATP6V1B2, ATRX, CASK, CHD8, GNAS, IFIH1, KCNQ2, KMT2A, KRAS, MAOA, MED12, MED13L, RIT1, SETD5, SIN3A, TCF4, TRAPPC11, TUBA1A, WAC, ZBTB18, ZMYND11), two in 543 (SysID) candidate genes (ZNF292, BPTF), and additionally a de novo loss-of-function variant in LRRC7, not previously implicated in NDDs. Most of them were confirmed to be de novo, but we also identified X-linked or autosomal-dominantly or autosomal-recessively inherited variants. With a detection rate of 28%, Exome Pool-Seq achieves comparable results to individual exome analyses but reduces costs by >85%. Compared with other large scale approaches using Molecular Inversion Probes (MIP) or gene panels, it allows flexible re-analysis of data. Exome Pool-Seq is thus well suited for large-scale, cost-efficient and flexible screening in characterized but heterogeneous entities like NDDs.

Decoding the disease-associated proteins encoded in the human chromosome 4.

PubMed

Chen, Lien-Chin; Liu, Mei-Ying; Hsiao, Yung-Chin; Choong, Wai-Kok; Wu, Hsin-Yi; Hsu, Wen-Lian; Liao, Pao-Chi; Sung, Ting-Yi; Tsai, Shih-Feng; Yu, Jau-Song; Chen, Yu-Ju

2013-01-04

Chromosome 4 is the fourth largest chromosome, containing approximately 191 megabases (~6.4% of the human genome) with 757 protein-coding genes. A number of marker genes for many diseases have been found in this chromosome, including genetic diseases (e.g., hepatocellular carcinoma) and biomedical research (cardiac system, aging, metabolic disorders, immune system, cancer and stem cell) related genes (e.g., oncogenes, growth factors). As a pilot study for the chromosome 4-centric human proteome project (Chr 4-HPP), we present here a systematic analysis of the disease association, protein isoforms, coding single nucleotide polymorphisms of these 757 protein-coding genes and their experimental evidence at the protein level. We also describe how the findings from the chromosome 4 project might be used to drive the biomarker discovery and validation study in disease-oriented projects, using the examples of secretomic and membrane proteomic approaches in cancer research. By integrating with cancer cell secretomes and several other existing databases in the public domain, we identified 141 chromosome 4-encoded proteins as cancer cell-secretable/shedable proteins. Additionally, we also identified 54 chromosome 4-encoded proteins that have been classified as cancer-associated proteins with successful selected or multiple reaction monitoring (SRM/MRM) assays developed. From literature annotation and topology analysis, 271 proteins were recognized as membrane proteins while 27.9% of the 757 proteins do not have any experimental evidence at the protein-level. In summary, the analysis revealed that the chromosome 4 is a rich resource for cancer-associated proteins for biomarker verification projects and for drug target discovery projects.

Pilot Comments From the Boeing High Speed Research Aircraft, Cycle 3, Simulation Study of the Effects of Aeroservoelasticity (LaRC.3)

NASA Technical Reports Server (NTRS)

Bailey, Melvin L. (Editor)

2000-01-01

This is a compilation of pilot comments from the Boeing High Speed Research Aircraft, Cycle 3, simulation study (LaRC.3) of the effects of aeroservoelasticity, conducted from October to December 1997 at NASA Langley Research Center. This simulation study was conducted using the Visual Motion Simulator. The comments are from direct tape transcriptions and have been edited for spelling only. These comments were made on tape following the completion of each flight card, immediately after the pilot was satisfied with his practice and data recording runs. Six pilots were used in the evaluation and they are identified as pilots A through F.

The use of total simulator training in transitioning air-carrier pilots: A field evaluation

NASA Technical Reports Server (NTRS)

Randle, R. J., Jr.; Tanner, T. A.; Hamerman, J. A.; Showalter, T. H.

1981-01-01

A field study was conducted in which the performance of air carrier transitioning pilots who had landing training in a landing maneuver approved simulator was compared with the performance of pilots who had landing training in the aircraft. Forty-eight trainees transitioning to the B-727 aircraft and eighty-seven trainees transitioning to the DC-10 were included in the study. The study results in terms of both objectively measured performance indicants and observer and check-pilot ratings did not demonstrate a clear distinction between the two training groups. The results suggest that, for these highly skilled transitioning pilots, a separate training module in the aircraft may be of dubious value.

Oregon department of transportation small business group twice-monthly payments pilot project : summary report.

DOT National Transportation Integrated Search

2008-07-01

Oregon Department of Transportation (ODOT) recently completed a pilot study on small business payment practices. In the study, three pilot projects were tested where payments to small business contractors were changed from a monthly payment to twice-...

Modeling human pilot cue utilization with applications to simulator fidelity assessment.

PubMed

Zeyada, Y; Hess, R A

2000-01-01

An analytical investigation to model the manner in which pilots perceive and utilize visual, proprioceptive, and vestibular cues in a ground-based flight simulator was undertaken. Data from a NASA Ames Research Center vertical motion simulator study of a simple, single-degree-of-freedom rotorcraft bob-up/down maneuver were employed in the investigation. The study was part of a larger research effort that has the creation of a methodology for determining flight simulator fidelity requirements as its ultimate goal. The study utilized a closed-loop feedback structure of the pilot/simulator system that included the pilot, the cockpit inceptor, the dynamics of the simulated vehicle, and the motion system. With the exception of time delays that accrued in visual scene production in the simulator, visual scene effects were not included in this study. Pilot/vehicle analysis and fuzzy-inference identification were employed to study the changes in fidelity that occurred as the characteristics of the motion system were varied over five configurations. The data from three of the five pilots who participated in the experimental study were analyzed in the fuzzy-inference identification. Results indicate that both the analytical pilot/vehicle analysis and the fuzzy-inference identification can be used to identify changes in simulator fidelity for the task examined.

A queueing model of pilot decision making in a multi-task flight management situation

NASA Technical Reports Server (NTRS)

Walden, R. S.; Rouse, W. B.

1977-01-01

Allocation of decision making responsibility between pilot and computer is considered and a flight management task, designed for the study of pilot-computer interaction, is discussed. A queueing theory model of pilot decision making in this multi-task, control and monitoring situation is presented. An experimental investigation of pilot decision making and the resulting model parameters are discussed.

Diversity of Cervical Microbiota in Asymptomatic Chlamydia trachomatis Genital Infection: A Pilot Study.

PubMed

Filardo, Simone; Di Pietro, Marisa; Porpora, Maria G; Recine, Nadia; Farcomeni, Alessio; Latino, Maria A; Sessa, Rosa

2017-01-01

Chlamydia trachomatis genital infection continues to be an important public health problem worldwide due to its increasing incidence. C. trachomatis infection can lead to severe sequelae, such as pelvic inflammatory disease, obstructive infertility, and preterm birth. Recently, it has been suggested that the cervico-vaginal microbiota may be an important defense factor toward C. trachomatis infection as well as the development of chronic sequelae. Therefore, the investigation of microbial profiles associated to chlamydial infection is of the utmost importance. Here we present a pilot study aiming to characterize, through the metagenomic analysis of sequenced 16s rRNA gene amplicons, the cervical microbiota from reproductive age women positive to C. trachomatis infection. The main finding of our study showed a marked increase in bacterial diversity in asymptomatic C. trachomatis positive women as compared to healthy controls in terms of Shannon's diversity and Shannon's evenness ( P = 0.031 and P = 0.026, respectively). More importantly, the cervical microbiota from C. trachomatis positive women and from healthy controls significantly separated into two clusters in the weighted UniFrac analysis ( P = 0.0027), suggesting that differences between the two groups depended entirely on the relative abundance of bacterial taxa rather than on the types of bacterial taxa present. Furthermore, C. trachomatis positive women showed an overall decrease in Lactobacillus spp. and an increase in anaerobes. These findings are part of an ongoing larger epidemiological study that will evaluate the potential role of distinct bacterial communities of the cervical microbiota in C. trachomatis infection.

Lunar Analog

NASA Technical Reports Server (NTRS)

Cromwell, Ronita L.

2009-01-01

In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

Study of occupational stress among railway engine pilots

PubMed Central

Kumar, Devesh; Singh, Jai Vir; Kharwar, Poonam S.

2011-01-01

Background: Traffic volume and speed is going to be increased in Indian Railways successively, leading to higher stress in staff connected with train operations. The jobs of railway engine pilots come under the category of high-strain jobs, necessitating a need to conduct multicentric study to unfold the factors associated with occupational stress and organizational strategies. Materials and Methods: Present study covered 185 railway engine pilots and office clerks working in various railway zones by incidental method. Occupational Stress Index (OSI) test developed by Srivastva and Singh, questionnaire of specific stressors constructed by authors and laboratory test battery for psychological screening of high-speed train pilots were used as tools. Results: Means of OSI and all the 12 occupational stressors of railway engine pilots were found significantly higher to that of office clerks. Means of OSI and occupational stressors of goods train pilots were significantly higher in comparison to high-speed train pilots and passenger train pilots. Study revealed positive correlation of speed perception and complex reaction time tests and negative correlation of other constituent tests of laboratory test battery to OSI test. Highest subgroup of stressor observedwas role overload followed by role conflict. Conclusions: These findings provide a prima facie evidence of higher occupational stress among railway engine pilots because of identified specific stressors prevalent in their job and explore the possible intervention strategies for its reduction. Significant correlation is noticed between OSI and laboratory test results, indicating its relevant utility in preliminary psychological screening. PMID:21808497

A simulator evaluation of an automatic terminal approach system

NASA Technical Reports Server (NTRS)

Hinton, D. A.

1983-01-01

The automatic terminal approach system (ATAS) is a concept for improving the pilot/machine interface with cockpit automation. The ATAS can automatically fly a published instrument approach by using stored instrument approach data to automatically tune airplane avionics, control the airplane's autopilot, and display status information to the pilot. A piloted simulation study was conducted to determine the feasibility of an ATAS, determine pilot acceptance, and examine pilot/ATAS interaction. Seven instrument-rated pilots each flew four instrument approaches with a base-line heading select autopilot mode. The ATAS runs resulted in lower flight technical error, lower pilot workload, and fewer blunders than with the baseline autopilot. The ATAS status display enabled the pilots to maintain situational awareness during the automatic approaches. The system was well accepted by the pilots.

Microbial diversity and activity in the Nematostella vectensis holobiont: insights from 16S rRNA gene sequencing, isolate genomes, and a pilot-scale survey of gene expression.

PubMed

Har, Jia Y; Helbig, Tim; Lim, Ju H; Fernando, Samodha C; Reitzel, Adam M; Penn, Kevin; Thompson, Janelle R

2015-01-01

We have characterized the molecular and genomic diversity of the microbiota of the starlet sea anemone Nematostella vectensis, a cnidarian model for comparative developmental and functional biology and a year-round inhabitant of temperate salt marshes. Molecular phylogenetic analysis of 16S rRNA gene clone libraries revealed four ribotypes associated with N. vectensis at multiple locations and times. These associates include two novel ribotypes within the ε-Proteobacterial order Campylobacterales and the Spirochetes, respectively, each sharing <85% identity with cultivated strains, and two γ-Proteobacterial ribotypes sharing >99% 16S rRNA identity with Endozoicomonas elysicola and Pseudomonas oleovorans, respectively. Species-specific PCR revealed that these populations persisted in N. vectensis asexually propagated under laboratory conditions. cDNA indicated expression of the Campylobacterales and Endozoicomonas 16S rRNA in anemones from Sippewissett Marsh, MA. A collection of bacteria from laboratory raised N. vectensis was dominated by isolates from P. oleovorans and Rhizobium radiobacter. Isolates from field-collected anemones revealed an association with Limnobacter and Stappia isolates. Genomic DNA sequencing was carried out on 10 cultured bacterial isolates representing field- and laboratory-associates, i.e., Limnobacter spp., Stappia spp., P. oleovorans and R. radiobacter. Genomes contained multiple genes identified as virulence (host-association) factors while S. stellulata and L. thiooxidans genomes revealed pathways for mixotrophic sulfur oxidation. A pilot metatranscriptome of laboratory-raised N. vectensis was compared to the isolate genomes and indicated expression of ORFs from L. thiooxidans with predicted functions of motility, nutrient scavenging (Fe and P), polyhydroxyalkanoate synthesis for carbon storage, and selective permeability (porins). We hypothesize that such activities may mediate acclimation and persistence of bacteria in a N. vectensis holobiont defined by both internal and external gradients of chemicals and nutrients in a dynamic coastal habitat.

Microbial diversity and activity in the Nematostella vectensis holobiont: insights from 16S rRNA gene sequencing, isolate genomes, and a pilot-scale survey of gene expression

PubMed Central

Har, Jia Y.; Helbig, Tim; Lim, Ju H.; Fernando, Samodha C.; Reitzel, Adam M.; Penn, Kevin; Thompson, Janelle R.

2015-01-01

We have characterized the molecular and genomic diversity of the microbiota of the starlet sea anemone Nematostella vectensis, a cnidarian model for comparative developmental and functional biology and a year-round inhabitant of temperate salt marshes. Molecular phylogenetic analysis of 16S rRNA gene clone libraries revealed four ribotypes associated with N. vectensis at multiple locations and times. These associates include two novel ribotypes within the ε-Proteobacterial order Campylobacterales and the Spirochetes, respectively, each sharing <85% identity with cultivated strains, and two γ-Proteobacterial ribotypes sharing >99% 16S rRNA identity with Endozoicomonas elysicola and Pseudomonas oleovorans, respectively. Species-specific PCR revealed that these populations persisted in N. vectensis asexually propagated under laboratory conditions. cDNA indicated expression of the Campylobacterales and Endozoicomonas 16S rRNA in anemones from Sippewissett Marsh, MA. A collection of bacteria from laboratory raised N. vectensis was dominated by isolates from P. oleovorans and Rhizobium radiobacter. Isolates from field-collected anemones revealed an association with Limnobacter and Stappia isolates. Genomic DNA sequencing was carried out on 10 cultured bacterial isolates representing field- and laboratory-associates, i.e., Limnobacter spp., Stappia spp., P. oleovorans and R. radiobacter. Genomes contained multiple genes identified as virulence (host-association) factors while S. stellulata and L. thiooxidans genomes revealed pathways for mixotrophic sulfur oxidation. A pilot metatranscriptome of laboratory-raised N. vectensis was compared to the isolate genomes and indicated expression of ORFs from L. thiooxidans with predicted functions of motility, nutrient scavenging (Fe and P), polyhydroxyalkanoate synthesis for carbon storage, and selective permeability (porins). We hypothesize that such activities may mediate acclimation and persistence of bacteria in a N. vectensis holobiont defined by both internal and external gradients of chemicals and nutrients in a dynamic coastal habitat. PMID:26388838

Revised NEO Personality Inventory profiles of male and female U.S. Air Force pilots.

PubMed

Callister, J D; King, R E; Retzlaff, P D; Marsh, R W

1999-12-01

The study of pilot personality characteristics has a long and controversial history. Personality characteristics seem to be fairly poor predictors of training outcome; however, valid personality assessment is essential to clinical psychological evaluations. Therefore, the personality characteristics of pilots must be studied to ensure valid clinical assessment. This paper describes normative personality characteristics of U.S. Air Force pilots based on the Revised NEO Personality Inventory profiles of 1,301 U.S. Air Force student pilots. Compared with male adult norms, male student pilots had higher levels of extraversion and lower levels of agreeableness. Compared with female adult norms, female student pilots had higher levels of extraversion and openness and lower levels of agreeableness. Descriptive statistics and percentile tables for the five domain scores and 30 facet scores are provided for clinical use, and a case vignette is provided as an example of the clinical utility of these U.S. Air Force norms.

Head positioning for high +Gz loads: an analysis of the techniques used by F/A-18 pilots.

PubMed

Newman, D G

1997-08-01

A study was undertaken among Royal Australian Air Force fighter pilots to determine whether, as an occupational group, they had developed any particular protective head positioning strategies in order to minimize their risk of sustaining a +Gz-induced neck injury during air combat maneuvering. There were 42 F/A-18 Hornet pilots who responded to an anonymous questionnaire which asked about head positioning strategies. Of these, 29 pilots reported using a protective strategy. Several pilots reported using several different techniques. The most popular strategy reported was positioning the head prior to the application of +Gz (13 respondents). Eleven pilots reported using aircraft structures to wedge or brace their heads against. The results of this study show that fighter pilots who are regularly exposed to high +Gz forces develop an individualized approach to protecting their cervical spines from +Gz-induced injury.

Effects of hydration on cognitive function of pilots.

PubMed

Lindseth, Paul D; Lindseth, Glenda N; Petros, Thomas V; Jensen, Warren C; Caspers, Julie

2013-07-01

The objective of this study was to examine the effect of fluid intake and possible dehydration on cognitive flight performance of pilots. A repeated-measures, counterbalanced, mixed study design was used to examine differences in working memory, spatial orientation, and cognitive flight performance of 40 randomly selected healthy pilots after having high and low fluid intakes. Serial weights were also analyzed to determine differences in cognitive flight performance of the dehydrated (1-3% weight loss) and hydrated study participants. Results showed flight performance and spatial cognition test scores were significantly (p < 0.05) poorer for pilots who had low fluid intakes and experienced dehydration in comparison to the hydrated pilots. These findings indicate fluid intake differences resulting in dehydration may have safety implications because peak cognitive performance among pilots is critical for flight safety. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Activated carbon enhanced anaerobic digestion of food waste - Laboratory-scale and Pilot-scale operation.

PubMed

Zhang, Le; Zhang, Jingxin; Loh, Kai-Chee

2018-05-01

Effects of activated carbon (AC) supplementation on anaerobic digestion (AD) of food waste were elucidated in lab- and pilot-scales. Lab-scale AD was performed in 1 L and 8 L digesters, while pilot-scale AD was conducted in a 1000 L digester. Based on the optimal dose of 15 g AC per working volume derived from the 1 L digester, for the same AC dosage in the 8 L digester, an improved operation stability coupled with a higher methane yield was achieved even when digesters without AC supplementation failed after 59 days due to accumulation of substantial organic intermediates. At the same time, color removal from the liquid phase of the digestate was dramatically enhanced and the particle size of the digestate solids was increased by 53% through AC supplementation after running for 59 days. Pyrosequencing of 16S rRNA gene showed the abundance of predominant phyla Firmicutes, Elusimicrobia and Proteobacteria selectively enhanced by 1.7-fold, 2.9-fold and 2.1-fold, respectively. Pilot-scale digester without AC gave an average methane yield of 0.466 L⋅(gVS) -1 ⋅d -1 at a composition of 53-61% v/v methane. With AC augmentation, an increase of 41% in methane yield was achieved in the 1000 L digester under optimal organic loading rate (1.6 g VS FW ·L -1 ·d -1 ). Copyright © 2018 Elsevier Ltd. All rights reserved.

Establishment of Bacterial Herbicide Degraders in a Rapid Sand Filter for Bioremediation of Phenoxypropionate-Polluted Groundwater

PubMed Central

Feld, Louise; Nielsen, Tue Kjærgaard; Hansen, Lars Hestbjerg; Aamand, Jens

2015-01-01

In this study, we investigated the establishment of natural bacterial degraders in a sand filter treating groundwater contaminated with the phenoxypropionate herbicides (RS)-2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP) and (RS)-2-(2,4-dichlorophenoxy)propanoic acid (DCPP) and the associated impurity/catabolite 4-chlorophenoxypropanoic acid (4-CPP). A pilot facility was set up in a contaminated landfill site. Anaerobic groundwater was pumped up and passed through an aeration basin and subsequently through a rapid sand filter, which is characterized by a short residence time of the water in the filter. For 3 months, the degradation of DCPP, MCPP, and 4-CPP in the sand filter increased to 15 to 30% of the inlet concentration. A significant selection for natural bacterial herbicide degraders also occurred in the sand filter. Using a most-probable-number (MPN) method, we found a steady increase in the number of culturable phenoxypropionate degraders, reaching approximately 5 × 105 degraders per g sand by the end of the study. Using a quantitative PCR targeting the two phenoxypropionate degradation genes, rdpA and sdpA, encoding stereospecific dioxygenases, a parallel increase was observed, but with the gene copy numbers being about 2 to 3 log units higher than the MPN. In general, the sdpA gene was more abundant than the rdpA gene, and the establishment of a significant population of bacteria harboring sdpA occurred faster than the establishment of an rdpA gene-carrying population. The identities of the specific herbicide degraders in the sand filter were assessed by Illumina MiSeq sequencing of 16S rRNA genes from sand filter samples and from selected MPN plate wells. We propose a list of potential degrader bacteria involved in herbicide degradation, including representatives belonging to the Comamonadaceae and Sphingomonadales. PMID:26590282

Pilot Age and Error in Air-Taxi Crashes

PubMed Central

Rebok, George W.; Qiang, Yandong; Baker, Susan P.; Li, Guohua

2010-01-01

Introduction The associations of pilot error with the type of flight operations and basic weather conditions are well documented. The correlation between pilot characteristics and error is less clear. This study aims to examine whether pilot age is associated with the prevalence and patterns of pilot error in air-taxi crashes. Methods Investigation reports from the National Transportation Safety Board for crashes involving non-scheduled Part 135 operations (i.e., air taxis) in the United States between 1983 and 2002 were reviewed to identify pilot error and other contributing factors. Crash circumstances and the presence and type of pilot error were analyzed in relation to pilot age using Chi-square tests. Results Of the 1751 air-taxi crashes studied, 28% resulted from mechanical failure, 25% from loss of control at landing or takeoff, 7% from visual flight rule conditions into instrument meteorological conditions, 7% from fuel starvation, 5% from taxiing, and 28% from other causes. Crashes among older pilots were more likely to occur during the daytime rather than at night and off airport than on airport. The patterns of pilot error in air-taxi crashes were similar across age groups. Of the errors identified, 27% were flawed decisions, 26% were inattentiveness, 23% mishandled aircraft kinetics, 15% mishandled wind and/or runway conditions, and 11% were others. Conclusions Pilot age is associated with crash circumstances but not with the prevalence and patterns of pilot error in air-taxi crashes. Lack of age-related differences in pilot error may be attributable to the “safe worker effect.” PMID:19601508

Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma.

PubMed

Abdelaziz, Mohamed; Sherif, Lotfy; ElKhiary, Mostafa; Nair, Sanjeeta; Shalaby, Shahinaz; Mohamed, Sara; Eziba, Noura; El-Lakany, Mohamed; Curiel, David; Ismail, Nahed; Diamond, Michael P; Al-Hendy, Ayman

2016-04-01

Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad-TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR. In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P < 0.05), reduced expression of proliferation marker (PCNA) (P < 0.05), induced expression of apoptotic protein, c-PARP-1, (P < 0.05) and inhibited expression of extracellular matrix-related genes (TGF beta 3) and angiogenesis-related genes (VEGF & IGF-1) (P < 0.01). There were no detectable adenovirus in tested tissues other than leiomyoma lesions with both targeted and untargeted adenovirus. Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. © The Author(s) 2016.

Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr Virus

PubMed Central

Vernon, Suzanne D; Whistler, Toni; Cameron, Barbara; Hickie, Ian B; Reeves, William C; Lloyd, Andrew

2006-01-01

Background Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection. Methods We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides. Results Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle. Conclusion These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis. PMID:16448567

Human risk factors associated with pilots in runway excursions.

PubMed

Chang, Yu-Hern; Yang, Hui-Hua; Hsiao, Yu-Jung

2016-09-01

A breakdown analysis of civil aviation accidents worldwide indicates that the occurrence of runway excursions represents the largest portion among all aviation occurrence categories. This study examines the human risk factors associated with pilots in runway excursions, by applying a SHELLO model to categorize the human risk factors and to evaluate the importance based on the opinions of 145 airline pilots. This study integrates aviation management level expert opinions on relative weighting and improvement-achievability in order to develop four kinds of priority risk management strategies for airline pilots to reduce runway excursions. The empirical study based on experts' evaluation suggests that the most important dimension is the liveware/pilot's core ability. From the perspective of front-line pilots, the most important risk factors are the environment, wet/containment runways, and weather issues like rain/thunderstorms. Finally, this study develops practical strategies for helping management authorities to improve major operational and managerial weaknesses so as to reduce the human risks related to runway excursions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study of the use of a nonlinear, rate limited, filter on pilot control signals

NASA Technical Reports Server (NTRS)

Adams, J. J.

1977-01-01

The use of a filter on the pilot's control output could improve the performance of the pilot-aircraft system. What is needed is a filter with a sharp high frequency cut-off, no resonance peak, and a minimum of lag at low frequencies. The present investigation studies the usefulness of a nonlinear, rate limited, filter in performing the needed function. The nonlinear filter is compared with a linear, first order filter, and no filter. An analytical study using pilot models and a simulation study using experienced test pilots was performed. The results showed that the nonlinear filter does promote quick, steady maneuvering. It is shown that the nonlinear filter attenuates the high frequency remnant and adds less phase lag to the low frequency signal than does the linear filter. It is also shown that the rate limit in the nonlinear filter can be set to be too restrictive, causing an unstable pilot-aircraft system response.

Airplane pilot mental health and suicidal thoughts: a cross-sectional descriptive study via anonymous web-based survey.

PubMed

Wu, Alexander C; Donnelly-McLay, Deborah; Weisskopf, Marc G; McNeely, Eileen; Betancourt, Theresa S; Allen, Joseph G

2016-12-15

The Germanwings Flight 9525 crash has brought the sensitive subject of airline pilot mental health to the forefront in aviation. Globally, 350 million people suffer from depression-a common mental disorder. This study provides further information on this important topic regarding mental health especially among female airline pilots. This is the first study to describe airline pilot mental health-with a focus on depression and suicidal thoughts-outside of the information derived from aircraft accident investigations, regulated health examinations, or identifiable self-reports, which are records protected by civil aviation authorities and airline companies. This is a descriptive cross-sectional study via an anonymous web-based survey administered between April and December 2015. Pilots were recruited from unions, airline companies, and airports via convenience sampling. Data analysis included calculating absolute number and prevalence of health characteristics and depression scores. One thousand eight hundred thirty seven (52.7%) of the 3485 surveyed pilots completed the survey, with 1866 (53.5%) completing at least half of the survey. 233 (12.6%) of 1848 airline pilots responding to the Patient Health Questionnaire 9 (PHQ-9), and 193 (13.5%) of 1430 pilots who reported working as an airline pilot in the last seven days at time of survey, met depression threshold-PHQ-9 total score ≥ 10. Seventy-five participants (4.1%) reported having suicidal thoughts within the past two weeks. We found a significant trend in proportions of depression at higher levels of use of sleep-aid medication (trend test z = 6.74, p < 0.001) and among those experiencing sexual harassment (z = 3.18, p = 0.001) or verbal harassment (z = 6.13, p < 0.001). Hundreds of pilots currently flying are managing depressive symptoms perhaps without the possibility of treatment due to the fear of negative career impacts. This study found 233 (12.6%) airline pilots meeting depression threshold and 75 (4.1%) pilots reporting having suicidal thoughts. Although results have limited generalizability, there are a significant number of active pilots suffering from depressive symptoms. We recommend airline organizations increase support for preventative mental health treatment. Future research will evaluate additional risk factors of depression such as sleep and circadian rhythm disturbances.

Pilot Convective Weather Decision Making in En Route Airspace

NASA Technical Reports Server (NTRS)

Wu, Shu-Chieh; Gooding, Cary L.; Shelley, Alexandra E.; Duong, Constance G.; Johnson, Walter W.

2012-01-01

The present research investigates characteristics exhibited in pilot convective weather decision making in en route airspace. In a part-task study, pilots performed weather avoidance under various encounter scenarios. Results showed that the margins of safety that pilots maintain from storms are as fluid as deviation decisions themselves.

Pilot age and expertise predict flight simulator performance: a 3-year longitudinal study.

PubMed

Taylor, Joy L; Kennedy, Quinn; Noda, Art; Yesavage, Jerome A

2007-02-27

Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance. Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score. More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots. These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults' skilled cognitive performances.

Feasibility and Pilot Studies in Palliative Care Research: A Systematic Review.

PubMed

Jones, Terry A; Olds, Timothy S; Currow, David C; Williams, Marie T

2017-07-01

Feasibility and pilot study designs are common in palliative care research. Finding standard guidelines on the structure and reporting of these study types is difficult. In feasibility and pilot studies in palliative care research, to determine 1) how commonly a priori feasibility are criteria reported and whether results are subsequently reported against these criteria? and 2) how commonly are participants' views on acceptability of burden of the study protocol assessed? Four databases (OVID Medline, EMBASE, CINAHL, and PubMed via caresearch.com.au.) were searched. Search terms included palliative care, terminal care, advance care planning, hospice, pilot, feasibility, with a publication date between January 1, 2012 and December 31, 2013. Articles were selected and appraised by two independent reviewers. Fifty-six feasibility and/or pilot studies were included in this review. Only three studies had clear a priori criteria to measure success. Sixteen studies reported participant acceptability or burden with measures. Forty-eight studies concluded feasibility. The terms "feasibility" and "pilot" are used synonymously in palliative care research when describing studies that test for feasibility. Few studies in palliative care research outline clear criteria for success. The assessment of participant acceptability and burden is uncommon. A gold standard for feasibility study design in palliative care research that includes both clear criteria for success and testing of the study protocol for participant acceptability and burden is needed. Such a standard would assist with consistency in the design, conduct and reporting of feasibility and pilot studies. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Intelligent Pilot Aids for Flight Re-Planning in Emergencies

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Ockerman, Jennifer

2005-01-01

Effective and safe control of an aircraft may be difficult or nearly impossible for a pilot following an unexpected system failure. Without prior training, the pilot must ascertain on the fly those changes in both manual control technique and procedures that will lead to a safe landing of the aircraft. Sophisticated techniques for determining the required control techniques are now available. Likewise, a body of literature on pilot decision making provides formalisms for examining how pilots approach discrete decisions framed as the selection between options. However, other aspects of behavior, such as the task of route planning and guidance, are not as well studied. Not only is the pilot faced with possible performance changes to the aircraft dynamics, but he or she is also tasked to create a plan of actions that will effectively take the aircraft down to a safe landing. In this plan, the many actions that the pilot can perform are closely intertwined with the trajectory of the aircraft, making it difficult to accurately predict the final outcome. Coupled with the vast number of potential actions to be taken, this problem may seem intractable. This is reflected in the lack of a pre-specified procedure capable of giving pilots the ability to find a resolution for this task. This report summarizes a multi-year effort to examine methods to aid pilots in planning an approach and arrival to an airport following an aircraft systems failure. Ultimately, we hypothesize that automatic assistance to pilots can be provided in real-time in the form of improving pilot control of a damaged aircraft and providing pilots with procedural directives suitable for critical flight conditions; such systems may also benefit pilot training and procedure design. To achieve this result, a systematic, comprehensive research program was followed, building on prior research. This approach included a pencil-and-paper study with airline pilots examining methods of representing a flight route in an immediately understandable manner, and in a manner that would allow the pilot to modify an automatically-generated route and/or detect any inappropriate elements in an automatically-generated route. Likewise, a flight simulator study examined different cockpit systems for the relative merits of providing pilots with any of a variety of automated functions for emergency flight planning. The results provide specific guidance for the design of such systems.

Airline Pilot Cosmic Radiation and Circadian Disruption Exposure Assessment from Logbooks and Company Records

PubMed Central

Grajewski, Barbara; Waters, Martha A.; Yong, Lee C.; Tseng, Chih-Yu; Zivkovich, Zachary; Cassinelli II, Rick T.

2011-01-01

Objectives: US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots. Methods: Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments’ block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty. Results: Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (Ptrend < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman’s r = 0.61–0.69). Conclusions: The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies. PMID:21610083

Airline pilot cosmic radiation and circadian disruption exposure assessment from logbooks and company records.

PubMed

Grajewski, Barbara; Waters, Martha A; Yong, Lee C; Tseng, Chih-Yu; Zivkovich, Zachary; Cassinelli, Rick T

2011-06-01

US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots. Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments' block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty. Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (P(trend) < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman's r = 0.61-0.69). The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies.

Is adding a new class of cones to the retina sufficient to cure color-blindness?

PubMed

Cornelissen, Frans W; Brenner, Eli

2015-01-01

New genetic methods have made it possible to substitute cone pigments in the retinas of adult nonhuman primates. Doing so influences the animals' visual abilities, demonstrating that the gene therapy was effective. However, we argue that no studies conducted so far have unambiguously demonstrated that the experimental animals have also acquired the ability to make new color distinctions. Simply put, it has been shown that animals that underwent the gene treatment can now-in addition to finding a red ball on a grayish background-find a green ball on a grayish background. However, it has not been shown that the animals can distinguish a red ball from a green one. For most people, that essential ability would be the primary reason for wanting to undergo a treatment for color-blindness in the first place, for instance, because their color-blindness currently prevents them from pursuing a career as a pilot or firefighter. It is important to point out such possible limitations of gene therapy for color-blindness to avoid unwarranted expectations in both clinicians and patients. To explain the origin of our concerns, we simulate how replacing the pigment of some cones is expected to influence the outcomes on the behavioral test used so far. The simulations show that this test does not provide conclusive evidence that the animals acquired the ability to make new chromatic distinctions. In our view, it is therefore premature to claim that human color-blindness can be cured through gene therapy. We propose a test that would provide more conclusive evidence of fundamentally altered color vision after gene therapy.

Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation.

PubMed

Gallon, Lorenzo; Mathew, James M; Bontha, Sai Vineela; Dumur, Catherine I; Dalal, Pranav; Nadimpalli, Lakshmi; Maluf, Daniel G; Shetty, Aneesha A; Ildstad, Suzanne T; Leventhal, Joseph R; Mas, Valeria R

2018-02-01

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways. Copyright © 2018 by the American Society of Nephrology.

Inhalation of Nebulized Perfluorochemical Enhances Recombinant Adenovirus and Adeno-Associated Virus-Mediated Gene Expression in Lung Epithelium

PubMed Central

Beckett, Travis; Bonneau, Laura; Howard, Alan; Blanchard, James; Borda, Juan; Weiner, Daniel J.; Wang, Lili; Gao, Guang Ping; Kolls, Jay K.; Bohm, Rudolf; Liggitt, Denny

2012-01-01

Abstract Use of perfluorochemical liquids during intratracheal vector administration enhances recombinant adenovirus and adeno-associated virus (AAV)-mediated lung epithelial gene expression. We hypothesized that inhalation of nebulized perfluorochemical vapor would also enhance epithelial gene expression after subsequent intratracheal vector administration. Freely breathing adult C57BL/6 mice were exposed for selected times to nebulized perflubron or sterile saline in a sealed Plexiglas chamber. Recombinant adenoviral vector was administered by transtracheal puncture at selected times afterward and mice were killed 3 days after vector administration to assess transgene expression. Mice tolerated the nebulized perflubron without obvious ill effects. Vector administration 6 hr after nebulized perflubron exposure resulted in an average 540% increase in gene expression in airway and alveolar epithelium, compared with that with vector alone or saline plus vector control (p<0.05). However, vector administration 1 hr, 1 day, or 3 days after perflubron exposure was not different from either nebulized saline with vector or vector alone and a 60-min exposure to nebulized perflubron is required. In parallel pilot studies in macaques, inhalation of nebulized perflubron enhanced recombinant AAV2/5 vector expression throughout the lung. Serial chest radiographs, bronchoalveolar lavages, and results of complete blood counts and serum biochemistries demonstrated no obvious adverse effects of nebulized perflubron. Further, one macaque receiving nebulized perflubron only was monitored for 1 year with no obvious adverse effects of exposure. These results demonstrate that inhalation of nebulized perflubron, a simple, clinically more feasible technique than intratracheal administration of liquid perflubron, safely enhances lung gene expression. PMID:22568624

Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design.

PubMed

Bastarrachea, Raul A; Chen, Jiaxi; Kent, Jack W; Nava-Gonzalez, Edna J; Rodriguez-Ayala, Ernesto; Daadi, Marcel M; Jorge, Barbara; Laviada-Molina, Hugo; Comuzzie, Anthony G; Chen, Shuyuan; Grayburn, Paul A

2017-09-01

Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with UCP-1 over-expression. © 2017 IUBMB Life, 69(9):745-755, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Integrating text mining into the MGI biocuration workflow

PubMed Central

Dowell, K.G.; McAndrews-Hill, M.S.; Hill, D.P.; Drabkin, H.J.; Blake, J.A.

2009-01-01

A major challenge for functional and comparative genomics resource development is the extraction of data from the biomedical literature. Although text mining for biological data is an active research field, few applications have been integrated into production literature curation systems such as those of the model organism databases (MODs). Not only are most available biological natural language (bioNLP) and information retrieval and extraction solutions difficult to adapt to existing MOD curation workflows, but many also have high error rates or are unable to process documents available in those formats preferred by scientific journals. In September 2008, Mouse Genome Informatics (MGI) at The Jackson Laboratory initiated a search for dictionary-based text mining tools that we could integrate into our biocuration workflow. MGI has rigorous document triage and annotation procedures designed to identify appropriate articles about mouse genetics and genome biology. We currently screen ∼1000 journal articles a month for Gene Ontology terms, gene mapping, gene expression, phenotype data and other key biological information. Although we do not foresee that curation tasks will ever be fully automated, we are eager to implement named entity recognition (NER) tools for gene tagging that can help streamline our curation workflow and simplify gene indexing tasks within the MGI system. Gene indexing is an MGI-specific curation function that involves identifying which mouse genes are being studied in an article, then associating the appropriate gene symbols with the article reference number in the MGI database. Here, we discuss our search process, performance metrics and success criteria, and how we identified a short list of potential text mining tools for further evaluation. We provide an overview of our pilot projects with NCBO's Open Biomedical Annotator and Fraunhofer SCAI's ProMiner. In doing so, we prove the potential for the further incorporation of semi-automated processes into the curation of the biomedical literature. PMID:20157492

Integrating text mining into the MGI biocuration workflow.

PubMed

Dowell, K G; McAndrews-Hill, M S; Hill, D P; Drabkin, H J; Blake, J A

2009-01-01

A major challenge for functional and comparative genomics resource development is the extraction of data from the biomedical literature. Although text mining for biological data is an active research field, few applications have been integrated into production literature curation systems such as those of the model organism databases (MODs). Not only are most available biological natural language (bioNLP) and information retrieval and extraction solutions difficult to adapt to existing MOD curation workflows, but many also have high error rates or are unable to process documents available in those formats preferred by scientific journals.In September 2008, Mouse Genome Informatics (MGI) at The Jackson Laboratory initiated a search for dictionary-based text mining tools that we could integrate into our biocuration workflow. MGI has rigorous document triage and annotation procedures designed to identify appropriate articles about mouse genetics and genome biology. We currently screen approximately 1000 journal articles a month for Gene Ontology terms, gene mapping, gene expression, phenotype data and other key biological information. Although we do not foresee that curation tasks will ever be fully automated, we are eager to implement named entity recognition (NER) tools for gene tagging that can help streamline our curation workflow and simplify gene indexing tasks within the MGI system. Gene indexing is an MGI-specific curation function that involves identifying which mouse genes are being studied in an article, then associating the appropriate gene symbols with the article reference number in the MGI database.Here, we discuss our search process, performance metrics and success criteria, and how we identified a short list of potential text mining tools for further evaluation. We provide an overview of our pilot projects with NCBO's Open Biomedical Annotator and Fraunhofer SCAI's ProMiner. In doing so, we prove the potential for the further incorporation of semi-automated processes into the curation of the biomedical literature.

Early Maladaptive Schemas in a Sample of Airline Pilots seeking Residential Substance Use Treatment: An Initial Investigation

PubMed Central

Shorey, Ryan C.; Brasfield, Hope; Anderson, Scott; Stuart, Gregory L.

2014-01-01

Background Recent research has begun to examine the early maladaptive schemas of substance abusers, as it is believed that targeting these core beliefs in treatment may result in improved substance use outcomes. One special population that has received scant attention in the research literature, despite high levels of substance use, is airline pilots. Aims The current study examined the early maladaptive schemas of a sample of airline pilots (n = 64) who were seeking residential treatment for alcohol dependence and whether they differed in early maladaptive schemas from non-pilot substance abusers who were also seeking residential treatment for alcohol dependence (n = 45). Method Pre-existing medical records from patients of a residential substance abuse treatment facility were reviewed for the current study. Results Of the 18 early maladaptive schemas, results demonstrated that pilots scored higher than non-pilots on the early maladaptive schema of unrelenting standards (high internalized standards of behavior), whereas non-pilots scored higher on insufficient self-control (low frustration tolerance and self-control). Conclusions Early maladaptive schemas may be a relevant treatment target for substance abuse treatment seeking pilots and non-pilots. PMID:24701252

Report of ejections in the Spanish Air Force, 1979-1995: an epidemiological and comparative study.

PubMed

Moreno Vázquez, J M; Durán Tejeda, M R; García Alcón, J L

1999-07-01

Ejection seats have saved many lives with more than 80% of pilots having survived an ejection. Nevertheless, ejection injuries are seen in all modern air forces. An epidemiological study has been carried out on the 48 ejections made by the Spanish Air Force (SpAF) from 1979-1995. From data facilitated by the Flight Safety Section of the SpAF Staff, by the Flight Safety Section of Squadrons, and from personal reports of pilots who survived ejections a form was created. Relationships between data concerning aeronautical parameters, pilot data and injuries have been found, and a comparative study was made between these results and data shown by air forces of other countries. Of 48 pilots who ejected, 7 died, 25 had severe injuries, 11 had minor injuries and 5 had no injuries. The reason for the ejections included 35 cases of technical failure, and 13 cases of human error. Of 43 surviving pilots, 23 were injured only at the egress phase, 1 1 only at landing, and 9 cases at both moments. None of the five pilots who ejected outside the ejection envelope were able to adopt the correct position. However, of 43 pilots who ejected within the envelope, 19 were seated in good position. Of 13 pilots who maintained control of the airplane, 9 were able to adopt a correct position. Of 35 pilots who effected the ejection without control of the aircraft, 25 were not able to achieve a correct seated position. The pilot position in the ejection seat, plane control, ejection inside the envelope, the pilot's training in how to assume the necessary body position at both egress and landing phases are determining factors for successful ejections.

Diagnosis of Cetacean morbillivirus: A sensitive one step real time RT fast-PCR method based on SYBR(®) Green.

PubMed

Sacristán, Carlos; Carballo, Matilde; Muñoz, María Jesús; Bellière, Edwige Nina; Neves, Elena; Nogal, Verónica; Esperón, Fernando

2015-12-15

Cetacean morbillivirus (CeMV) (family Paramyxoviridae, genus Morbillivirus) is considered the most pathogenic virus of cetaceans. It was first implicated in the bottlenose dolphin (Tursiops truncatus) mass stranding episode along the Northwestern Atlantic coast in the late 1980s, and in several more recent worldwide epizootics in different Odontoceti species. This study describes a new one step real-time reverse transcription fast polymerase chain reaction (real-time RT-fast PCR) method based on SYBR(®) Green to detect a fragment of the CeMV fusion protein gene. This primer set also works for conventional RT-PCR diagnosis. This method detected and identified all three well-characterized strains of CeMV: porpoise morbillivirus (PMV), dolphin morbillivirus (DMV) and pilot whale morbillivirus (PWMV). Relative sensitivity was measured by comparing the results obtained from 10-fold dilution series of PMV and DMV positive controls and a PWMV field sample, to those obtained by the previously described conventional phosphoprotein gene based RT-PCR method. Both the conventional and real-time RT-PCR methods involving the fusion protein gene were 100- to 1000-fold more sensitive than the previously described conventional RT-PCR method. Copyright © 2015 Elsevier B.V. All rights reserved.

Cyclin-dependent Kinase 5: Novel role of gene variants identified in ADHD.

PubMed

Maitra, Subhamita; Chatterjee, Mahasweta; Sinha, Swagata; Mukhopadhyay, Kanchan

2017-07-28

Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic. Significant difference in rs2069456 "AC" genotype frequency was noticed in the probands, more specifically in the males. Family based analysis revealed over transmission of rs2069454 "C" and rs2069456 "A" to the probands. Quantitative trait analysis exhibited association of haplotypes with inattention, domain specific impulsivity, and behavioral problem, though no significant contribution was noticed on the age of onset of ADHD. Gene variants also showed significant association with cognitive function and co-morbidity. Probands having rs2069459 "TT" showed betterment during follow up. It may be inferred from this pilot study that CDK5 may affect ADHD etiology, possibly by attenuating synaptic neurotransmission and could be a useful target for therapeutic intervention.

Cardiac responses to long duration and high magnitude +Gz exposure in pilots: an observational study.

PubMed

Öztürk, Cengiz; İlbasmış, M Savaş; Akın, Ahmet

2012-12-01

In military aviation, high performance aircraft pilots are exposed to +Gz acceleration at longer durations and higher magnitude than transport/helicopter pilots. The purpose of this study was to reveal the negative or positive cardiac responses to this occupational high +Gz exposure. Our study design was cross-sectional and observational. We have evaluated 21 echocardiographic parameters of 63 pilots who applied for aircrew periodic medical examination. Of 63 pilots, 33 were grouped as high performance aircraft pilots group (Group A) and 30 were grouped as control group (Group B) whose aircraft type was transport or helicopter. Means of demographic and echocardiography parameters between two groups were compared statistically with Student's t-test, Mann- Whitney U or Chi-square test as appropriate. Among all echocardiographic parameters, mean TV A (tricuspid valve peak velocity during late diastolic filling) was significantly higher and TV E (peak velocity during early diastolic filling)/ A ratio was significantly lower for Group A pilots (p<0.05). In Group A pilots, mean TV A and TV E/A ratio were (52.12 ± 13.85) and (1.36 ± 0.30) respectively. In Group B pilots, mean TV A and TV E/A ratio were (42.61 ± 6.42) and (1.53 ± 0.20) respectively (p=0.001 for TVA and p=0.005 for TV E/A). Mean pulmonary artery pressure (PAP) of Group A pilots (32.04 ± 9.09) was higher than Group B pilots (28.76 ± 7.9) but it was not statistically significant (p>0.05). We conclude that according to the results of our study, long term +Gz exposure has no effects on cardiac morphologic and systolic functions but has effects on right ventricular diastolic functions. We have considered that these effects may be a result of chronic +Gz adaptation or high PAP levels.

Evaluation of a low density DNA microarray for small B-cell non-Hodgkin lymphoma differential diagnosis.

PubMed

Gillet, Jean-Pierre; Molina, Thierry Jo; Jamart, Jacques; Gaulard, Philippe; Leroy, Karen; Briere, Josette; Theate, Ivan; Thieblemont, Catherine; Bosly, Andre; Herin, Michel; Hamels, Jacques; Remacle, Jose

2009-03-01

Lymphomas are classified according to the World Health Organisation (WHO) classification which defines subtypes on the basis of clinical, morphological, immunophenotypic, molecular and cytogenetic criteria. Differential diagnosis of the subtypes is sometimes difficult, especially for small B-cell lymphoma (SBCL). Standardisation of molecular genetic assays using multiple gene expression analysis by microarrays could be a useful complement to the current diagnosis. The aim of the present study was to develop a low density DNA microarray for the analysis of 107 genes associated with B-cell non-Hodgkin lymphoma and to evaluate its performance in the diagnosis of SBCL. A predictive tool based on Fisher discriminant analysis using a training set of 40 patients including four different subtypes (follicular lymphoma n = 15, mantle cell lymphoma n = 7, B-cell chronic lymphocytic leukemia n = 6 and splenic marginal zone lymphoma n = 12) was designed. A short additional preliminary analysis to gauge the accuracy of this signature was then performed on an external set of nine patients. Using this model, eight of nine of those samples were classified successfully. This pilot study demonstrates that such a microarray tool may be a promising diagnostic approach for small B-cell non-Hodgkin lymphoma.

An empirical Bayes approach to network recovery using external knowledge.

PubMed

Kpogbezan, Gino B; van der Vaart, Aad W; van Wieringen, Wessel N; Leday, Gwenaël G R; van de Wiel, Mark A

2017-09-01

Reconstruction of a high-dimensional network may benefit substantially from the inclusion of prior knowledge on the network topology. In the case of gene interaction networks such knowledge may come for instance from pathway repositories like KEGG, or be inferred from data of a pilot study. The Bayesian framework provides a natural means of including such prior knowledge. Based on a Bayesian Simultaneous Equation Model, we develop an appealing Empirical Bayes (EB) procedure that automatically assesses the agreement of the used prior knowledge with the data at hand. We use variational Bayes method for posterior densities approximation and compare its accuracy with that of Gibbs sampling strategy. Our method is computationally fast, and can outperform known competitors. In a simulation study, we show that accurate prior data can greatly improve the reconstruction of the network, but need not harm the reconstruction if wrong. We demonstrate the benefits of the method in an analysis of gene expression data from GEO. In particular, the edges of the recovered network have superior reproducibility (compared to that of competitors) over resampled versions of the data. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dietary Effects on Cognition and Pilots' Flight Performance.

PubMed

Lindseth, Glenda N; Lindseth, Paul D; Jensen, Warren C; Petros, Thomas V; Helland, Brian D; Fossum, Debra L

2011-01-01

The purpose of this study was to investigate the effects of diet on cognition and flight performance of 45 pilots. Based on a theory of self-care, this clinical study used a repeated-measure, counterbalanced crossover design. Pilots were randomly rotated through 4-day high-carbohydrate, high-protein, high-fat, and control diets. Cognitive flight performance was evaluated using a GAT-2 full-motion flight simulator. The Sternberg short-term memory test and Vandenberg's mental rotation test were used to validate cognitive flight test results. Pilots consuming a high-protein diet had significantly poorer ( p < .05) overall flight performance scores than pilots consuming high-fat and high-carbohydrate diets.

Where have all the pilot studies gone? A follow-up on 30 years of pilot studies in Clinical Rehabilitation

PubMed Central

Kaur, Navaldeep; Figueiredo, Sabrina; Bouchard, Vanessa; Moriello, Carolina; Mayo, Nancy

2017-01-01

Introduction: Pilot studies are meritorious for determining the feasibility of a definitive clinical trial in terms of conduct and potential for efficacy, but their possible applications for planning a future trial are not always fully realized. The purpose of this review was to estimate the extent to which pilot/feasibility studies: (i) addressed needed objectives; (ii) led to definitive trials; and (iii) whether the subsequent undertaking of a definitive trial was influenced by the strength of the evidence of outcome improvement. Methods: Trials published in the journal Clinical Rehabilitation, since its inception, were eligible if the word ‘pilot’ or ‘feasibility’ was specified somewhere in the article. A total of 191 studies were reviewed, results were summarized descriptively, and between-group effect sizes were computed. Results: The specific purposes of piloting were stated in only 58% (n = 110) of the studies. The most frequent purpose was to estimate the potential for efficacy (85%), followed by testing the feasibility of the intervention (60%). Only 12% of the studies were followed by a definitive trial; <4% of studies had a main study underway or a published study protocol. There was no relationship between observed effect size and follow-up of pilot studies, although the confidence intervals were very wide owing to small number of trials that followed on. Discussion: Labelling and reporting of pilot studies needs to be improved to be concordant with the recently issued CONSORT guidelines. Feasibility needs to be fully tested and demonstrated prior to committing considerable human and monetary resources. PMID:28786333

Pilot Decision-Making in Irreversible Emergencies

ERIC Educational Resources Information Center

Winter, Scott R.

2013-01-01

The purpose of this study was to determine if a reflexive learning treatment utilizing select case studies could enhance the decision-making of pilots who encounter an irreversible emergency. Participants, who consisted of members of the subject university's professional pilot program, were divided into either a control or experimental group and…

77 FR 69658 - Agency Information Collection Activities; Proposed Collection; Comment Request: Generic Clearance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

... Activities; Proposed Collection; Comment Request: Generic Clearance for Cognitive, Pilot and Field Studies...) Title of the Form/Collection: BJS Generic Clearance for Cognitive, Pilot, and Field Test Studies. (3... respondents will be involved in exploratory, field test, pilot, cognitive, and focus group work conducted...

A Study of Longitudinal Control Problems at Low and Negative Damping and Stability with Emphasis on Effects of Motion Cues

NASA Technical Reports Server (NTRS)

Sadoff, Melvin; McFadden, Norman M.; Heinle, Donovan R.

1961-01-01

As part of a general investigation to determine the effects of simulator motions on pilot opinion and task performance over a wide range of vehicle longitudinal dynamics, a cooperative NASA-AMAL program was conducted on the centrifuge at Johnsville, Pennsylvania. The test parameters and measurements for this program duplicated those of earlier studies made at Ames Research Center with a variable-stability airplane and with a pitch-roll chair flight simulator. Particular emphasis was placed on the minimum basic damping and stability the pilots would accept and on the minimum dynamics they considered controllable in the event of stability-augmentation system failure. Results of the centrifuge-simulator program indicated that small positive damping was required by the pilots over most of the frequency range covered for configurations rated acceptable for emergency conditions only (e.g., failure of a pitch damper). It was shown that the pilot's tolerance for unstable dynamics was dependent primarily on the value of damping. For configurations rated acceptable for emergency operation only, the allowable instability and damping corresponded to a divergence time to double amplitude of about 1 second. Comparisons were made of centrifuge, pitch-chair and fixed-cockpit simulator tests with flight tests. Pilot ratings indicated that the effects of incomplete or spurious motion cues provided by these three modes of simulation were important only for high-frequency, lightly damped dynamics or unstable, moderately damped dynamics. The pitch- chair simulation, which provided accurate angular-acceleration cues to the pilot, compared most favorably with flight. For the centrifuge simulation, which furnished accurate normal accelerations but spurious pitching and longitudinal accelerations, there was a deterioration of pilots' opinion relative to flight results. Results of simulator studies with an analog pilot replacing the human pilot illustrated the adaptive capability of human pilots in coping with the wide range of vehicle dynamics and the control problems covered in this study. It was shown that pilot-response characteristics, deduced by the analog-pilot method, could be related to pilot opinion. Possible application of these results for predicting flight-control problems was illustrated by means of an example control-problem analysis. The results of a brief evaluation of a pencil-type side-arm controller in the centrifuge showed a considerable improvement in the pilots' ability to cope with high-frequency, low-damping dynamics, compared to results obtained with the center stick. This improvement with the pencil controller was attributed primarily to a marked reduction in the adverse effects of large and exaggerated pitching and longitudinal accelerations on pilot control precision.

Design of a multiplex PCR for Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae and Chlamydophila pneumoniae to be used on sputum samples.

PubMed

Strålin, Kristoffer; Bäckman, Anders; Holmberg, Hans; Fredlund, Hans; Olcén, Per

2005-02-01

A multiplex PCR (mPCR) was developed for simultaneous detection of specific genes for Streptococcus pneumoniae (lytA), Mycoplasma pneumoniae (P1), Chlamydophila pneumoniae (ompA), and Haemophilus influenzae (16S rRNA, with verification PCR for P6). When the protocol was tested on 257 bacterial strains belonging to 37 different species, no false negatives and only one false positive were noted. One Streptococcus mitis out of thirty was positive for lytA. In a pilot application study of 81 sputum samples from different patients with suspected lower respiratory tract infection (LRTI), mPCR identified S. pneumoniae in 25 samples, H. influenzae in 29, M. pneumoniae in 3, and C. pneumoniae in 1. All samples culture positive for S. pneumoniae (n=15) and H. influenzae (n=15) were mPCR positive for the same bacteria. In a pilot control study with nasopharyngeal swabs and aspirates from 10 healthy adults, both culture and mPCR were negative. No PCR inhibition was found in any of the mPCR-negative sputum or nasopharyngeal samples. Whether all samples identified as positive by mPCR are truly positive in an aetiological perspective regarding LRTI remains to be evaluated in a well-defined patient material. In conclusion, the mPCR appears to be a promising tool in the aetiological diagnostics of LRTI.

Field Collection Methods for an EPA Pilot Study Evaluating Personal, Housing, and Community Factors Influencing Children’s Potential Exposures to Indoor Contaminants at Various Lifestages (EPA Pilot Study Add-On to the GreenHousing Study)

EPA Science Inventory

This compilation of field collection standard operating procedures (SOPs) was assembled for the U.S. Environmental Protection Agency’s (EPA) Pilot Study add-on to the Green Housing Study (GHS). A detailed description of this add-on study can be found in the peer reviewed research...

Effects of malicious ocular laser exposure in commercial airline pilots.

PubMed

Palakkamanil, Mathew M; Fielden, Michael P

2015-12-01

Intentional malicious laser strikes on commercial pilots are committed by individuals who target a laser into airplane cockpits during takeoff and landing. Because laser exposure to pilots is a relatively new but growing occurrence, our study investigates the ocular effect of this laser exposure in pilots. Retrospective chart review by a single ophthalmologist. All commercial airline pilots (58 male, 3 female) who experienced a laser strike while flying between April 2012 and November 2014 who presented to our clinic were included. A retrospective chart review was performed in a retinal specialist's practice. Ocular assessment was performed within 3 days of laser exposure. A complete ophthalmic evaluation was conducted, including Early Treatment Diabetic Retinopathy Study visual acuity, colour vision, visual fields, intraocular pressure, slit-lamp examination, dilated fundus examination, colour fundus photographs, and ocular coherence tomography. Sixty-four laser strike incidents involving commercial pilots were included. All pilots in the study experienced some degree of immediate ocular irritation or light sensitivity. No definite cases of ocular damage were attributed to laser strikes. No pilot had any functional ocular deficits. Our study revealed that laser strikes on aircraft did not result in permanent visual functional or structural deficits. However, laser strikes cause immediate visual effects, including glare, flash blindness, and ocular irritation that can interfere with a pilot's visual function. Given the widespread accessibility of high-power lasers and the rapid increase in incidents, laser strikes threaten to jeopardize aviation safety unless effective preventative measures are put in place. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Neo-Institutional Analysis on Response Patterns of Pilot Schools

ERIC Educational Resources Information Center

Shin, Chol-Kyun

2016-01-01

This study examines response patterns of pilot schools in the neo-institutional perspective to make improvements on the pilot school systematic framework. In order to achieve this goal, in-depth interviews were conducted to obtain qualitative data. The results show that pilot schools either (a) actively adopt or (b) ceremonially adopt an education…

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens.

PubMed

Canfield, Dennis V; Dubowski, Kurt M; Whinnery, James M; Forster, Estrella M

2018-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approach: Compare the drug found by toxicology analysis with the drug reported by the pilot. This study uniquely examined first the pilot-reported medication and then compared it to that detected by toxicology analysis. This study will serve two purposes: (i) to determine the capability of a toxicology laboratory to detect reported medications, and (ii) to identify pilots with medications below detectable limits. All information required for this study was extracted from the Toxicology Data Base system and was searched using ToxFlo or SQL Server Management Studio. The following information was collected and analyzed: pilot-reported trade and/or generic drug, date specimens received, time of accident, type of aviation operations (CFR), state, pilot level, age, class of medical, specimen type, specimen concentration, dose reported, frequency reported associated with the accident, quantity reported, National Transportation Safety Board (NTSB) accident event number, and all NTSB reports. There were 319 pilots that either reported taking a beta-blocker or were found to be taking a beta-blocker by postmortem toxicology analysis. Time of death, therapeutic concentration and specimen type were found to be factors in the ability of the laboratory to detect beta-blockers. Beta-blockers taken by pilots will, in most cases, be found by a competent postmortem forensic toxicology laboratory at therapeutic concentrations. The dose taken by the pilot was not found to be a factor in the ability of the laboratory to identify beta-blockers. Time of dose, route of administration, specimen tested and therapeutic concentration of the drug were found to be factors in the ability of the laboratory to identify beta-blockers in postmortem specimens. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

First results of GEN-AU: Cloning of Deoxynivalenol- and Zearalenone-inactivating UDP-glucosyltransferase genes fromArabidopsis thaliana and expression in yeast for production of mycotoxin-glucosides.

PubMed

Poppenberger, B; Berthiller, F; Lucyshyn, D; Schuhmacher, R; Krska, R; Adam, G

2005-06-01

First results of the GEN-AU pilot project "Fusarium virulence and plant resistance mechanisms" are reported. Employing genetically engineered yeast strains we have been able to clone genes from the model plantArabidopsis thaliana encoding UDP-glucosyltransferases which can inactivate deoxynivalenol (DON) and zearalenone (ZON). The structure of the metabolites produced by the transformed yeast strains were determined by LC-MS/MS as DON-3O-glucoside and ZON-4O-glucoside, respectively. ZON and derivatives added to glucosyltransferase expressing yeast cultures are converted into the corresponding glucosides in very high yield, opening an efficient way to produce reference materials for these masked mycotoxins.

Molecular characterization and expression analysis of heat shock protein 70 and 90 from Hermetia illucens reared in a food waste bioconversion pilot plant.

PubMed

Giannetto, Alessia; Oliva, Sabrina; Mazza, Lorenzo; Mondello, Giovanni; Savastano, Domenico; Mauceri, Angela; Fasulo, Salvatore

2017-09-05

Two full-length cDNAs of heat shock protein (HSP) genes (Hihsp70 and Hihsp90) were cloned from the black soldier fly (BSF) Hermetia illucens larvae reared in a food waste bioconversion pilot plant. The Hihsp70 and Hihsp90 transcripts were 2243 and 2507bp long, contained 1923 and 2166bp open reading frames encoding proteins of 640 and 721 amino acids with a molecular mass of 69.8 and 83kDa, respectively. Comparative analysis of protein sequences revealed the presence of the conserved HSP motifs in both proteins, showing high homology to their counterparts in other insect species from six different orders. Hihsp70 and Hihsp90 transcriptional expression profiles during two key developmental stages in the bioconversion process were evaluated by quantitative real time PCR showing that both genes were modulated during larval development. HiHsp70 mRNA expression levels during the II instar larvae was higher in respect to the V instar larvae. A similar difference in mRNA expression levels, but in a less extent, was found for the Hihsp90. Moreover, a diverse transcript level between the two genes at the V larval stage was observed where Hihsp90 was up-regulated compared to Hihsp70. These results suggested the involvement of Hsp70 and Hsp90 in H. illucens development and provide further evidences on the ecological and evolutionary importance of HSPs in the insect developmental processes together with valuable information on molecular features of adaptability to peculiar rearing conditions during food waste bioconversion. Copyright © 2017 Elsevier B.V. All rights reserved.

Cosmic Radiation and Cataracts in Airline Pilots

NASA Astrophysics Data System (ADS)

Rafnsson, V.; Olafsdottir, E.; Hrafnkelsson, J.; de Angelis, G.; Sasaki, H.; Arnarson, A.; Jonasson, F.

Nuclear cataracts have been associated with ionising radiation exposure in previous studies. A population based case-control study on airline pilots has been performed to investigate whether employment as a commercial pilot and consequent exposure to cosmic radiation were associated to lens opacification, when adjusted for known risk factors for cataracts. Cases of opacification of the ocular lens were found in surveys among pilots and a random sample of the Icelandic population. Altogether 445 male subjects underwent a detailed eye examination and answered a questionnaire. Information from the airline company on the 79 pilots employment time, annual hours flown per aircraft type, the timetables and the flight profiles made calculation of individual cumulated radiation dose (mSv) possible. Lens opacification were classified and graded according to WHO simplified cataracts grading system using slit lamp. The odds ratio from logistic regression of nuclear cataracts risk among cases and controls was 3.02 (95% CI 1.44 to 6.35) for pilots compared with non-pilots, adjusted for age, smoking and sunbathing habits, whereas that of cortical cataracts risk among cases and controls was lower than unity (non significant) for pilots compared with non-pilots in a logistic regression analysis adjusted for same factors. Length of employment as a pilot and cumulated radiation dose (mSv) were significantly related to the risk of nuclear cataracts. So the association between radiation exposure of pilots and the risk of nuclear cataracts, adjusted for age, smoking and sunbathing habits, indicates that cosmic radiation may be cause of nuclear cataract among commercial pilots.

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework

PubMed Central

Eldridge, Sandra M.; Lancaster, Gillian A.; Campbell, Michael J.; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L.; Bond, Christine M.

2016-01-01

We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms ‘pilot’ and ‘feasibility’ in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms ‘feasibility’ or ‘pilot’ as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term ‘feasibility’ in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention. PMID:26978655

Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

PubMed Central

Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

2013-01-01

Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small proportion of perturbed genes were overlapped between American (AA) and Caucasian American (CA) patients with prostate cancer. Our study indicates that identifying gene expression and/or epigenetic differences between TdECs and NdECs may provide us with new anti-angiogenic targets. Future studies will be required to further characterize the isolated ECs and determine the biological features that can be exploited in the prognosis and therapy of prostate cancer. PMID:23978847

A study on aircraft map display location and orientation

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T.; Huff, E.

1973-01-01

Six airline pilots participated in a fixed-based simulator study to determine the effects of two horizontal situation display (HSD/map) panel locations relative to the vertical situation display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions and among pilots but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

Visual cues to geographical orientation during low-level flight

NASA Technical Reports Server (NTRS)

Battiste, Vernol; Delzell, Suzanne

1991-01-01

A field study of an operational Emergency Medical Service (EMS) unit was conducted to investigate the relationships among geographical orientation, pilot decision making, and workload in EMS flights. The map data collected during this study were compared to protocols gathered in the laboratory, where pilots viewed a simulated flight over different types of unfamiliar terrain and verbally identified the features utilized to maintain geographical orientation. The EMS pilot's questionnaire data were compared with data from non-EMS helicopter pilots with comparable flight experience.

A study on aircraft map display location and orientation

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T. E.; Huff, E. M.

1974-01-01

Six airline pilots participated in a fixed-base simulator study to determine the effects of two horizontal situation display (HSD/map) panel locations relative to the vertical situation display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions and among pilots, but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

The Internet and Some International Regulatory Issues Relating to Content: A Pilot Comparative Study.

ERIC Educational Resources Information Center

Australian Broadcasting Authority.

In December 1996 UNESCO commissioned the Australian Broadcasting Authority to conduct a pilot study which considered a range of online issues; this report outlines the findings of the pilot study, based on data collected between February and May 1997 and updated in July 1997. The objective is to identify the main types of Internet content which…

Assessing five pilot carbon trading programs in China from a perspective of efficiency analysis

NASA Astrophysics Data System (ADS)

Yu, Xianyu; Shi, Guo; Wang, Jinghan

2018-02-01

In order to overcome the challenge of growing carbon emissions in China, the pilot carbon emissions trading systems (ETSs) serve as precursors of the national carbon ETS. Five province-level pilot ETSs in Beijing, Tianjin, Shanghai, Guangdong and Hubei are assessed from the view of carbon emission efficiency analysis in this study. Firstly, both the environmental production technology and the Malmquist index are adopted to evaluate the carbon emission efficiency of 28 provinces in China. Then, the regression significance analysis of carbon emission efficiency and the operational information evaluation for pilot ETSs are combined to develop an integrated approach for assessing five considered pilot ETSs. The Efficiency analysis of carbon emissions indicate that the effect of ETS in Beijing is significant, the effect of ETS in Tianjin is weak significant, and those of the other three pilot ETSs are not significant. Based on the operational information for pilot ETSs, the evaluating results of pilot ETSs in Beijing and Hubei are better than those of other pilot ETSs. This study highlights two main findings. First, the pilot ETS in Beijing has better performance than the other considered pilot ETSs, and its operational experience should be promoted throughout the country to improve the construction of national carbon ETS. Second, the successful cooperation between the ETSs in Beijing and Tianjin implies that the regional cooperation among neighbouring ETSs should be encouraged and further implemented to enhance the overall performance of the regional ETSs.

Microarray characterization of gene expression changes in blood during acute ethanol exposure

PubMed Central

2013-01-01

Background As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we performed a DNA microarray analysis of human whole blood samples from a five-time point study of subjects administered ethanol orally, followed by breathalyzer analysis, to monitor blood alcohol concentration (BAC) to discover significant gene expression changes in response to the ethanol exposure. Methods Subjects were administered either orange juice or orange juice with ethanol. Blood samples were taken based on BAC and total RNA was isolated from PaxGene™ blood tubes. The amplified cDNA was used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR) analyses to evaluate differential gene expression. Microarray data was analyzed in a pipeline fashion to summarize and normalize and the results evaluated for relative expression across time points with multiple methods. Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. RT-qPCR was used with representative genes to confirm relative transcript levels across time to those detected in microarrays. Results Microarray analysis of samples representing 0%, 0.04%, 0.08%, return to 0.04%, and 0.02% wt/vol BAC showed that changes in gene expression could be detected across the time course. The expression changes were verified by qRT-PCR. The candidate genes of interest (GOI) identified from the microarray analysis and clustered by expression pattern across the five BAC points showed seven coordinately expressed groups. Analysis showed function-based networks, shared transcription factor binding sites and signaling pathways for members of the clusters. These include hematological functions, innate immunity and inflammation functions, metabolic functions expected of ethanol metabolism, and pancreatic and hepatic function. Five of the seven clusters showed links to the p38 MAPK pathway. Conclusions The results of this study provide a first look at changing gene expression patterns in human blood during an acute rise in blood ethanol concentration and its depletion because of metabolism and excretion, and demonstrate that it is possible to detect changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study serves as a workflow to investigate the biology linked to expression changes across a time course and from these changes, to identify target genes that could serve as biomarkers linked to pilot performance. PMID:23883607

Anaerobic treatment of antibiotic production wastewater pretreated with enhanced hydrolysis: Simultaneous reduction of COD and ARGs.

PubMed

Yi, Qizhen; Zhang, Yu; Gao, Yingxin; Tian, Zhe; Yang, Min

2017-03-01

The presence of high concentration antibiotics in wastewater can disturb the stability of biological wastewater treatment systems and promote generation of antibiotic resistance genes (ARGs) during the treatment. To solve this problem, a pilot system consisting of enhanced hydrolysis pretreatment and an up-flow anaerobic sludge bed (UASB) reactor in succession was constructed for treating oxytetracycline production wastewater, and the performance was evaluated in a pharmaceutical factory in comparison with a full-scale anaerobic system operated in parallel. After enhanced hydrolysis under conditions of pH 7 and 85 °C for 6 h, oxytetracycline production wastewater with an influent chemical oxygen demand (COD) of 11,086 ± 602 mg L -1 was directly introduced into the pilot UASB reactor. With the effective removal of oxytetracycline and its antibacterial potency (from 874 mg L -1 to less than 0.61 mg L -1 and from 900 mg L -1 to less than 0.84 mg L -1 , respectively) by the enhanced hydrolysis pretreatment, an average COD removal rate of 83.2%, 78.5% and 68.9% was achieved at an organic loading rate of 3.3, 4.8 and 5.9 kg COD m -3  d -1 , respectively. At the same time, the relative abundances of the total tetracycline (tet) genes and a mobile element (Class 1 integron (intI1)) in anaerobic sludge on day 96 were one order of magnitude lower than those in inoculated sludge on day 0 (P < 0.01). The reduction of ARGs was further demonstrated by metagenomic sequencing. By comparison, the full-scale anaerobic system treating oxytetracycline production wastewater with an influent COD of 3720 ± 128 mg L -1 after dilution exhibited a COD removal of 51 ± 4% at an organic loading rate (OLR) 1.2 ± 0.2 kg m -3  d -1 , and a total tet gene abundance in sludge was five times higher than the pilot-scale system (P < 0.01). The above result demonstrated that enhanced hydrolysis as a pretreatment method could enable efficient anaerobic treatment of oxytetracycline production wastewater containing high concentrations of oxytetracycline with significantly lower generation of ARGs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Flight Simulator Visual-Display Delay Compensation

NASA Technical Reports Server (NTRS)

Crane, D. Francis

1981-01-01

A piloted aircraft can be viewed as a closed-loop man-machine control system. When a simulator pilot is performing a precision maneuver, a delay in the visual display of aircraft response to pilot-control input decreases the stability of the pilot-aircraft system. The less stable system is more difficult to control precisely. Pilot dynamic response and performance change as the pilot attempts to compensate for the decrease in system stability. The changes in pilot dynamic response and performance bias the simulation results by influencing the pilot's rating of the handling qualities of the simulated aircraft. The study reported here evaluated an approach to visual-display delay compensation. The objective of the compensation was to minimize delay-induced change in pilot performance and workload, The compensation was effective. Because the compensation design approach is based on well-established control-system design principles, prospects are favorable for successful application of the approach in other simulations.

Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients - a randomized double-blind placebo-controlled pilot study

PubMed Central

2013-01-01

Background Gut lactobacilli can affect the metabolic functions of healthy humans. We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA (Deutsche Sammlung für Mikroorganismen, DSM 21380) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension. Methods In this 3-week, randomized, double-blind, placebo-controlled, parallel pilot study, 25 subjects ingested probiotic cheese and 15 ingested control cheese. Fifty grams of each cheese provided 175 kcal of energy. Blood pressure (BP), anthropometric characteristics, markers of liver and kidney function, metabolic indices (plasma glucose, lipids, and cholesterol), and urine polyamines were measured. Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods. The data were analyzed by t-test for independent samples and Spearman’s partial correlation analysis. Results The probiotic L. plantarum TENSIA was present in variable amounts (529.6 ± 232.5 gene copies) in 16/25 (64%) study subjects. Body mass index (BMI) was significantly reduced (p = 0.031) in the probiotic cheese group versus the control cheese group. The changes in BMI were closely associated with the water content of the body (r = 0.570, p = 0.0007) when adjusted for sex and age. Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI (r = 0.383, p = 0.0305) and urinary putrescine content (r = 0.475, p = 0.006). In patients simultaneously treated with BP-lowering drugs, similar reductions of BP were observed in both groups. A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP (r = 0.617, p = 0.0248) and a trend toward lower values of morning systolic BP (r = −0.527, p = 0.0640) at the end of the study after adjusting for BMI, age, and sex. Conclusion In a pilot study of obese hypertensive patients, a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values, recognized symptoms of metabolic syndrome. Trial registration Current Controlled Trials ISRCTN76271778 PMID:24120179

Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients--a randomized double-blind placebo-controlled pilot study.

PubMed

Sharafedtinov, Khaider K; Plotnikova, Oksana A; Alexeeva, Ravilay I; Sentsova, Tatjana B; Songisepp, Epp; Stsepetova, Jelena; Smidt, Imbi; Mikelsaar, Marika

2013-10-12

Gut lactobacilli can affect the metabolic functions of healthy humans. We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA (Deutsche Sammlung für Mikroorganismen, DSM 21380) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension. In this 3-week, randomized, double-blind, placebo-controlled, parallel pilot study, 25 subjects ingested probiotic cheese and 15 ingested control cheese. Fifty grams of each cheese provided 175 kcal of energy. Blood pressure (BP), anthropometric characteristics, markers of liver and kidney function, metabolic indices (plasma glucose, lipids, and cholesterol), and urine polyamines were measured. Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods. The data were analyzed by t-test for independent samples and Spearman's partial correlation analysis. The probiotic L. plantarum TENSIA was present in variable amounts (529.6 ± 232.5 gene copies) in 16/25 (64%) study subjects. Body mass index (BMI) was significantly reduced (p = 0.031) in the probiotic cheese group versus the control cheese group. The changes in BMI were closely associated with the water content of the body (r = 0.570, p = 0.0007) when adjusted for sex and age. Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI (r = 0.383, p = 0.0305) and urinary putrescine content (r = 0.475, p = 0.006). In patients simultaneously treated with BP-lowering drugs, similar reductions of BP were observed in both groups. A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP (r = 0.617, p = 0.0248) and a trend toward lower values of morning systolic BP (r = -0.527, p = 0.0640) at the end of the study after adjusting for BMI, age, and sex. In a pilot study of obese hypertensive patients, a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values, recognized symptoms of metabolic syndrome.

The size of a pilot study for a clinical trial should be calculated in relation to considerations of precision and efficiency.

PubMed

Sim, Julius; Lewis, Martyn

2012-03-01

To investigate methods to determine the size of a pilot study to inform a power calculation for a randomized controlled trial (RCT) using an interval/ratio outcome measure. Calculations based on confidence intervals (CIs) for the sample standard deviation (SD). Based on CIs for the sample SD, methods are demonstrated whereby (1) the observed SD can be adjusted to secure the desired level of statistical power in the main study with a specified level of confidence; (2) the sample for the main study, if calculated using the observed SD, can be adjusted, again to obtain the desired level of statistical power in the main study; (3) the power of the main study can be calculated for the situation in which the SD in the pilot study proves to be an underestimate of the true SD; and (4) an "efficient" pilot size can be determined to minimize the combined size of the pilot and main RCT. Trialists should calculate the appropriate size of a pilot study, just as they should the size of the main RCT, taking into account the twin needs to demonstrate efficiency in terms of recruitment and to produce precise estimates of treatment effect. Copyright © 2012 Elsevier Inc. All rights reserved.

Treatment of autistic spectrum disorder with insulin-like growth factors.

PubMed

Riikonen, Raili

2016-11-01

There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism-based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity-dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD-like behavior defects. The molecular basis for a cerebellar contribution has been demonstrated in a mouse model. These have led to a potential mechanism-based use of drug targets and mouse models. Neurotrophic factors are potential candidates for the treatment. Insulin-like growth factor-1 (IGF-1) is altered in autism. It reduces neuro-inflammation: by causing changes of cytokines such as IL-6 and microglial function. IGF-1 reduces the defects in the synapse. It alleviates NMDA-induced neurotoxicity via the IGF-AKT-mTor pathway in microglia. IGF-1 may rescue function in Rett syndrome and ASD caused by changes of the SCHANK3 gene. There are recently pilot studies of the treatment of Rett syndrome and of SCHANK3 gene deficiency syndromes. The FDA has granted Orphan drug designations for Fragile X syndrome, SCHANK3 gene deficiency syndrome and Rett syndrome. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Pilots' monitoring strategies and performance on automated flight decks: an empirical study combining behavioral and eye-tracking data.

PubMed

Sarter, Nadine B; Mumaw, Randall J; Wickens, Christopher D

2007-06-01

The objective of the study was to examine pilots' automation monitoring strategies and performance on highly automated commercial flight decks. A considerable body of research and operational experience has documented breakdowns in pilot-automation coordination on modern flight decks. These breakdowns are often considered symptoms of monitoring failures even though, to date, only limited and mostly anecdotal data exist concerning pilots' monitoring strategies and performance. Twenty experienced B-747-400 airline pilots flew a 1-hr scenario involving challenging automation-related events on a full-mission simulator. Behavioral, mental model, and eye-tracking data were collected. The findings from this study confirm that pilots monitor basic flight parameters to a much greater extent than visual indications of the automation configuration. More specifically, they frequently fail to verify manual mode selections or notice automatic mode changes. In other cases, they do not process mode annunciations in sufficient depth to understand their implications for aircraft behavior. Low system observability and gaps in pilots' understanding of complex automation modes were shown to contribute to these problems. Our findings describe and explain shortcomings in pilot's automation monitoring strategies and performance based on converging behavioral, eye-tracking, and mental model data. They confirm that monitoring failures are one major contributor to breakdowns in pilot-automation interaction. The findings from this research can inform the design of improved training programs and automation interfaces that support more effective system monitoring.

Pilot Study and Review: Physiological Differences in BDNF, a Potential Biomarker in Males and Females with Autistic Disorder.

PubMed

Spratt, Eve G; Granholm, Ann-Charlotte; Carpenter, Laura A; Boger, Heather A; Papa, Carrie E; Logan, Sarah; Chaudhary, Humera; Boatwright, Sarah-Wade; Brady, Kathleen T

There is a need for more biologic research in autistic disorder (AD) to determine if biomarkers exist that would be useful for correlating to symptom severity and/or clinical improvement during treatment. Given the fact that AD is 4 times more common in males than females, gender differences in physiological biomarkers may be present. One potential biomarker that has begun to be studied is brain-derived neurotropic factor (BDNF), a peptide involved in the regulation of neuronal cell survival, differentiation, and plasticity, and possessing an ability to influence neurotransmitter systems by modulating gene expression. This pilot study examined whether serum BDNF differed according to gender in children with AD and whether differences were associated with a behavioral phenotype or severity of illness. Data for this investigation were collected during the participants' baseline visit of an intervention study. Participants were males (n=29) and females (n=7), aged 5 to 12 years diagnosed with AD. Baseline serum BDNF concentration was determined for comparison to clinical ratings using an autism severity measure and the Pervasive Developmental Disorder-Behavior Inventory (PDD-BI). BDNF serum concentrations were higher in females (p<0.049). The baseline BDNF value corresponded significantly to hyperactivity in females (p<0.0002) but not in males. BDNF did not correlate with severity of disease in either gender. Although this is a small study, a better understanding of the central role of BDNF may provide insight into the pathophysiology of the disease and elucidate why gender differences exist in prevalence and behavioral phenotype of AD.

An investigation into pilot and system response to critical in-flight events. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Rockwell, T. H.; Griffin, W. C.

1981-01-01

Critical in-flight events (CIFE) that threaten the aircraft were studied. The scope of the CIFE was described and defined with emphasis on characterizing event development, detection and assessment; pilot information requirements, sources, acquisition, and interpretation, pilot response options, decision processed, and decision implementation and event outcome. Detailed scenarios were developed for use in simulators and paper and pencil testing for developing relationships between pilot performance and background information as well as for an analysis of pilot reaction decision and feedback processes. Statistical relationships among pilot characteristics and observed responses to CIFE's were developed.

Operational problems experienced by single pilots in instrument meteorological conditions

NASA Technical Reports Server (NTRS)

Weislogel, S.

1981-01-01

The development and implementation of a search strategy to extract pertinent reports from the Aviation Safety Reporting System-2 (ASRS-2) database are described. For any particular occurence to be pertinent to the study, it must have satisfied the following conditions: the aircraft must be of the type usually flown by a single pilot; operation on an IFR flight plan in instrument meteorological conditions; pilot experienced an operational problem. The occurances consist of reports by the pilot about his own performance, by the pilot about the system performance, or by an air traffic controller about a pilot's performance.

SRD5A1 genotype frequency differences in women with mild versus severe premenstrual symptoms.

PubMed

Adams, Marlene; McCrone, Susan

2012-02-01

The aims of this small pilot study were to explore the association between premenstrual symptom severity and two genes from the gamma-aminobutyric acid (GABA) pathway: steroid-5-alpha-reductase, alpha polypeptide 1 (SRD5A1) and gamma-aminobutyric acid receptor subunit alpha-4 (GABRA4). Saliva samples were obtained from a convenience sample of 19 Caucasian females ages 18-25 years, ten cases and nine controls. Deoxyribonucleic acid (DNA) was isolated, and genotyping performed on ten single nucleotide polymorphisms (SNPs). Ten percent of cases and 44% of controls had the cytosine/cytosine (C/C) genotype for the SRD5A1 SNP, rs501999 indicating that this genotype may protect women against severe premenstrual symptoms. Replication of this study using an adequately powered sample size is warranted.

75 FR 75725 - Financial Management Service; Proposed Collection of Information: Tax Time Card Account Pilot...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... Information: Tax Time Card Account Pilot, Screening, Focus Groups, and Study AGENCY: Financial Management... general public and other Federal agencies to take this opportunity to comment on a continuing information... Account Pilot Screening, Focus Groups, and Study.'' DATES: Written comments should be received on or...

PILOT-SCALE STUDIES ON THE EFFECT OF BROMINE ADDITION ON THE EMISSIONS OF CHLORINATED ORGANIC COMBUSTION BY-PRODUCTS

EPA Science Inventory

The paper reports on a study to evaluate organic combustion by-product emissions while feeding varying amounts of bromine (Br) and chlorine (Cl) into a pilot-scale incinerator burning surrogate waste materials. (NOTE: Adding brominated organic compounds to a pilot-scale incinerat...

Final Report of NATO/SPS Pilot Study on Clean Products and Processes (Phase I and II)

EPA Science Inventory

Early in 1998 the NATO Committee for Challenges to Modern Society (SPS) (Science for Peace and Security) approved the Pilot Study on Clean Products and Processes for an initial period of five years. The pilot was to provide a forum for member country representatives to discuss t...

Fixed-Base Simulator Studies of the Ability of the Human Pilot to Provide Energy Management Along Abort and Deep-Space Entry Trajectories

NASA Technical Reports Server (NTRS)

Young, J. W.; Goode, M. W.

1962-01-01

A simulation study has been made to determine a pilot's ability to control a low L/D vehicle to a desired point on the earth with initial conditions ranging from parabolic orbits to abort conditions along the boost phase of a deep-space mission. The program was conducted to develop procedures which would allow the pilot to perform the energy management functions required while avoiding the high deceleration or skipout region and to determine the information display required to aid the pilot in flying these procedures. The abort conditions studied extend from a region of relatively high flight-path angles at suborbital velocities while leaving the atmosphere to a region between orbital and near-escape velocity outside the atmosphere. The conditions studied included guidance from suborbital and superorbital aborts as well as guidance following return from a deepspace mission. In this paper, the role of the human pilot?s ability to combine safe return abort procedures with guidance procedures has been investigated. The range capability from various abort and entry conditions is also presented.

Manpower Projections, Recruitment Needs and Training Requirements for Commercial Airline Pilots in the United States 1968-1979.

ERIC Educational Resources Information Center

Simons, Robert Marchand

This study evaluated the reported airline pilot shortage in relation to certified air carriers; recruitment needs for qualified applicants; training requirements as recommended by air carriers, airline captains, and flight officers; and airline pilot supply and demand during 1968-79. A literature review on foreign and domestic pilot shortages was…

THE EFFECTIVENESS OF PILOT PROGRAMS COMPARED TO OTHER PROGRAMS OF VOCATIONAL AGRICULTURE IN TENNESSEE.

ERIC Educational Resources Information Center

LEGG, OTTO

THE OBJECTIVE OF THIS COMPARATIVE STUDY WAS TO EVALUATE THE RELATIVE EFFECTIVENESS OF TENNESSEE VOCATIONAL AGRICULTURE PROGRAMS IN FOUR CATEGORIES -- (1) PILOT SCHOOLS, (2) LIKE-PILOT SCHOOLS OR SCHOOLS RESEMBLING PILOT SCHOOLS, (3) STUDENT TEACHING CENTERS, AND (4) NEGRO SCHOOLS. THE RANDOM SAMPLE INCLUDED 800 STUDENTS FROM 20 SCHOOLS DIVIDED…

Investigating the impact of the properties of pilot points on calibration of groundwater models: case study of a karst catchment in Rote Island, Indonesia

NASA Astrophysics Data System (ADS)

Klaas, Dua K. S. Y.; Imteaz, Monzur Alam

2017-09-01

A robust configuration of pilot points in the parameterisation step of a model is crucial to accurately obtain a satisfactory model performance. However, the recommendations provided by the majority of recent researchers on pilot-point use are considered somewhat impractical. In this study, a practical approach is proposed for using pilot-point properties (i.e. number, distance and distribution method) in the calibration step of a groundwater model. For the first time, the relative distance-area ratio ( d/ A) and head-zonation-based (HZB) method are introduced, to assign pilot points into the model domain by incorporating a user-friendly zone ratio. This study provides some insights into the trade-off between maximising and restricting the number of pilot points, and offers a relative basis for selecting the pilot-point properties and distribution method in the development of a physically based groundwater model. The grid-based (GB) method is found to perform comparably better than the HZB method in terms of model performance and computational time. When using the GB method, this study recommends a distance-area ratio of 0.05, a distance-x-grid length ratio ( d/ X grid) of 0.10, and a distance-y-grid length ratio ( d/ Y grid) of 0.20.

Evaluation of Existing Methods for Human Blood mRNA Isolation and Analysis for Large Studies

PubMed Central

Meyer, Anke; Paroni, Federico; Günther, Kathrin; Dharmadhikari, Gitanjali; Ahrens, Wolfgang; Kelm, Sørge; Maedler, Kathrin

2016-01-01

Aims Prior to implementing gene expression analyses from blood to a larger cohort study, an evaluation to set up a reliable and reproducible method is mandatory but challenging due to the specific characteristics of the samples as well as their collection methods. In this pilot study we optimized a combination of blood sampling and RNA isolation methods and present reproducible gene expression results from human blood samples. Methods The established PAXgeneTM blood collection method (Qiagen) was compared with the more recent TempusTM collection and storing system. RNA from blood samples collected by both systems was extracted on columns with the corresponding Norgen and PAX RNA extraction Kits. RNA quantity and quality was compared photometrically, with Ribogreen and by Real-Time PCR analyses of various reference genes (PPIA, β-ACTIN and TUBULIN) and exemplary of SIGLEC-7. Results Combining different sampling methods and extraction kits caused strong variations in gene expression. The use of PAXgeneTM and TempusTM collection systems resulted in RNA of good quality and quantity for the respective RNA isolation system. No large inter-donor variations could be detected for both systems. However, it was not possible to extract sufficient RNA of good quality with the PAXgeneTM RNA extraction system from samples collected by TempusTM collection tubes. Comparing only the Norgen RNA extraction methods, RNA from blood collected either by the TempusTM or PAXgeneTM collection system delivered sufficient amount and quality of RNA, but the TempusTM collection delivered higher RNA concentration compared to the PAXTM collection system. The established Pre-analytix PAXgeneTM RNA extraction system together with the PAXgeneTM blood collection system showed lowest CT-values, i.e. highest RNA concentration of good quality. Expression levels of all tested genes were stable and reproducible. Conclusions This study confirms that it is not possible to mix or change sampling or extraction strategies during the same study because of large variations of RNA yield and expression levels. PMID:27575051

Innovations in the brewing industry: light beer.

PubMed

Blanco, Carlos A; Caballero, Isabel; Barrios, Rosa; Rojas, Antonio

2014-09-01

The demand for light beers has led brewers to innovate by developing light beer. However, these products are not widely accepted in Europe compared to North America and Australasia because of their lack of fullness in the taste and low bitterness compared with conventional beer. The lower levels of some important compounds, present in light beer, can explain these features since they are responsible for the characteristics of the beer. These include alcohol soluble proteins, oligosaccharides, glycerol, polyphenols, iso-α-acids, fusel alcohols and trihydroxy fatty acids. Light beer is produced by several methods, the most commonly used is the addition of glucoamylase to the wort before or during fermentation. This enzyme metabolizes residual carbohydrates (mainly dextrins) transforming them into fermentable sugars and reducing the caloric and alcohol content in this type of beer. Recently pilot studies have been carried out with genetically engineered yeast strains in which amylolytic genes are introduced into the yeast genome in order to metabolize carbohydrate residues. When introducing amylolytic genes, a better fermentability occurs although the fullness of flavor still becomes reduced.

The impact of transition training on adapting to Technically Advanced Aircraft at regional airlines: Perceptions of pilots and instructor pilots

NASA Astrophysics Data System (ADS)

di Renzo, John Carl, Jr.

Scope and method of study. The purpose of this study was to test a hypothesis about pilot and instructor pilot perceptions of how effectively pilots learn and use new technology, found in Technically Advanced Aircraft (TAA), given initial type of instrumentation training. New aviation technologies such as Glass Cockpits in technically advanced aircraft are complex and can be difficult to learn and use. The research questions focused on the type of initial instrumentation training to determine the differences among pilots trained using various types of instrumentation ranging from aircraft equipped with traditional analog instrumentation to aircraft equipped with glass cockpits. A convenience sample of Pilots in Training (PT) and Instructor Pilots (IP) was selected from a regional airline. The research design used a mixed methodology. Pilots in training completed a thirty-two question quantitative questionnaire and instructor pilots completed a five question qualitative questionnaire. Findings and conclusions. This investigation failed to disprove the null hypothesis. The type of instrumentation training has no significant effect on newly trained regional airline pilot perceived ability to adapt to advanced technology cockpits. Therefore, no evidence exists from this investigation to support the early introduction and training of TAA. While the results of this investigation were surprising, they are nonetheless, instructive. Even though it would seem that there would be a relationship between exposure to and use of technically advanced instrumentation, apparently there was no perceived relationship for this group of airline transport pilots. However, a point of interest is that these pilots were almost evenly divided in their opinion of whether or not their previous training had prepared them for transition to TAA. The majority also believed that the type of initial instrumentation training received does make a difference when transitioning to TAA. Pilots believed that TAA made them safer pilots, but were not convinced it made them better pilots. The results of this investigation raise many new questions and provide a number of ideas for future research projects.

A mixed method pilot study: the researchers' experiences.

PubMed

Secomb, Jacinta M; Smith, Colleen

2011-08-01

This paper reports on the outcomes of a small well designed pilot study. Pilot studies often disseminate limited or statistically meaningless results without adding to the body knowledge on the comparative research benefits. The design a pre-test post-test group parallel randomised control trial and inductive content analysis of focus group transcripts was tested specifically to increase outcomes in a proposed larger study. Strategies are now in place to overcome operational barriers and recruitment difficulties. Links between the qualitative and quantitative arms of the proposed larger study have been made; it is anticipated that this will add depth to the final report. More extensive reporting on the outcomes of pilot studies would assist researchers and increase the body of knowledge in this area.

Successful implementation of clinical practice guidelines for pressure risk management in a home nursing setting.

PubMed

Kapp, Suzanne

2013-10-01

This paper reports an initiative which promoted evidence-based practice in pressure risk assessment and management among home nursing clients in Melbourne, Australia. The aim of this study was to evaluate the introduction and uptake of the Australian Wound Management Association Guidelines for the Prediction and Prevention of Pressure Ulcers. In 2007 a pilot study was conducted. Nurse perspectives (n=21) were obtained via survey and a client profile (n=218) was generated. Audit of the uptake and continued use of the pressure risk screening tool, during the pilot study and later once implemented as standard practice organizational wide, was conducted. Nurses at the pilot site successfully implemented the practice guidelines, pressure risk screening was adopted and supporting resources were well received. Most clients were at low risk of pressure ulcer development. The pilot site maintained and extended their pilot study success, ensuring more than 90% of clients were screened for pressure risk over the 18 months which followed. All other sites performed less well initially, however subsequently improved, meeting the pilot sites success after 18 months. Two years later, the organization continues to screen more than 90% of all clients for pressure risk. Implementation of clinical practice guidelines was successful in the pilot project and pressure risk screening became a well-adopted practice. Success continued following organizational wide implementation. Pilot study findings suggest it may be prudent to monitor the pressure ulcer risk status of low risk clients so as to prevent increasing risk and pressure ulcer development among this group. © 2012 John Wiley & Sons Ltd.

Structural Differences in Gray Matter between Glider Pilots and Non-Pilots. A Voxel-Based Morphometry Study

PubMed Central

Ahamed, Tosif; Kawanabe, Motoaki; Ishii, Shin; Callan, Daniel E.

2014-01-01

Glider flying is a unique skill that requires pilots to control an aircraft at high speeds in three dimensions and amidst frequent full-body rotations. In the present study, we investigated the neural correlates of flying a glider using voxel-based morphometry. The comparison between gray matter densities of 15 glider pilots and a control group of 15 non-pilots exhibited significant gray matter density increases in left ventral premotor cortex, anterior cingulate cortex, and the supplementary eye field. We posit that the identified regions might be associated with cognitive and motor processes related to flying, such as joystick control, visuo-vestibular interaction, and oculomotor control. PMID:25506339

Analysis of aircraft longitudinal handling qualities

NASA Technical Reports Server (NTRS)

Hess, R. A.

1981-01-01

The optimal control model (OCM) of the human pilot is applied to the study of aircraft handling qualities. Attention is focused primarily on longitudinal tasks. The modeling technique differs from previous applications of the OCM in that considerable effort is expended in simplifying the pilot/vehicle analysis. After briefly reviewing the OCM, a technique for modeling the pilot controlling higher order systems is introduced. Following this, a simple criterion for determining the susceptibility of an aircraft to pilot induced oscillations (PIO) is formulated. Finally, a model-based metric for pilot rating prediction is discussed. The resulting modeling procedure provides a relatively simple, yet unified approach to the study of a variety of handling qualities problems.

[Adaptive process in Vietnamese military pilots during the flights on modern Russian aircraft].

PubMed

Ushakov, I V; Pham Xuan, Nihn; Bukhtiaiarov, I V; Ushakov, B N

2013-04-01

Study on health status of 156 Vietnamese military pilots on Russian modern jet planes (Su-22, Su-27, Su-30, MiG-21B). The results showed that unprofitable factors in working environment (acceleration, radiation, high temperature, humidity, noise) have an impact on the health of pilots during the flight, leading to deterioration of professional health and physiological functions (cardiovascular, respiratory and nervous system) and obesity of pilots after 35 years old. Basing on the studies, we suggested some measures for health protecting, safety of flight and prolonging flight-activity of pilots (training in decompression chamber, vestibular training) and balance in food ration for prevention of professional diseases.

Structural Differences in Gray Matter between Glider Pilots and Non-Pilots. A Voxel-Based Morphometry Study.

PubMed

Ahamed, Tosif; Kawanabe, Motoaki; Ishii, Shin; Callan, Daniel E

2014-01-01

Glider flying is a unique skill that requires pilots to control an aircraft at high speeds in three dimensions and amidst frequent full-body rotations. In the present study, we investigated the neural correlates of flying a glider using voxel-based morphometry. The comparison between gray matter densities of 15 glider pilots and a control group of 15 non-pilots exhibited significant gray matter density increases in left ventral premotor cortex, anterior cingulate cortex, and the supplementary eye field. We posit that the identified regions might be associated with cognitive and motor processes related to flying, such as joystick control, visuo-vestibular interaction, and oculomotor control.

Pilot interaction with cockpit automation - Operational experiences with the Flight Management System

NASA Technical Reports Server (NTRS)

Sarter, Nadine B.; Woods, David D.

1992-01-01

Results are presented of two studies on the potential effect of cockpit automation on the pilot's performance, which provide data on pilots' difficulties with understanding and operating one of the core systems of cockpit automation, the Flight Management System (FMS). The results of both studies indicate that, although pilots do become proficient in standard FMS operations through ground training and subsequent flight experience, they still have difficulties tracking the FMS status and behavior in certain flight contexts and show gaps in the understanding of the functional structure of the system. The results suggest that design-related factors such as opaque interfaces contribute to these difficulties, which can affect the pilot's situation awareness.

Training General Aviation Pilots for Convective Weather Situations.

PubMed

Blickensderfer, Elizabeth L; Lanicci, John M; Vincent, Michael J; Thomas, Robert L; Smith, MaryJo; Cruit, Jessica K

2015-10-01

Over the past 10-15 yr, considerable research has occurred for the development, testing, and fielding of real-time Datalink weather products for general aviation (GA) pilots to use before and during flight. As is the case with the implementation of most new technologies, work is needed to ensure that the users (in this case, the pilots) understand both the capabilities and limitations of the new technologies as well as how to use the new systems to improve their task performance. The purpose of this study was to replicate and extend a previous study on training pilots how and when to use these new weather technologies. This field study used a quasi-experimental design (pre- vs. post-test with a control group). There were 91 GA pilots from the Midwest, Northeastern, and Southeastern United States who participated in a 2-h short course or a control activity. The lecture-based short course covered radar basics, Next Generation Weather Radar (NEXRAD), NEXRAD specifics/limitations, thunderstorm basics, radar products, and decision making. The pilots who participated in the course earned higher knowledge test scores, improved at applying the concepts in paper-based flight scenarios, had higher self-efficacy in post-training assessments as compared to pre-training assessments, and also performed better than did control subjects on post-test knowledge and skills assessments. GA pilots lack knowledge about real-time Datalink weather technology. This study indicates that a relatively short training program was effective for fostering Datalink weather-related knowledge and skills in GA pilots.

Occupational Stress and Hypertension among Railway Loco Pilots and Section Controllers.

PubMed

Jayakumar, Devasigamoney

2017-01-01

A cross-sectional study on occupational stress was conducted on loco pilots in 2008, in view of loco pilots being one of the high strain jobs in Indian Railways. Subsequently, a comparative cross-sectional study on occupational stress was conducted among section controllers in 2011, which is another high strain job of Indian Railways. The studies were conducted to analyze and compare occupational stress and hypertension. A cross-sectional study on occupational stress and hypertension was conducted among 230 loco pilots in 2008, and subsequently, a comparative cross-sectional study was conducted among 82 section controllers in 2011. A closed end 24 item questionnaire on occupational stress was administered. Systolic blood pressure above 140 mmHg and diastolic blood pressure above 90 mmHg were considered as hypertension as per the VII Joint National Committee. Chi-square test and t -test were used for testing significance at P < 0.05. The mean stress score was 8.56 in loco pilots and 7.32 in section controllers. The number of loco pilots with more than 12 stress factors was 49 (21.3%) and the number of section controllers with more than 12 stress factors was 7 (8.5%). The number employees with more than 12 stress factors in different categories of loco pilots were 30 (32%) in the goods category, 12 (12%) in the mail/passenger category, and 7 (19%) in the shunter category, and 3 (11%) in the supervisory category and 4 (7%) in the on-board category of section controllers. The prevalence of hypertension in loco pilots was 36.52% (84) and in the section controllers was 53.66% (44). The prevalence of hypertension in the category with more than 12 stress factors was 30.61% (15) in the loco pilots and 28.57% (2) in the section controllers. The prevalence of hypertension in the both the study groups were higher in the older age, with a family history of hypertension, and with a body mass index of more than 25 kg/m 2 . The mean occupational stress and employees with more than 12 stress factors were higher in the loco pilots group. The goods category of loco pilots had highest stress factors. The prevalence of hypertension was high in the category with risk factors such as older age, family history of hypertension and BMI above 25 kg/m 2 .

Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

PubMed Central

Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric A.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Korzenik, Joshua; Denninger, John W.

2015-01-01

Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. Trial Registration ClinicalTrials.Gov NCT02136745 PMID:25927528

Pilot Biofeedback Training in the Cognitive Awareness Training Study (CATS)

NASA Technical Reports Server (NTRS)

Uenking, M.

2000-01-01

One of the ongoing problems that pilots face today is a diminished state of awareness such as boredom, sleepiness, or fatigue during cruise conditions that could result in various pilot errors. This study utilized a cognitive training exercise to sharpen the pilot's awareness during simulated flight thereby providing them with a means to overcome these diminished states of awareness. This study utilizes psychophysiological methods in an attempt to assess a pilot's state of awareness more directly. In turn, the pilots will be able to train themselves to recognize these states of awareness and be more mentally sharp during mundane tasks such as those experienced in cruise conditions. The use of these measurement tools may be beneficial for researchers working within the NASA Aviation Safety Program. This paper will provide the reader with some background information concerning the motivation for the study, a brief description of the experimental setup and design matrix, the dependent and independent variables that were employed, and some preliminary findings based on some of the subjective and objective data that was collected. These preliminary findings are of part of an ongoing study being conducted at the NASA Langley Research Center in Hampton, Virginia.

Occupational cosmic radiation exposure in Portuguese airline pilots: study of a possible correlation with oxidative biological markers.

PubMed

Silva, Rodrigo; Folgosa, Filipe; Soares, Paulo; Pereira, Alice S; Garcia, Raquel; Gestal-Otero, Juan Jesus; Tavares, Pedro; Gomes da Silva, Marco D R

2013-05-01

Several studies have sought to understand the health effects of occupational exposure to cosmic radiation. However, only few biologic markers or associations with disease outcomes have so far been identified. In the present study, 22 long- and 26 medium-haul male Portuguese airline pilots and 36 factory workers who did not fly regularly were investigated. The two groups were comparable in age and diet, were non-smokers, never treated with ionizing radiation and other factors. Cosmic radiation exposure in pilots was quantified based on direct monitoring of 51 flights within Europe, and from Europe to North and South America, and to Africa. Indirect dose estimates in pilots were performed based on the SIEVERT (Système informatisé d'évaluation par vol de l'exposition au rayonnement cosmique dans les transports aériens) software for 6,039 medium- and 1,366 long-haul flights. Medium-haul pilots had a higher cosmic radiation dose rate than long-haul pilots, that is, 3.3 ± 0.2 μSv/h and 2.7 ± 0.3 μSv/h, respectively. Biological tests for oxidative stress on blood and urine, as appropriate, at two time periods separated by 1 year, included measurements of antioxidant capacity, total protein, ferritin, hemoglobin, creatinine and 8-hydroxy-2-deoxyguanosine (8OHdG). Principal components analysis was used to discriminate between the exposed and unexposed groups based on all the biological tests. According to this analysis, creatinine and 8OHdG levels were different for the pilots and the unexposed group, but no distinctions could be made among the medium- and the long-haul pilots. While hemoglobin levels seem to be comparable between the studied groups, they were directly correlated with ferritin values, which were lower for the airline pilots.

Cross-sectional study of neck pain and cervical sagittal alignment in air force pilots.

PubMed

Moon, Bong Ju; Choi, Kyong Ho; Yun, Chul; Ha, Yoon

2015-05-01

There is a high prevalence of neck pain in air force pilots; however, the causes are not clear and are considered work-related. Kyphotic changes in the cervical spine have been known to cause neck pain. In this study, we investigated the association between neck pain and cervical kyphosis in air force pilots. This is a cross-sectional study of 63 Republic of South Korea Air Force pilots. We examined the C2-7 absolute rotation angle (ARA) using the posterior tangent method and other radiologic parameters on whole spine lateral radiographs. We divided the participants into a neck pain group (N = 32) and no neck pain group (N = 31), and subsequently analyzed the difference in radiographic parameters and clinical data between the two groups. There were no significant differences found in age, body mass index, total flight time, or aerobic or anaerobic exercise between the neck pain and control groups. The fighter pilots had higher 1-yr prevalence of neck pain than nonfighter pilots (84.4% vs. 15.6%). The lower C2-7 ARA (OR = 0.91, 95% CI 0.846, 0.979) and fighter type aircrafts (OR = 3.93, 95% CI 1.104, 13.989) were associated with neck pain. Fighter pilots experienced neck pain more frequently than the nonfighter pilots. Those fighter pilots suffering from neck pain were shown to have more kyphotic changes in the cervical spine than control pilots through evaluation of whole spine lateral radiographs using the posterior tangent method. These key findings suggest that the forces involved in flying a fighter type aircraft may affect cervical alignment and neck pain.

The effects of pilot stress factors on handling quality assessments during US/German helicopter agility flight tests

NASA Technical Reports Server (NTRS)

Pausder, H. J.; Gerdes, R. M.

1982-01-01

Flight tests were conducted with two helicopters to study and evaluate the effects of helicopter characteristics and pilot and task demands on performance in nap-of-the-Earth flight. Different, low-level slalom courses were set up and were flown by three pilots with different levels of flight experience. A pilot rating questionnaire was used to obtain redundant information and to gain more insight into factors that influence pilot ratings. The flight test setups and procedures are described, and the pilot ratings are summarized and interpreted in close connection with the analyzed test data. Pilot stress is discussed. The influence of demands on the pilot, of the helicopter characteristics, and of other stress factors are outlined with particular emphasis on how these factors affect handling-qualities assessment.

Changes in the Structure and Function of Microbial Communities in Drinking Water Treatment Bioreactors upon Addition of Phosphorus▿ †

PubMed Central

Li, Xu; Upadhyaya, Giridhar; Yuen, Wangki; Brown, Jess; Morgenroth, Eberhard; Raskin, Lutgarde

2010-01-01

Phosphorus was added as a nutrient to bench-scale and pilot-scale biologically active carbon (BAC) reactors operated for perchlorate and nitrate removal from contaminated groundwater. The two bioreactors responded similarly to phosphorus addition in terms of microbial community function (i.e., reactor performance), while drastically different responses in microbial community structure were detected. Improvement in reactor performance with respect to perchlorate and nitrate removal started within a few days after phosphorus addition for both reactors. Microbial community structures were evaluated using molecular techniques targeting 16S rRNA genes. Clone library results showed that the relative abundance of perchlorate-reducing bacteria (PRB) Dechloromonas and Azospira in the bench-scale reactor increased from 15.2% and 0.6% to 54.2% and 11.7% after phosphorus addition, respectively. Real-time quantitative PCR (qPCR) experiments revealed that these increases started within a few days after phosphorus addition. In contrast, after phosphorus addition, the relative abundance of Dechloromonas in the pilot-scale reactor decreased from 7.1 to 0.6%, while Zoogloea increased from 17.9 to 52.0%. The results of this study demonstrated that similar operating conditions for bench-scale and pilot-scale reactors resulted in similar contaminant removal performances, despite dramatically different responses from microbial communities. These findings suggest that it is important to evaluate the microbial community compositions inside bioreactors used for drinking water treatment, as they determine the microbial composition in the effluent and impact downstream treatment requirements for drinking water production. This information could be particularly relevant to drinking water safety, if pathogens or disinfectant-resistant bacteria are detected in the bioreactors. PMID:20889793

Epigenetic Patterns in Successful Weight Loss Maintainers: A Pilot Study

PubMed Central

Hawley, Nicola L.; Wing, Rena R.; Kelsey, Karl T.; McCaffery, Jeanne M.

2014-01-01

DNA methylation changes occur in animal models of calorie restriction, simulating human dieting, and in human subjects undergoing behavioral weight loss interventions. This suggests that obese individuals may possess unique epigenetic patterns that may vary with weight loss. Here, we examine whether methylation patterns in leukocytes differ in individuals who lost sufficient weight to go from obese to normal weight (successful weight loss maintainers; SWLM) vs currently obese (OB) or normal weight (NW) individuals. This study examined peripheral blood mononuclear cell (PBMC) methylation patterns in NW (n=16, current/lifetime BMI 18.5-24.9) and OB individuals (n=16, current BMI≥30), and SWLM (n=16, current BMI 18.5-24.9, lifetime maximum BMI ≥30, average weight loss 57.4 lbs) using an Illumina Infinium HumanMethylation450 BeadArray. No leukocyte population-adjusted epigenome-wide analyses were significant; however, potentially differentially methylated loci across groups were observed in RYR1 (p=1.54E-6), MPZL3 (p=4.70E-6), and TUBA3C (p=4.78E-6). In 32 obesity-related candidate genes, differential methylation patterns were found in BDNF (gene-wide p=0.00018). In RYR1, TUBA3C and BDNF, SWLM differed from OB but not NW. In this preliminary investigation, leukocyte SWLM DNA methylation patterns more closely resembled NW than OB individuals in three gene regions. These results suggest that PBMC methylation is associated with weight status. PMID:25520250

Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases the risk of idiopathic male infertility.

PubMed

Yarosh, Sergey L; Kokhtenko, Elena V; Churnosov, Mikhail I; Ataman, Alexander V; Solodilova, Maria A; Polonikov, Alexey V

2014-09-01

N-acetyltransferase (NAT2) is a phase-II xenobiotic-metabolizing enzyme participating in the detoxification of toxic arylamines, aromatic amines and hydrazines. The present study was designed to investigate whether two common single-nucleotide polymorphisms (SNP) of the NAT2 gene (481C>T, rs1799929; 590G>A, rs1799930) are associated with susceptibility to idiopathic male infertility and to assess if the risk is modified by oxidant and antioxidant exposures. A total 430 DNA samples (203 infertile patients and 227 fertile men) were genotyped for the polymorphisms by PCR and restriction fragment length polymorphism. No association was found between the NAT2 polymorphisms and idiopathic male infertility. However, gene-environment interaction analysis revealed that a low-acetylation genotype, 590GA, was significantly associated with increased disease risk in men who had environmental risk factors such as cigarette smoking (OR 1.71, 95% CI 1.02-2.87, P = 0.042), alcohol abuse (OR 2.14, 95% CI 1.08-4.27, P = 0.029) and low fruit/vegetable intake (OR 1.68, 95% CI 1.01-2.79, P = 0.04). This pilot study found, as far as is known for the first time, that the polymorphism 590G>A of NAT2 is a novel genetic marker for susceptibility to idiopathic male infertility, but the risk is potentiated by exposure to various environmental oxidants. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cyclooxygenase 2 gene polymorphisms and chronic periodontitis in a North Indian population: a pilot study

PubMed Central

Daing, Anika; Singh, Sarvendra Vikram; Saimbi, Charanjeet Singh; Khan, Mohammad Akhlaq

2012-01-01

Purpose Cyclooxygenase (COX) enzyme catalyzes the production of prostaglandins, which are important mediators of tissue destruction in periodontitis. Single nucleotide polymorphisms of COX2 enzyme have been associated with increasing susceptibility to inflammatory diseases. The present study evaluates the association of two single nucleotide polymorphisms in COX2 gene (-1195G>A and 8473C>T) with chronic periodontitis in North Indians. Methods Both SNPs and their haplotypes were used to explore the associations between COX2 polymorphisms and chronic periodontitis in 56 patients and 60 controls. Genotyping was done by polymerase chain reaction followed by restriction fragment length polymorphism. Chi-square test and logistic regression analysis were performed for association analysis. Results By the individual genotype analysis, mutant genotypes (GA and AA) of COX2 -1195 showed more than a two fold risk (odds ratio [OR]>2) and COX2 8473 (TC and CC) showed a reduced risk for the disease, but the findings were not statistically significant. Haplotype analysis showed that the frequency of the haplotype AT was higher in the case group and a significant association was found for haplotype AT (OR, 1.79; 95% confidence interval, 1.03 to 3.11; P=0.0370) indicating an association between the AT haplotype of COX2 gene SNPs and chronic periodontitis. Conclusions Individual genotypes of both the SNPs were not associated while haplotype AT was found to be associated with chronic periodontitis in North Indians. PMID:23185695

GST-M1 is transcribed moreso than AKR7A2 in AFB₁-exposed human monocytes and lymphocytes.

PubMed

Bahari, Abbas; Mehrzad, Jalil; Mahmoudi, Mahmoud; Bassami, Mohammad Reza; Dehghani, Hesam

2015-01-01

Glutathione-S-transferases (GST) and aldo-keto reductases (AKR) are key aflatoxin (AF)-detoxifying enzymes. In this study, the expression of GST-M1, GST-T1, AKR-7A2, and AKR-7A3 genes in human monocytes and lymphocytes was analyzed after in vitro exposure to 10 or 100 ng AFB1/ml for 2 h. Unlike in pilot studies that showed that all four examined genes were present in HepG2 cells, in lymphocytes and monocytes, only GST-M1 and AKR-7A2 were detected. In fact, the induced expression of both GST-M1 and AKR-7A2 genes in human monocytes was moreso than that seen in AFB1-exposed lymphocytes. In addition, analyses of the effects of the exposures on cell cycle status were performed as, in cells lacking adequate detoxification capacities, it would be expected the cells would arrest at checkpoints in the cell cycle or progress to apoptotic/necrotic states. The results here indicated that only the high dose of AFB1 led to a change in cell cycle profiles and only in the monocytes (i.e. cells in S phase were significantly reduced). In general, the results here strongly suggest that human immune cell lineages appear to be able to increase their expression of AFB1-detoxifying enzymes (albeit to differing degrees) and, as a result, are able to counter potential toxicities from AFB1 and (likely) its metabolites.

A Pilot Study of Noninvasive Prenatal Diagnosis of Alpha- and Beta-Thalassemia with Target Capture Sequencing of Cell-Free Fetal DNA in Maternal Blood.

PubMed

Wang, Wenjuan; Yuan, Yuan; Zheng, Haiqing; Wang, Yaoshen; Zeng, Dan; Yang, Yihua; Yi, Xin; Xia, Yang; Zhu, Chunjiang

2017-07-01

Thalassemia is a dangerous hematolytic genetic disease. In south China, ∼24% Chinese carry alpha-thalassemia or beta-thalassemia gene mutations. Given the fact that the invasive sampling procedures can only be performed by professionals in experienced centers, it may increase the risk of miscarriage or infection. Thus, most people are worried about the invasive operation. As such, a noninvasive and accurate prenatal diagnosis is needed for appropriate genetic counseling for families with high risks. Here we sought to develop capture probes and their companion analysis methods for the noninvasive prenatal detection of deletional and nondeletional thalassemia. Two families diagnosed as carriers of either beta-thalassemia gene or Southeast Asian deletional alpha-thalassemia gene mutation were recruited. The maternal plasma and amniotic fluid were collected for prenatal diagnosis. Probes targeting exons of the genes of interest and the highly heterozygous SNPs within the 1Mb flanking region were designed. The target capture sequencing was performed with plasma DNA from the pregnant woman and genomic DNA from the couples and their children. Then the parental haplotype was constructed by the trios-based strategy. The fetal haplotype was deduced from the parental haplotype with a hidden Markov model-based algorithm. The fetal genotypes were successfully deduced in both families noninvasively. The noninvasively constructed haplotypes of both fetuses were identical to the invasive prenatal diagnosis results with an accuracy rate of 100% in the target region. Our study demonstrates that the effective noninvasive prenatal diagnosis of alpha-thalassemia and beta-thalassemia can be achieved with the targeted capture sequencing and the haplotype-assisted analysis method.

Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study.

PubMed

Ream, Margie A; Mikati, Mohamad A

2014-08-01

The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined. To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center. We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES). We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29). We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing. Copyright © 2014. Published by Elsevier Inc.

Enhancing pilot situational awareness of the airport surface movement area

NASA Technical Reports Server (NTRS)

Jones, D. R.; Young, S. D.

1994-01-01

Two studies are being conducted to address airport surface movement area safety and capacity issues by providing enhanced situational awareness information to pilots. One study focuses on obtaining pilot opinion of the Runway Status Light System (RSLS). This system has been designed to reduce the likelihood of runway incursions by informing pilots when a runway is occupied. The second study is a flight demonstration of an rate integrated system consisting of an electronic moving map in the cockpit and display of the aircraft identification to the controller. Taxi route and hold warning information will be sent to the aircraft data link for display on the electronic moving map. This paper describes the plans for the two studies.

The effects of staged intra-articular injection of cultured autologous mesenchymal stromal cells on the repair of damaged cartilage: a pilot study in caprine model.

PubMed

Nam, Hui Yin; Karunanithi, Puvanan; Loo, Wagner Cheng; Naveen, Sangeetha; Chen, Hui; Hussin, Paisal; Chan, Lucy; Kamarul, Tunku

2013-09-20

Treatment of chondral injuries remains a major issue despite the many advances made in cartilage repair techniques. Although it has been postulated that the use of marrow stimulation in combination with cell-based therapy may provide superior outcome, this has yet to be demonstrated. A pilot study was thus conducted to determine if bone marrow derived mesenchymal stromal cells (BM-MSCs) have modulatory effects on the repair outcomes of bone marrow stimulation (BMS) techniques. Two full-thickness chondral 5 mm diameter defects were created in tandem on the medial condyle of left stifle joints of 18 Boer caprine (N = 18). Goats were then divided equally into three groups. Simultaneously, bone marrow aspirates were taken from the iliac crests from the goats in Group 1 and were sent for BM-MSC isolation and expansion in vitro. Six weeks later, BMS surgery, which involves subchondral drilling at the defect sites, was performed. After two weeks, the knees in Group 1 were given autologous intra-articular BM-MSCs (N = 6). In Group 2, although BMS was performed there were no supplementations provided. In Group 3, no intervention was administered. The caprines were sacrificed after six months. Repairs were evaluated using macroscopic assessment through the International Cartilage Repair Society (ICRS) scoring, histologic grading by O'Driscoll score, biochemical assays for glycosaminoglycans (GAGs) and gene expressions for aggrecan, collagen II and Sox9. Histological and immunohistochemical analyses demonstrated hyaline-like cartilage regeneration in the transplanted sites particularly in Group 1. In contrast, tissues in Groups 2 and 3 demonstrated mainly fibrocartilage. The highest ICRS and O'Driscoll scorings was also observed in Group 1, while the lowest score was seen in Group 3. Similarly, the total GAG/total protein as well as chondrogenic gene levels were expressed in the same order, that is highest in Group 1 while the lowest in Group three. Significant differences between these 3 groups were observed (P <0.05). This study suggests that supplementing intra-articular injections of BM-MSCs following BMS knee surgery provides superior cartilage repair outcomes.

The Pilot Training Study: A Cost-Estimating Model for Advanced Pilot Training (APT).

ERIC Educational Resources Information Center

Knollmeyer, L. E.

The Advanced Pilot Training Cost Model is a statement of relationships that may be used, given the necessary inputs, for estimating the resources required and the costs to train pilots in the Air Force formal flying training schools. Resources and costs are computed by weapon system on an annual basis for use in long-range planning or sensitivity…

The Relationship of a Pilot's Educational Background, Aeronautical Experience and Recency of Experience to Performance In Initial Training at a Regional Airline

NASA Astrophysics Data System (ADS)

Shane, Nancy R.

The purpose of this study was to determine how a pilot's educational background, aeronautical experience and recency of experience relate to their performance during initial training at a regional airline. Results show that variables in pilots' educational background, aeronautical experience and recency of experience do predict performance in training. The most significant predictors include years since graduation from college, multi-engine time, total time and whether or not a pilot had military flying experience. Due to the pilot shortage, the pilots entering regional airline training classes since August 2013 have varied backgrounds, aeronautical experience and recency of experience. As explained by Edward Thorndike's law of exercise and the law of recency, pilots who are actively using their aeronautical knowledge and exercising their flying skills should exhibit strong performance in those areas and pilots who have not been actively using their aeronautical knowledge and exercising their flying skills should exhibit degraded performance in those areas. Through correlation, chi-square and multiple regression analysis, this study tests this theory as it relates to performance in initial training at a regional airline.

An Assessment of Teacher Education Students' Perceptions and Satisfaction of Their Learning Experiences in a Summer Pilot Program

ERIC Educational Resources Information Center

Hicks, Terence; Lewis, Leontye; Munn, Geraldine; Jordon, Earlyn; Charles, Kelly

2010-01-01

This study assessed teacher education students' perceptions and satisfaction of their learning experiences concerning an accelerated summer pilot program. In addition, the study provided information on the impact and teaching effectiveness of the accelerated teacher education summer pilot program on participating students. Results from this study…

Supporting Parents to Facilitate Communication and Joint Attention in Their Young Children with Autism Spectrum Disorders: Two Pilot Studies

ERIC Educational Resources Information Center

Prelock, Patricia A.; Calhoun, James; Morris, Hope; Platt, Gretchen

2011-01-01

This article describes 2 pilot studies partnering early interventionists and families in targeting social communication and joint attention abilities for young children with autism spectrum disorders. Both parent-intervention trainings involved opportunities for interventionists to partner with families. One pilot utilized "More than Words" (MTW;…

Testing Telephone and Web Surveys for Studying Men's Sexual Assault Perpetration Behaviors

ERIC Educational Resources Information Center

DiNitto, Diana M.; Busch-Armendariz, Noel Bridget; Bender, Kimberly; Woo, Hyeyoung; Tackett-Gibson, Melissa; Dyer, James

2008-01-01

Three pilot studies were conducted to obtain information about sexual assault perpetration from adult men in the United States. Each used the same random digit-dial sampling and recruitment strategy. One pilot was administered by telephone and two via the Web. Response rates in all pilots were low. Although results cannot be generalized beyond the…

An Exploration of the Importance of Piloting and Access as Action Research

ERIC Educational Resources Information Center

Gudmundsdottir, Greta Bjork; Brock-Utne, Birgit

2010-01-01

In this article we illustrate how the piloting process has influenced two widely different studies within the educational sciences. These studies differ in design but have as a common denominator that they used piloting methods in their preparatory process. They are also similar in the intention of the main researchers of conducting research with…

The association of pineal gland volume and body mass in obese and normal weight individuals: a pilot study.

PubMed

Grosshans, Martin; Vollmert, Christian; Vollstaedt-Klein, Sabine; Nolte, Ingo; Schwarz, Emanuel; Wagner, Xenija; Leweke, Markus; Mutschler, Jochen; Kiefer, Falk; Bumb, Jan Malte

2016-09-01

In obese individuals impaired sleep and neuroendocrine alterations such as melatonin deficits are associated with circadian rhythm disruption, altered circadian clock gene expression, and bright light at night. While the relation of pineal gland volume (PGV) and melatonin levels has recently been documented in humans, surprisingly little is known about the possible interference of the PGV and the pathophysiology of obesity in humans. We therefore compared the PGV of obese with non-obese individuals; both groups were matched by age and gender. Volumetric analyses were performed on the basis of 3 Tesla high resolution Magnetic Resonance Imaging (MRI). We found, that the PGV was significantly smaller in obese individuals than in lean controls (P=0.036). Moreover, PGV and waist-hip ratio showed a significant negative association in controls (P=0.018, r s =-0.602) whereas no association of both variables was found in obese individuals (P=0.856, r s =-0.051). Thus, the current pilot investigation suggests that pineal gland function, reflected by PGV might be involved in the energy homeostasis and pathophysiological mechanisms that contribute to the development and the maintenance of obesity in humans. Moreover, our data supports the notion that the replacement of melatonin deficits might be a novel strategy in the treatment of obesity.

Discovery of Novel Cell Wall-Active Compounds Using PywaC, a Sensitive Reporter of Cell Wall Stress, in the Model Gram-Positive Bacterium Bacillus subtilis

PubMed Central

Czarny, T. L.; Perri, A. L.; French, S.

2014-01-01

The emergence of antibiotic resistance in recent years has radically reduced the clinical efficacy of many antibacterial treatments and now poses a significant threat to public health. One of the earliest studied well-validated targets for antimicrobial discovery is the bacterial cell wall. The essential nature of this pathway, its conservation among bacterial pathogens, and its absence in human biology have made cell wall synthesis an attractive pathway for new antibiotic drug discovery. Herein, we describe a highly sensitive screening methodology for identifying chemical agents that perturb cell wall synthesis, using the model of the Gram-positive bacterium Bacillus subtilis. We report on a cell-based pilot screen of 26,000 small molecules to look for cell wall-active chemicals in real time using an autonomous luminescence gene cluster driven by the promoter of ywaC, which encodes a guanosine tetra(penta)phosphate synthetase that is expressed under cell wall stress. The promoter-reporter system was generally much more sensitive than growth inhibition testing and responded almost exclusively to cell wall-active antibiotics. Follow-up testing of the compounds from the pilot screen with secondary assays to verify the mechanism of action led to the discovery of 9 novel cell wall-active compounds. PMID:24687489

Identification of Compounds That Prolong Type I Interferon Signaling as Potential Vaccine Adjuvants.

PubMed

Shukla, Nikunj M; Arimoto, Kei-Ichiro; Yao, Shiyin; Fan, Jun-Bao; Zhang, Yue; Sato-Kaneko, Fumi; Lao, Fitzgerald S; Hosoya, Tadashi; Messer, Karen; Pu, Minya; Cottam, Howard B; Carson, Dennis A; Hayashi, Tomoko; Zhang, Dong-Er; Corr, Maripat

2018-05-01

Vaccines are reliant on adjuvants to enhance the immune stimulus, and type I interferons (IFNs) have been shown to be beneficial in augmenting this response. We were interested in identifying compounds that would sustain activation of an endogenous type I IFN response as a co-adjuvant. We began with generation of a human monocytic THP-1 cell line with an IFN-stimulated response element (ISRE)-β-lactamase reporter construct for high-throughput screening. Pilot studies were performed to optimize the parameters and conditions for this cell-based Förster resonance energy transfer (FRET) reporter assay for sustaining an IFN-α-induced ISRE activation signal. These conditions were confirmed in an initial pilot screen, followed by the main screen for evaluating prolongation of an IFN-α-induced ISRE activation signal at 16 h. Hit compounds were identified using a structure enrichment strategy based on chemoinformatic clustering and a naïve "Top X" approach. A select list of confirmed hits was then evaluated for toxicity and the ability to sustain IFN activity by gene and protein expression. Finally, for proof of concept, a panel of compounds was used to immunize mice as co-adjuvant with a model antigen and an IFN-inducing Toll-like receptor 4 agonist, lipopolysaccharide, as an adjuvant. Selected compounds significantly augmented antigen-specific immunoglobulin responses.

Cell-free fetal DNA testing: A pilot study of obstetric healthcare provider attitudes towards clinical implementation

PubMed Central

Sayres, Lauren; Allyse, Megan; Norton, Mary; Cho, Mildred

2011-01-01

Objective To provide a preliminary assessment of obstetric healthcare provider opinions surrounding implementation of cell-free fetal DNA testing. Methods A 37-question pilot survey was used to address questions around the translation and use of non-invasive prenatal testing using cell-free fetal DNA. The survey was distributed and collected at a Continuing Medical Education course on obstetrics and gynecology. Results Of 62 survey respondents, 73% are female and 87% hold MD/DO degrees. Respondents generally agree that patients want prenatal diagnostic information to help make decisions about a pregnancy and that cell-free fetal DNA testing will encourage the testing of more patients for more conditions. However, there is an overall lack of knowledge or conviction about using this technology. Genetic counseling and professional society approval are deemed important to implementation whereas the possibility of direct-to-consumer testing and government regulation produce mixed responses. Respondents indicate that they are more likely to offer cell-free fetal DNA testing for chromosomal abnormalities and single-gene disorders, but are cautious with respect to determination of sex and behavioral or late-onset conditions. Conclusion Preliminary assessment indicates uncertainty among obstetric providers about the details of implementing cell-free fetal DNA testing and suggests expanded research on perspectives of this stakeholder group. PMID:21793012

FMP study of pilot workload. Qualification of workload via instrument scan

NASA Technical Reports Server (NTRS)

Tolel, J. R.; Vivaudou, M.; Harris, R. L., Sr.; Ephrath, A.

1982-01-01

Various methods of measuring a pilot's mental workload are discussed. Scanning the various flight instruments with good scan pattern and other verbal tasks during instrument landings is given special attention for measuring pilot workload.

Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood.

PubMed

Aspler, Anne L; Bolshin, Carly; Vernon, Suzanne D; Broderick, Gordon

2008-09-26

Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS) however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention) and unsupervised latent cluster analysis (LCA). Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01) due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p < 0.05, patterns of co-expression in each group differed markedly. Significant co-expression of CD14+ monocyte with CD16+ neutrophil (p = 0.01) and CD19+ B cell sets (p = 0.00) characterized CFS and fatigue phenotype groups. Also in CFS was a significant negative correlation between CD8+ and both CD19+ up-regulated (p = 0.02) and NK gene sets (p = 0.08). These patterns were absent in controls. Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

DHT and IGF-1 in peripheral blood lymphocytes: new markers for the biological passport of athletes.

PubMed

Mancini, A; Imperlini, E; Alfieri, A; Spaziani, S; Martone, D; Parisi, A; Orru, S; Buono, P

2013-01-01

We performed a pilot study using human peripheral blood lymphocytes (PBL) as a novel system to identify new biomarkers of dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-1) abuse in sport. First, to obtain a gene signature, we treated cultures of lymphocytes from sedentary males with three doses of 0.237 microg/ml DHT, each of which is 80-fold the physiological concentration in young adult male serum, at days 0, 2 and 4, or with a single dose of 1.25 microg/ml IGF-1, which is 5-fold the physiological concentration in young adult male serum. We then used the Human Genome U133 Plus 2.0 microarray to identify a gene signature related to DHT or IGF-1 administration. Gene expression was evaluated after 7 and 21 days of DHT treatment, and after 24 h, 72 h and 7 days of IGF-1 treatment. Microarray analysis yielded a list of genes whose expression was altered after DHT or IGF-1 treatment. Among these we selected the genes that are most representative of the pathways associated with skeletal and muscular disorders using the IPA bioinformatics tool. We identified six (IDO1, CXCL13, CCL1, GZMB, VDR and IL2RA) and two (FN1 and RAB31) genes that were up-regulated in lymphocytes from sedentary subjects after 7 days of DHT and IGF-1 treatment, respectively. The expression of these genes in lymphocytes from differently trained athletes was either down-regulated or similar to that in lymphocytes from sedentary subjects. This finding suggests that up-regulation was due to the drug and not to physical exercise. In conclusion, we demonstrate that PBL can be useful in anti-doping checks, and we describe new biomarkers of DHT and IGF-1 abuse which can be included in the Athlete's Biological Passport.

Epigenetic Biomarkers as Predictors and Correlates of Symptom Improvement Following Psychotherapy in Combat Veterans with PTSD

PubMed Central

Yehuda, Rachel; Daskalakis, Nikolaos P.; Desarnaud, Frank; Makotkine, Iouri; Lehrner, Amy L.; Koch, Erin; Flory, Janine D.; Buxbaum, Joseph D.; Meaney, Michael J.; Bierer, Linda M.

2013-01-01

Epigenetic alterations offer promise as diagnostic or prognostic markers, but it is not known whether these measures associate with, or predict, clinical state. These questions were addressed in a pilot study with combat veterans with PTSD to determine whether cytosine methylation in promoter regions of the glucocorticoid related NR3C1 and FKBP51 genes would predict or associate with treatment outcome. Veterans with PTSD received prolonged exposure (PE) psychotherapy, yielding responders (n = 8), defined by no longer meeting diagnostic criteria for PTSD, and non-responders (n = 8). Blood samples were obtained at pre-treatment, after 12 weeks of psychotherapy (post-treatment), and after a 3-month follow-up. Methylation was examined in DNA extracted from lymphocytes. Measures reflecting glucocorticoid receptor (GR) activity were also obtained (i.e., plasma and 24 h-urinary cortisol, plasma ACTH, lymphocyte lysozyme IC50-DEX, and plasma neuropeptide-Y). Methylation of the GR gene (NR3C1) exon 1F promoter assessed at pre-treatment predicted treatment outcome, but was not significantly altered in responders or non-responders at post-treatment or follow-up. In contrast, methylation of the FKBP5 gene (FKBP51) exon 1 promoter region did not predict treatment response, but decreased in association with recovery. In a subset, a corresponding group difference in FKBP5 gene expression was observed, with responders showing higher gene expression at post-treatment than non-responders. Endocrine markers were also associated with the epigenetic markers. These preliminary observations require replication and validation. However, the results support research indicating that some glucocorticoid related genes are subject to environmental regulation throughout life. Moreover, psychotherapy constitutes a form of “environmental regulation” that may alter epigenetic state. Finally, the results further suggest that different genes may be associated with prognosis and symptom state, respectively. PMID:24098286

Evaluation of miRNA-196a2 and apoptosis-related target genes: ANXA1, DFFA and PDCD4 expression in gastrointestinal cancer patients: A pilot study

PubMed Central

Toraih, Eman A.; Ibrahiem, Afaf; Abdeldayem, Hala; Mohamed, Amany O.; Abdel-Daim, Mohamed M.

2017-01-01

Previous reports have suggested the significant association of miRNAs aberrant expression with tumor initiation, progression and metastasis in cancer, including gastrointestinal (GI) cancers. The current preliminary study aimed to evaluate the relative expression levels of miR-196a2 and three of its selected apoptosis-related targets; ANXA1, DFFA and PDCD4 in a sample of GI cancer patients. Quantitative real-time PCR for miR-196a2 and its selected mRNA targets, as well as immunohistochemical assay for annexin A1 protein expression were detected in 58 tissues with different GI cancer samples. In addition, correlation with the clinicopathological features and in silico network analysis of the selected molecular markers were analyzed. Stratified analyses by cancer site revealed elevated levels of miR-196a2 and low expression of the selected target genes. Annexin protein expression was positively correlated with its gene expression profile. In colorectal cancer, miR-196a over-expression was negatively correlated with annexin A1 protein expression (r = -0.738, p < 0.001), and both were indicators of unfavorable prognosis in terms of poor differentiation, larger tumor size, and advanced clinical stage. Taken together, aberrant expression of miR-196a2 and the selected apoptosis-related biomarkers might be involved in GI cancer development and progression and could have potential diagnostic and prognostic roles in these types of cancer; particularly colorectal cancer, provided the results experimentally validated and confirmed in larger multi-center studies. PMID:29091952

A Piloted Simulator Evaluation of Transport Aircraft Rudder Pedal Force/Feel Characteristics

NASA Technical Reports Server (NTRS)

Stewart, Eric C.

2008-01-01

A piloted simulation study has been conducted in a fixed-base research simulator to assess the directional handling qualities for various rudder pedal feel characteristics for commercial transport airplanes. That is, the effects of static pedal force at maximum pedal travel, breakout force, and maximum pedal travel on handling qualities were studied. An artificial maneuver with a severe lateral wind shear and requiring runway tracking at an altitude of 50 feet in a crosswind was used to fully exercise the rudder pedals. Twelve active airline pilots voluntarily participated in the study and flew approximately 500 maneuvers. The pilots rated the maneuver performance with various rudder pedal feel characteristics using the Cooper- Harper rating scale. The test matrix had 15 unique combinations of the 3 static pedal feel characteristics. A 10-term, second-order equation for the Cooper-Harper pilot rating as a function of the 3 independent pedal feel parameters was fit to the data. The test matrix utilized a Central Composite Design that is very efficient for fitting an equation of this form. The equation was used to produce contour plots of constant pilot ratings as a function of two of the parameters with the third parameter held constant. These contour plots showed regions of good handling qualities as well as regions of degraded handling qualities. In addition, a numerical equation solver was used to predict the optimum parameter values (those with the lowest pilot rating). Quantitative pilot performance data were also analyzed. This analysis found that the peak values of the cross power spectra of the pedal force and heading angle could be used to quantify the tendency toward directional pilot induced oscillations (PIO). Larger peak values of the cross power spectra were correlated with larger (degraded) Cooper-Harper pilot ratings. Thus, the subjective data (Cooper-Harper pilot ratings) were consistent with the objective data (peak values of the cross power spectra).

Visual/motion cue mismatch in a coordinated roll maneuver

NASA Technical Reports Server (NTRS)

Shirachi, D. K.; Shirley, R. S.

1981-01-01

The effects of bandwidth differences between visual and motion cueing systems on pilot performance for a coordinated roll task were investigated. Visual and motion cue configurations which were acceptable and the effects of reduced motion cue scaling on pilot performance were studied to determine the scale reduction threshold for which pilot performance was significantly different from full scale pilot performance. It is concluded that: (1) the presence or absence of high frequency error information in the visual and/or motion display systems significantly affects pilot performance; and (2) the attenuation of motion scaling while maintaining other display dynamic characteristics constant, affects pilot performance.

Techniques for Improving Pilot Recovery from System Failures

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.

2001-01-01

This project examined the application of intelligent cockpit systems to aid air transport pilots at the tasks of reacting to in-flight system failures and of planning and then following a safe four dimensional trajectory to the runway threshold during emergencies. Two studies were conducted. The first examined pilot performance with a prototype awareness/alerting system in reacting to on-board system failures. In a full-motion, high-fidelity simulator, Army helicopter pilots were asked to fly a mission during which, without warning or briefing, 14 different failures were triggered at random times. Results suggest that the amount of information pilots require from such diagnostic systems is strongly dependent on their training; for failures they are commonly trained to react to with a procedural response, they needed only an indication of which failure to follow, while for 'un-trained' failures, they benefited from more intelligent and informative systems. Pilots were also found to over-rely on the system in conditions were it provided false or mis-leading information. In the second study, a proof-of-concept system was designed suitable for helping pilots replan their flights in emergency situations for quick, safe trajectory generation. This system is described in this report, including: the use of embedded fast-time simulation to predict the trajectory defined by a series of discrete actions; the models of aircraft and pilot dynamics required by the system; and the pilot interface. Then, results of a flight simulator evaluation with airline pilots are detailed. In 6 of 72 simulator runs, pilots were not able to establish a stable flight path on localizer and glideslope, suggesting a need for cockpit aids. However, results also suggest that, to be operationally feasible, such an aid must be capable of suggesting safe trajectories to the pilot; an aid that only verified plans entered by the pilot was found to have significantly detrimental effects on performance and pilot workload. Results also highlight that the trajectories suggested by the aid must capture the context of the emergency; for example, in some emergencies pilots were willing to violate flight envelope limits to reduce time in flight - in other emergencies the opposite was found.

LAM Pilot Study with Imatinib Mesylate (LAMP-1)

DTIC Science & Technology

2015-10-01

AD______________ AWARD NUMBER: W81XWH-14-1-0132 TITLE: LAM Pilot Study with Imatinib Mesylate (LAMP-1) PRINCIPAL INVESTIGATOR: Charlie...AND SUBTITLE LAM Pilot Study with Imatinib Mesylate (LAMP-1) 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0132 5c. PROGRAM ELEMENT...designed to generate short-term safety and efficacy data regarding imatinib mesylate (imatinib) in the treatment of Lymphangioleiomyomatosis ( LAM

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

PubMed Central

Braga, D; Barcella, M; D’Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, MH; DeLano, FA; Baselli, G; Schmid-Schönbein, GW; Kistler, EB; Aletti, F

2017-01-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger’s shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients. PMID:28661205

Pilot Domain Task Experience in Night Fatal Helicopter Emergency Medical Service Accidents.

PubMed

Aherne, Bryan B; Zhang, Chrystal; Newman, David G

2016-06-01

In the United States, accident and fatality rates in helicopter emergency medical service (HEMS) operations increase significantly under nighttime environmentally hazardous operational conditions. Other studies have found pilots' total flight hours unrelated to HEMS accident outcomes. Many factors affect pilots' decision making, including their experience. This study seeks to investigate whether pilot domain task experience (DTE) in HEMS plays a role against likelihood of accidents at night when hazardous operational conditions are entered. There were 32 flights with single pilot nighttime fatal HEMS accidents between 1995 and 2013 with findings of controlled flight into terrain (CFIT) and loss of control (LCTRL) due to spatial disorientation (SD) identified. The HEMS DTE of the pilots were compared with industry survey data. Of the pilots, 56% had ≤2 yr of HEMS experience and 9% had >10 yr of HEMS experience. There were 21 (66%) accidents that occurred in non-visual flight rules (VFR) conditions despite all flights being required to be conducted under VFR. There was a statistically significant increase in accident rates in pilots with <2 and <4 yr HEMS DTE and a statistically significant decrease in accident rates in pilots with >10 yr HEMS DTE. HEMS DTE plays a preventive role against the likelihood of a night operational accident. Pilots with limited HEMS DTE are more likely to make a poor assessment of hazardous conditions at night, and this will place HEMS flight crew at high risk in the VFR night domain.

Variations Among Pilots from Different Flight Operations in Party Line Information Requirements for Situation Awareness

NASA Technical Reports Server (NTRS)

Pritchett, Amy; Hansman, John

1997-01-01

Current air traffic control communications use shared VHF voice frequencies from which pilots can obtain 'party line' information (PLI) by overhearing communications addressed to other aircraft. Previous studies have shown that pilots perceive PLI to be important. There is concern that some critical PLI may be lost in the proposed data link environment, where communications will be discretely addressed. Different types of flight operations will be equipped with data link equipment at different times, generating a mixed environment in which some pilots will rely on PLI, while others will receive their information by data link. To research the importance, availability, and accuracy of PLI and to query pilots on the information they feel is necessary for global situation awareness, a survey was distributed to pilots. The pilots were selected from four flight operation groups to study the variations in PLI requirements in the mixed data link environment. Pilots perceived PLI to be important overall, with specific traffic and weather information elements identified as critical. Most PLI elements followed a pattern of higher perceived importance during terminal area operations, final approach, and landing. Pilots from the different flight operation groups identified some elements as particularly important. In a free-response question designed to identify the information requirements for global situation awareness, pilots frequently indicated a need for traffic and weather information. The results of this survey reveal specific concerns to be addressed when implementing data link communications.

Assessment of sleepiness, fatigue, and depression among Gulf Cooperation Council commercial airline pilots.

PubMed

Aljurf, Tareq M; Olaish, Awad H; BaHammam, Ahmed S

2018-05-01

No studies have assessed the prevalence of fatigue, depression, sleepiness, and the risk of obstructive sleep apnea (OSA) among commercial airlines pilots in the Gulf Cooperation Council (GCC). This was a quantitative cross-sectional study conducted among pilots who were on active duty and had flown during the past 6 months for one of three commercial airline companies. We included participants with age between 20 and 65 years. Data were collected using a predesigned electronic questionnaire composed of questions related to demographic information in addition to the Fatigue Severity Scale (FSS), the Berlin Questionnaire, the Epworth Sleepiness Scale (ESS), and the Hospital Anxiety and Depression Scale (HADS). The study included 328 pilots with a mean age ± standard deviation of 41.4 ± 9.7 years. Overall, 224 (68.3%) pilots had an FSS score ≥ 36 indicating severe fatigue and 221 (67.4%) reported making mistakes in the cockpit because of fatigue. One hundred and twelve (34.1%) pilots had an ESS score ≥ 10 indicating excessive daytime sleepiness and 148 (45.1%) reported falling asleep at the controls at least once without previously agreeing with their colleagues. One hundred and thirteen (34.5%) pilots had an abnormal HADS depression score (≥ 8), and 96 (29.3%) pilots were at high risk for OSA requiring further assessment. Fatigue, sleepiness, risk of OSA, and depression are prevalent among GCC commercial airline pilots. Regular assessment by aviation authorities is needed to detect and treat these medical problems.

The Salivary Microbiome in Polycystic Ovary Syndrome (PCOS) and Its Association with Disease-Related Parameters: A Pilot Study.

PubMed

Lindheim, Lisa; Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Pieber, Thomas R; Gorkiewicz, Gregor; Obermayer-Pietsch, Barbara

2016-01-01

Polycystic ovary syndrome (PCOS) is a common female endocrine condition of unclear etiology characterized by hyperandrogenism, oligo/amenorrhoea, and polycystic ovarian morphology. PCOS is often complicated by infertility, overweight/obesity, insulin resistance, and low-grade inflammation. The gut microbiome is known to contribute to several of these conditions. Recently, an association between stool and saliva microbiome community profiles was shown, making saliva a possible convenient, non-invasive sample type for detecting gut microbiome changes in systemic disease. In this study, we describe the saliva microbiome of PCOS patients and the association of microbiome features with PCOS-related parameters. 16S rRNA gene amplicon sequencing was performed on saliva samples from 24 PCOS patients and 20 healthy controls. Data processing and microbiome analyses were conducted in mothur and QIIME. All study subjects were characterized regarding reproductive, metabolic, and inflammatory parameters. PCOS patients showed a decrease in bacteria from the phylum Actinobacteria and a borderline significant shift in bacterial community composition in unweighted UniFrac analysis. No differences between patients and controls were found in alpha diversity, weighted UniFrac analysis, or on other taxonomic levels. We found no association of saliva alpha diversity, beta diversity, or taxonomic composition with serum testosterone, oligo/amenorrhoea, overweight, insulin resistance, inflammatory markers, age, or diet. In this pilot study, patients with PCOS showed a reduced salivary relative abundance of Actinobacteria. Reproductive and metabolic components of the syndrome were not associated with saliva microbiome parameters, indicating that the majority of between-subject variation in saliva microbiome profiles remains to be explained.

Diversity of Cervical Microbiota in Asymptomatic Chlamydia trachomatis Genital Infection: A Pilot Study

PubMed Central

Filardo, Simone; Di Pietro, Marisa; Porpora, Maria G.; Recine, Nadia; Farcomeni, Alessio; Latino, Maria A.; Sessa, Rosa

2017-01-01

Chlamydia trachomatis genital infection continues to be an important public health problem worldwide due to its increasing incidence. C. trachomatis infection can lead to severe sequelae, such as pelvic inflammatory disease, obstructive infertility, and preterm birth. Recently, it has been suggested that the cervico-vaginal microbiota may be an important defense factor toward C. trachomatis infection as well as the development of chronic sequelae. Therefore, the investigation of microbial profiles associated to chlamydial infection is of the utmost importance. Here we present a pilot study aiming to characterize, through the metagenomic analysis of sequenced 16s rRNA gene amplicons, the cervical microbiota from reproductive age women positive to C. trachomatis infection. The main finding of our study showed a marked increase in bacterial diversity in asymptomatic C. trachomatis positive women as compared to healthy controls in terms of Shannon's diversity and Shannon's evenness (P = 0.031 and P = 0.026, respectively). More importantly, the cervical microbiota from C. trachomatis positive women and from healthy controls significantly separated into two clusters in the weighted UniFrac analysis (P = 0.0027), suggesting that differences between the two groups depended entirely on the relative abundance of bacterial taxa rather than on the types of bacterial taxa present. Furthermore, C. trachomatis positive women showed an overall decrease in Lactobacillus spp. and an increase in anaerobes. These findings are part of an ongoing larger epidemiological study that will evaluate the potential role of distinct bacterial communities of the cervical microbiota in C. trachomatis infection. PMID:28770172

Impact characteristics for high-pressure large-flow water-based emulsion pilot operated check valve reverse opening

NASA Astrophysics Data System (ADS)

Liu, Lei; Huang, Chuanhui; Yu, Ping; Zhang, Lei

2017-10-01

To improve the dynamic characteristics and cavitation characteristics of large-flow pilot operated check valve, consider the pilot poppet as the research object, analyses working principle and design three different kinds of pilot poppets. The vibration characteristics and impact characteristics are analyzed. The simulation model is established through flow field simulation software. The cavitation characteristics of large-flow pilot operated check valve are studied and discussed. On this basis, high-pressure large-flow impact experimental system is used for impact experiment, and the cavitation index is discussed. Then optimal structure is obtained. Simulation results indicate that the increase of pilot poppet half cone angle can effectively reduce the cavitation area, reducing the generation of cavitation. Experimental results show that the pressure impact is not decreasing with increasing of pilot poppet half cone angle in process of unloading, but the unloading capacity, response speed and pilot poppet half cone angle are positively correlated. The impact characteristics of 60° pilot poppet, and its cavitation index is lesser, which indicates 60° pilot poppet is the optimal structure, with the theory results are basically identical.

A simulation evaluation of a pilot interface with an automatic terminal approach system

NASA Technical Reports Server (NTRS)

Hinton, David A.

1987-01-01

The pilot-machine interface with cockpit automation is a critical factor in achieving the benefits of automation and reducing pilot blunders. To improve this interface, an automatic terminal approach system (ATAS) was conceived that can automatically fly a published instrument approach by using stored instrument approach data to automatically tune airplane radios and control an airplane autopilot and autothrottle. The emphasis in the ATAS concept is a reduction in pilot blunders and work load by improving the pilot-automation interface. A research prototype of an ATAS was developed and installed in the Langley General Aviation Simulator. A piloted simulation study of the ATAS concept showed fewer pilot blunders, but no significant change in work load, when compared with a baseline heading-select autopilot mode. With the baseline autopilot, pilot blunders tended to involve loss of navigational situational awareness or instrument misinterpretation. With the ATAS, pilot blunders tended to involve a lack of awareness of the current ATAS mode state or deficiencies in the pilots' mental model of how the system operated. The ATAS display provided adequate approach status data to maintain situational awareness.

Symptoms of fatigue and coping strategies in maritime pilotage.

PubMed

Chambers, Timothy P; Main, Luana C

2015-01-01

Little is known regarding the symptoms of fatigue that maritime pilots experience during shift work. Moreover, the strategies these individuals use to cope with the onset of fatigue are also unknown. The current study explored the symptoms of fatigue and coping strategies experienced by maritime pilots when on-shift. Fifty maritime pilots were recruited via an advertisement in the national association's quarterly newsletter (Mage = 51.42; SD = 9.81). Participants responded to a modified version of the questionnaire used with aviation pilots that assessed overall fatigue, and the symptoms pilots associated with fatigue on duty. Methods pilots used to cope with fatigue before shift and when on the bridge were also assessed. There were significant effects for pilot vitality on 4 categories of fatigue: cognitive dysfunction; emotional disturbance; mean physical effects; and sleepiness. There were no significant effects for vitality on any of the self-reported coping strategy factors. The findings indicated that maritime pilots experience a variety of physical, behavioural, and cognitive fatigue symptoms when on shift. Some of these symptoms are similar to those reported by aviation pilots. However, unlike aviation pilots, maritime pilots reported utilising self-sufficient coping strategies to deal with the experience of fatigue.

The effects of pilot stress factors on handling quality assessments during US/German helicopter agility flight tests

NASA Technical Reports Server (NTRS)

Pausder, H.-J.; Gerdes, R. M.

1982-01-01

Flight tests were conducted with two helicopters to study and evaluate the effects of helicopter characteristics and pilot and task demands on performance in nap-of-the-earth flight. Different, low-level slalom courses were set up and were flown by three pilots with different levels of flight experience. A pilot rating questionnaire was used to obtain redundant information and to gain more insight into factors that influence pilot ratings. The flight test setups and procedures are described, and the pilot ratings are summarized and interpreted in close connection with the analyzed test data. Pilot stress is discussed. The influence of demands on the pilot, of the helicopter characteristics, and of other stress factors are outlined with particular emphasis on how these factors affect handling-qualities assessment. Previously announced in STAR as N83-13114

Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

PubMed Central

2013-01-01

Introduction Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD. Methods Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 106 cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 106 cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 106 aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction. Results Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3. Conclusions Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters. PMID:23632128

Development and pilot testing of daily Interactive Voice Response (IVR) calls to support antiretroviral adherence in India: A mixed-methods pilot study

PubMed Central

Swendeman, Dallas; Jana, Smarajit; Ray, Protim; Mindry, Deborah; Das, Madhushree; Bhakta, Bhumi

2015-01-01

This two-phase pilot study aimed to design, pilot, and refine an automated Interactive Voice Response (IVR) intervention to support antiretroviral adherence for people living with HIV (PLH), in Kolkata, India. Mixed-methods formative research included a community advisory board (CAB) for IVR message development, one-month pre-post pilot, post-pilot focus groups, and further message development. Two IVR calls are made daily, timed to patients’ dosing schedules, with brief messages (<1-minute) on strategies for self-management of three domains: medical (adherence, symptoms, co-infections), mental health (social support, stress, positive cognitions), and nutrition and hygiene (per PLH preferences). Three ART appointment reminders are also sent each month. One-month pilot results (n=46, 80% women, 60% sex workers) found significant increases in self-reported ART adherence, both within past three days (p=0.05) and time since missed last dose (p=0.015). Depression was common. Messaging content and assessment domains were expanded for testing in a randomized trial is currently underway. PMID:25638037

Development and Pilot Testing of Daily Interactive Voice Response (IVR) Calls to Support Antiretroviral Adherence in India: A Mixed-Methods Pilot Study.

PubMed

Swendeman, Dallas; Jana, Smarajit; Ray, Protim; Mindry, Deborah; Das, Madhushree; Bhakta, Bhumi

2015-06-01

This two-phase pilot study aimed to design, pilot, and refine an automated interactive voice response (IVR) intervention to support antiretroviral adherence for people living with HIV (PLH), in Kolkata, India. Mixed-methods formative research included a community advisory board for IVR message development, 1-month pre-post pilot, post-pilot focus groups, and further message development. Two IVR calls are made daily, timed to patients' dosing schedules, with brief messages (<1-min) on strategies for self-management of three domains: medical (adherence, symptoms, co-infections), mental health (social support, stress, positive cognitions), and nutrition and hygiene (per PLH preferences). Three ART appointment reminders are also sent each month. One-month pilot results (n = 46, 80 % women, 60 % sex workers) found significant increases in self-reported ART adherence, both within past three days (p = 0.05) and time since missed last dose (p = 0.015). Depression was common. Messaging content and assessment domains were expanded for testing in a randomized trial currently underway.

Understanding Teachers' Pedagogical Knowledge: Report on an International Pilot Study. OECD Education Working Papers, No. 159

ERIC Educational Resources Information Center

Sonmark, Kristina; Révai, Nóra; Gottschalk, Francesca; Deligiannidi, Karolina; Burns, Tracey

2017-01-01

What is the nature of teachers' pedagogical knowledge? The Innovative Teaching for Effective Learning Teacher Knowledge Survey (ITEL TKS) set out to answer this question in a pilot study that ran in five countries: Estonia, Greece, Hungary Israel, and the Slovak Republic. Using convenience samples, the pilot assessed the pedagogical knowledge base…

2012 Preschool Pilot Study of PBS KIDS Transmedia Mathematics Content: A Report to the CPB-PBS "Ready to Learn Initiative"

ERIC Educational Resources Information Center

Pasnik, Shelley; Llorente, Carlin

2012-01-01

The 2012 Preschool Pilot Study of PBS KIDS Transmedia Mathematics Content (Preschool Pilot) is an important part of the authors' multiyear "Ready To Learn" (RTL) summative evaluation initiative. Through this initiative funded by the Corporation for Public Broadcasting (CPB) and Public Broadcasting Service (PBS), it was the responsibility…

A Pilot Systematic Review and Meta-Analysis on the Effectiveness of Problem Based Learning.

ERIC Educational Resources Information Center

Newman, Mark

This paper reports on the development and piloting of a systematic review and meta analysis of research on the effectiveness of problem based learning (PBL). The systematic review protocol was pilot tested with a sample of studies cited as providing "evidence" about the effectiveness of PBL. From the 5 studies mentioned in the sample of reviews,…

Pilots using selective serotonin reuptake inhibitors compared to other fatally injured pilots.

PubMed

Rogers, Paul; Hileman, Christy; Salazar, Guillermo; Cliburn, Kacey; Paskoff, Lawrence; Hathaway, William; Gildea, Kevin; Tejera Villalaz, Victor Hugo

2017-10-01

Selective Serotonin Reuptake Inhibitors (SSRI) were a disqualifying medication for U.S. civil pilots before April 5, 2010. After this date, a Federal Aviation Administration policy was created that allowed airmen, on select SSRIs, a pathway to hold a valid medical certificate. The purpose of this study was to provide a detailed look at SSRIs in the U.S. pilot population since the inception of this new policy. We examined the toxicology results from fatally injured airmen in addition to outcomes concerning pilots who are participating in the program. This study examined data from the Civil Aerospace Medical Institute's Bioaeronautical Sciences Research Laboratory in conjunction with the Medical Analysis Tracking Registry and the Document Imaging and Workflow System. A count-based regression model quantified the relationships between positive SSRI findings with additional factors of interest. These factors included pilot rating, ethanol, and first generation antihistamines. There were 1484 fatally injured airmen over the six year study period, of which 44-tested positive for an SSRI. First-generation antihistamines were statistically associated with positive findings of SSRIs. Published by Elsevier Ltd.

Investigating gender differences under conditions of fatigue in a simulated high G aerial combat environment.

PubMed

Chelette, T L

1997-06-01

Advances in technology have equipped high-performance combat aircraft with the capability of delivering higher and higher sustained acceleration or G-forces on the pilots flying them. While the physiological effects of increased g-forces on the human body continue to be investigated, studies examining the effects of acceleration on the cognitive abilities of high-performance aircraft pilots remain sparse. Additionally, as higher technology is making its way into the cockpit, so are female pilots. With even fewer studies investigating women's physiological and cognitive tolerances to the stressors in the high-performance cockpit and flight environment, Dr. Chelette's study aimed to investigate these issues. Examining pilot workload, flight task abilities, and the effects of sleeplessness on both male and female pilots, Dr. Chelette's results revealed findings that will make their way into the high-performance cockpit of the future.

Alcohol rehabilitation of airline pilots.

DOT National Transportation Integrated Search

1985-10-01

This study involves a survey of medical records for over 500 airline pilots who have been medically certified by the FAA after a diagnosis of alcoholism. The program demonstrates an 85% rate of success since 1976. If a pilot experiences a relapse, he...

Service Quality, User Satisfaction and Net-Benefits' Effect on e-School Success: The Case of NEPAD's e-School Pilot in Kenya

ERIC Educational Resources Information Center

Nyagowa, Hesbon O.; Ocholla, Dennis N.; Mutula, Stephen M.

2013-01-01

This study was conducted to determine the effect of a set of dimensions on e-School success in a cross-sectional study of NEPAD's e-School pilot in Kenya. All of the six e-Schools participating in the NEPAD's e-School pilot in Kenya were selected. The study used survey methodology. Students and teachers in those schools formed the study…

The effects of workload on respiratory variables in simulated flight: a preliminary study.

PubMed

Karavidas, Maria Katsamanis; Lehrer, Paul M; Lu, Shou-En; Vaschillo, Evgeny; Vaschillo, Bronya; Cheng, Andrew

2010-04-01

In this pilot study, we investigated respiratory activity and end-tidal carbon dioxide (P(et)CO(2)) during exposure to varying levels of work load in a simulated flight environment. Seven pilots (age: 34-60) participated in a one-session test on the Boeing 737-800 simulator. Physiological data were collected while pilots wore an ambulatory multi-channel recording device. Respiratory variables, including inductance plethysmography (respiratory pattern) and pressure of end-tidal carbon dioxide (P(et)CO(2)), were collected demonstrating change in CO(2) levels proportional to changes in flight task workload. Pilots performed a set of simulation flight tasks. Pilot performance was rated for each task by a test pilot; and self-report of workload was taken using the NASA-TLX scale. Mixed model analysis revealed that respiration rate and minute ventilation are significantly associated with workload levels and evaluator scores controlling for "vanilla baseline" condition. Hypocapnia exclusively occurred in tasks where pilots performed more poorly. This study was designed as a preliminary investigation in order to develop a psychophysiological assessment methodology, rather than to offer conclusive findings. The results show that the respiratory system is very reactive to high workload conditions in aviation and suggest that hypocapnia may pose a flight safety risk under some circumstances. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of a Data-Linked Weather Information Display and Effects on Pilot Navigation Decision Making in a Piloted Simulation Study

NASA Technical Reports Server (NTRS)

Yuchnovicz, Daniel E.; Novacek, Paul F.; Burgess, Malcolm A.; Heck, Michael L.; Stokes, Alan F.

2001-01-01

This study provides recommendations to the FAA and to prospective manufacturers based on an exploration of the effects of data link weather displays upon pilot decision performance. An experiment was conducted with twenty-four current instrument rated pilots who were divided into two equal groups and presented with a challenging but realistic flight scenario involving weather containing significant embedded convective activity. All flights were flown in a full-mission simulation facility within instrument meteorological conditions. The inflight weather display depicted NexRad images, graphical METARs and textual METARs. The objective was to investigate the potential for misuse of a weather display, and incorporate recommendations for the design and use of these displays. The primary conclusion of the study found that the inflight weather display did not improve weather avoidance decision making. Some of the reasons to support this finding include: the pilot's inability to easily perceive their proximity to the storms, increased workload and difficulty in deciphering METAR textual data. The compelling nature of a graphical weather display caused many pilots to reduce their reliance on corroborating weather information from other sources. Minor changes to the weather display could improve the ability of a pilot to make better decisions on hazard avoidance.

Impact of a daily 10-minute strength and flexibility program in a manufacturing plant.

PubMed

Pronk, S J; Pronk, N P; Sisco, A; Ingalls, D S; Ochoa, C

1995-01-01

In summary, employees' flexibility and mood showed modest improvements following the implementation of a plant-wide, 10-minute, daily flexibility and strength program. The initial six-week pilot study, administered prior to the plant-wide program implementation, successfully assessed program feasibility, assessed the efficiency of program implementation, identified administrative and logistical concerns, and generated pilot data needed to secure managerial support. Despite the noted significant increases in grip strength in the pilot study, no increases were observed following the six months of plant-wide implementation. This may be related to the differences in low average pretest grip strength for the pilot study compared to the higher scores for the main study population. The pilot study subjects may have received a sufficient exercise stimulus to increase grip strength over the course of six weeks. In contrast, this may not have been the case for the main study subjects due to their higher initial mean grip strength. An increased number of exercises designed to directly impact grip strength may be needed to improve this parameter.

Review of performance, medical, and operational data on pilot aging issues

NASA Technical Reports Server (NTRS)

Stoklosa, J. H.

1992-01-01

An extensive review of the literature and studies relating to performance, medical, operational, and legal data regarding pilot aging issues was performed in order to determine what evidence there is, if any, to support mandatory pilot retirement. Popular misconceptions about aging, including the failure to distinguish between the normal aging process and disease processes that occur more frequently in older individuals, continue to contribute to much of the misunderstanding and controversy that surround this issue. Results: Review of medical data related to the pilot aging issue indicate that recent improvement in medical diagnostics and treatment technology have made it possible to identify to a high degree individuals who are at risk for developing sudden incapacitating illness and for treating those with disqualifying medical conditions. Performance studies revealed that after controlling for the presence of disease states, older pilots are able to perform as well as younger pilots on many performance tasks. Review of accident data showed that older, healthy pilots do not have higher accident rates than younger pilots, and indeeed, evidence suggests that older pilots have an advantage in the cockpit due to higher experience levels. The Man-Machine-Mission-Environment interface of factors can be managed through structured, supervised, and enhanced operations, maintenance, flight reviews, and safety procedures in order to ensure safe and productive operations by reducing the margin of error and by increasing the margin of safety. Conclusions: There is no evidence indicating any specific age as an arbitrary cut-off point for pilots to perform their fight duties. A combination of regular medical screening, performance evaluation, enhanced operational maintenance, and safety procedures can most effectively ensure a safe pilot population than can a mandatory retirement policy based on arbitrary age restrictions.

A pilot study to evaluate mindfulness as a strategy to improve inpatient nurse and patient experiences.

PubMed

Horner, Janice K; Piercy, Brigit S; Eure, Lois; Woodard, Elizabeth K

2014-08-01

The purpose of the Mindful Nursing Pilot Study was to explore the impact of mindfulness training for nursing staff on levels of mindfulness, compassion satisfaction, burnout, and stress. In addition, the study attempted to determine the impact on patient satisfaction scores. The pilot was designed as a quasi-experimental research study; staff on one nursing unit participated in the 10-week mindfulness training program while another, similar nursing unit served as the control group. The intervention group showed improvement in levels of mindfulness, burnout, and stress as well as patient satisfaction while the control group remained largely the same. This pilot provides encouraging results that suggest that replication and further study of mindfulness in the workplace would be beneficial. Copyright © 2014 Elsevier Inc. All rights reserved.

The epilepsy phenome/genome project.

PubMed

Abou-Khalil, Bassel; Alldredge, Brian; Bautista, Jocelyn; Berkovic, Sam; Bluvstein, Judith; Boro, Alex; Cascino, Gregory; Consalvo, Damian; Cristofaro, Sabrina; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael; Fahlstrom, Robyn; Fiol, Miguel; Fountain, Nathan; Fox, Kristen; French, Jacqueline; Freyer Karn, Catharine; Friedman, Daniel; Geller, Eric; Glauser, Tracy; Glynn, Simon; Haas, Kevin; Haut, Sheryl; Hayward, Jean; Helmers, Sandra; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi; Knowlton, Robert; Kossoff, Eric; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel; McGuire, Shannon; Motika, Paul; Nesbitt, Gerard; Novotny, Edward; Ottman, Ruth; Paolicchi, Juliann; Parent, Jack; Park, Kristen; Poduri, Annapurna; Risch, Neil; Sadleir, Lynette; Scheffer, Ingrid; Shellhaas, Renee; Sherr, Elliott; Shih, Jerry J; Shinnar, Shlomo; Singh, Rani; Sirven, Joseph; Smith, Michael; Sullivan, Joe; Thio, Liu Lin; Venkat, Anu; Vining, Eileen; von Allmen, Gretchen; Weisenberg, Judith; Widdess-Walsh, Peter; Winawer, Melodie

2013-08-01

Epilepsy is a common neurological disorder that affects approximately 50 million people worldwide. Both risk of epilepsy and response to treatment partly depend on genetic factors, and gene identification is a promising approach to target new prediction, treatment, and prevention strategies. However, despite significant progress in the identification of genes causing epilepsy in families with a Mendelian inheritance pattern, there is relatively little known about the genetic factors responsible for common forms of epilepsy and so-called epileptic encephalopathies. Study design The Epilepsy Phenome/Genome Project (EPGP) is a multi-institutional, retrospective phenotype-genotype study designed to gather and analyze detailed phenotypic information and DNA samples on 5250 participants, including probands with specific forms of epilepsy and, in a subset, parents of probands who do not have epilepsy. EPGP is being executed in four phases: study initiation, pilot, study expansion/establishment, and close-out. This article discusses a number of key challenges and solutions encountered during the first three phases of the project, including those related to (1) study initiation and management, (2) recruitment and phenotyping, and (3) data validation. The study has now enrolled 4223 participants. EPGP has demonstrated the value of organizing a large network into cores with specific roles, managed by a strong Administrative Core that utilizes frequent communication and a collaborative model with tools such as study timelines and performance-payment models. The study also highlights the critical importance of an effective informatics system, highly structured recruitment methods, and expert data review.

A Methodology for Evaluating the Fidelity of Ground-Based Flight Simulators

NASA Technical Reports Server (NTRS)

Zeyada, Y.; Hess, R. A.

1999-01-01

An analytical and experimental investigation was undertaken to model the manner in which pilots perceive and utilize visual, proprioceptive, and vestibular cues in a ground-based flight simulator. The study was part of a larger research effort which has the creation of a methodology for determining flight simulator fidelity requirements as its ultimate goal. The study utilized a closed-loop feedback structure of the pilot/simulator system which included the pilot, the cockpit inceptor, the dynamics of the simulated vehicle and the motion system. With the exception of time delays which accrued in visual scene production in the simulator, visual scene effects were not included in this study. The NASA Ames Vertical Motion Simulator was used in a simple, single-degree of freedom rotorcraft bob-up/down maneuver. Pilot/vehicle analysis and fuzzy-inference identification were employed to study the changes in fidelity which occurred as the characteristics of the motion system were varied over five configurations i The data from three of the five pilots that participated in the experimental study were analyzed in the fuzzy inference identification. Results indicate that both the analytical pilot/vehicle analysis and the fuzzyinference identification can be used to reflect changes in simulator fidelity for the task examined.

A Methodology for Evaluating the Fidelity of Ground-Based Flight Simulators

NASA Technical Reports Server (NTRS)

Zeyada, Y.; Hess, R. A.

1999-01-01

An analytical and experimental investigation was undertaken to model the manner in which pilots perceive and utilize visual, proprioceptive, and vestibular cues in a ground-based flight simulator. The study was part of a larger research effort which has the creation of a methodology for determining flight simulator fidelity requirements as its ultimate goal. The study utilized a closed-loop feedback structure of the pilot/simulator system which included the pilot, the cockpit inceptor, the dynamics of the simulated vehicle and the motion system. With the exception of time delays which accrued in visual scene production in the simulator, visual scene effects were not included in this study. The NASA Ames Vertical Motion Simulator was used in a simple, single-degree of freedom rotorcraft bob-up/down maneuver. Pilot/vehicle analysis and fuzzy-inference identification were employed to study the changes in fidelity which occurred as the characteristics of the motion system were varied over five configurations. The data from three of the five pilots that participated in the experimental study were analyzed in the fuzzy-inference identification. Results indicate that both the analytical pilot/vehicle analysis and the fuzzy-inference identification can be used to reflect changes in simulator fidelity for the task examined.

Influence of Cultural, Organizational, and Automation Capability on Human Automation Trust: A Case Study of Auto-GCAS Experimental Test Pilots

NASA Technical Reports Server (NTRS)

Koltai, Kolina; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Cacanindin, Artemio; Johnson, Walter; Lyons, Joseph

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Force's newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the case's politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerability/ high risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

Occupational exposure to noise and hypertension in pilots.

PubMed

Tomei, Francesco; De Sio, Simone; Tomao, Enrico; Anzelmo, Vincenza; Baccolo, Tiziana Paola; Ciarrocca, Manuela; Cherubini, Emilia; Valentini, Valentina; Capozzella, Assunta; Rosati, Maria Valeria

2005-04-01

The role of occupational exposure to noise as a hypertension risk factor has not been established sufficiently. The aim of the study is to evaluate whether chronic exposure to different levels of noise in two groups of pilots, operating with two types of aircraft, could be a risk for hypertension, what relevance the parameters (intensity, duration and type) of exposure can have and, lastly, whether there are any links between hearing impairment and hypertension. After excluding pilots with confounding factors, a study was made of 77 male pilots of turboprop planes (group A) and 224 male pilots of jet aircraft (group B), matched by age and working life. Blood pressure (supine and standing positions) and heart rate were measured. Electrocardiogram, stress tests on a cycle ergometer, sound-level measurement and audiometric tests were also done. Pilots of group A were exposed to Leq of 93 dBA while pilots of group B were exposed to the Leq of 79 dBA. Significant results in group A compared to group B were found between heart rate, blood pressure, drop in blood pressure, parameters (intensity, duration and type) of exposure to noise and between hearing damage and hypertension. The findings suggest that chronic exposure to noise is a risk factor for blood hypertension in pilots exposed to high noise levels, and that the drop in blood pressure may be a sign of more sensitive effect of noise on blood pressure, according to other studies in literature.

Occupational Stress and Hypertension among Railway Loco Pilots and Section Controllers

PubMed Central

Jayakumar, Devasigamoney

2017-01-01

Introduction: A cross-sectional study on occupational stress was conducted on loco pilots in 2008, in view of loco pilots being one of the high strain jobs in Indian Railways. Subsequently, a comparative cross-sectional study on occupational stress was conducted among section controllers in 2011, which is another high strain job of Indian Railways. Objective: The studies were conducted to analyze and compare occupational stress and hypertension. Setting and Design: A cross-sectional study on occupational stress and hypertension was conducted among 230 loco pilots in 2008, and subsequently, a comparative cross-sectional study was conducted among 82 section controllers in 2011. Materials and Methods: A closed end 24 item questionnaire on occupational stress was administered. Systolic blood pressure above 140 mmHg and diastolic blood pressure above 90 mmHg were considered as hypertension as per the VII Joint National Committee. Chi-square test and t-test were used for testing significance at P < 0.05. Results: The mean stress score was 8.56 in loco pilots and 7.32 in section controllers. The number of loco pilots with more than 12 stress factors was 49 (21.3%) and the number of section controllers with more than 12 stress factors was 7 (8.5%). The number employees with more than 12 stress factors in different categories of loco pilots were 30 (32%) in the goods category, 12 (12%) in the mail/passenger category, and 7 (19%) in the shunter category, and 3 (11%) in the supervisory category and 4 (7%) in the on-board category of section controllers. The prevalence of hypertension in loco pilots was 36.52% (84) and in the section controllers was 53.66% (44). The prevalence of hypertension in the category with more than 12 stress factors was 30.61% (15) in the loco pilots and 28.57% (2) in the section controllers. The prevalence of hypertension in the both the study groups were higher in the older age, with a family history of hypertension, and with a body mass index of more than 25 kg/m2. The mean occupational stress and employees with more than 12 stress factors were higher in the loco pilots group. The goods category of loco pilots had highest stress factors. The prevalence of hypertension was high in the category with risk factors such as older age, family history of hypertension and BMI above 25 kg/m2. PMID:29391744

Cognitive engineering in aerospace application: Pilot interaction with cockpit automation

NASA Technical Reports Server (NTRS)

Sarter, Nadine R.; Woods, David D.

1993-01-01

Because of recent incidents involving glass-cockpit aircraft, there is growing concern with cockpit automation and its potential effects on pilot performance. However, little is known about the nature and causes of problems that arise in pilot-automation interaction. The results of two studies that provide converging, complementary data on pilots' difficulties with understanding and operating one of the core systems of cockpit automation, the Flight Management System (FMS) is reported. A survey asking pilots to describe specific incidents with the FMS and observations of pilots undergoing transition training to a glass cockpit aircraft served as vehicles to gather a corpus on the nature and variety of FMS-related problems. The results of both studies indicate that pilots become proficient in standard FMS operations through ground training and subsequent line experience. But even with considerable line experience, they still have difficulties tracking FMS status and behavior in certain flight contexts, and they show gaps in their understanding of the functional structure of the system. The results suggest that design-related factors such as opaque interfaces contribute to these difficulties which can affect pilots' situation awareness. The results of this research are relevant for both the design of cockpit automation and the development of training curricula specifically tailored to the needs of glass cockpits.

Evaluative Priming in the Pronunciation Task.

PubMed

Klauer, Karl Christoph; Becker, Manuel; Spruyt, Adriaan

2016-01-01

We replicated and extended a study by Spruyt and Hermans (2008) in which picture primes engendered an evaluative-priming effect on the pronunciation of target words. As preliminary steps, we assessed data reproducibility of the original study, conducted Pilot Study I to identify highly semantically related prime-target pairs, reanalyzed the original data excluding such pairs, conducted Pilot Study II to demonstrate that we can replicate traditional associative priming effects in the pronunciation task, and conducted Pilot Study III to generate relatively unrelated sets of prime pictures and target words. The main study comprised three between-participants conditions: (1) a close replication of the original study, (2) the same condition excluding highly related prime-target pairs, and (3) a condition based on the relatively unrelated sets of prime pictures and target words developed in Pilot Study III. There was little evidence for an evaluative priming effect independent of semantic relatedness.

Pilot interaction with cockpit automation 2: An experimental study of pilots' model and awareness of the Flight Management System

NASA Technical Reports Server (NTRS)

Sarter, Nadine B.; Woods, David D.

1994-01-01

Technological developments have made it possible to automate more and more functions on the commercial aviation flight deck and in other dynamic high-consequence domains. This increase in the degrees of freedom in design has shifted questions away from narrow technological feasibility. Many concerned groups, from designers and operators to regulators and researchers, have begun to ask questions about how we should use the possibilities afforded by technology skillfully to support and expand human performance. In this article, we report on an experimental study that addressed these questions by examining pilot interaction with the current generation of flight deck automation. Previous results on pilot-automation interaction derived from pilot surveys, incident reports, and training observations have produced a corpus of features and contexts in which human-machine coordination is likely to break down (e.g., automation surprises). We used these data to design a simulated flight scenario that contained a variety of probes designed to reveal pilots' mental model of one major component of flight deck automation: the Flight Management System (FMS). The events within the scenario were also designed to probe pilots' ability to apply their knowledge and understanding in specific flight contexts and to examine their ability to track the status and behavior of the automated system (mode awareness). Although pilots were able to 'make the system work' in standard situations, the results reveal a variety of latent problems in pilot-FMS interaction that can affect pilot performance in nonnormal time critical situations.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies.

PubMed

Avery, Kerry N L; Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M

2017-02-17

Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or 'progression' criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies

PubMed Central

Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M

2017-01-01

Objectives Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or ‘progression’ criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. PMID:28213598

The Effects of Aviation Weather Information Systems on General Aviation Weather Information Systems on General Pilots' Workload

NASA Technical Reports Server (NTRS)

Scerbo, Mark; Coyne, Joseph; Burt, Jennifer L. (Technical Monitor)

2002-01-01

My work at NASA Langley has focused around Aviation Weather Information CAWING displays. The majority of my time at LYRIC has been spent on the Workload and Relative Position (WaRP) Study. The goal of this project is to determine how an AWIN display at various positions within the cockpit affects pilot performance and workload. The project is being conducted in Languages Cessna 206H research aircraft. During the past year the design of the experiment was finalized and approved. Despite facing several delays the data collection was completed in early February. Alter the completion of the data collection an extensive data entry task began. This required recording air speed, altitude, course heading, bank angle, and vertical speed information from videos of the primary flight displays. This data was then used to determine root mean square error (RMSE) for each experimental condition. In addition to the performance data (RMSE) taken from flight path deviation, the study also collected data on pilot;s accuracy in reporting weather information, and a subjective rating of workload from the pilot. The data for this experiment is currently being analyzed. Overall the current experiment should help to determine potential costs and benefits associated with AWIN displays. The data will be used to determine if a private pilot can safely fly a general aviation aircraft while operating a weather display. Clearly a display that adds to the pilot#s already heavy workload represents a potential problem. The study will compare the use of an AWIN display to conventional means of acquiring weather data. The placement of the display within the cockpit (i.e., either on the yoke, kneeboard, or panel) will be also compared in terms of workload, performance, and pilot preference.

Integrating Research-Informed Teaching within an Undergraduate Level 4 (Year 1) Diagnostic Radiography Curriculum: A Pilot Study

ERIC Educational Resources Information Center

Higgins, Robert; Hogg, Peter; Robinson, Leslie

2013-01-01

This article discusses the piloting and evaluation of the Research-informed Teaching experience (RiTe) project. The aim of RiTe was to link teaching and learning with research within an undergraduate diagnostic radiography curriculum. A preliminary pilot study of RiTe was undertaken with a group of level 4 (year 1) volunteer BSc (Hons) diagnostic…

A 454 multiplex sequencing method for rapid and reliable genotyping of highly polymorphic genes in large-scale studies.

PubMed

Galan, Maxime; Guivier, Emmanuel; Caraux, Gilles; Charbonnel, Nathalie; Cosson, Jean-François

2010-05-11

High-throughput sequencing technologies offer new perspectives for biomedical, agronomical and evolutionary research. Promising progresses now concern the application of these technologies to large-scale studies of genetic variation. Such studies require the genotyping of high numbers of samples. This is theoretically possible using 454 pyrosequencing, which generates billions of base pairs of sequence data. However several challenges arise: first in the attribution of each read produced to its original sample, and second, in bioinformatic analyses to distinguish true from artifactual sequence variation. This pilot study proposes a new application for the 454 GS FLX platform, allowing the individual genotyping of thousands of samples in one run. A probabilistic model has been developed to demonstrate the reliability of this method. DNA amplicons from 1,710 rodent samples were individually barcoded using a combination of tags located in forward and reverse primers. Amplicons consisted in 222 bp fragments corresponding to DRB exon 2, a highly polymorphic gene in mammals. A total of 221,789 reads were obtained, of which 153,349 were finally assigned to original samples. Rules based on a probabilistic model and a four-step procedure, were developed to validate sequences and provide a confidence level for each genotype. The method gave promising results, with the genotyping of DRB exon 2 sequences for 1,407 samples from 24 different rodent species and the sequencing of 392 variants in one half of a 454 run. Using replicates, we estimated that the reproducibility of genotyping reached 95%. This new approach is a promising alternative to classical methods involving electrophoresis-based techniques for variant separation and cloning-sequencing for sequence determination. The 454 system is less costly and time consuming and may enhance the reliability of genotypes obtained when high numbers of samples are studied. It opens up new perspectives for the study of evolutionary and functional genetics of highly polymorphic genes like major histocompatibility complex genes in vertebrates or loci regulating self-compatibility in plants. Important applications in biomedical research will include the detection of individual variation in disease susceptibility. Similarly, agronomy will benefit from this approach, through the study of genes implicated in productivity or disease susceptibility traits.

Burnout among pilots: psychosocial factors related to happiness and performance at simulator training.

PubMed

Demerouti, Evangelia; Veldhuis, Wouter; Coombes, Claire; Hunter, Rob

2018-06-18

In this study among airline pilots, we aim to uncover the work characteristics (job demands and resources) and the outcomes (job crafting, happiness and simulator training performance) that are related to burnout for this occupational group. Using a large sample of airline pilots, we showed that 40% of the participating pilots experience high burnout. In line with Job Demands-Resources theory, job demands were detrimental for simulator training performance because they made pilots more exhausted and less able to craft their job, whereas job resources had a favourable effect because they reduced feelings of disengagement and increased job crafting. Moreover, burnout was negatively related to pilots' happiness with life. These findings highlight the importance of psychosocial factors and health for valuable outcomes for both pilots and airlines. Practitioner Summary: Using an online survey among the members of a European pilots' professional association, we examined the relationship between psychosocial factors (work characteristics, burnout) and outcomes (simulator training performance, happiness). Forty per cent of the participating pilots experience high burnout. Job demands were detrimental, whereas job resources were favourable for simulator training performance/happiness. Twitter text: 40% of airline pilots experience burnout and psychosocial work factors and burnout relate to performance at pilots' simulator training.

Soluble Fibre Meal Challenge Reduces Airway Inflammation and Expression of GPR43 and GPR41 in Asthma.

PubMed

Halnes, Isabel; Baines, Katherine J; Berthon, Bronwyn S; MacDonald-Wicks, Lesley K; Gibson, Peter G; Wood, Lisa G

2017-01-10

Short chain fatty acids (SCFAs) are produced following the fermentation of soluble fibre by gut bacteria. In animal models, both dietary fibre and SCFAs have demonstrated anti-inflammatory effects via the activation of free fatty acid receptors, such as G protein-coupled receptor 41 and 43 (GPR41 and GPR43). This pilot study examined the acute effect of a single dose of soluble fibre on airway inflammation-including changes in gene expression of free fatty acid receptors-in asthma. Adults with stable asthma consumed a soluble fibre meal ( n = 17) containing 3.5 g inulin and probiotics, or a control meal ( n = 12) of simple carbohydrates. Exhaled nitric oxide (eNO) was measured and induced sputum was collected at 0 and 4 h for differential cell counts, measurement of interleukin-8 (IL-8) protein concentration, and GPR41 and GPR43 gene expression. At 4 h after meal consumption, airway inflammation biomarkers, including sputum total cell count, neutrophils, macrophages, lymphocytes, sputum IL-8, and eNO significantly decreased compared to baseline in the soluble fibre group only. This corresponded with upregulated GPR41 and GPR43 sputum gene expression and improved lung function in the soluble fibre group alone. Soluble fibre has acute anti-inflammatory effects in asthmatic airways. Long-term effects of soluble fibre as an anti-inflammatory therapy in asthma warrants further investigation.

[Familial hypophosphatemic rickets].

PubMed

Reusz, G

2001-12-02

Familiar hypophosphatemic rickets (FHR) is characterized by isolated defect of renal phosphate reabsorption, hypophosphataemia, rickets and poor growth. In untreated cases parathyroid hormone and calcitriol levels are normal. FHR is caused by mutations of the PHEX gene encoding a zinc-binding metalloprotease enzyme. PHEX is expressed in bones and the parathyroid gland but not in the kidney. The gene product is involved in the inactivation of a phosphate regulating hormone (phosphatonin). The presence of this hormone through unknown mechanisms decreases the sodium-dependent phosphate cotransporter in the kidney resulting in impaired phosphate transport. In addition the PHEX gene product exerts autocrine and paracrine effects on the bone. Despite recent advances in the understanding of the pathomechanism, treatment of FHR is still symptomatic. It consists of active vitamin D analogues and oral phosphate supplementation. Nephrocalcinosis is a well-known, usually non-progressive side effect of the conventional therapy. As shown by pilot studies, poorly growing children with FHR may benefit from the positive effect of human recombinant growth hormone (rhGH). However, rhGH treatment could aggravate the already existing tendency to disproportionate growth resulting in the overgrowth of the trunk. The disturbed phosphate homeostasis persists during the whole life span of the FHR patients. It is therefore essential to provide lifelong care, to prevent late skeletal and dental consequences or to treat them if already established. That care should be done by the teamwork of the pediatrician, internist, orthopedist, dentist and the psychologist.

Treatment of textile wastewater by submerged membrane bioreactor: In vitro bioassays for the assessment of stress response elicited by raw and reclaimed wastewater.

PubMed

Friha, Inès; Bradai, Mohamed; Johnson, Daniel; Hilal, Nidal; Loukil, Slim; Ben Amor, Fatma; Feki, Firas; Han, Junkuy; Isoda, Hiroko; Sayadi, Sami

2015-09-01

The performance of a pilot-scale membrane bioreactor (MBR) system for the treatment of textile wastewater was investigated. The MBR was continuously operated for 7 months. Very high treatment efficiencies were achieved (color, 100%; chemical oxygen demand (COD), 98%; biochemical oxygen demand (BOD5), 96%; suspended solids (SS), 100%). Furthermore, the MBR treatment efficiency was analyzed from a toxicological-risk assessment point of view, via different In vitro bioassays using Caco-2 cells, a widely used cell model in toxicological studies. Results showed that MBR treatment significantly reduced the raw textile wastewater (RTWW) cytotoxicity on Caco-2 cells by 53% for a hydraulic retention time (HRT) of 2 days. Additionally, the RTWW-induced disruption in the barrier function (BF) of the Caco-2 cell monolayer was also significantly reduced after MBR treatment under a HRT of 2 days (no disruption of BF was observed). Moreover, the effect of RTWW and treated wastewater on stress response was investigated using different stress genes: AHSA1, HSPD1, HSPA1A, HSPA5 and HSPA8. The cell exposure to RTWW significantly increased the expression of all used stress genes; interestingly, the treated wastewater (HRT 2 days) did not show any significant modulation of the stress genes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Digestive functional symptoms among commercial pilots in relation to diet, insomnia, and lifestyle factors.

PubMed

Lindgren, Torsten; Runeson, Roma; Wahlstedt, Kurt; Wieslander, Gunilla; Dammström, Bo-Göran; Norbäck, Dan

2012-09-01

The aim of our study was to identify associations between digestive symptoms among pilots and diet, insomnia, and lifestyle factors. A standardized questionnaire was mailed to all Stockholm pilots on duty in a Swedish airline company: 354 pilots and 564 office workers from the same company participated. Associations were analyzed by multiple logistic regressions with mutual adjustment. Of the pilots, 9.9% reported poor appetite, 15.2% heartburn, 12.4% diarrhea, 62.1% bloating, 9.3% constipation, and 14.4% epigastralgia. Pilots reported more bloating and poor appetite compared with office workers. The prevalence of insomnia was 70.6% among pilots and 63.1% among office workers. Among pilots, insomnia was related to poor appetite, heartburn, diarrhea, bloating, constipation, and epigastralgia. There were no associations between insomnia and digestive symptoms among office workers. Among pilots, higher body mass index (BMI) was related to heartburn and smokers more often suffered from constipation. Frequent milk consumption was associated with heartburn and less constipation; female pilots suffered from more constipation. The number of years as an active pilot was negatively associated with epigastralgia and bloating. Insomnia and some digestive symptoms were more common among pilots than office workers. In addition to insomnia, BMI, smoking, female gender, and milk consumption were associated with some digestive symptoms. The strong association between insomnia and digestive symptoms among pilots, but not among office workers, suggests a stress component related to this occupation.

Modeling Pilot Pulse Control

NASA Technical Reports Server (NTRS)

Bachelder, Edward; Hess, Ronald; Godfroy-Cooper, Martine; Aponso, Bimal

2017-01-01

In this study, behavioral models are developed that closely reproduced pulsive control response of two pilots from the experimental pool using markedly different control techniques (styles) while conducting a tracking task. An intriguing find was that the pilots appeared to: 1) produce a continuous, internally-generated stick signal that they integrated in time; 2) integrate the actual stick position; and 3) compare the two integrations to issue and cease pulse commands. This suggests that the pilots utilized kinesthetic feedback in order to perceive and integrate stick position, supporting the hypothesis that pilots can access and employ the proprioceptive inner feedback loop proposed by Hess' pilot Structural Model. The Pulse Models used in conjunction with the pilot Structural Model closely recreated the pilot data both in the frequency and time domains during closed-loop simulation. This indicates that for the range of tasks and control styles encountered, the models captured the fundamental mechanisms governing pulsive and control processes. The pilot Pulse Models give important insight for the amount of remnant (stick output uncorrelated with the forcing function) that arises from nonlinear pilot technique, and for the remaining remnant arising from different sources unrelated to tracking control (i.e. neuromuscular tremor, reallocation of cognitive resources, etc.).

Autogenic-feedback training improves pilot performance during emergency flying conditions

NASA Technical Reports Server (NTRS)

Kellar, Michael A.; Folen, Raymond A.; Cowings, Patricia S.; Toscano, William B.; Hisert, Glen L.

1993-01-01

Studies have shown that autonomous mode behavior is one cause of aircraft fatalities due to pilot error. In such cases, the pilot is in a high state of psychological and physiological arousal and tends to focus on one problem, while ignoring more critical information. The effect of training in physiological self-recognition and regulation, as a means of improving crew cockpit performance was examined. Seventeen pilots were assigned to the treatment and control groups matched for accumulated flight hours. The treatment group comprised four pilots of HC-130 Hercules aircraft and four HH-65 Dolphin helicopter pilots; the control group comprised three pilots of HC-130's and six Dolphin helicopter pilots. During an initial flight physiological data were recorded for each crewmember and individual crew performance and rated by an instructor pilot. Eight crewmembers were then taught to regulate their own physiological response levels using Autogenic-Feedback Training (AFT). The remaining subjects received no training. During a second flight, treatment subjects showed significant improvement in performance, while controls did not improve. The results indicate that AFT management of high states of physiological arousal may improve pilot performance during emergency flying conditions.

Fatigue in trans-Atlantic airline operations: diaries and actigraphy for two- vs. three-pilot crews.

PubMed

Eriksen, Claire A; Akerstedt, Torbjörn; Nilsson, Jens P

2006-06-01

The aim was to compare intercontinental flights with two-pilot and three-pilot crews with respect to fatigue/sleepiness and sleep, as there is considerable economic pressure on the airlines to use two-pilot crews. Twenty pilots participated. Data were collected before, during, and after outbound and homebound flights using a sleep/wake diary (sleepiness ratings every 2-3 h) and wrist actigraphy. The duration of flights was approximately 8 h, and six time zones were crossed. The same pilots participated in both conditions. Napping during the outbound flight was 26 min for the two-pilot crew, and 48 min for the three-pilot crew. Napping during the homebound flight was 54 min and 1 h 6 min, respectively, and the difference was directly related to the time allotted for sleep. Subjective sleepiness was significantly higher for the two-pilot condition in both directions, peaking a few hours into the flight. Performance at top of descent for the two-pilot condition was rated as lower than the three-pilot condition. In the overall evaluation questionnaire there was a significant negative attitude toward two-crew operations. Sleep, sleepiness, subjective performance, boredom, mood, and layover sleep were assessed as having deteriorated in the two-pilot condition. The homebound flight was associated with considerably higher levels of sleepiness than the outbound flight. The study indicates that the reduction of crew size by one pilot is associated with moderately increased levels of sleepiness. It is also suggested that time allotted to sleep in the two-pilot condition might be somewhat extended to improve alertness.

A pilot evaluation of text display formats for weather information in the cockpit

DOT National Transportation Integrated Search

1995-10-01

This study focuses on the weather (WX) services portion of Data Link. A : two-phase evaluation was conducted with 16 air transport (ATP) and general : aviation (GA) pilots. The pilots evaluated four data formatting options and : four data entry metho...

Agricultural aviation versus other general aviation : toxicological findings in fatal accidents.

DOT National Transportation Integrated Search

1978-09-01

Results from the toxicological study of samples from 174 pilots killed while engaged in aerial application and samples from 2,449 other general aviation pilots are compared. The incidence of alcohol in specimens was similar for ag pilots and other ge...

Effect of motion cues during complex curved approach and landing tasks: A piloted simulation study

NASA Technical Reports Server (NTRS)

Scanlon, Charles H.

1987-01-01

A piloted simulation study was conducted to examine the effect of motion cues using a high fidelity simulation of commercial aircraft during the performance of complex approach and landing tasks in the Microwave Landing System (MLS) signal environment. The data from these tests indicate that in a high complexity MLS approach task with moderate turbulence and wind, the pilot uses motion cues to improve path tracking performance. No significant differences in tracking accuracy were noted for the low and medium complexity tasks, regardless of the presence of motion cues. Higher control input rates were measured for all tasks when motion was used. Pilot eye scan, as measured by instrument dwell time, was faster when motion cues were used regardless of the complexity of the approach tasks. Pilot comments indicated a preference for motion. With motion cues, pilots appeared to work harder in all levels of task complexity and to improve tracking performance in the most complex approach task.

Driving-while-intoxicated history as a risk marker for general aviation pilots.

PubMed

Li, Guohua; Baker, Susan P; Qiang, Yandong; Grabowski, Jurek G; McCarthy, Melissa L

2005-01-01

The Federal Aviation Administration conducts background checking for driving-while-intoxicated (DWI) convictions on all pilots. This study examined the association between DWI history and crash risk in a cohort of 335,672 general aviation pilots. These pilots were followed up from 1994 to 2000 through the aviation crash surveillance system of the National Transportation Safety Board. At baseline, 3.4% of the pilots had a DWI history. DWI history was associated with a 43% increased risk of crash involvement (adjusted relative risk: 1.43; 95% confidence interval: 1.15-1.77). The population-attributable risk fraction for DWI history was estimated as 1.4%. In addition to DWI history, male gender, older age, and inexperience were associated with significantly increased risk of crash involvement. The results of this study support DWI history as a valid risk marker for general aviation pilots. The safety benefit of background checking for DWI history needs to be further evaluated.

PRACA Enhancement Pilot Study Report: Engineering for Complex Systems Program (formerly Design for Safety), DFS-IC-0006

NASA Technical Reports Server (NTRS)

Korsmeyer, David; Schreiner, John

2002-01-01

This technology evaluation report documents the findings and recommendations of the Engineering for Complex Systems Program (formerly Design for Safety) PRACA Enhancement Pilot Study of the Space Shuttle Program's (SSP's) Problem Reporting and Corrective Action (PRACA) System. A team at NASA Ames Research Center (ARC) performed this Study. This Study was initiated as a follow-on to the NASA chartered Shuttle Independent Assessment Team (SIAT) review (performed in the Fall of 1999) which identified deficiencies in the current PRACA implementation. The Pilot Study was launched with an initial qualitative assessment and technical review performed during January 2000 with the quantitative formal Study (the subject of this report) started in March 2000. The goal of the PRACA Enhancement Pilot Study is to evaluate and quantify the technical aspects of the SSP PRACA systems and recommend enhancements to address deficiencies and in preparation for future system upgrades.

Piloted simulation study of two tilt-wing control concepts

NASA Technical Reports Server (NTRS)

Birckelbaw, Lourdes G.; Corliss, Lloyd D.

1994-01-01

A two-phase piloted simulation study was conducted to investigate alternative wing and flap controls for tilt-wing aircraft. The initial phase of the study compared the flying qualities of both a conventional (programmed) flap and an innovative geared flap. The second phase of the study introduced an alternate method of pilot control for the geared flap and further studied the flying qualities of the programmed flap, and two geared flap configurations. In general, the pilot rating showed little variation between the programmed flap and the geared flap control concepts. Some differences between the two concepts were noticed and are discussed in this paper. The addition of pitch attitude stabilization in the second phase of the study greatly enhanced the aircraft flying qualities. This paper describes the simulated tilt-wing aircraft and the flap control concepts and presents the results of both phases of the simulation study.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials.

PubMed

Cooper, Cindy L; Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-04-01

External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate.

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

PubMed Central

Whitehead, Amy; Pottrill, Edward; Julious, Steven A; Walters, Stephen J

2018-01-01

Background/aims: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. Methods: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland–Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. Results: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was −4.4% with limits of agreement of −37.1% to 28.2%. Limits of agreement for randomisation rates were −47.8% to 77.5%. Conclusion: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate. PMID:29361833

Development and validation of Aviation Causal Contributors for Error Reporting Systems (ACCERS).

PubMed

Baker, David P; Krokos, Kelley J

2007-04-01

This investigation sought to develop a reliable and valid classification system for identifying and classifying the underlying causes of pilot errors reported under the Aviation Safety Action Program (ASAP). ASAP is a voluntary safety program that air carriers may establish to study pilot and crew performance on the line. In ASAP programs, similar to the Aviation Safety Reporting System, pilots self-report incidents by filing a short text description of the event. The identification of contributors to errors is critical if organizations are to improve human performance, yet it is difficult for analysts to extract this information from text narratives. A taxonomy was needed that could be used by pilots to classify the causes of errors. After completing a thorough literature review, pilot interviews and a card-sorting task were conducted in Studies 1 and 2 to develop the initial structure of the Aviation Causal Contributors for Event Reporting Systems (ACCERS) taxonomy. The reliability and utility of ACCERS was then tested in studies 3a and 3b by having pilots independently classify the primary and secondary causes of ASAP reports. The results provided initial evidence for the internal and external validity of ACCERS. Pilots were found to demonstrate adequate levels of agreement with respect to their category classifications. ACCERS appears to be a useful system for studying human error captured under pilot ASAP reports. Future work should focus on how ACCERS is organized and whether it can be used or modified to classify human error in ASAP programs for other aviation-related job categories such as dispatchers. Potential applications of this research include systems in which individuals self-report errors and that attempt to extract and classify the causes of those events.

Simulation Evaluation of Pilot Inputs for Real Time Modeling During Commercial Flight Operations

NASA Technical Reports Server (NTRS)

Martos, Borja; Ranaudo, Richard; Oltman, Ryan; Myhre, Nick

2017-01-01

Aircraft dynamics characteristics can only be identified from flight data when the aircraft dynamics are excited sufficiently. A preliminary study was conducted into what types and levels of manual piloted control excitation would be required for accurate Real-Time Parameter IDentification (RTPID) results by commercial airline pilots. This includes assessing the practicality for the pilot to provide this excitation when cued, and to further understand if pilot inputs during various phases of flight provide sufficient excitation naturally. An operationally representative task was evaluated by 5 commercial airline pilots using the NASA Ice Contamination Effects Flight Training Device (ICEFTD). Results showed that it is practical to use manual pilot inputs only as a means of achieving good RTPID in all phases of flight and in flight turbulence conditions. All pilots were effective in satisfying excitation requirements when cued. Much of the time, cueing was not even necessary, as just performing the required task provided enough excitation for accurate RTPID estimation. Pilot opinion surveys reported that the additional control inputs required when prompted by the excitation cueing were easy to make, quickly mastered, and required minimal training.

Conflict Resolution Automation and Pilot Situation Awareness

NASA Technical Reports Server (NTRS)

Dao, Arik-Quang V.; Brandt, Summer L.; Bacon, Paige; Kraut, Josh; Nguyen, Jimmy; Minakata, Katsumi; Raza, Hamzah; Rozovski, David; Johnson, Walter W.

2010-01-01

This study compared pilot situation awareness across three traffic management concepts. The Concepts varied in terms of the allocation of traffic avoidance responsibility between the pilot on the flight deck, the air traffic controllers, and a conflict resolution automation system. In Concept 1, the flight deck was equipped with conflict resolution tools that enable them to fully handle the responsibility of weather avoidance and maintaining separation between ownship and surrounding traffic. In Concept 2, pilots were not responsible for traffic separation, but were provided tools for weather and traffic avoidance. In Concept 3, flight deck tools allowed pilots to deviate for weather, but conflict detection tools were disabled. In this concept pilots were dependent on ground based automation for conflict detection and resolution. Situation awareness of the pilots was measured using online probes. Results showed that individual situation awareness was highest in Concept 1, where the pilots were most engaged, and lowest in Concept 3, where automation was heavily used. These findings suggest that for conflict resolution tasks, situation awareness is improved when pilots remain in the decision-making loop.

Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.

PubMed

Dingemans, Jozef; Eyns, Hanneke; Willekens, Julie; Monsieurs, Pieter; Van Houdt, Rob; Cornelis, Pierre; Malfroot, Anne; Crabbé, Aurélie

2018-06-01

High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.

Comparison of proposed frameworks for grouping polychlorinated biphenyl congener data applied to a case-control pilot study of prostate cancer.

PubMed

Ritchie, Justine M; Vial, Scott L; Fuortes, Laurence J; Robertson, Larry W; Guo, Haijun; Reedy, Victoria E; Smith, Elaine M

2005-05-01

Although the commercial synthesis of polychlorinated biphenyls (PCBs) has been banned in the United States for several decades, they are persistent in the environment with exposure mainly being through diet. The biologic and toxic effects of PCBs and their metabolites are due in part to their ability to interact with several cellular and nuclear receptors, thereby altering signaling pathways and gene transcription. These effects include endocrine modulation and disruption. Therefore, the natural history of cancer in tissues expressing these receptors may be modulated by PCB congeners, which are known to have estrogenic, antiestrogenic, and other hormonal effects. Several frameworks for grouping PCB congeners based on these interactions have been proposed. We conducted a hospital-based, case-control pilot study of 58 prostate cancer cases and 99 controls to evaluate the association between the proposed PCB groupings and the risk of prostate cancer. Serum samples were analyzed for a total of 30 PCBs. In multivariate analyses, the odds of prostate cancer among men with the highest concentrations of moderately chlorinated PCBs or PCBs with phenobarbital-like activities (constitutively active receptor (CAR) agonists) was over two times that among men with the lowest concentrations. Increasing trends in risk across the concentration levels were also observed. These results suggest that a higher burden of PCBs that are CAR agonists may be positively associated with an increased risk of prostate cancer and they encourage further research in this area.

The oral microbiota in patients with pancreatic cancer, patients with IPMNs, and controls: a pilot study.

PubMed

Olson, Sara H; Satagopan, Jaya; Xu, Youming; Ling, Lilan; Leong, Siok; Orlow, Irene; Saldia, Amethyst; Li, Peter; Nunes, Pamela; Madonia, Vincent; Allen, Peter J; O'Reilly, Eileen; Pamer, Eric; Kurtz, Robert C

2017-09-01

Poor oral health appears to be a risk factor for pancreatic cancer, possibly implicating the oral microbiota. In this pilot study, we evaluated the characteristics of the oral microbiota in patients with pancreatic ductal adenocarcinoma (PDAC), intraductal papillary mucinous neoplasms (IPMN), and healthy controls. Forty newly diagnosed PDAC patients, 39 IPMN patients, and 58 controls, excluding current smokers and users of antibiotics, provided saliva samples. Common oral bacterial species were comprehensively surveyed by sequencing of the 16S rRNA microbial genes. We obtained measures of diversity and the mean relative proportions of individual taxa. We explored the degree to which these measures differed according to respondent characteristics based on individual interviews. PDAC cases did not differ in diversity measures from either controls or IPMN cases. PDAC cases had higher mean relative proportions of Firmicutes and related taxa, while controls had higher mean relative proportions of Proteobacteria and related taxa. Results were generally similar when comparing PDAC to IPMN cases. Among IPMNs and controls combined, younger individuals had higher levels of several taxa within the Proteobacteria. The only other variable consistently related to mean relative proportions was mouthwash use, with taxa within Firmicutes more common among users. While there were no differences in diversity of the oral microbiota among these groups, there were differences in the mean relative proportions of some taxa. Characteristics of the oral microbiota are not associated with most measures of oral health.

Pilot Alcohol Violations Reported in U.S. Newspapers, 1990–2006

PubMed Central

Kraus, Chadd K.; Li, Guohua

2009-01-01

Introduction Alcohol violations by airline pilots are rare yet remain a public concern. Such incidents often generate widespread news coverage. This study examines the frequency and characteristics of alcohol violation incidents involving airline pilots reported in U.S. newspapers. Methods The database of Lexis-Nexis™, which contains full-text articles for over 350 newspapers, was searched to identify alcohol violation incidents involving airline pilots in the U.S. between January 1990 and June 2006. Information pertaining to the pilot, flight, blood alcohol concentration (BAC), and consequence was ascertained for each incident based on the newspaper coverage. Results During the study period, newspapers reported on a total of 13 incidents of alcohol violations involving 17 pilots. All but two of the incidents occurred during January 2002 through June 2006. The majority (85%) of the incidents were first identified by airport personnel, such as security screeners, based on suspicion of alcohol use by the pilot. Subsequent alcohol testing revealed a mean BAC of 90 mg/dL (ranging from 10 mg · dL−1 to 182 mg · dL−1). Of the 17 pilots, 6 were known to be prosecuted criminally, including 5 who were sentenced to jail terms. Discussion Incidents of alcohol violations by airline pilots reported in U.S. newspapers have increased in recent years. This increase is likely due in part to increased detection resulting from enhanced aviation security and enforcement following the September 2001 terrorist attacks. PMID:17183928

MAISTAS: a tool for automatic structural evaluation of alternative splicing products.

PubMed

Floris, Matteo; Raimondo, Domenico; Leoni, Guido; Orsini, Massimiliano; Marcatili, Paolo; Tramontano, Anna

2011-06-15

Analysis of the human genome revealed that the amount of transcribed sequence is an order of magnitude greater than the number of predicted and well-characterized genes. A sizeable fraction of these transcripts is related to alternatively spliced forms of known protein coding genes. Inspection of the alternatively spliced transcripts identified in the pilot phase of the ENCODE project has clearly shown that often their structure might substantially differ from that of other isoforms of the same gene, and therefore that they might perform unrelated functions, or that they might even not correspond to a functional protein. Identifying these cases is obviously relevant for the functional assignment of gene products and for the interpretation of the effect of variations in the corresponding proteins. Here we describe a publicly available tool that, given a gene or a protein, retrieves and analyses all its annotated isoforms, provides users with three-dimensional models of the isoform(s) of his/her interest whenever possible and automatically assesses whether homology derived structural models correspond to plausible structures. This information is clearly relevant. When the homology model of some isoforms of a gene does not seem structurally plausible, the implications are that either they assume a structure unrelated to that of the other isoforms of the same gene with presumably significant functional differences, or do not correspond to functional products. We provide indications that the second hypothesis is likely to be true for a substantial fraction of the cases. http://maistas.bioinformatica.crs4.it/.

Hunner's Ulcers

MedlinePlus

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Bladder Retraining

MedlinePlus

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Portable Weather Applications for General Aviation Pilots.

PubMed

Ahlstrom, Ulf; Ohneiser, Oliver; Caddigan, Eamon

2016-09-01

The objective of this study was to examine the potential benefits and impact on pilot behavior from the use of portable weather applications. Seventy general aviation (GA) pilots participated in the study. Each pilot was randomly assigned to an experimental or a control group and flew a simulated single-engine GA aircraft, initially under visual meteorological conditions (VMC). The experimental group was equipped with a portable weather application during flight. We recorded measures for weather situation awareness (WSA), decision making, cognitive engagement, and distance from the aircraft to hazardous weather. We found positive effects from the use of the portable weather application, with an increased WSA for the experimental group, which resulted in credibly larger route deviations and credibly greater distances to hazardous weather (≥30 dBZ cells) compared with the control group. Nevertheless, both groups flew less than 20 statute miles from hazardous weather cells, thus failing to follow current weather-avoidance guidelines. We also found a credibly higher cognitive engagement (prefrontal oxygenation levels) for the experimental group, possibly reflecting increased flight planning and decision making on the part of the pilots. Overall, the study outcome supports our hypothesis that portable weather displays can be used without degrading pilot performance on safety-related flight tasks, actions, and decisions as measured within the constraints of the present study. However, it also shows that an increased WSA does not automatically translate to enhanced flight behavior. The study outcome contributes to our knowledge of the effect of portable weather applications on pilot behavior and decision making. © 2016, Human Factors and Ergonomics Society.

Ball Powder Production Wastewater Biodegradation Support Studies - With Nitroglycerine

DTIC Science & Technology

1989-02-01

in the wastewater. Characterization of the ball powder wastewater stream showed an actual average NG inlet concentration of 192 mg/L. Pilot test...the first phase of pilot testing, the recommendation was made to conduct an additional pilot test phase to determine the effect of nitroglycerin (NG...NG by aerobic bacteria, a pilot program was undertaken with the following objectives: 1) to determine the concentration of NG in the ball powder

V/STOL tilt rotor aircraft study. Volume 9: Piloted simulator evaluation of the Boeing Vertol model 222 tilt rotor aircraft

NASA Technical Reports Server (NTRS)

Rosenstein, H.; Mcveigh, M. A.; Mollenkof, P. A.

1973-01-01

The results of a real time piloted simulation to investigate the handling qualities and performance of a tilting rotor aircraft design are presented. The aerodynamic configuration of the aircraft is described. The procedures for conducting the simulator evaluation are reported. Pilot comments of the aircraft handling qualities under various simulated flight conditions are included. The time histories of selected pilot maneuvers are shown.

The functional spectrum of low-frequency coding variation.

PubMed

Marth, Gabor T; Yu, Fuli; Indap, Amit R; Garimella, Kiran; Gravel, Simon; Leong, Wen Fung; Tyler-Smith, Chris; Bainbridge, Matthew; Blackwell, Tom; Zheng-Bradley, Xiangqun; Chen, Yuan; Challis, Danny; Clarke, Laura; Ball, Edward V; Cibulskis, Kristian; Cooper, David N; Fulton, Bob; Hartl, Chris; Koboldt, Dan; Muzny, Donna; Smith, Richard; Sougnez, Carrie; Stewart, Chip; Ward, Alistair; Yu, Jin; Xue, Yali; Altshuler, David; Bustamante, Carlos D; Clark, Andrew G; Daly, Mark; DePristo, Mark; Flicek, Paul; Gabriel, Stacey; Mardis, Elaine; Palotie, Aarno; Gibbs, Richard

2011-09-14

Rare coding variants constitute an important class of human genetic variation, but are underrepresented in current databases that are based on small population samples. Recent studies show that variants altering amino acid sequence and protein function are enriched at low variant allele frequency, 2 to 5%, but because of insufficient sample size it is not clear if the same trend holds for rare variants below 1% allele frequency. The 1000 Genomes Exon Pilot Project has collected deep-coverage exon-capture data in roughly 1,000 human genes, for nearly 700 samples. Although medical whole-exome projects are currently afoot, this is still the deepest reported sampling of a large number of human genes with next-generation technologies. According to the goals of the 1000 Genomes Project, we created effective informatics pipelines to process and analyze the data, and discovered 12,758 exonic SNPs, 70% of them novel, and 74% below 1% allele frequency in the seven population samples we examined. Our analysis confirms that coding variants below 1% allele frequency show increased population-specificity and are enriched for functional variants. This study represents a large step toward detecting and interpreting low frequency coding variation, clearly lays out technical steps for effective analysis of DNA capture data, and articulates functional and population properties of this important class of genetic variation.

Analysis of RTEL1 and PCDHGB6 promoter methylation in circulating-free DNA of lung cancer patients using liquid biopsy: A pilot study.

PubMed

Powrózek, Tomasz; Krawczyk, Paweł; Kuźnar-Kamińska, Barbara; Batura-Gabryel, Halina; Milanowski, Janusz

2016-08-01

Analysis of epigenetic alterations such as methylation of circulating-free DNA (cf-DNA) expression significantly broadened perspectives of lung cancer (LC) screening. Moreover, methylation of tumor suppressor genes may be analyzed with non-invasive manner in patients' blood samples (liquid biopsy), what underline necessity of detailed investigation of tumor cf-DNA. The purpose of current study was to assess methylation of RTEL1 and PCDHGB6 promoter regions in cf-DNA of 70 LC patients and 80 healthy individuals using qMSP-PCR technique. Methylation status of both genes has not been investigated in cf-DNA of LC patients before. PCDHGB6 promoter methylation was found in 41.4% of LC patients and in 1.3% of healthy individuals, whereas promoter of RTEL1 was found methylated in 51.4% of LC patients and in 8.8% of healthy individuals. Combined analysis of two markers improved test sensitivity up to 62.9% and specificity up to 90% with area under the curve (AUC) in receiver operating curve (ROC) of 0.755. The evaluation of RTEL1 and PCDHGB6 promoter methylation may be an useful tool for non-invasive diagnosis of LC in liquid biopsy.

Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia.

PubMed

Khulan, Batbayar; Cooper, Wendy N; Skinner, Benjamin M; Bauer, Julien; Owens, Stephen; Prentice, Andrew M; Belteki, Gusztav; Constancia, Miguel; Dunger, David; Affara, Nabeel A

2012-05-01

In addition to the genetic constitution inherited by an organism, the developmental trajectory and resulting mature phenotype are also determined by mechanisms acting during critical windows in early life that influence and establish stable patterns of gene expression. This is the crux of the developmental origins of health and disease hypothesis that suggests undernutrition during gestation and infancy predisposes to ill health in later life. The hypothesis that periconceptional maternal micronutrient supplementation might affect fetal genome-wide methylation within gene promoters was explored in cord blood samples from offspring of Gambian women enrolled into a unique randomized, double blind controlled trial. Significant changes in the epigenome in cord blood DNA samples were further explored in a subset of offspring at 9 months. Gender-specific changes related to periconceptional nutritional supplementation were identified in cord blood DNA samples, some of which showed persistent changes in infant blood DNA samples. Significant effects of periconceptional micronutrient supplementation were also observed in postnatal samples which were not evident in cord blood. In this Gambian population, the increased death rate of individuals born in nutritionally poor seasons has been related to infection and it is of interest that we identified differential methylation at genes associated with defence against infection and immune response. Although the sample size was relatively small, these pilot data suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal developmental patterns of gene promoter methylation linking early with disease risk.

Structural and functional assessment of intense therapeutic ultrasound effects on partial Achilles tendon transection

NASA Astrophysics Data System (ADS)

Barton, Jennifer K.; Rice, Photini S.; Howard, Caitlin C.; Koevary, Jen W.; Danford, Forest; Gonzales, David A.; Vande Geest, Jon; Latt, L. Daniel; Szivek, John A.; Amodei, Richard; Slayton, Michael

2018-02-01

Tendinopathies and tendon tears heal slowly because tendons have a limited blood supply. Intense therapeutic ultrasound (ITU) is a treatment modality that creates very small, focal coagula in tissue, which can stimulate a healing response. This pilot study investigated the effects of ITU on rabbit and rat models of partial Achilles tendon rupture. The right Achilles tendons of 20 New Zealand White rabbits and 118 rats were partially transected. Twenty-four hours after surgery, ITU coagula were placed in the tendon and surrounding tissue, alternating right and left legs. At various time points, the following data were collected: ultrasound imaging, optical coherence tomography (OCT) imaging, mechanical testing, gene expression analysis, histology, and multiphoton microscopy (MPM) of sectioned tissue. Ultrasound visualized cuts and treatment lesions. OCT showed the effect of the interventions on birefringence banding caused by collagen organization. MPM showed inflammatory infiltrate, collagen synthesis and organization. By day 14- 28, all tendons had a smooth appearance and histology, MPM and OCT still could still visualize residual healing processes. Few significant results in gene expression were seen, but trends were that ITU treatment caused an initial decrease in growth and collagen gene expression followed by an increase. No difference in failure loads was found between control, cut, and ITU treatment groups, suggesting that sufficient healing had occurred by 14 days to restore all test tissue to control mechanical properties. These results suggest that ITU does not cause harm to tendon tissue. Upregulation of some genes suggests that ITU may increase healing response.

TAMPA ASTHMATIC CHILDREN'S STUDY (TACS)

EPA Science Inventory

The Tampa Asthmatic Children's Study (TACS) was a pilot research study to assess methodologies and research instruments needed for including asthma as a health outcome in the National Children's Study (NCS). This was one of a series of pilot studies focusing on (a) simple, cos...

The Impact of Suggestive Maneuver Guidance on UAS Pilots Performing the Detect and Avoid Function

NASA Technical Reports Server (NTRS)

Rorie, Conrad; Fern, Lisa; Shively, Jay

2016-01-01

This presentation discusses the results of a recent UAS Integration into the NAS human-in-the-loop simulation. In the study, 16 active UAS pilots flew a UAS through civil airspace and were tasked with maintaining well clear from other aircraft in the area. Pilots performed the task with four different detect and avoid (DAA) traffic displays, each of which varied in the form of guidance it provided to pilots The present findings focus on how the different displays impacted pilots' measured response to scripted conflicts with their aircraft. Measured response is made up of several components, each of which help inform our understanding of the pilots' role in the overall detect and avoid task.

Applications of pilot scanning behavior to integrated display research

NASA Technical Reports Server (NTRS)

Waller, M. C.

1977-01-01

The oculometer is an electrooptical device designed to measure pilot scanning behavior during instrument approaches and landing operations. An overview of some results from a simulation study is presented to illustrate how information from the oculometer installed in a visual motion simulator, combined with measures of performance and control input data, can provide insight into the behavior and tactics of individual pilots during instrument approaches. Differences in measured behavior of the pilot subjects are pointed out; these differences become apparent in the way the pilots distribute their visual attention, in the amount of control activity, and in selected performance measures. Some of these measured differences have diagnostic implications, suggesting the use of the oculometer along with performance measures as a pilot training tool.

Impact of gender, age and experience of pilots on general aviation accidents.

PubMed

Bazargan, Massoud; Guzhva, Vitaly S

2011-05-01

General aviation (GA) accounts for more than 82% of all air transport-related accidents and air transport-related fatalities in the U.S. In this study, we conduct a series of statistical analyses to investigate the significance of a pilot's gender, age and experience in influencing the risk for pilot errors and fatalities in GA accidents. There is no evidence from the Chi-square tests and logistic regression models that support the likelihood of an accident caused by pilot error to be related to pilot gender. However, evidence is found that male pilots, those older than 60 years of age, and with more experience, are more likely to be involved in a fatal accident. Copyright © 2010 Elsevier Ltd. All rights reserved.

Functional aging in pilots : an examination of a mathematical model based on medical data on general aviation pilots.

DOT National Transportation Integrated Search

1982-06-01

The purpose of this study was to apply mathematical procedures to the Federal Aviation Administration (FAA) pilot medical data to examine the feasibility of devising a linear numbering system such that (1) the cumulative probability distribution func...

The influence of ATC message length and timing on pilot communication

NASA Technical Reports Server (NTRS)

Morrow, Daniel; Rodvold, Michelle

1993-01-01

Pilot-controller communication is critical to safe and efficient flight. It is often a challenging component of piloting, which is reflected in the number of incidents and accidents involving miscommunication. Our previous field study identified communication problems that disrupt routine communication between pilots and controllers. The present part-task simulation study followed up the field results with a more controlled investigation of communication problems. Pilots flew a simulation in which they were frequently vectored by Air Traffic Control (ATC), requiring intensive communication with the controller. While flying, pilots also performed a secondary visual monitoring task. We examined the influence of message length (one message with four commands vs. two messages with two commands each) and noncommunication workload on communication accuracy and length. Longer ATC messages appeared to overload pilot working memory, resulting in more incorrect or partial readbacks, as well as more requests to repeat the message. The timing between the two short messages also influenced communication. The second message interfered with memory for or response to the first short message when it was delivered too soon after the first message. Performing the secondary monitoring task did not influence communication. Instead, communication reduced monitoring accuracy.

Effects of False Tilt Cues on the Training of Manual Roll Control Skills

NASA Technical Reports Server (NTRS)

Zaal, Peter M. T.; Popovici, Alexandru; Zavala, Melinda A.

2015-01-01

This paper describes a transfer-of-training study performed in the NASA Ames Vertica lMotion Simulator. The purpose of the study was to investigate the effect of false tilt cues on training and transfer of training of manual roll control skills. Of specific interest were the skills needed to control unstable roll dynamics of a mid-size transport aircraft close to the stall point. Nineteen general aviation pilots trained on a roll control task with one of three motion conditions: no motion, roll motion only, or reduced coordinated roll motion. All pilots transferred to full coordinated roll motion in the transfer session. A novel multimodal pilot model identification technique was successfully applied to characterize how pilots' use of visual and motion cues changed over the course of training and after transfer. Pilots who trained with uncoordinated roll motion had significantly higher performance during training and after transfer, even though they experienced the false tilt cues. Furthermore, pilot control behavior significantly changed during the two sessions, as indicated by increasing visual and motion gains, and decreasing lead time constants. Pilots training without motion showed higher learning rates after transfer to the full coordinated roll motion case.

Comparison of Postural Responses to Galvanic Vestibular Stimulation between Pilots and the General Populace

PubMed Central

Yang, Yang; Pu, Fang; Lv, Xiaoning; Li, Shuyu; Li, Jing; Li, Deyu; Li, Minggao

2015-01-01

Galvanic vestibular stimulation (GVS) can be used to study the body's response to vestibular stimuli. This study aimed to investigate whether postural responses to GVS were different between pilots and the general populace. Bilateral bipolar GVS was applied with a constant-current profile to 12 pilots and 12 control subjects via two electrodes placed over the mastoid processes. Both GVS threshold and the center of pressure's trajectory (COP's trajectory) were measured. Position variability of COP during spontaneous body sway and peak displacement of COP during GVS-induced body sway were calculated in the medial-lateral direction. Spontaneous body sway was slight for all subjects, and there was no significant difference in the value of COP position variability between the pilots and controls. Both the GVS threshold and magnitude of GVS-induced body deviation were similar for different GVS polarities. GVS thresholds were similar between the two groups, but the magnitude of GVS-induced body deviation in the controls was significantly larger than that in the pilots. The pilots showed less GVS-induced body deviation, meaning that pilots may have a stronger ability to suppress vestibular illusions. PMID:25632395

Men and IC

MedlinePlus

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IC Associated Conditions

MedlinePlus

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General IC Symptoms

MedlinePlus

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Children and IC

MedlinePlus

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Statistical analysis plan of the head position in acute ischemic stroke trial pilot (HEADPOST pilot).

PubMed

Olavarría, Verónica V; Arima, Hisatomi; Anderson, Craig S; Brunser, Alejandro; Muñoz-Venturelli, Paula; Billot, Laurent; Lavados, Pablo M

2017-02-01

Background The HEADPOST Pilot is a proof-of-concept, open, prospective, multicenter, international, cluster randomized, phase IIb controlled trial, with masked outcome assessment. The trial will test if lying flat head position initiated in patients within 12 h of onset of acute ischemic stroke involving the anterior circulation increases cerebral blood flow in the middle cerebral arteries, as measured by transcranial Doppler. The study will also assess the safety and feasibility of patients lying flat for ≥24 h. The trial was conducted in centers in three countries, with ability to perform early transcranial Doppler. A feature of this trial was that patients were randomized to a certain position according to the month of admission to hospital. Objective To outline in detail the predetermined statistical analysis plan for HEADPOST Pilot study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with comparisons made between randomized groups. For the outcomes, statistical comparisons to be made between groups are planned and described. Results This statistical analysis plan was developed for the analysis of the results of the HEADPOST Pilot study to be transparent, available, verifiable, and predetermined before data lock. Conclusions We have developed a statistical analysis plan for the HEADPOST Pilot study which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. Trial registration The study is registered under HEADPOST-Pilot, ClinicalTrials.gov Identifier NCT01706094.

Methods for Aiding Height Determination in Pseudolite-Based Reference Systems Using Batch Least-Squares Estimation

DTIC Science & Technology

2006-03-01

LocataLite Test Examples. LocataLites have been used in several experimental trials as pilot studies of the system. 1.7.5.1 BlueScope Steel. In this pilot...study, [2], the Locata system is shown to give centimeter level relative positioning precision in a severe multipath en- vironment. The BlueScope ...Using Locata: A pilot study at BlueScope Steel.” Proceedings of the 2004 Annual Meeting of the U.S. Institute of Navigation. Dayton, OH, June 2004. 3

Integrating Virtual Worlds with Tangible User Interfaces for Teaching Mathematics: A Pilot Study.

PubMed

Guerrero, Graciela; Ayala, Andrés; Mateu, Juan; Casades, Laura; Alamán, Xavier

2016-10-25

This article presents a pilot study of the use of two new tangible interfaces and virtual worlds for teaching geometry in a secondary school. The first tangible device allows the user to control a virtual object in six degrees of freedom. The second tangible device is used to modify virtual objects, changing attributes such as position, size, rotation and color. A pilot study on using these devices was carried out at the "Florida Secundaria" high school. A virtual world was built where students used the tangible interfaces to manipulate geometrical figures in order to learn different geometrical concepts. The pilot experiment results suggest that the use of tangible interfaces and virtual worlds allowed a more meaningful learning (concepts learnt were more durable).

Study of Synthetic Vision Systems (SVS) and Velocity-vector Based Command Augmentation System (V-CAS) on Pilot Performance

NASA Technical Reports Server (NTRS)

Liu, Dahai; Goodrich, Ken; Peak, Bob

2006-01-01

This study investigated the effects of synthetic vision system (SVS) concepts and advanced flight controls on single pilot performance (SPP). Specifically, we evaluated the benefits and interactions of two levels of terrain portrayal, guidance symbology, and control-system response type on SPP in the context of lower-landing minima (LLM) approaches. Performance measures consisted of flight technical error (FTE) and pilot perceived workload. In this study, pilot rating, control type, and guidance symbology were not found to significantly affect FTE or workload. It is likely that transfer from prior experience, limited scope of the evaluation task, specific implementation limitations, and limited sample size were major factors in obtaining these results.

Salivary alpha-amylase activity and stress in Japan air self-defense force cargo pilots involved in Iraq reconstruction.

PubMed

Iizuka, Naotaka; Awano, Shuji; Ansai, Toshihiro

2012-01-01

This study aimed to verify whether salivary α-amylase enzyme activity (Amy) is useful as a biomarker of stress in pilots working in a stressful environment. The subjects in this study were nine Japan air self-defense force pilots who participated in Iraq reconstruction support activity in Kuwait. Amy was measured using a portable salivary amylase monitor at preflight, postflight, and on stand-by day. In addition, the state-trait anxiety inventory was administered with state scores (STAI-S) compared to Amy levels. There were greater differences in Amy levels at baseline compared to STAI-S scores between subjects on the stand-by day. Amy levels at preflight tended to increase compared to those on stand-by day as did STAI-S. The change in Amy level at postflight varied among the pilots. The Amy levels of four subjects at postflight were elevated compared to levels at preflight, while the STAI-S scores for all pilots at postflight were lower than at preflight. This study suggests that the Amy level of pilots can reflect subtle individual differences in response to the psychological and physiological stress of a flight task. Thus, monitoring Amy level may be useful for stress evaluation of pilots working in a stressful environment, providing data that might be used as an impetus for addressing stress management for this population. Copyright © 2012 Wiley Periodicals, Inc.

OTEC riser cable system, Phase II: conceptual design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-10-01

Studies are summarized of conceptual designs of riser cable systems for OTEC pilot plants of both the spar and plantship configurations located at sites off the southeast coast of Puerto Rico. The studies utilize a baseline pilot plant riser cable, the design of which has been developed and reported on in other reports. Baseline riser cable systems for OTEC pilot plants are identified, system hardware consistent with these designs are conceptualized, and comparisons of the various system concepts are provided. It is concluded that there are three riser cable systems feasible for a spar pilot plant platform at the Puntamore » Yeguas site, and two riser cable systems feasible at the plantship pilot plant at the Punta Tuna site. Recommendations for further investigations in the areas of materials, hardware design and pre-installation site surveys are also addressed.« less

Pilot performance

NASA Technical Reports Server (NTRS)

Nicholls, Jennifer

1988-01-01

For many years, the emphasis has been placed on the performance of the aircraft, rather than on those who fly the aircraft. This is largely due to the relative safety of flying. Just in the last few years there have been several major accidents that have shown that flying is not quite as safe as it was thought to be. Sixty-five percent of these accidents are a result of pilot performance decrements, and so it is obvious that there is a need to reduce that figure. A study has been mandated to evaluate the performance of pilots. This includes workload, circadium rhythms, jet lag, and any other factors which might affect a pilot's performance in the cockpit. The purpose of this study is to find out when and why the decrement in a pilot's performance occur and how to remedy the situation.

On the development of a new methodology in sub-surface parameterisation on the calibration of groundwater models

NASA Astrophysics Data System (ADS)

Klaas, D. K. S. Y.; Imteaz, M. A.; Sudiayem, I.; Klaas, E. M. E.; Klaas, E. C. M.

2017-10-01

In groundwater modelling, robust parameterisation of sub-surface parameters is crucial towards obtaining an agreeable model performance. Pilot point is an alternative in parameterisation step to correctly configure the distribution of parameters into a model. However, the methodology given by the current studies are considered less practical to be applied on real catchment conditions. In this study, a practical approach of using geometric features of pilot point and distribution of hydraulic gradient over the catchment area is proposed to efficiently configure pilot point distribution in the calibration step of a groundwater model. A development of new pilot point distribution, Head Zonation-based (HZB) technique, which is based on the hydraulic gradient distribution of groundwater flow, is presented. Seven models of seven zone ratios (1, 5, 10, 15, 20, 25 and 30) using HZB technique were constructed on an eogenetic karst catchment in Rote Island, Indonesia and their performances were assessed. This study also concludes some insights into the trade-off between restricting and maximising the number of pilot points and offers a new methodology for selecting pilot point properties and distribution method in the development of a physically-based groundwater model.

A piloted simulation investigation of yaw dynamics requirements for turreted gun use in low-level helicopter air combat

NASA Technical Reports Server (NTRS)

Decker, William A.; Morris, Patrick M.; Williams, Jeffrey N.

1988-01-01

A piloted, fixed-base simulation study was conducted to investigate the handling qualities requirements for helicopter air-to-air combat using turreted guns in the near-terrain environment. The study used a version of the helicopter air combat system developed at NASA Ames Research Center for one-on-one air combat. The study focused on the potential trade-off between gun angular movement capability and required yaw axis response. Experimental variables included yaw axis response frequency and damping and the size of the gun-movement envelope. A helmet position and sighting system was used for pilot control of gun aim. Approximately 340 simulated air combat engagements were evaluated by pilots from the Army and industry. Results from the experiment indicate that a highly-damped, high frequency yaw response was desired for Level I handling qualities. Pilot preference for those characteristics became more pronounced as gun turret movement was restricted; however, a stable, slow-reacting platform could be used with a large turret envelope. Most pilots preferred to engage with the opponent near the own-ship centerline. Turret elevation restriction affected the engagement more than azimuth restrictions.

Integration of Diagnostic and Interventional MRI for the Study of Persistent Prostate Cancer after External Beam Radiotherapy

DTIC Science & Technology

2009-10-01

1500 ms). A clinical pilot study reported equivalence between central gland (CG) and peripheral zone (PZ) T1 values (CG: 1321±45 ms, n=14; PZ: 1359...across variable TI, the period of longitudinal recovery is kept independent of TI selection for any TR. Central to T1prep is RF cycling of an...pilot study A clinical pilot study involved 15 patients with low or intermediate risk localized prostate cancer and no history of prior therapy. The

Conservative Management of Mechanical Neck Pain in a Helicopter Pilot.

PubMed

Alagha, Babak

2015-10-01

Acute and chronic spinal symptoms such as neck pain may limit flying performance significantly and disqualify the pilot from flight duty. Mechanical neck pain is very common among pilots because of their exposure to vibration, +GZ forces, helmet weight, poor neck posture during air combat maneuvers, previous neck injuries, and poor treatment plans for such injuries. Successful treatment of such injuries requires appropriate therapeutic procedures as well as an aeromedical assessment. The aim of this case study was to demonstrate the benefits of conservative procedures such as spinal manipulation and mobilization therapy (SMMT) and exercise therapy (ET) in treating chronic mechanical neck pain in an Iranian commercial helicopter pilot. A 36-yr-old male patient presented to the clinic with moderate, intermittent nonradicular chronic neck pain and limited range of motion over a 2-yr period. The patient was treated with cervical and upper thoracic SMMT followed by home ET for 5 wk. After this period, the patient reported significant recovery and improvement in range of motion in his neck. Mechanical neck pain is very common among helicopter pilots. Although Air Force and Navy waiver guides recommend nonsteroidal anti-inflammatory medications as well as SMMT and ET, there are currently very few published studies that examine the benefits of manual and exercise therapy for treating mechanical neck pain in commercial and military pilots. Based on the results of this study, it seems that SMMT and ET may be a safe and effective in treatment of uncomplicated mechanical neck pain in helicopter pilots. Alagha B. Conservative management of mechanical neck pain in a helicopter pilot.

An approach to the determination of aircraft handling qualities using pilot transfer functions

NASA Technical Reports Server (NTRS)

Adams, J. J.; Hatch, H. G., Jr.

1978-01-01

It was shown that a correlation exists between pilot-aircraft system closed-loop characteristics, determined by using analytical expressions for pilot response along with the analytical expression for the aircraft response, and pilot ratings obtained in many previous flight and simulation studies. Two different levels of preferred pilot response were used. These levels were: (1) a static gain and a second-order lag function with a lag time constant of 0.2 second; and (2) a static gain, a lead time constant of 1 second, and a 0.2-second lag time constant. If a system response with a pitch-angle time constant of 2.6 seconds and a stable oscillatory mode of motion with a period of 2.5 seconds could be achieved with the first-level pilot model, it was shown that the pilot rating will be satisfactory for that vehicle.

Interstitial Cystitis and Diet

MedlinePlus

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IC Treatment: Surgical Procedures

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Variations in Party Line Information Requirements for Flight Crew Situation Awareness in the Datalink Environment

NASA Technical Reports Server (NTRS)

Pritchett, Amy R.; Hansman, R. John

1994-01-01

Current Air Traffic Control communications use shared very high frequency (VHF) voice frequencies from which pilots can obtain 'Party Line' Information (PLI) by overhearing communications addressed to other aircraft. A prior study has shown pilots perceive this PLI to be important. There is concern that some critical PLI may be lost in the proposed datalink environment where communications will be discretely addressed. Different types of flight operations will be, equipped with datalink equipment at different times, generating a 'mixed environment' where some pilots may rely on PLI while others will receive their information by datalink. To research the importance, availability and accuracy of PLI and to query pilots on the information they feel is necessary, a survey was distributed to pilots. The pilots were selected from four flight operation groups to study the variations in PLI requirements in the mixed datalink environment. Pilots perceived PLI to be important overall. Specific information elements pertaining to traffic and weather information were identified as Critical. Most PLI elements followed a pattern of higher perceived importance during terminal area operations, final approach and landing. Pilots from the different flight operation groups identified some elements as particularly important. Pilots perceived PLI to be only moderately available and accurate overall. Several PLI elements received very low availability and accuracy ratings but are perceived as important. In a free response question designed to find the information requirements for global situation awareness, pilots frequently indicated a need for traffic and weather information. These elements were also frequently cited by them as information that could be presented by a datalink system. The results of this survey identify specific concerns to be addressed when implementing datalink communications.

Placental Growth Factor Levels in Populations with High Versus Low Risk for Cardiovascular Disease and Stressful Physiological Environments such as Microgravity: A Pilot Study

NASA Astrophysics Data System (ADS)

Sundaresan, Alamelu; Mehta, Satish K.; Schlegel, Todd. T.; Russomano, Thais; Pierson, Duane L.; Mann, Vivek; Mansoor, Elvedina; Olamigoke, Loretta; Okoro, Elvis

2017-02-01

This pilot study compared placental growth factor (PIGF) levels in populations with high versus low risk for cardiovascular disease. Previous experiments from our laboratory (Sundaresan et al. 2005, 2009) revealed that the angiogenic factor PIGF was up regulated in modeled microgravity conditions in human lymphocytes leading to possible atherogenesis and pathogenesis in microgravity. Since the findings came from microgravity analog experiments, there is a strong link to its usefulness in the microgravity field as a biomarker. It is important to understand, that these findings came from both studies on expression levels of this cardiovascular marker in human lymphocytes in microgravity ( in vitro microgravity analog), and a follow up gene expression study in hind limb suspended mice ( in vivo microgravity analog). The relevance is enhanced because in life on earth, PIGF is an inflammatory biomarker for cardiovascular disease. Studies on the levels of PIGF would help to reduce the risk and prevention of heart failures in astronauts. If we can use this marker to predict and reduce the risk of cardiac events in astronauts and pilots, it would significantly help aerospace medicine operations. The investigations here confirmed that in a cardiovascular stressed population such as coronary artery disease (CAD) and acute coronary syndrome (ACS) patients, PIGF could be overexpressed. We desired to re-evaluate this marker in patients with cardiovascular disease in our own study. PIGF is a marker of inflammation and a predictor of short-term and long-term adverse outcome in ACS. In addition, elevated PIGF levels may be associated with increased risk for CAD.PIGF levels were determined in thirty-one patients undergoing cardiovascular catheterization for reasons other than ACS and in thirty-three low-risk asymptomatic subjects. Additional data on traditional cardiovascular risk factors for both populations were also compiled and compared. We found that PIGF levels were significantly higher in the high-risk population as compared to low-risk population. Also we were able to ascertain that PIGF levels were inversely correlated with HDL-cholesterol but directly correlated with the triglyceride levels. With further validation, PIGF may prove a useful addition to the armamentarium of noninvasive biomarkers for cardiovascular disease including a new area of stressful physiological conditions such as microgravity.

Motivational Engineering for Pilot Training.

ERIC Educational Resources Information Center

Herzberg, Frederick I.; And Others

The study was an investigation of student pilot motivation for, and toward, the Air Training Command's undergraduate pilot training (UPT) program. The motivation hygiene approach was used to identify the motivational factors operating in the UPT program systematically. This approach has been used extensively in industry and with success in a…

The Pilot Staffing Conundrum: A Delphi Study

DTIC Science & Technology

2009-06-01

Project, AFIT/ GMO /LAL/98J-2. School of Logistics and Acquisition Management, Air Force Institute of Technology (AU), Wright Patterson AFB, OH, June...Kafer, John H. Relationship of Airline Pilot Demand and Air Force Pilot Retention. Graduate Research Project, AFIT/ GMO /LAL/98J-11. School of Logistics

Effects of milk product intake on thigh muscle strength and NFKB gene methylation during home-based interval walking training in older women: A randomized, controlled pilot study

PubMed Central

Masuki, Shizue; Nishida, Kensei; Hashimoto, Shigenari; Morikawa, Mayuko; Takasugi, Satoshi; Nagata, Masashi; Taniguchi, Shun'ichiro; Rokutan, Kazuhito

2017-01-01

Background Muscle atrophy with aging is closely associated with chronic systemic inflammation and lifestyle-related diseases. In the present study, we assessed whether post-exercise milk product intake during 5-month interval walking training (IWT) enhanced the increase in thigh muscle strength and ameliorated susceptibility to inflammation in older women. Methods Subjects [n = 37, 66±5 (standard deviation) yrs] who had been performing IWT for >6 months participated in this study. They were randomly divided into the following 3 groups: IWT alone (CNT, n = 12), IWT + low-dose post-exercise milk product intake (LD, n = 12; 4 g protein and 3 g carbohydrate) or IWT + a 3-times higher dose of milk product intake than the LD group (HD, n = 13). They were instructed to repeat ≥5 sets of fast and slow walking for 3 min each at ≥70% and 40% peak aerobic capacity for walking, respectively, per day for ≥4 days/week. Results After IWT, thigh muscle strength increased in the HD group (8±2%) more than in the CNT group (-2±3%, P = 0.022), despite similar IWT achievements between the groups (P>0.15). Pyrosequencing analysis using whole blood showed that methylation of NFKB1 and NFKB2, master genes of inflammation, was enhanced in the HD group (29±7% and 44±11%, respectively) more than in the CNT group (-20±6% and -10±6%, respectively; P<0.001). Moreover, the genome-wide DNA methylation analysis showed that several inflammation-related genes were hyper-methylated in the HD group compared with that in the CNT group, suggesting greater pro-inflammatory cytokine gene suppression in the HD group. Conclusion HD milk product intake after exercise produced a greater percent increase in thigh muscle strength and NFKB1 and NFKB2 gene methylation during IWT in physically active older women. Trial registration UMIN-CTR No. UMIN000024544 and No. UMIN000024912 PMID:28520754

The HLA linked iron loading gene in an Afrikaner population.

PubMed

Meyer, T E; Ballot, D; Bothwell, T H; Green, A; Derman, D P; Baynes, R D; Jenkins, T; Jooste, P L; du Toit, E D; Jacobs, P J

1987-06-01

The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape.

The HLA linked iron loading gene in an Afrikaner population.

PubMed Central

Meyer, T E; Ballot, D; Bothwell, T H; Green, A; Derman, D P; Baynes, R D; Jenkins, T; Jooste, P L; du Toit, E D; Jacobs, P J

1987-01-01

The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape. PMID:2886665

GIS data for the Seaside, Oregon, Tsunami Pilot Study to modernize FEMA flood hazard maps

USGS Publications Warehouse

Wong, Florence L.; Venturato, Angie J.; Geist, Eric L.

2007-01-01

A Tsunami Pilot Study was conducted for the area surrounding the coastal town of Seaside, Oregon, as part of the Federal Emergency Management's (FEMA) Flood Insurance Rate Map Modernization Program (Tsunami Pilot Study Working Group, 2006). The Cascadia subduction zone extends from Cape Mendocino, California, to Vancouver Island, Canada. The Seaside area was chosen because it is typical of many coastal communities subject to tsunamis generated by far- and near-field (Cascadia) earthquakes. Two goals of the pilot study were to develop probabilistic 100-year and 500-year tsunami inundation maps using Probabilistic Tsunami Hazard Analysis (PTHA) and to provide recommendations for improving tsunami hazard assessment guidelines for FEMA and state and local agencies. The study was an interagency effort by the National Oceanic and Atmospheric Administration, U.S. Geological Survey, and FEMA, in collaboration with the University of Southern California, Middle East Technical University, Portland State University, Horning Geoscience, Northwest Hydraulics Consultants, and the Oregon Department of Geological and Mineral Industries. The pilot study model data and results are published separately as a geographic information systems (GIS) data report (Wong and others, 2006). The flood maps and GIS data are briefly described here.

Early intervention following trauma may mitigate genetic risk for PTSD in civilians: a pilot prospective emergency department study.

PubMed

Rothbaum, Barbara O; Kearns, Megan C; Reiser, Emily; Davis, Jennifer S; Kerley, Kimberly A; Rothbaum, Alex O; Mercer, Kristina B; Price, Matthew; Houry, Debra; Ressler, Kerry J

2014-12-01

Civilian posttraumatic stress disorder (PTSD) and combat PTSD are major public health concerns. Although a number of psychosocial risk factors have been identified related to PTSD risk, there are no accepted, robust biological predictors that identify who will develop PTSD or who will respond to early intervention following trauma. We wished to examine whether genetic risk for PTSD can be mitigated with an early intervention. 65 emergency department patients recruited in 2009-2010 at Grady Memorial Hospital in Atlanta, Georgia, who met criterion A of DSM-IV PTSD received either 3 sessions of an exposure intervention, beginning in the emergency department shortly after trauma exposure or assessment only. PTSD symptoms were assessed 4 and 12 weeks after trauma exposure. A composite additive risk score was derived from polymorphisms in 10 previously identified genes associated with stress-response (ADCYAP1R1, COMT, CRHR1, DBH, DRD2, FAAH, FKBP5, NPY, NTRK2, and PCLO), and gene x treatment effects were examined. The intervention included 3 sessions of imaginal exposure to the trauma memory and additional exposure homework. The primary outcome measure was the PTSD Symptom Scale-Interview Version or DSM-IV-based PTSD diagnosis in patients related to genotype and treatment group. A gene x intervention x time effect was detected for individual polymorphisms, in particular the PACAP receptor, ADCYAP1R1, as well as with a combined genotype risk score created from independent SNP markers. Subjects who did not receive treatment had higher symptoms than those who received intervention. Furthermore, subjects with the "risk" genotypes who did not receive intervention had higher PTSD symptoms compared to those with the "low-risk" or "resilience" genotypes or those who received intervention. Additionally, PTSD symptoms correlated with level of genetic risk at week 12 (P < .005) in the assessment-only group, but with no relationship in the intervention group, even after controlling for age, sex, race, education, income, and childhood trauma. Using logistic regression, the number of risk alleles was significantly associated with likelihood of PTSD diagnosis at week 12 (P < .05). This pilot prospective study suggests that combined genetic variants may serve to predict those most at risk for developing PTSD following trauma. A psychotherapeutic intervention initiated in the emergency department within hours of the trauma may mitigate this risk. The role of genetic predictors of risk and resilience should be further evaluated in larger, prospective intervention and prevention trials. ClinicalTrials.gov identifier: NCT00895518. © Copyright 2014 Physicians Postgraduate Press, Inc.

Enhanced Flight Vision Systems Operational Feasibility Study Using Radar and Infrared Sensors

NASA Technical Reports Server (NTRS)

Etherington, Timothy J.; Kramer, Lynda J.; Severance, Kurt; Bailey, Randall E.; Williams, Steven P.; Harrison, Stephanie J.

2015-01-01

Approach and landing operations during periods of reduced visibility have plagued aircraft pilots since the beginning of aviation. Although techniques are currently available to mitigate some of the visibility conditions, these operations are still ultimately limited by the pilot's ability to "see" required visual landing references (e.g., markings and/or lights of threshold and touchdown zone) and require significant and costly ground infrastructure. Certified Enhanced Flight Vision Systems (EFVS) have shown promise to lift the obscuration veil. They allow the pilot to operate with enhanced vision, in lieu of natural vision, in the visual segment to enable equivalent visual operations (EVO). An aviation standards document was developed with industry and government consensus for using an EFVS for approach, landing, and rollout to a safe taxi speed in visibilities as low as 300 feet runway visual range (RVR). These new standards establish performance, integrity, availability, and safety requirements to operate in this regime without reliance on a pilot's or flight crew's natural vision by use of a fail-operational EFVS. A pilot-in-the-loop high-fidelity motion simulation study was conducted at NASA Langley Research Center to evaluate the operational feasibility, pilot workload, and pilot acceptability of conducting straight-in instrument approaches with published vertical guidance to landing, touchdown, and rollout to a safe taxi speed in visibility as low as 300 feet RVR by use of vision system technologies on a head-up display (HUD) without need or reliance on natural vision. Twelve crews flew various landing and departure scenarios in 1800, 1000, 700, and 300 RVR. This paper details the non-normal results of the study including objective and subjective measures of performance and acceptability. The study validated the operational feasibility of approach and departure operations and success was independent of visibility conditions. Failures were handled within the lateral confines of the runway for all conditions tested. The fail-operational concept with pilot in the loop needs further study.

A simulator investigation of the use of digital data link for pilot/ATC communications in a single pilot operation

NASA Technical Reports Server (NTRS)

Hinton, David A.; Lohr, Gary W.

1988-01-01

Studies have shown that radio communications between pilots and air traffic control contribute to high pilot workload and are subject to various errors. These errors result from congestion on the voice radio channel, and missed and misunderstood messages. The use of digital data link has been proposed as a means of reducing this workload and error rate. A critical factor, however, in determining the potential benefit of data link will be the interface between future data link systems and the operator of those systems, both in the air and on the ground. The purpose of this effort was to evaluate the pilot interface with various levels of data link capability, in simulated general aviation, single-pilot instrument flight rule operations. Results show that the data link reduced demands on pilots' short-term memory, reduced the number of communication transmissions, and permitted the pilots to more easily allocate time to critical cockpit tasks while receiving air traffic control messages. The pilots who participated unanimously indicated a preference for data link communications over voice-only communications. There were, however, situations in which the pilot preferred the use of voice communications, and the ability for pilots to delay processing the data link messages, during high workload events, caused delays in the acknowledgement of messages to air traffic control.

Accident rates for novice glider pilots vs. pilots with experience.

PubMed

Jarvis, Steve; Harris, Don

2007-12-01

It is a popular notion in gliding that newly soloed pilots have a low accident rate. The intention of this study was to review the support for such a hypothesis from literature and to explore it using UK accident totals and measures of flying exposure. Log sheets from UK gliding clubs were used to estimate flying exposure for inexperienced glider pilots. This was used along with accident data and annual flight statistics for the period 2004-2006 in order to estimate accident rates that could be compared between the pilot groups. The UK accident rate for glider pilots from 2004-2006 was 1 accident in every 3534 launches and 1590 flying hours. The lowest estimated rate for pilots with up to 1 h of experience was 1 accident every 976 launches and 149 h flown. For pilots with up to 10 h of experience the figures were 1 accident in 1274 launches and 503 h. From 2004-2006 UK glider pilots with 10 h or less experience in command had twice the number of accidents per launch and three times as many accidents per hour flown than average for UK glider pilots. Pilots with only 1 h of experience or less were involved in at least 10 times the number of accidents per hour flown than the UK average and had more than 3.5 times the number of accidents per launch.

Leptin promotes ossification through multiple ways of bone metabolism in osteoblast: a pilot study.

PubMed

Zhang, Jing; Li, Tingting; Xu, Liangzhi; Li, Wenjuan; Cheng, Meng; Zhuang, Jing; Chen, Yan; Xu, Wenming

2013-08-01

Leptin may be a potential option in preventing osteoporosis for menopausal women. The objective of this study is to explore the molecular mechanism of leptin on bone metabolism in osteoblast. Primary osteoblasts were isolated from parietal bone of adult female rats. mRNA level of OB-Rb in osteoblasts was inhibited by siRNA to block leptin signal transmission. The whole genome expression was tested by using gene chip to preliminarily explore the molecular mechanism of leptin in regulating osteoblast activity. The optimal concentration of siRNA was 25 nM, resulting in a maximal inhibition of OB-Rb mRNA. Ossification (p < 0.05) and bone mineralization (p = 0.0001) were downregulated by inhibiting leptin signal transmission, while bone resorption (p = 0.007), osteoblast differentiation (p = 0.026) and negative regulation of bone remodeling (p = 0.004) were upregulated. The expressions of some genes were regulated by OB-Rb siRNA. The expressions of alkaline phosphatase (p = 0.014) and osteocalcin (p = 0.002) were reduced, while that of vascular endothelial growth factor A (p = 0.0076) and IL-6 (p = 0.021) were increased. In a model of osteoblast, leptin positively promotes ossification through multiple ways including bone mineralization, remodeling, resorption and osteoblast differentiation, but which way plays the most critical role is not discussed in this study and needs to be clarified in future.

Greater muscle damage in athletes with ACTN3 R577X (RS1815739) gene polymorphism after an ultra-endurance race: a pilot study

PubMed Central

Crisp, AH; Verlengia, R

2017-01-01

In this study, we aimed to investigate the influence of ACTN3 R577X gene polymorphism on muscle damage responses in athletes competing in an ultra-endurance race. Twenty moderate to well-trained ultra-runners who had entered in an official 37.1 km adventure race (22.1 km mountain biking, 10.9 km trekking, 4.1 km water trekking, 30 m rope course, and orienteering) volunteered for the study. Blood samples were collected for genotyping and analysis of muscle protein levels before and after the race. Percentage changes (pre- to post-race) of serum myoglobin [XX = 5,377% vs. RX/RR = 1,666%; P = 0.005, effect size (ES) = 1.73], creatine kinase (XX = 836.5% vs. RX/RR = 455%; P = 0.04, ES = 1.29), lactate dehydrogenase (XX = 82% vs. RX/RR = 65%; P = 0.002, ES = 1.61), and aspartate aminotransferase (XX = 148% vs. RX/RR = 75%; P = 0.02, ES = 1.77) were significantly greater for XX than RX/RR genotypes. ES analysis confirmed a large magnitude of muscle damage in XX genotype ultra-runners. Therefore, athletes with the ACTN3 577XX genotype experienced more muscle damage after an adventure race. This suggests that ultra-runners with alpha-actinin-3 deficiency may be more susceptible to rhabdomyolysis and associated health complications during ultra-endurance competitions. PMID:28566803

Isolation and Characterization of Brewer's Yeast Variants with Improved Fermentation Performance under High-Gravity Conditions▿

PubMed Central

Blieck, Lies; Toye, Geert; Dumortier, Françoise; Verstrepen, Kevin J.; Delvaux, Freddy R.; Thevelein, Johan M.; Van Dijck, Patrick

2007-01-01

To save energy, space, and time, today's breweries make use of high-gravity brewing in which concentrated medium (wort) is fermented, resulting in a product with higher ethanol content. After fermentation, the product is diluted to obtain beer with the desired alcohol content. While economically desirable, the use of wort with an even higher sugar concentration is limited by the inability of brewer's yeast (Saccharomyces pastorianus) to efficiently ferment such concentrated medium. Here, we describe a successful strategy to obtain yeast variants with significantly improved fermentation capacity under high-gravity conditions. We isolated better-performing variants of the industrial lager strain CMBS33 by subjecting a pool of UV-induced variants to consecutive rounds of fermentation in very-high-gravity wort (>22° Plato). Two variants (GT336 and GT344) showing faster fermentation rates and/or more-complete attenuation as well as improved viability under high ethanol conditions were identified. The variants displayed the same advantages in a pilot-scale stirred fermenter under high-gravity conditions at 11°C. Microarray analysis identified several genes whose altered expression may be responsible for the superior performance of the variants. The role of some of these candidate genes was confirmed by genetic transformation. Our study shows that proper selection conditions allow the isolation of variants of commercial brewer's yeast with superior fermentation characteristics. Moreover, it is the first study to identify genes that affect fermentation performance under high-gravity conditions. The results are of interest to the beer and bioethanol industries, where the use of more-concentrated medium is economically advantageous. PMID:17158628

Epigenetic patterns in successful weight loss maintainers: a pilot study.

PubMed

Huang, Yen-Tsung; Maccani, Jennifer Z J; Hawley, Nicola L; Wing, Rena R; Kelsey, Karl T; McCaffery, Jeanne M

2015-05-01

DNA methylation changes occur in animal models of calorie restriction, simulating human dieting, and in human subjects undergoing behavioral weight loss interventions. This suggests that obese (OB) individuals may possess unique epigenetic patterns that may vary with weight loss. Here, we examine whether methylation patterns in leukocytes differ in individuals who lost sufficient weight to go from OB to normal weight (NW; successful weight loss maintainers; SWLMs) vs currently OB or NW individuals. This study examined peripheral blood mononuclear cell (PBMC) methylation patterns in NW (n=16, current/lifetime BMI 18.5-24.9) and OB individuals (n=16, current body mass index (BMI)⩾30), and SWLM (n=16, current BMI 18.5-24.9, lifetime maximum BMI ⩾30, average weight loss 57.4 lbs) using an Illumina Infinium HumanMethylation450 BeadArray. No leukocyte population-adjusted epigenome-wide analyses were significant; however, potentially differentially methylated loci across the groups were observed in ryanodine receptor-1 (RYR1; P=1.54E-6), myelin protein zero-like 3 (MPZL3; P=4.70E-6) and alpha 3c tubulin (TUBA3C; P=4.78E-6). In 32 obesity-related candidate genes, differential methylation patterns were found in brain-derived neurotrophic factor (BDNF; gene-wide P=0.00018). In RYR1, TUBA3C and BDNF, SWLM differed from OB but not NW. In this preliminary investigation, leukocyte SWLM DNA methylation patterns more closely resembled NW than OB individuals in three gene regions. These results suggest that PBMC methylation is associated with weight status.

A hospital based pilot study on Epstein-Barr virus in suspected infectious mononucleosis pediatric patients in India.

PubMed

Janani, Madhuravasal Krishnan; Malathi, Jambulingam; Appaswamy, Andal; Singha, Nishi Rani; Madhavan, Hajib Nariharirao

2015-10-29

Infectious mononucleosis (IM) caused by the Epstein-Barr virus (EBV) is commonly diagnosed by detection of antibodies in the patient's sera. Differentiation of acute from chronic and differential diagnosis of EBV-induced IM from IM-like syndrome caused by human cytomegalovirus (CMV) is important. The objective of this study was to standardize and use polymerase chain reaction (PCR) for diagnosis of EBV and evaluate it against enzyme-linked immunosorbent assay (ELISA). ELISA for detection of IgM and IgG antibodies to viral capsid antigen (VCA) and PCR targeting the VCA and EBNA1 gene of EBV and mtrII gene of CMV were performed on180 peripheral blood samples collected from 180 patients with suspected IM. The analytical sensitivity of PCR was evaluated against that of ELISA. Using the standard serological profile as the reference, the EBV-VCA gene was detected in 41 (95%) of 45 samples collected from patients with early primary infections, in 41 (54%) of 75 with recent primary infections, and in7 (17%) of 39 with past infections. The result of VCA PCR was statistically significant in virus detection during early or primary stage of infection. Nineteen (49%) EBV-seropositive samples were positive for CMV by PCR. All control samples tested negative for both VCA and EBNA1by PCR. VCA PCR is sensitive for the detection of EBV DNA in the early or primary stage of infection and can be considered a reliable method to rule out the cross-reactivity and differential diagnosis of EBV-induced IM from IM-like syndrome.

Pilot age and expertise predict flight simulator performance

PubMed Central

Kennedy, Quinn; Noda, Art; Yesavage, Jerome A.

2010-01-01

Background Expert knowledge may compensate for age-related declines in basic cognitive and sensory-motor abilities in some skill domains. We investigated the influence of age and aviation expertise (indexed by Federal Aviation Administration pilot ratings) on longitudinal flight simulator performance. Methods Over a 3-year period, 118 general aviation pilots aged 40 to 69 years were tested annually, in which their flight performance was scored in terms of 1) executing air-traffic controller communications; 2) traffic avoidance; 3) scanning cockpit instruments; 4) executing an approach to landing; and 5) a flight summary score. Results More expert pilots had better flight summary scores at baseline and showed less decline over time. Secondary analyses revealed that expertise effects were most evident in the accuracy of executing aviation communications, the measure on which performance declined most sharply over time. Regarding age, even though older pilots initially performed worse than younger pilots, over time older pilots showed less decline in flight summary scores than younger pilots. Secondary analyses revealed that the oldest pilots did well over time because their traffic avoidance performance improved more vs younger pilots. Conclusions These longitudinal findings support previous cross-sectional studies in aviation as well as non-aviation domains, which demonstrated the advantageous effect of prior experience and specialized expertise on older adults’ skilled cognitive performances. PMID:17325270

Selection of starter cultures for the production of sour cassava starch in a pilot-scale fermentation process.

PubMed

Penido, Fernanda Corrêa Leal; Piló, Fernanda Barbosa; Sandes, Sávio Henrique de Cicco; Nunes, Álvaro Cantini; Colen, Gecernir; Oliveira, Evelyn de Souza; Rosa, Carlos Augusto; Lacerda, Inayara Cristina Alves

2018-02-28

Sour cassava starch (Polvilho azedo) is obtained from a spontaneous fermentation conducted by microorganisms from raw materials and fermentation tanks. This product is traditionally used in the baking industry for the manufacture of biscuits and Brazilian cheese breads. However, the end of fermentation is evaluated empirically, and the process occurs without standardization, which results in products of inconsistent quality. Predominant microbiota from a cassava flour manufacturer was isolated in order to select starter cultures for the production of sour cassava starch in a pilot-scale fermentation process. Lactic acid bacteria and yeasts were isolated, enumerated and grouped by Restriction Fragment Length Polymorphism, and PCR fingerprinting, respectively. One isolate of each molecular profile was identified by sequencing of the rRNA gene. LAB were prevalent throughout the entire process. Lactobacillus brevis (21.5%), which produced the highest values of acidity, and Lactobacillus plantarum (13.9%) were among the most frequent species. Pichia scutulata (52.2%) was the prevalent yeast and showed amylolytic activity. The aforementioned species were tested as single and mixed starter cultures in a pilot-scale fermentation process for 28 days. L. plantarum exhibited better performance as a starter culture, which suggests its potential for the production of sour cassava starch. Copyright © 2018 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Conducting pilot and feasibility studies.

PubMed

Cope, Diane G

2015-03-01

Planning a well-designed research study can be tedious and laborious work. However, this process is critical and ultimately can produce valid, reliable study findings. Designing a large-scale randomized, controlled trial (RCT)-the gold standard in quantitative research-can be even more challenging. Even the most well-planned study potentially can result in issues with research procedures and design, such as recruitment, retention, or methodology. One strategy that may facilitate sound study design is the completion of a pilot or feasibility study prior to the initiation of a larger-scale trial. This article will discuss pilot and feasibility studies, their advantages and disadvantages, and implications for oncology nursing research. 
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The Impact of Integrated Maneuver Guidance Information on UAS Pilots Performing the Detect and Avoid Task

NASA Technical Reports Server (NTRS)

Rorie, Conrad; Fern, Lisa

2015-01-01

The integrated human-in-the-loop (iHITL) simulation examined the effect of four different Detect-and-Avoid (DAA) display concepts on unmanned aircraft system (UAS) pilots' ability to maintain safe separation. The displays varied in the type and amount of guidance they provided to pilots. The study's background and methodology are discussed, followed by the 'measured response' data (i.e., pilots' end-to-end response time in reacting to traffic alerts on their DAA display). Results indicate that display type had a significant impact on how long pilot's spent interacting with the interface (i.e., edit times).

An investigation of correlation between pilot scanning behavior and workload using stepwise regression analysis

NASA Technical Reports Server (NTRS)

Waller, M. C.

1976-01-01

An electro-optical device called an oculometer which tracks a subject's lookpoint as a time function has been used to collect data in a real-time simulation study of instrument landing system (ILS) approaches. The data describing the scanning behavior of a pilot during the instrument approaches have been analyzed by use of a stepwise regression analysis technique. A statistically significant correlation between pilot workload, as indicated by pilot ratings, and scanning behavior has been established. In addition, it was demonstrated that parameters derived from the scanning behavior data can be combined in a mathematical equation to provide a good representation of pilot workload.