CCI-007, a novel small molecule with cytotoxic activity against infant leukemia with MLL rearrangements

PubMed Central

Middlemiss, Shiloh M.C.; Wen, Victoria W.; Clifton, Molly; Kwek, Alan; Liu, Bing; Mayoh, Chelsea; Bongers, Angelika; Karsa, Mawar; Pan, Sukey; Cruikshank, Sarah; Scandlyn, Marissa; Hoang, Wendi; Imamura, Toshihiko; Kees, Ursula R.; Gudkov, Andrei V.; Chernova, Olga B.

2016-01-01

There is an urgent need for the development of less toxic, more selective and targeted therapies for infants with leukemia characterized by translocation of the mixed lineage leukemia (MLL) gene. In this study, we performed a cell-based small molecule library screen on an infant MLL-rearranged (MLL-r) cell line, PER-485, in order to identify selective inhibitors for MLL-r leukemia. After screening initial hits for a cytotoxic effect against a panel of 30 cell lines including MLL-r and MLL wild-type (MLL-wt) leukemia, solid tumours and control cells, small molecule CCI-007 was identified as a compound that selectively and significantly decreased the viability of a subset of MLL-r and related leukemia cell lines with CALM-AF10 and SET-NUP214 translocation. CCI-007 induced a rapid caspase-dependent apoptosis with mitochondrial depolarization within twenty-four hours of treatment. CCI-007 altered the characteristic MLL-r gene expression signature in sensitive cells with downregulation of the expression of HOXA9, MEIS1, CMYC and BCL2, important drivers in MLL-r leukemia, within a few hours of treatment. MLL-r leukemia cells that were resistant to the compound were characterised by significantly higher baseline gene expression levels of MEIS1 and BCL2 in comparison to CCI-007 sensitive MLL-r leukemia cells. In conclusion, we have identified CCI-007 as a novel small molecule that displays rapid toxicity towards a subset of MLL-r, CALM-AF10 and SET-NUP214 leukemia cell lines. Our findings suggest an important new avenue in the development of targeted therapies for these deadly diseases and indicate that different therapeutic strategies might be needed for different subtypes of MLL-r leukemia. PMID:27317766

Analysis of circulating angiogenic biomarkers from patients in two phase III trials in lung cancer of chemotherapy alone or chemotherapy and thalidomide

PubMed Central

Young, R J; Tin, A W; Brown, N J; Jitlal, M; Lee, S M; Woll, P J

2012-01-01

Background: Thalidomide has potent anti-inflammatory and anti-angiogenic properties. It was evaluated in combination with chemotherapy in two randomised placebo-controlled trials in patients with small cell lung cancer (SCLC, n=724) and advanced non-small cell lung cancer (NSCLC, n=722). Neither study demonstrated an improvement in overall survival with the addition of thalidomide to chemotherapy. This study investigated circulating angiogenic biomarkers in a subset of these patients. Methods: Serial plasma samples were collected in a cohort of patients enrolled in these two trials (n=95). Vascular endothelial growth factor (VEGF), soluble truncated form of VEGF receptor-2 (sVEGFR-2), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF) and soluble intercellular adhesion molecule-1 (sICAM-1) levels were measured by enzyme-linked immunosorbent assays. Results were correlated with patient clinical data including stage, response rate and progression-free survival (PFS). Results: Baseline biomarker levels were not significantly different between SCLC and NSCLC. For pooled treatment groups, limited stage SCLC was associated with lower baseline VEGF (P=0.046), sICAM-1 (P=0.008) and IL-8 (P=0.070) than extensive stage disease. Low baseline IL-8 was associated with a significantly improved PFS in both SCLC and NSCLC (P=0.028), and a greater reduction in IL-8 was associated with a significantly improved tumour response (P=0.035). Baseline angiogenic factor levels, however, did not predict response to thalidomide. Conclusion: Circulating angiogenic biomarkers did not identify patients who benefited from thalidomide treatment. PMID:22353811

Using Parental Profiles to Predict Membership in a Subset of College Students Experiencing Excessive Alcohol Consequences: Findings From a Longitudinal Study

PubMed Central

Varvil-Weld, Lindsey; Mallett, Kimberly A.; Turrisi, Rob; Abar, Caitlin C.

2012-01-01

Objective: Previous research identified a high-risk subset of college students experiencing a disproportionate number of alcohol-related consequences at the end of their first year. With the goal of identifying pre-college predictors of membership in this high-risk subset, the present study used a prospective design to identify latent profiles of student-reported maternal and paternal parenting styles and alcohol-specific behaviors and to determine whether these profiles were associated with membership in the high-risk consequences subset. Method: A sample of randomly selected 370 incoming first-year students at a large public university reported on their mothers’ and fathers’ communication quality, monitoring, approval of alcohol use, and modeling of drinking behaviors and on consequences experienced across the first year of college. Results: Students in the high-risk subset comprised 15.5% of the sample but accounted for almost half (46.6%) of the total consequences reported by the entire sample. Latent profile analyses identified four parental profiles: positive pro-alcohol, positive anti-alcohol, negative mother, and negative father. Logistic regression analyses revealed that students in the negative-father profile were at greatest odds of being in the high-risk consequences subset at a follow-up assessment 1 year later, even after drinking at baseline was controlled for. Students in the positive pro-alcohol profile also were at increased odds of being in the high-risk subset, although this association was attenuated after baseline drinking was controlled for. Conclusions: These findings have important implications for the improvement of existing parent- and individual-based college student drinking interventions designed to reduce alcohol-related consequences. PMID:22456248

Using parental profiles to predict membership in a subset of college students experiencing excessive alcohol consequences: findings from a longitudinal study.

PubMed

Varvil-Weld, Lindsey; Mallett, Kimberly A; Turrisi, Rob; Abar, Caitlin C

2012-05-01

Previous research identified a high-risk subset of college students experiencing a disproportionate number of alcohol-related consequences at the end of their first year. With the goal of identifying pre-college predictors of membership in this high-risk subset, the present study used a prospective design to identify latent profiles of student-reported maternal and paternal parenting styles and alcohol-specific behaviors and to determine whether these profiles were associated with membership in the high-risk consequences subset. A sample of randomly selected 370 incoming first-year students at a large public university reported on their mothers' and fathers' communication quality, monitoring, approval of alcohol use, and modeling of drinking behaviors and on consequences experienced across the first year of college. Students in the high-risk subset comprised 15.5% of the sample but accounted for almost half (46.6%) of the total consequences reported by the entire sample. Latent profile analyses identified four parental profiles: positive pro-alcohol, positive anti-alcohol, negative mother, and negative father. Logistic regression analyses revealed that students in the negative-father profile were at greatest odds of being in the high-risk consequences subset at a follow-up assessment 1 year later, even after drinking at baseline was controlled for. Students in the positive pro-alcohol profile also were at increased odds of being in the high-risk subset, although this association was attenuated after baseline drinking was controlled for. These findings have important implications for the improvement of existing parent- and individual-based college student drinking interventions designed to reduce alcohol-related consequences.

Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model

PubMed Central

Ebersole, J L; Steffen, M J; Holt, S C; Kesavalu, L; Chu, L; Cappelli, D

2010-01-01

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E2 (PGE2) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE2, LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE2, macrophage chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature-induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals. PMID:21070210

Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the Lamina Propria and Peyer’s Patches

PubMed Central

Morikawa, Masatoshi; Tsujibe, Satoshi; Kiyoshima-Shibata, Junko; Watanabe, Yohei; Kato-Nagaoka, Noriko; Shida, Kan; Matsumoto, Satoshi

2016-01-01

Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer’s patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe in the small intestine), whereas CD11bhi and CD11bhiCD11chi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the Lactobacillus species engulfed by the SILP cell subsets, L. murinus was engulfed more frequently than L. taiwanensis, although both these Lactobacillus species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa. PMID:27701454

Microbiota of the Small Intestine Is Selectively Engulfed by Phagocytes of the Lamina Propria and Peyer's Patches.

PubMed

Morikawa, Masatoshi; Tsujibe, Satoshi; Kiyoshima-Shibata, Junko; Watanabe, Yohei; Kato-Nagaoka, Noriko; Shida, Kan; Matsumoto, Satoshi

2016-01-01

Phagocytes such as dendritic cells and macrophages, which are distributed in the small intestinal mucosa, play a crucial role in maintaining mucosal homeostasis by sampling the luminal gut microbiota. However, there is limited information regarding microbial uptake in a steady state. We investigated the composition of murine gut microbiota that is engulfed by phagocytes of specific subsets in the small intestinal lamina propria (SILP) and Peyer's patches (PP). Analysis of bacterial 16S rRNA gene amplicon sequences revealed that: 1) all the phagocyte subsets in the SILP primarily engulfed Lactobacillus (the most abundant microbe in the small intestine), whereas CD11bhi and CD11bhiCD11chi cell subsets in PP mostly engulfed segmented filamentous bacteria (indigenous bacteria in rodents that are reported to adhere to intestinal epithelial cells); and 2) among the Lactobacillus species engulfed by the SILP cell subsets, L. murinus was engulfed more frequently than L. taiwanensis, although both these Lactobacillus species were abundant in the small intestine under physiological conditions. These results suggest that small intestinal microbiota is selectively engulfed by phagocytes that localize in the adjacent intestinal mucosa in a steady state. These observations may provide insight into the crucial role of phagocytes in immune surveillance of the small intestinal mucosa.

Medical students perceive better group learning processes when large classes are made to seem small.

PubMed

Hommes, Juliette; Arah, Onyebuchi A; de Grave, Willem; Schuwirth, Lambert W T; Scherpbier, Albert J J A; Bos, Gerard M J

2014-01-01

Medical schools struggle with large classes, which might interfere with the effectiveness of learning within small groups due to students being unfamiliar to fellow students. The aim of this study was to assess the effects of making a large class seem small on the students' collaborative learning processes. A randomised controlled intervention study was undertaken to make a large class seem small, without the need to reduce the number of students enrolling in the medical programme. The class was divided into subsets: two small subsets (n=50) as the intervention groups; a control group (n=102) was mixed with the remaining students (the non-randomised group n∼100) to create one large subset. The undergraduate curriculum of the Maastricht Medical School, applying the Problem-Based Learning principles. In this learning context, students learn mainly in tutorial groups, composed randomly from a large class every 6-10 weeks. The formal group learning activities were organised within the subsets. Students from the intervention groups met frequently within the formal groups, in contrast to the students from the large subset who hardly enrolled with the same students in formal activities. Three outcome measures assessed students' group learning processes over time: learning within formally organised small groups, learning with other students in the informal context and perceptions of the intervention. Formal group learning processes were perceived more positive in the intervention groups from the second study year on, with a mean increase of β=0.48. Informal group learning activities occurred almost exclusively within the subsets as defined by the intervention from the first week involved in the medical curriculum (E-I indexes>-0.69). Interviews tapped mainly positive effects and negligible negative side effects of the intervention. Better group learning processes can be achieved in large medical schools by making large classes seem small.

Medical Students Perceive Better Group Learning Processes when Large Classes Are Made to Seem Small

PubMed Central

Hommes, Juliette; Arah, Onyebuchi A.; de Grave, Willem; Schuwirth, Lambert W. T.; Scherpbier, Albert J. J. A.; Bos, Gerard M. J.

2014-01-01

Objective Medical schools struggle with large classes, which might interfere with the effectiveness of learning within small groups due to students being unfamiliar to fellow students. The aim of this study was to assess the effects of making a large class seem small on the students' collaborative learning processes. Design A randomised controlled intervention study was undertaken to make a large class seem small, without the need to reduce the number of students enrolling in the medical programme. The class was divided into subsets: two small subsets (n = 50) as the intervention groups; a control group (n = 102) was mixed with the remaining students (the non-randomised group n∼100) to create one large subset. Setting The undergraduate curriculum of the Maastricht Medical School, applying the Problem-Based Learning principles. In this learning context, students learn mainly in tutorial groups, composed randomly from a large class every 6–10 weeks. Intervention The formal group learning activities were organised within the subsets. Students from the intervention groups met frequently within the formal groups, in contrast to the students from the large subset who hardly enrolled with the same students in formal activities. Main Outcome Measures Three outcome measures assessed students' group learning processes over time: learning within formally organised small groups, learning with other students in the informal context and perceptions of the intervention. Results Formal group learning processes were perceived more positive in the intervention groups from the second study year on, with a mean increase of β = 0.48. Informal group learning activities occurred almost exclusively within the subsets as defined by the intervention from the first week involved in the medical curriculum (E-I indexes>−0.69). Interviews tapped mainly positive effects and negligible negative side effects of the intervention. Conclusion Better group learning processes can be achieved in large medical schools by making large classes seem small. PMID:24736272

The effect of tracking network configuration on Global Positioning System (GPS) baseline estimates for the CASA (Central and South America) Uno experiment

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

Wolf, S.K.; Dixon, T.H.; Freymueller, J.T.

1990-04-01

Geodetic monitoring of subduction of the Nazca and Cocos plates is a goal of the CASA (Central and South America) Global Positioning System (GPS) experiments, and requires measurement of intersite distances (baselines) in excess of 500 km. The major error source in these measurements is the uncertainty in the position of the GPS satellites at the time of observation. A key aspect of the first CASA experiment, CASA Uno, was the initiation of a global network of tracking stations minimize these errors. The authors studied the effect of using various subsets of this global tracking network on long (>100 km)more » baseline estimates in the CASA region. Best results were obtained with a global tracking network consisting of three U.S. fiducial stations, two sites in the southwest pacific and two sites in Europe. Relative to smaller subsets, this global network improved baseline repeatability, resolution of carrier phase cycle ambiguities, and formal errors of the orbit estimates. Describing baseline repeatability for horizontal components as {sigma}=(a{sup 2} + b{sup 2}L{sup 2}){sup 1/2} where L is baseline length, the authors obtained a = 4 and 9 mm and b = 2.8{times}10{sup {minus}8} and 2.3{times}10{sup {minus}8} for north and east components, respectively, on CASA baselines up to 1,000 km in length with this global network.« less

TerraSAR-X interferometry reveals small-scale deformation associated with the summit eruption of Kīlauea Volcano, Hawai`i

NASA Astrophysics Data System (ADS)

Richter, Nicole; Poland, Michael P.; Lundgren, Paul R.

2013-04-01

On 19 March 2008, a small explosive eruption at the summit of Kīlauea Volcano, Hawai`i, heralded the formation of a new vent along the east wall of Halema`uma`u Crater. In the ensuing years, the vent widened due to collapses of the unstable rim and conduit wall; some collapses impacted an actively circulating lava pond and resulted in small explosive events. We used synthetic aperture radar data collected by the TerraSAR-X satellite, a joint venture between the German Aerospace Center (DLR) and EADS Astrium, to identify and analyze small-scale surface deformation around the new vent during 2008-2012. Lidar data were used to construct a digital elevation model to correct for topographic phase, allowing us to generate differential interferograms with a spatial resolution of about 3 m in Kīlauea's summit area. These interferograms reveal subsidence within about 100 m of the rim of the vent. Small baseline subset time series analysis suggests that the subsidence rate is not constant and, over time, may provide an indication of vent stability and potential for rim and wall collapse—information with obvious hazard implications. The deformation is not currently detectable by other space- or ground-based techniques.

TerraSAR-X interferometry reveals small-scale deformation associated with the summit eruption of Kilauea Volcano, Hawai‘i

USGS Publications Warehouse

Richter, Nichole; Poland, Michael P.; Lundgren, Paul R.

2013-01-01

On 19 March 2008, a small explosive eruption at the summit of Kīlauea Volcano, Hawai‘i, heralded the formation of a new vent along the east wall of Halema‘uma‘u Crater. In the ensuing years, the vent widened due to collapses of the unstable rim and conduit wall; some collapses impacted an actively circulating lava pond and resulted in small explosive events. We used synthetic aperture radar data collected by the TerraSAR-X satellite, a joint venture between the German Aerospace Center (DLR) and EADS Astrium, to identify and analyze small-scale surface deformation around the new vent during 2008-2012. Lidar data were used to construct a digital elevation model to correct for topographic phase, allowing us to generate differential interferograms with a spatial resolution of about 3 m in Kīlauea's summit area. These interferograms reveal subsidence within about 100 m of the rim of the vent. Small baseline subset time series analysis suggests that the subsidence rate is not constant and, over time, may provide an indication of vent stability and potential for rim and wall collapse -- information with obvious hazard implications. The deformation is not currently detectable by other space- or ground-based techniques.

The effect of perceptual grouping on haptic numerosity perception.

PubMed

Verlaers, K; Wagemans, J; Overvliet, K E

2015-01-01

We used a haptic enumeration task to investigate whether enumeration can be facilitated by perceptual grouping in the haptic modality. Eight participants were asked to count tangible dots as quickly and accurately as possible, while moving their finger pad over a tactile display. In Experiment 1, we manipulated the number and organization of the dots, while keeping the total exploration area constant. The dots were either evenly distributed on a horizontal line (baseline condition) or organized into groups based on either proximity (dots placed in closer proximity to each other) or configural cues (dots placed in a geometric configuration). In Experiment 2, we varied the distance between the subsets of dots. We hypothesized that when subsets of dots can be grouped together, the enumeration time will be shorter and accuracy will be higher than in the baseline condition. The results of both experiments showed faster enumeration for the configural condition than for the baseline condition, indicating that configural grouping also facilitates haptic enumeration. In Experiment 2, faster enumeration was also observed for the proximity condition than for the baseline condition. Thus, perceptual grouping speeds up haptic enumeration by both configural and proximity cues, suggesting that similar mechanisms underlie perceptual grouping in both visual and haptic enumeration.

InSAR Time Series to Characterize Landslide Ground Deformations in a Tropical Urban Environment: Focus on Bukavu, East African Rift System (RD Congo).

NASA Astrophysics Data System (ADS)

Nobile, A.; d'Oreye, N.; Monsieurs, E.; Dewitte, O.; Kervyn, F.

2016-12-01

The western branch of the East African Rift System, in Central Africa, is a region naturally prone to landslides due to factors such as heavy rainfall, tectonic activity and steep topography. In addition, sensibility to slope instability is expected to increase in the future in response to increasing demographic pressure and land use/land cover changes. The Rift flanks west of Lake Kivu (DRC) are one of the Congolese regions most affected by landslides. Although heavy rainfall periods and earthquakes are the main triggering factors, nothing is known on their potential role on the current dynamics of existing landslides Here we used InSAR time series to monitor ground deformations associated to large slow-moving landslides that continuously affect highly populated slopes in the city of Bukavu (DRC). Bukavu is located within the Rift, on the southern shore of Lake Kivu, in a tropical environment. Using >100 Cosmo-SkyMed SAR images, acquired between March 2015 and June 2016 with a mean revisiting time of 8 days per orbit (ascending and descending), we produce displacement-rate maps and ground deformation time series using different techniques: Persistent Scatter (PS), Small Baseline Subset (SBAS) and Multidimensional Small Baseline Subsets (MSBAS). The three techniques provides similar results in areas with relatively small displacements (few mm per months). However, in areas where displacements are much higher and where coherence is lost by traditional techniques, MSBAS, that process concurrently the two satellite orbits improving temporal resolution, is more efficient. It allows to measure higher ground deformation rates by keeping the coherence. For one specific landslide where intense field mapping was done, the results show clearly the pattern of the deformations that divides the landslide in blocks that move with different velocity (up to 20 cm/yr). This pattern is consistent with field observations and possibly related to the anthropic activity. Furthermore, DGPS measurements, taken at 21 benchmarks in the area during the same period, allow validating the InSAR results. The combination of InSAR data with rainfall and seismic monitoring, and field observations should help us, when longer time-series will be available, to better understand the mechanisms (both natural and human) that affect this landslide.

Orogen-Wide InSAR Time Series for Detecting Deformation Sources: The Zagros and Makran of Southern Iran

NASA Astrophysics Data System (ADS)

Lohman, R. B.; Barnhart, W. D.

2011-12-01

We present interferometric synthetic aperture radar (InSAR) time series maps that span the eastern Zagros (Fars Arc) collisional belt and western Makran accretionary prism of Southern Iran. Given the upcoming availability of large volumes of SAR data from new platforms, such as Sentinel 1 and potentially DESDynI, we explore computationally efficient approaches for extracting deformation time series when the signal of interest is small compared to the level of noise in individual interferograms. We use 12 descending and 2 ascending multi-frame (2-4 frames) Envisat tracks and 2 ascending ALOS tracks spanning 2003-2010 and 2006-2010. We implement a linear inversion, similar to the Small Baseline Subset (SBaS) technique, to derive surface displacements at individual acquisition dates from trees of interferograms with perpendicular baselines less than 350m for Envisat and 1500m for ALOS pairs. This spatially extensive dataset allows us to investigate several attributes of interferometry that vary spatially and temporally over large distances, including changes in phase coherence relative to elevation and relief as well as land use. Through synthetic tests and observed data, we explore various sources of potential error in calculation of time series, including variable coherence of pixels between interferograms in a single track, ambiguities in phase unwrapping, and orbital ramp estimation over scenes with variable correlated noise structure. We present examples of detected signals with both temporally variable characteristics and small magnitudes, including surface/subsurface salt deformation, aseismic deformation across Minab-Zendan-Palami strike-slip zone, and subsidence due to hydrocarbon extraction.

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

PubMed Central

Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

PubMed

Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

Treatment of Primary Cutaneous CD4 Small/Medium T cell Lymphoproliferative Disorder with Intralesional Triamcinolone Acetonide.

DTIC Science & Technology

2018-02-15

12. REPORT TYPE 02/15/2018 Poster 4. TITLE AND SUBTITLE Treatment of Primary Cutaneous CD4+ Small/Medium T- cell Lymphoproliferative Disorder with...cutaneous CD4+ small/medium T- cell lymphoproliferative disorder (LPD) is a generally indolent cutaneous T- cell proliferation. Most cases follow a benign...lmmunohistochemistry showed diffuse CD3+ CD4+ T- cells without CD30, TIA1 or CD10. A subset of medium to large cells expressed BCL-6. Small subsets of B- cells and CDB

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

PubMed Central

Kapetanovic, Suad; Aaron, Lisa; Montepiedra, Grace; Anthony, Patricia; Thuvamontolrat, Kasalyn; Pahwa, Savita; Burchett, Sandra; Weinberg, Adriana; Kovacs, Andrea

2015-01-01

Background We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Methods Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system. PMID:25794163

Deriving a time series of 3D glacier motion to investigate interactions of a large mountain glacial system with its glacial lake: Use of Synthetic Aperture Radar Pixel Offset-Small Baseline Subset technique

NASA Astrophysics Data System (ADS)

Li, Jia; Li, Zhi-wei; Wu, Li-xin; Xu, Bing; Hu, Jun; Zhou, Yu-shan; Miao, Ze-lang

2018-04-01

We investigated the interactions of Lake Merzbacher with the Southern Inylchek Glacier (Central Tien Shan) using the Synthetic Aperture Radar (SAR) Pixel Offset-Small Baseline Subset (PO-SBAS) to derive a time series of three-dimensional (3D) glacier motion. The measurements of 3D glacier velocity were ∼17% more precise than a previous study that did not use the SBAS estimation. The velocities of the glacier were up to 58 cm/day east, 70 cm/day north, and 113 cm/day vertically. Combining these data with Landsat images indicated that movement of the glacier is sensitive to changes of Lake Merzbacher. Specifically, the entry of more lake water into the glacier during the ablation season increased englacial ablation due to thermal erosion. Moreover, ice calving begins when the lake water gradually lifts the ice dam. Calving can cause greater loss of glacier mass than normal ablation. Trying to replenish the front mass loss, the distributary accelerates and the mass loss further intensifies. A time series of the vertical velocity indicates that the glacier tongue has a huge englacial cavity. We suggest that the lake outburst is directly related to the crack of this cavity. Bursting of the lake triggers a mini-surge at the glacier tongue. The vertical velocity at the ice dam was ∼+60 cm/day before the lake outburst, and ∼-113 cm/day afterwards. After drainage of the lake, flow velocities at the distributary, do not sharply decrease because pre-drainage mass loss needs to be replenished by fast flow. Based on comparisons with previous measurements, our results indicate that the lake had an increasing influence on the glacier from 2005 to 2009. This study demonstrates that a time series of 3D glacier motion based on the PO-SBAS technique is effective for assessing the dynamics of a mountain glacial system and interactions with its glacial lake.

Multi-interferogram method for measuring interseismic deformation: Denali Fault, Alaska

USGS Publications Warehouse

Biggs, Juliet; Wright, Tim; Lu, Zhong; Parsons, Barry

2007-01-01

Studies of interseismic strain accumulation are crucial to our understanding of continental deformation, the earthquake cycle and seismic hazard. By mapping small amounts of ground deformation over large spatial areas, InSAR has the potential to produce continental-scale maps of strain accumulation on active faults. However, most InSAR studies to date have focused on areas where the coherence is relatively good (e.g. California, Tibet and Turkey) and most analysis techniques (stacking, small baseline subset algorithm, permanent scatterers, etc.) only include information from pixels which are coherent throughout the time-span of the study. In some areas, such as Alaska, where the deformation rate is small and coherence very variable, it is necessary to include information from pixels which are coherent in some but not all interferograms. We use a three-stage iterative algorithm based on distributed scatterer interferometry. We validate our method using synthetic data created using realistic parameters from a test site on the Denali Fault, Alaska, and present a preliminary result of 10.5 ?? 5.0 mm yr-1 for the slip rate on the Denali Fault based on a single track of radar data from ERS1/2. ?? 2007 The Authors Journal compilation ?? 2007 RAS.

Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

PubMed

Martyanov, Viktor; Whitfield, Michael L

2016-01-01

The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

PubMed

Asherson, P; Stes, S; Nilsson Markhed, M; Berggren, L; Svanborg, P; Kutzelnigg, A; Deberdt, W

2015-06-01

To investigate the effects of atomoxetine on emotional control in adults with ADHD. We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life. Copyright © 2015. Published by Elsevier Masson SAS.

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults.

PubMed

Stermole, Benjamin M; Grandits, Greg A; Roediger, Mollie P; Clark, Brychan M; Ganesan, Anuradha; Weintrob, Amy C; Crum-Cianflone, Nancy F; Ferguson, Tomas M; Macalino, Grace E; Landrum, Michael L

2011-04-05

We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/μL greater for cases than controls (p=0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change -0.04 (±0.18) log(10) copies/mL; p=0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

SBAS-InSAR analysis of surface deformation at Mauna Loa and Kilauea volcanoes in Hawaii

USGS Publications Warehouse

Casu, F.; Lanari, Riccardo; Sansosti, E.; Solaro, G.; Tizzani, Pietro; Poland, M.; Miklius, Asta

2009-01-01

We investigate the deformation of Mauna Loa and K??lauea volcanoes, Hawai'i, by exploiting the advanced differential Synthetic Aperture Radar Interferometry (InSAR) technique referred to as the Small BAseline Subset (SBAS) algorithm. In particular, we present time series of line-of-sight (LOS) displacements derived from SAR data acquired by the ASAR instrument, on board the ENVISAT satellite, from the ascending (track 93) and descending (track 429) orbits between 2003 and 2008. For each coherent pixel of the radar images we compute time-dependent surface displacements as well as the average LOS deformation rate. Our results quantify, in space and time, the complex deformation of Mauna Loa and K??lauea volcanoes. The derived InSAR measurements are compared to continuous GPS data to asses the quality of the SBAS-InSAR products. ??2009 IEEE.

Intermittent Small Baseline Subset (ISBAS) InSAR of rural and vegetated terrain: a new method to monitor land motion applied to peatlands in Wales, UK

NASA Astrophysics Data System (ADS)

Cigna, Francesca; Rawlins, Barry G.; Jordan, Colm J.; Sowter, Andrew; Evans, Christopher D.

2014-05-01

It is renowned that the success of multi-interferometric Synthetic Aperture Radar (SAR) methods such as Persistent Scatterer Interferometry (PSI) and Small BASeline Subset (SBAS) is controlled by not only the availability of data, but also local topography and land cover. Locations with sufficient temporal phase stability and coherence are typically limited to either built-up, urban areas or areas of exposed bedrock. Whilst conventional PSI and SBAS approaches have limited potential to monitor surface motions in areas where few (or zero) scatterers or coherent targets exist, the newly developed Intermittent SBAS (ISBAS) technique (Sowter et al. 2013) can fill the gap by providing a more complete picture of ground movement in rural and vegetated regions. ISBAS is a small baseline, multi-look, coherent target method, which considers the intermittent coherence of rural areas and can work over a wide range of land cover classes including agriculture and grassland. Building upon a nationwide study that the British Geological Survey (BGS) undertook to assess the feasibility of InSAR techniques to monitor the landmass of Great Britain (Cigna et al. 2013), we identified a rural region in North Wales as an appropriate target area to evaluate the efficacy of ISBAS, where conventional SBAS and PSI approaches are unlikely to succeed. According to the UK Land Cover Map 2007 (LCM2007) from the Centre for Ecology & Hydrology (CEH), this area is dominated by improved and acid grassland, heather, bog and coniferous woodland, which are likely to result into extremely low PSI or SBAS point densities and sparse coverage of monitoring results. We employed 53 ERS-1/2 C-band (5.3GHz frequency) SAR data acquired in descending mode between 1993 and 2000, which were made available to BGS via the ESA Category 1 project id.13543. In the framework of the Glastir Monitoring & Evaluation Programme (Emmett et al. 2013), funded by the Welsh Government, we processed these using ISBAS covering a 4,460 km2 region of interest. By using thresholds for perpendicular and temporal baselines of 200 m and 4 years respectively, a total of 300 small baseline interferograms were generated and good network redundancy was obtained. Average temporal coherence of the processed scenes was rather low, with only ~4% of the processed area showing values exceeding 0.25 (hence suitable for an SBAS analysis), and most of the region revealed very low coherence, especially over areas of peat, grass, forest and heather. Processing with ISBAS allowed us to consider the intermittent behaviour of rural scatterers, dramatically improving the point density and achieving areal coverage results of around 99%. This increased the total number of monitored points by a factor of 25. The greatest improvement in terms of point density was achieved for coniferous woodland, which showed ISBAS/SBAS ratios exceeding 300, and densities increasing up to 150 points/km2 with ISBAS. Bog, acid grassland and dwarf shrub heath showed densities increasing from 2-10 to 150-160 points/km2 when using ISBAS with respect to conventional SBAS. It is worth noting that despite intermittence and the fact of relying only on a temporal subset of interferograms, the vast majority of the ISBAS points showed velocity standard deviations lower than 1.0-1.5 mm/yr, hence good quality of the estimated ground motion rates was retained using ISBAS and intermittently coherent targets. Geological interpretation, analysis and further discussion of the results in relation to changes in surface elevation of blanket peat are presented by Rawlins et al. 2014 (cf. BG2.3/SSS6.6). REFERENCES Cigna, F., Bateson, L., Jordan, C., & Dashwood, C. (2013). Nationwide monitoring of geohazards in Great Britain with InSAR: feasibility mapping based on ERS-1/2 and ENVISAT imagery. IEEE International Geoscience and Remote Sensing Symposium (IGARSS), pp. 672:675. Emmett B. E. & the GMEP team (2013). Glastir Monitoring & Evaluation Programme. First Year Annual Report to Welsh Government (Contract reference: C147/2010/11). NERC Centre for Ecology & Hydrology (CEH Project: NEC04780), pp. 393. Rawlins, B. G., Cigna, F., Jordan, C., Sowter, A., & Evans, C. (2014). Monitoring changes in surface elevation of blanket peat and other land cover types using a novel InSAR processing technique. EGU 2014, Session BG2.3/SSS6.6. Sowter, A., Bateson, L., Strange, P., Ambrose, K., & Syafiudin, M. (2013). DInSAR estimation of land motion using intermittent coherence with application to the South Derbyshire and Leicestershire coalfield. Remote Sensing Letters, 4, 979:987.

Characterization of Functional Antibody and Memory B-Cell Responses to pH1N1 Monovalent Vaccine in HIV-Infected Children and Youth

PubMed Central

Curtis, Donna J.; Muresan, Petronella; Nachman, Sharon; Fenton, Terence; Richardson, Kelly M.; Dominguez, Teresa; Flynn, Patricia M.; Spector, Stephen A.; Cunningham, Coleen K.; Bloom, Anthony; Weinberg, Adriana

2015-01-01

Objectives We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children. Methods Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1. Results At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets. Conclusions HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load. Trial Registration ClinicalTrials.gov NCT00992836 PMID:25785995

The Small Aircraft Transportation System Higher Volume Operations (SATS HVO) Flight Experiment

NASA Technical Reports Server (NTRS)

Williams, Daniel M.; Murdoch, Jennifer L.; Adams, Catherine H.

2005-01-01

This paper provides a summary of conclusions from the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) Flight Experiment which NASA conducted to determine pilot acceptability of the HVO concept for normal conditions. The SATS HVO concept improves efficiency at non-towered, non-radar airports in Instrument Meteorological Conditions (IMC) while achieving a level of safety equal to today s system. Reported are results from flight experiment data that indicate that the SATS HVO concept is viable. The success of the SATS HVO concept is based on acceptable pilot workload, performance, and subjective criteria when compared to the procedural control operations in use today at non-towered, non-radar controlled airfields in IMC. The HVO Flight Experiment, flown on NASA's Cirrus SR22, used a subset of the HVO Simulation Experiment scenarios and evaluation pilots in order to validate the simulation experiment results. HVO and Baseline (today s system) scenarios flown included: single aircraft arriving for a GPS non-precision approach; aircraft arriving for the approach with multiple traffic aircraft; and aircraft arriving for the approach with multiple traffic aircraft and then conducting a missed approach. Results reveal that all twelve low-time instrument-rated pilots preferred SATS HVO when compared to current procedural separation operations. These pilots also flew the HVO procedures safely and proficiently without additional workload in comparison to today s system (Baseline). Detailed results of pilot flight technical error, and their subjective assessments of workload and situation awareness are presented in this paper.

Second thoughts on the final rule: An analysis of baseline participant characteristics reports on ClinicalTrials.gov.

PubMed

Cahan, Amos; Anand, Vibha

2017-01-01

ClinicalTrials.gov is valuable for aggregate-level analysis of trials. The recently published final rule aims to improve reporting of trial results. We aimed to assess variability in ClinicalTirals.gov records reporting participants' baseline measures. The September 2015 edition of the database for Aggregate Analysis of ClinicalTrials.gov (AACT), was used in this study. To date, AACT contains 186,941 trials of which 16,660 trials reporting baseline (participant) measures were analyzed. We also analyzed a subset of 13,818 Highly Likely Applicable Clinical Trials (HLACT), for which reporting of results is likely mandatory and compared a random sample of 30 trial records to their journal articles. We report counts for each mandatory baseline measure and variability reporting in their formats. The AACT dataset contains 8,161 baseline measures with 1206 unique measurement units. However, of these 6,940 (85%) variables appear only once in the dataset. Age and Gender are reported using many different formats (178 and 49 respectively). "Age" as the variable name is reported in 60 different formats. HLACT subset reports measures using 3,931 variables. The most frequent Age format (i.e. mean (years) ± sd) is found in only 45% of trials. Overall only 4 baseline measures (Region of Enrollment, Age, Number of Participants, and Gender) are reported by > 10% of trials. Discrepancies are found in both the types and formats of ClinicalTrials.gov records and their corresponding journal articles. On average, journal articles include twice the number of baseline measures (13.6±7.1 (sd) vs. 6.6±7.6) when compared to the ClinicalTrials.gov records that report any results. We found marked variability in baseline measures reporting. This is not addressed by the final rule. To support secondary use of ClinicalTrials.gov, a uniform format for baseline measures reporting is warranted.

ALK mutation and inhibition in lung cancer

PubMed Central

Le, Tri; Gerber, David E.

2016-01-01

The advent of precision medicine in non-small cell lung cancer has remarkably altered the direction of research and improved clinical outcomes. The identification of molecular subsets with differential response to targeted therapies began with the identification of epidermal growth factor receptor mutated tumors in subsets of non-small cell lung cancer (NSCLC). Emboldened by unprecedented response rates to kinase inhibitors seen in that subset, the oncologic community searched for other molecular subsets featuring oncogene addiction. An early result of this search was the discovery of NSCLC driven by activating rearrangements of the anaplastic lymphoma kinase (ALK) gene. In an astoundingly brief period following the recognition of ALK-positive NSCLC, details of the biology, clinicopathologic features, development of targeted inhibitors, mechanisms of therapeutic resistance, and new generations of treatment were elucidated. This review summarizes the current understanding of the pathologic features, diagnostic approach, treatment options, resistance mechanisms, and future research areas for ALK-positive NSCLC. PMID:27637426

Application of Time Series Insar Technique for Deformation Monitoring of Large-Scale Landslides in Mountainous Areas of Western China

NASA Astrophysics Data System (ADS)

Qu, T.; Lu, P.; Liu, C.; Wan, H.

2016-06-01

Western China is very susceptible to landslide hazards. As a result, landslide detection and early warning are of great importance. This work employs the SBAS (Small Baseline Subset) InSAR Technique for detection and monitoring of large-scale landslides that occurred in Li County, Sichuan Province, Western China. The time series INSAR is performed using descending scenes acquired from TerraSAR-X StripMap mode since 2014 to get the spatial distribution of surface displacements of this giant landslide. The time series results identify the distinct deformation zone on the landslide body with a rate of up to 150mm/yr. The deformation acquired by SBAS technique is validated by inclinometers from diverse boreholes of in-situ monitoring. The integration of InSAR time series displacements and ground-based monitoring data helps to provide reliable data support for the forecasting and monitoring of largescale landslide.

High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer

PubMed Central

Pailler, E.; Auger, N.; Lindsay, C. R.; Vielh, P.; Islas-Morris-Hernandez, A.; Borget, I.; Ngo-Camus, M.; Planchard, D.; Soria, J.-C.; Besse, B.; Farace, F.

2015-01-01

Background Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Patients and methods Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. Results ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24–55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7–11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. Conclusion We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene abnormalities and elevated numerical CIN, a potential mechanism to escape ROS1-inhibitor therapy in ROS1-rearranged NSCLC tumors. PMID:25846554

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a case cohort study.

PubMed

Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A

2008-08-01

A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.

Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

PubMed Central

Law, Matthew G; Achhra, Amit; Deeks, Steven G; Gazzard, Brian; Migueles, Stephen A; Novak, Richard M; Ristola, Matti

2014-01-01

Objectives A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined. Methods We assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomisation. The key covariables considered for this analysis were race, hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤50 and ≤400 copies/mL using logistic regression. Because of the strong association between region of randomisation and baseline low HIV RNA, analyses were stratified by region. Results We found that of 4676 eligible participants randomised in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher HDL levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA. Conclusion In a modern cohort of early untreated HIV infection we found that HIV exposure routes other than male homosexual contact and higher HDL were associated with increased odds of low HIV RNA. PMID:25711322

Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.

PubMed

Turner, K; Pflugfelder, S C; Ji, Z; Feuer, W J; Stern, M; Reis, B L

2000-07-01

To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared. There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining. This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.

Decreased platelet APP isoform ratios in autosomal dominant Alzheimer's disease: baseline data from a DIAN cohort subset.

PubMed

Chatterjee, Pratishtha; Gupta, Veer B; Fagan, Anne M; Jasielec, Mateusz S; Xiong, Chengjie; Sohrabi, Hamid R; Dhaliwal, Satvinder; Taddei, Kevin; Bourgeat, Pierrick; Brown, Belinda M; Benzinger, Tammie; Bateman, Randall J; Morris, John C; Martins, Ralph N

2015-01-01

This study examines platelet amyloid precursor protein (APP) isoform ratios of 120KDa to 110KDa (APPr) between mutation carriers (MC) carrying a mutation for autosomal dominant Alzheimer's disease (ADAD) and non-carriers (NC). Two previous studies reported no significant difference in APPr between ADAD MC and NC, which may have been due to the small sample size in both studies. The current study examines APPr in MC versus NC in a larger sample. In addition, it investigated whether APPr correlate with neuroimaging data, neuropsychological data and cerebrospinal fluid biomarkers in a cohort subset derived from the Dominantly Inherited Alzheimer Network (DIAN) study. APPr were quantified by western blotting. Fifteen MC (symptomatic and asymptomatic) were compared against twelve NC using univariate general linear model. All participants underwent neuroimaging and neuropsychological testing which were correlated with APPr using Pearson's correlation coefficient (r). APPr were lower in MC compared to NC (p=0.003) while Mini-Mental State Examination (MMSE) scores were not significantly different (p>0.1). Furthermore, APPr inversely correlated with amyloid imaging in the Caudate Nucleus (r=-0.505; p<0.05) and Precuneus (r=-0.510; p<0.05). APPr are lower in ADAD MC compared to NC, and inversely correlated with brain amyloid load prior to significant differences in cognitive health. However, the use of APPr as a biomarker needs to be explored further.

High Resolution Digital Surface Model For Production Of Airport Obstruction Charts Using Spaceborne SAR Sensors

NASA Astrophysics Data System (ADS)

Oliveira, Henrique; Rodrigues, Marco; Radius, Andrea

2012-01-01

Airport Obstruction Charts (AOCs) are graphical representations of natural or man-made obstructions (its locations and heights) around airfields, according to International Civil Aviation Organization (ICAO) Annexes 4, 14 and 15. One of the most important types of data used in AOCs production/update tasks is a Digital Surface Model (first reflective surface) of the surveyed area. The development of advanced remote sensing technologies provide the available tools for obstruction data acquisition, while Geographic Information Systems (GIS) present the perfect platform for storing and analyzing this type of data, enabling the production of digital ACOs, greatly contributing to the increase of the situational awareness of pilots and enhancing the air navigation safety level [1]. Data acquisition corresponding to the first reflective surface can be obtained through the use of Airborne Laser-Scanning and Light Detection and Ranging (ALS/LIDAR) or Spaceborne SAR Systems. The need of surveying broad areas, like the entire territory of a state, shows that Spaceborne SAR systems are the most adequate in economic and feasibility terms of the process, to perform the monitoring and producing a high resolution Digital Surface Model (DSM). The high resolution DSM generation depends on many factors: the available data set, the used technique and the setting parameters. To increase the precision and obtain high resolution products, two techniques are available using a stack of data: the PS (Permanent Scatterers) technique [2], that uses large stack of data to identify many stable and coherent targets through multi- temporal analysis, removing the atmospheric contribution and to minimize the estimation errors, and the Small Baseline Subset (SBAS) technique ([3],[4]), that relies on the use of small baseline SAR interferograms and on the application of the so called singular value decomposition (SVD) method, in order to link independent SAR acquisition data sets, separated by large baselines, thus increasing the number of data used for the analysis.

Strains, functions, and dynamics in the expanded Human Microbiome Project

PubMed Central

Lloyd-Price, Jason; Mahurkar, Anup; Rahnavard, Gholamali; Crabtree, Jonathan; Orvis, Joshua; Hall, A. Brantley; Brady, Arthur; Creasy, Heather H.; McCracken, Carrie; Giglio, Michelle G.; McDonald, Daniel; Franzosa, Eric A.; Knight, Rob; White, Owen; Huttenhower, Curtis

2018-01-01

Summary The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, microbial population diversity, biogeography, and molecular function. The NIH Human Microbiome Project (HMP) has provided one of the broadest such characterizations to date. Here, we introduce an expanded second phase of the study, abbreviated HMP1-II, comprising 1,631 new metagenomic samples (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to these data to provide new characterizations of microbiome personalization. Strain identification revealed distinct subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity, thus enabling an understanding of personalized microbiome function and dynamics. PMID:28953883

Effect of CPAP on Cardiac Function in Minimally Symptomatic Patients with OSA: Results from a Subset of the MOSAIC Randomized Trial.

PubMed

Craig, Sonya; Kylintireas, Ilias; Kohler, Malcolm; Nicoll, Debby; Bratton, Daniel J; Nunn, Andrew J; Leeson, Paul; Neubauer, Stefan; Stradling, John R

2015-09-15

Minimally symptomatic obstructive sleep apnea (OSA) is highly prevalent, and the effects of continuous positive airway pressure (CPAP) on myocardial function in these patients are unknown. The MOSAIC randomized, controlled trial of CPAP for minimally symptomatic OSA assessed the effect of CPAP on myocardial function in a subset of patients. Two centers taking part in the MOSAIC trial randomized 238 patients in parallel to 6 months of CPAP (120) or standard care (118). Of these, 168 patients had echocardiograms, and 68 patients had a cardiac magnetic resonance scan (CMR). A larger group (314) from 4 centers had brain natriuretic peptide (BNP) measured. Mean (SD) baseline oxygen desaturation index (ODI) and Epworth sleepiness score (ESS) were 13.5 (13.2), and 8.4 (4.0), respectively. CPAP significantly reduced ESS and ODI. Baseline LV ejection fraction (LVEF) was well preserved (60.4%). CPAP had no significant effect on echo-derived left atrial (LA) area (-1.0 cm2, 95% CI -2.6 to +0.6, p = 0.23) or early to late left ventricular filling velocity (E/A) ratio (-0.01, 95% CI -0.07 to +0.05, p = 0.79). There was a small change in echo-derived LV end diastolic volume (EDV) with CPAP (-5.9 mL, 95% CI -10.6 to -1.2, p = 0.015). No significant changes were detected by CMR on LV mass index (+1.1 g/m(2), 95% CI -5.9 to +8.0, p = 0.76) or LVEF (+0.8%, 95% CI -1.2 to +2.8, p = 0.41). CPAP did not affect BNP levels (p = 0.16). Six months of CPAP therapy does not change cardiac functional or structural parameters measured by echocardiogram or CMR in patients with minimally symptomatic mild-to-moderate OSA. ISRCTN 34164388 (http://isrctn.org). © 2015 American Academy of Sleep Medicine.

Evaluating the transport, health and economic impacts of new urban cycling infrastructure in Sydney, Australia – protocol paper

PubMed Central

2013-01-01

Background There are repeated calls to build better cycling paths in Australian cities if the proportion of people cycling is to increase. Yet the full range of transport, health, environmental and economic impacts of new cycling infrastructure and the extent to which observed changes are sustained is not well understood. The City of Sydney is currently building a new bicycle network, which includes a new bicycle path separated from road traffic in the south Sydney area. This protocol paper describes a comprehensive method to evaluate this new cycling infrastructure. Method A cohort of residents within two kilometres of the new bicycle path will be surveyed at baseline before a new section of bicycle path is built, and again 12 and 24 months later to assess changes in travel behaviour, sense of community, quality of life and health behaviours. Residents in a comparable area of Sydney that will not get a new separated bike path will act as a comparison group. At baseline a sub-set of residents who volunteer will also take a small GPS device with them for one week to assess travel behaviour. Discussion This research should contribute to the advancement in evaluation and appraisal methods for cycling projects. PMID:24131667

A small number of candidate gene SNPs reveal continental ancestry in African Americans

PubMed Central

KODAMAN, NURI; ALDRICH, MELINDA C.; SMITH, JEFFREY R.; SIGNORELLO, LISA B.; BRADLEY, KEVIN; BREYER, JOAN; COHEN, SARAH S.; LONG, JIRONG; CAI, QIUYIN; GILES, JUSTIN; BUSH, WILLIAM S.; BLOT, WILLIAM J.; MATTHEWS, CHARLES E.; WILLIAMS, SCOTT M.

2013-01-01

SUMMARY Using genetic data from an obesity candidate gene study of self-reported African Americans and European Americans, we investigated the number of Ancestry Informative Markers (AIMs) and candidate gene SNPs necessary to infer continental ancestry. Proportions of African and European ancestry were assessed with STRUCTURE (K=2), using 276 AIMs. These reference values were compared to estimates derived using 120, 60, 30, and 15 SNP subsets randomly chosen from the 276 AIMs and from 1144 SNPs in 44 candidate genes. All subsets generated estimates of ancestry consistent with the reference estimates, with mean correlations greater than 0.99 for all subsets of AIMs, and mean correlations of 0.99±0.003; 0.98± 0.01; 0.93±0.03; and 0.81± 0.11 for subsets of 120, 60, 30, and 15 candidate gene SNPs, respectively. Among African Americans, the median absolute difference from reference African ancestry values ranged from 0.01 to 0.03 for the four AIMs subsets and from 0.03 to 0.09 for the four candidate gene SNP subsets. Furthermore, YRI/CEU Fst values provided a metric to predict the performance of candidate gene SNPs. Our results demonstrate that a small number of SNPs randomly selected from candidate genes can be used to estimate admixture proportions in African Americans reliably. PMID:23278390

When self-reliance is not safe: associations between reduced help-seeking and subsequent mental health symptoms in suicidal adolescents.

PubMed

Labouliere, Christa D; Kleinman, Marjorie; Gould, Madelyn S

2015-04-01

The majority of suicidal adolescents have no contact with mental health services, and reduced help-seeking in this population further lessens the likelihood of accessing treatment. A commonly-reported reason for not seeking help is youths' perception that they should solve problems on their own. In this study, we explore associations between extreme self-reliance behavior (i.e., solving problems on your own all of the time), help-seeking behavior, and mental health symptoms in a community sample of adolescents. Approximately 2150 adolescents, across six schools, participated in a school-based suicide prevention screening program, and a subset of at-risk youth completed a follow-up interview two years later. Extreme self-reliance was associated with reduced help-seeking, clinically-significant depressive symptoms, and serious suicidal ideation at the baseline screening. Furthermore, in a subset of youth identified as at-risk at the baseline screening, extreme self-reliance predicted level of suicidal ideation and depressive symptoms two years later even after controlling for baseline symptoms. Given these findings, attitudes that reinforce extreme self-reliance behavior may be an important target for youth suicide prevention programs. Reducing extreme self-reliance in youth with suicidality may increase their likelihood of appropriate help-seeking and concomitant reductions in symptoms.

Monocyte Phenotype and IFN-γ-Inducible Cytokine Responses Are Associated with Cryptococcal Immune Reconstitution Inflammatory Syndrome

PubMed Central

Meya, David B.; Okurut, Samuel; Zziwa, Godfrey; Cose, Stephen; Bohjanen, Paul R.; Mayanja-Kizza, Harriet; Joloba, Moses; Boulware, David R.; Yukari Manabe, Carol; Wahl, Sharon; Janoff, Edward N.

2017-01-01

A third of adults with AIDS and cryptococcal meningitis (CM) develop immune reconstitution inflammatory syndrome (IRIS) after initiating antiretroviral therapy (ART), which is thought to result from exaggerated inflammatory antigen-specific T cell responses. The contribution of monocytes to the immunopathogenesis of cryptococcal IRIS remains unclear. We compared monocyte subset frequencies and immune responses in HIV-infected Ugandans at time of CM diagnosis (IRIS-Baseline) for those who later developed CM-IRIS, controls who did not develop CM-IRIS (Control-Baseline) at CM-IRIS (IRIS-Event), and for controls at a time point matched for ART duration (Control-Event) to understand the association of monocyte distribution and immune responses with cryptococcal IRIS. At baseline, stimulation with IFN-γ ex vivo induced a higher frequency of TNF-α- and IL-6-producing monocytes among those who later developed IRIS. Among participants who developed IRIS, ex vivo IFN-γ stimulation induced higher frequencies of activated monocytes, IL-6+, TNF-α+ classical, and IL-6+ intermediate monocytes compared with controls. In conclusion, we have demonstrated that monocyte subset phenotype and cytokine responses prior to ART are associated with and may be predictive of CM-IRIS. Larger studies to further delineate innate immunological responses and the efficacy of immunomodulatory therapies during cryptococcal IRIS are warranted. PMID:29371546

When Self-Reliance Is Not Safe: Associations between Reduced Help-Seeking and Subsequent Mental Health Symptoms in Suicidal Adolescents

PubMed Central

Labouliere, Christa D.; Kleinman, Marjorie; Gould, Madelyn S.

2015-01-01

The majority of suicidal adolescents have no contact with mental health services, and reduced help-seeking in this population further lessens the likelihood of accessing treatment. A commonly-reported reason for not seeking help is youths’ perception that they should solve problems on their own. In this study, we explore associations between extreme self-reliance behavior (i.e., solving problems on your own all of the time), help-seeking behavior, and mental health symptoms in a community sample of adolescents. Approximately 2150 adolescents, across six schools, participated in a school-based suicide prevention screening program, and a subset of at-risk youth completed a follow-up interview two years later. Extreme self-reliance was associated with reduced help-seeking, clinically-significant depressive symptoms, and serious suicidal ideation at the baseline screening. Furthermore, in a subset of youth identified as at-risk at the baseline screening, extreme self-reliance predicted level of suicidal ideation and depressive symptoms two years later even after controlling for baseline symptoms. Given these findings, attitudes that reinforce extreme self-reliance behavior may be an important target for youth suicide prevention programs. Reducing extreme self-reliance in youth with suicidality may increase their likelihood of appropriate help-seeking and concomitant reductions in symptoms. PMID:25837350

Changes in hematological indices and lymphocyte subsets in response to whole blood donation in healthy male donors.

PubMed

Borai, Anwar; Livingstone, Callum; Alsobhi, Enaam; Al Sofyani, Abeer; Balgoon, Dalal; Farzal, Anwar; Almohammadi, Mohammed; Al-Amri, Abdulafattah; Bahijri, Suhad; Alrowaili, Daad; Bassiuni, Wafaa; Saleh, Ayman; Alrowaili, Norah; Abdelaal, Mohamed

2017-04-01

Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation. Repeated measures ANOVA were used to compare quantitative variables between different visits. Following blood donation, changes in CBC and erythropoietin were as expected. The neutrophil count increased by 11.3% at 8 days (p < .001). Novel changes were observed in lymphocyte subsets as the CD4/CD8 ratio increased by 9.2% (p < .05) at 8 days and 13.7% (p < .05) at 22 days. CD16-56 cells decreased by 16.2% (p < .05) at 8 days. All the subsets had returned to baseline by 106 days. Regression analysis showed that the changes in CD16-56 cells and CD4/CD8 ratio were not significant (Wilk's lambda = 0.15 and 0.94, respectively) when adjusted for BMI. In conclusion, following whole blood donation, there are transient changes in lymphocyte subsets. The effect of BMI on lymphocyte subsets and the effect of this immunomodulation on the immune response merit further investigation.

An enhancement of binary particle swarm optimization for gene selection in classifying cancer classes

PubMed Central

2013-01-01

Background Gene expression data could likely be a momentous help in the progress of proficient cancer diagnoses and classification platforms. Lately, many researchers analyze gene expression data using diverse computational intelligence methods, for selecting a small subset of informative genes from the data for cancer classification. Many computational methods face difficulties in selecting small subsets due to the small number of samples compared to the huge number of genes (high-dimension), irrelevant genes, and noisy genes. Methods We propose an enhanced binary particle swarm optimization to perform the selection of small subsets of informative genes which is significant for cancer classification. Particle speed, rule, and modified sigmoid function are introduced in this proposed method to increase the probability of the bits in a particle’s position to be zero. The method was empirically applied to a suite of ten well-known benchmark gene expression data sets. Results The performance of the proposed method proved to be superior to other previous related works, including the conventional version of binary particle swarm optimization (BPSO) in terms of classification accuracy and the number of selected genes. The proposed method also requires lower computational time compared to BPSO. PMID:23617960

40 CFR 80.245 - How does a small refiner apply for a sulfur baseline?

Code of Federal Regulations, 2011 CFR

2011-07-01

... sulfur baseline? 80.245 Section 80.245 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.245 How does a small refiner apply for a sulfur baseline? (a) Any refiner seeking small...

40 CFR 80.245 - How does a small refiner apply for a sulfur baseline?

Code of Federal Regulations, 2014 CFR

2014-07-01

... sulfur baseline? 80.245 Section 80.245 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.245 How does a small refiner apply for a sulfur baseline? (a) Any refiner seeking small...

40 CFR 80.245 - How does a small refiner apply for a sulfur baseline?

Code of Federal Regulations, 2010 CFR

2010-07-01

... sulfur baseline? 80.245 Section 80.245 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.245 How does a small refiner apply for a sulfur baseline? (a) Any refiner seeking small...

40 CFR 80.245 - How does a small refiner apply for a sulfur baseline?

Code of Federal Regulations, 2013 CFR

2013-07-01

... sulfur baseline? 80.245 Section 80.245 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.245 How does a small refiner apply for a sulfur baseline? (a) Any refiner seeking small...

40 CFR 80.245 - How does a small refiner apply for a sulfur baseline?

Code of Federal Regulations, 2012 CFR

2012-07-01

... sulfur baseline? 80.245 Section 80.245 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.245 How does a small refiner apply for a sulfur baseline? (a) Any refiner seeking small...

Transcriptional and functional profiling defines human small intestinal macrophage subsets.

PubMed

Bujko, Anna; Atlasy, Nader; Landsverk, Ole J B; Richter, Lisa; Yaqub, Sheraz; Horneland, Rune; Øyen, Ole; Aandahl, Einar Martin; Aabakken, Lars; Stunnenberg, Hendrik G; Bækkevold, Espen S; Jahnsen, Frode L

2018-02-05

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos. © 2018 Bujko et al.

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

PubMed Central

2010-01-01

Background Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD. Methods Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA. Results Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes. Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients. In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A. Conclusions Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis. PMID:20307269

Monocyte Subset Dynamics in Human Atherosclerosis Can Be Profiled with Magnetic Nano-Sensors

PubMed Central

Wildgruber, Moritz; Lee, Hakho; Chudnovskiy, Aleksey; Yoon, Tae-Jong; Etzrodt, Martin; Pittet, Mikael J.; Nahrendorf, Matthias; Croce, Kevin; Libby, Peter; Weissleder, Ralph; Swirski, Filip K.

2009-01-01

Monocytes are circulating macrophage and dendritic cell precursors that populate healthy and diseased tissue. In humans, monocytes consist of at least two subsets whose proportions in the blood fluctuate in response to coronary artery disease, sepsis, and viral infection. Animal studies have shown that specific shifts in the monocyte subset repertoire either exacerbate or attenuate disease, suggesting a role for monocyte subsets as biomarkers and therapeutic targets. Assays are therefore needed that can selectively and rapidly enumerate monocytes and their subsets. This study shows that two major human monocyte subsets express similar levels of the receptor for macrophage colony stimulating factor (MCSFR) but differ in their phagocytic capacity. We exploit these properties and custom-engineer magnetic nanoparticles for ex vivo sensing of monocytes and their subsets. We present a two-dimensional enumerative mathematical model that simultaneously reports number and proportion of monocyte subsets in a small volume of human blood. Using a recently described diagnostic magnetic resonance (DMR) chip with 1 µl sample size and high throughput capabilities, we then show that application of the model accurately quantifies subset fluctuations that occur in patients with atherosclerosis. PMID:19461894

To expand coverage, or increase frequency: Quantifying the tradeoffs between equity and efficiency facing cervical cancer screening programs in low‐resource settings

PubMed Central

Tsu, Vivien; Jeronimo, Jose; Mvundura, Mercy; Lee, Kyueun; Kim, Jane J.

2017-01-01

Cervical cancer is a leading cause of cancer death worldwide, with 85% of the disease burden residing in less developed regions. To inform evidence‐based decision‐making as cervical cancer screening programs are planned, implemented, and scaled in low‐ and middle‐income countries, we used cost and test performance data from the START‐UP demonstration project in Uganda and a microsimulation model of HPV infection and cervical carcinogenesis to quantify the health benefits, distributional equity, cost‐effectiveness, and financial impact of either (1) improving access to cervical cancer screening or (2) increasing the number of lifetime screening opportunities for women who already have access. We found that when baseline screening coverage was low (i.e., 30%), expanding coverage of screening once in a lifetime to 50% can yield comparable reductions in cancer risk to screening two or three times in a lifetime at 30% coverage, lead to greater reductions in health disparities, and cost 150 international dollars (I$) per year of life saved (YLS). At higher baseline screening coverage levels (i.e., 70%), screening three times in a lifetime yielded greater health benefits than expanding screening once in a lifetime to 90% coverage, and would have a cost‐effectiveness ratio (I$590 per YLS) below Uganda's per capita GDP. Given very low baseline coverage at present, we conclude that a policy focus on increasing access for previously unscreened women appears to be more compatible with improving both equity and efficiency than a focus on increasing frequency for a small subset of women. PMID:27925175

Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease: Methodology and Baseline Sample Characteristics.

PubMed

Byun, Min Soo; Yi, Dahyun; Lee, Jun Ho; Choe, Young Min; Sohn, Bo Kyung; Lee, Jun-Young; Choi, Hyo Jung; Baek, Hyewon; Kim, Yu Kyeong; Lee, Yun-Sang; Sohn, Chul-Ho; Mook-Jung, Inhee; Choi, Murim; Lee, Yu Jin; Lee, Dong Woo; Ryu, Seung-Ho; Kim, Shin Gyeom; Kim, Jee Wook; Woo, Jong Inn; Lee, Dong Young

2017-11-01

The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90 years, to search for new biomarkers of Alzheimer's disease (AD) and to investigate how multi-faceted lifetime experiences and bodily changes contribute to the brain changes or brain pathologies related to the AD process. All participants received comprehensive clinical and neuropsychological evaluations, multi-modal brain imaging, including magnetic resonance imaging, magnetic resonance angiography, [ 11 C]Pittsburgh compound B-positron emission tomography (PET), and [ 18 F]fluorodeoxyglucose-PET, blood and genetic marker analyses at baseline, and a subset of participants underwent actigraph monitoring and completed a sleep diary. Participants are to be followed annually with clinical and neuropsychological assessments, and biannually with the full KBASE assessment, including neuroimaging and laboratory tests. As of March 2017, in total, 758 individuals had volunteered for this study. Among them, in total, 591 participants-291 cognitively normal (CN) old-aged individuals, 74 CN young- and middle-aged individuals, 139 individuals with mild cognitive impairment (MCI), and 87 individuals with AD dementia (ADD)-were enrolled at baseline, after excluding 162 individuals. A subset of participants (n=275) underwent actigraph monitoring. The KBASE cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (CN, MCI, and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.

Work situation and self-perceived economic situation as predictors of change in burnout--a prospective general population-based cohort study.

PubMed

Norlund, Sofia; Reuterwall, Christina; Höög, Jonas; Janlert, Urban; Slunga Järvholm, Lisbeth

2015-04-03

Sick leave rates due to mental and behavioural disorders have increased in Sweden during the last decades. The aim of this prospective study was to investigate changes in the level of burnout in a working subset of the general population and to identify how such changes relate to changes in work situation and self-perceived economic situation. A cohort of 1000 persons from a subset of the 2004 northern Sweden MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) general population survey was followed over a five-year period (2004-2009). In total, 623 persons (323 women and 300 men) were included in the analysis. Burnout levels were measured at baseline and follow-up using the Shirom Melamed Burnout Questionnaire. Risk factors were assessed at both measuring points. In the whole study cohort, a small (-0.15) but statistically significant reduction in burnout level was found. No differences in change of burnout were found between men and women. Constant strain at work, an increased risk of unemployment, and a perceived worsening of economic situation during the study time period were related to an increased burnout level. An accumulation of these risk factors was associated with increased burnout level. Risk factors in work situation and self-perceived economy are related to changes in burnout level, and special attention should be directed towards persons exposed to multiple risk factors.

High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

PubMed

Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

2015-07-01

Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene abnormalities and elevated numerical CIN, a potential mechanism to escape ROS1-inhibitor therapy in ROS1-rearranged NSCLC tumors. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Telescopes in Near Space: Balloon Exoplanet Nulling Interferometer (BigBENI)

NASA Technical Reports Server (NTRS)

Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Mauk, Robin

2012-01-01

A significant and often overlooked path to advancing both science and technology for direct imaging and spectroscopic characterization of exosolar planets is to fly "near space" missions, i.e. balloon borne exosolar missions. A near space balloon mission with two or more telescopes, coherently combined, is capable of achieving a subset of the mission science goals of a single large space telescope at a small fraction of the cost. Additionally such an approach advances technologies toward flight readiness for space flight. Herein we discuss the feasibility of flying two 1.2 meter telescopes, with a baseline separation of 3.6 meters, operating in visible light, on a composite boom structure coupled to a modified visible nulling coronagraph operating to achieve an inner working angle of 60 milli-arcseconds. We discuss the potential science return, atmospheric residuals at 135,000 feet, pointing control and visible nulling and evaluate the state-or-art of these technologies with regards to balloon missions.

InSAR Monitoring OF Landslides In Britain: BGS' Feasibility Map And First ISBAS Studies Over The South Wales Coalfield

NASA Astrophysics Data System (ADS)

Cigna, F.; Bateson, L.; Dashwood, C.; Jordan, C. J.; Sowter, A.; Boon, D.

2013-12-01

InSAR is an accepted method for monitoring ground motion, however its applicability in non-urban areas is generally limited except for rocky terrains. This paper investigates a new method for deriving improved results outside the urban environment. Topographic distortions to the ERS-1/2 and ENVISAT SAR acquisition modes are simulated based on high resolution DTMs of the landmass of Britain. Persistent Scatterers (PS) densities are predicted by calibrating the CORINE Land Cover 2006 dataset using PS data available via the ESA Terrafirma and EC FP7 PanGeo projects. The InSAR feasibility to monitor land motions is discussed for the South Wales Coalfield, and the Intermittent Small Baseline Subset (ISBAS) technique is tested over the Coalfield using 55 ERS-1/2 images (1992-1999). With unprecedented target coverage, ISBAS reveals up to 1cm/yr uplift in areas of former coal mining, likely associated with groundwater rebound following cessation of mine water pumping.

Diabetes Care Management Teams Did Not Reduce Utilization When Compared With Traditional Care: A Randomized Cluster Trial.

PubMed

Kearns, Patrick

2017-10-01

PURPOSE: Health services research evaluates redesign models for primary care. Care management is one alternative. Evaluation includes resource utilization as a criterion. Compare the impact of care-manager teams on resource utilization. The comparison includes entire panes of patients and the subset of patients with diabetes. DESIGN: Randomized, prospective, cohort study comparing change in utilization rates between groups, pre- and post-intervention. METHODOLOGY: Ten primary care physician panels in a safety-net setting. Ten physicians were randomized to either a care-management approach (Group 1) or a traditional approach (Group 2). Care managers focused on diabetes and the cardiovascular cluster of diseases. Analysis compared rates of hospitalization, 30-day readmission, emergency room visits, and urgent care visits. Analysis compared baseline rates to annual rates after a yearlong run-in for entire panels and the subset of patients with diabetes. RESULTS: Resource utilization showed no statistically significant change between baseline and Year 3 (P=.79). Emergency room visits and hospital readmission increased for both groups (P=.90), while hospital admissions and urgent care visits decreased (P=.73). Similarly, utilization was not significantly different for patients with diabetes (P=.69). CONCLUSIONS: A care-management team approach failed to improve resource utilization rates by entire panels and the subset of diabetic patients compared to traditional care. This reinforces the need for further evidentiary support for the care-management model's hypothesis in the safety net.

Reduced numbers of mucosal DR(int) macrophages and increased numbers of CD103(+) dendritic cells during anti-TNF-α treatment in patients with Crohn's disease.

PubMed

Dige, Anders; Magnusson, Maria K; Öhman, Lena; Hvas, Christian Lodberg; Kelsen, Jens; Wick, Mary Jo; Agnholt, Jørgen

2016-01-01

Anti-TNF-α treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-α antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood. Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DR(int) and CD14 (+) DR(hi) MQs, CD141(+), CD141(-) and CD103(+) DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry. At baseline, we observed higher numbers of DR(int) MQs and lower numbers of CD103(+) DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 × 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DR(int) MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+) DCs increased [9-20 × 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4. In CD, mucosal inflammation is associated with high numbers of DR(int) MQs and low numbers of CD103(+) DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-α treatment. These results suggest that DR(int) MQs play a pivotal role in CD inflammation.

Usability-driven pruning of large ontologies: the case of SNOMED CT.

PubMed

López-García, Pablo; Boeker, Martin; Illarramendi, Arantza; Schulz, Stefan

2012-06-01

To study ontology modularization techniques when applied to SNOMED CT in a scenario in which no previous corpus of information exists and to examine if frequency-based filtering using MEDLINE can reduce subset size without discarding relevant concepts. Subsets were first extracted using four graph-traversal heuristics and one logic-based technique, and were subsequently filtered with frequency information from MEDLINE. Twenty manually coded discharge summaries from cardiology patients were used as signatures and test sets. The coverage, size, and precision of extracted subsets were measured. Graph-traversal heuristics provided high coverage (71-96% of terms in the test sets of discharge summaries) at the expense of subset size (17-51% of the size of SNOMED CT). Pre-computed subsets and logic-based techniques extracted small subsets (1%), but coverage was limited (24-55%). Filtering reduced the size of large subsets to 10% while still providing 80% coverage. Extracting subsets to annotate discharge summaries is challenging when no previous corpus exists. Ontology modularization provides valuable techniques, but the resulting modules grow as signatures spread across subhierarchies, yielding a very low precision. Graph-traversal strategies and frequency data from an authoritative source can prune large biomedical ontologies and produce useful subsets that still exhibit acceptable coverage. However, a clinical corpus closer to the specific use case is preferred when available.

Evaluation of intranuclear BrdU detection procedures for use in multicolor flow cytometry*

PubMed Central

Rothaeusler, Kristina; Baumgarth, Nicole

2010-01-01

Background Measurement of cell proliferation via BrdU incorporation in combination with multicolor cell surface staining would facilitate studies on cell subsets that require multiple markers for their identification. However, the extent to which the often harsh cell preparation procedures required affect the staining quality of more recently developed fluorescent dyes has not been assessed. Methods Three cell preparation protocols for BrdU measurement were compared for their ability to maintain fluorescent surface staining and scatter parameters of in vivo BrdU-labeled cells by flow cytometry. A 10-color fluorescent panel was developed to test the quality of surface staining following cell treatment and the ability to perform BrdU measurements on even small B lymphocyte subsets. Results All cell preparation procedures affected the quality of fluorescent and/or scatter parameters to varying degrees. Paraformaldehyde / saponin-based procedures preserved sufficient fluorescent surface staining to determine BrdU incorporation rates among all splenic B cell subsets, including B-1a cells, which constitute roughly 0.5% of cells. Turnover rates of B-1a cells were similar to immature B cells and higher than those of the other mature B cell subsets. Conclusion Paraformaldehyde / saponin-based cell preparation procedures facilitate detailed cell turnover studies on small cell subsets in vivo, revealing new functional information on rare cell populations. PMID:16538653

Association analysis using USDA diverse rice (Oryza sativa L.) germplasm collections to identify loci influencing grain quality traits

USDA-ARS?s Scientific Manuscript database

he USDA rice (Oryza sativa L.) core subset (RCS) was assembled to represent the genetic diversity of the entire USDA-ARS National Small Grains Collection and consists of 1,794 accessions from 114 countries. The USDA rice mini-core (MC) is a subset of 217 accessions from the RCS and was selected to ...

A Submodularity Framework for Data Subset Selection

DTIC Science & Technology

2013-09-01

37 7 List of Language Modeling Corpora in thet Arabic -to-English NIST Task ............. 37 8...Task ( Arabic -to-English) ................. 39 10 Baseline BLEU (%) PER Scores on Transtac Task (English-to- Arabic ) ................. 39 11...Comparison of BLEU (%) PER Scores on Transtac Task ( Arabic -to-English) ....... 39 12 Comparison of BLEU (%) PER Scores on Transtac Task (English-to- Arabic

Mayo Registry for Telemetry Efficacy in Arrest (MR TEA) study: An analysis of code status change following cardiopulmonary arrest.

PubMed

Snipelisky, David; Ray, Jordan; Matcha, Gautam; Roy, Archana; Chirila, Razvan; Maniaci, Michael; Bosworth, Veronica; Whitman, Anastasia; Lewis, Patricia; Vadeboncoeur, Tyler; Kusumoto, Fred; Burton, M Caroline

2015-07-01

Code status discussions are important during a hospitalization, yet variation in its practice exists. No data have assessed the likelihood of patients to change code status following a cardiopulmonary arrest. A retrospective review of all patients that experienced a cardiopulmonary arrest between May 1, 2008 and June 30, 2014 at an academic medical center was performed. The proportion of code status modifications to do not resuscitate (DNR) from full code was assessed. Baseline clinical characteristics, resuscitation factors, and 24-h post-resuscitation, hospital, and overall survival rates were compared between the two subsets. A total of 157 patients survived the index event and were included. One hundred and fifteen (73.2%) patients did not have a change in code status following the index event, while 42 (26.8%) changed code status to DNR. Clinical characteristics were similar between subsets, although patients in the change to DNR subset were older (average age 67.7 years) compared to the full code subset (average age 59.2 years; p = 0.005). Patients in the DNR subset had longer overall resuscitation efforts with less attempts at defibrillation. Compared to the DNR subset, patients that remained full code demonstrated higher 24-h post-resuscitation (n = 108, 93.9% versus n = 32, 76.2%; p = 0.001) and hospital (n = 50, 43.5% versus n = 6, 14.3%; p = 0.001) survival rates. Patients in the DNR subset were more likely to have neurologic deficits on discharge and shorter overall survival. Patient code status wishes do tend to change during critical periods within a hospitalization, adding emphasis for continued code status evaluation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Efficacy of T Regulatory Cells, Th17 Cells and the Associated Markers in Monitoring Tuberculosis Treatment Response

PubMed Central

Agrawal, Sonali; Parkash, Om; Palaniappan, Alangudi Natarajan; Bhatia, Ashok Kumar; Kumar, Santosh; Chauhan, Devendra Singh; Madhan Kumar, M.

2018-01-01

Treatment monitoring is an essential aspect for tuberculosis (TB) disease management. Sputum smear microscopy is the only available tool for monitoring, but it suffers from demerits. Therefore, we sought to evaluate markers and cellular subsets of T regulatory (Treg) cells and T helper (Th) 17 cells in pulmonary TB patients (PTB) for TB treatment monitoring. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro (with purified protein derivative (PPD)) overnight which was followed by a polychromatic flow cytometry approach to study Treg and Th17 markers and cellular subsets in PTB (n = 12) undergoing antituberculous treatment (ATT). The baseline levels of these markers and cellular subsets were evaluated in normal healthy subjects (NHS). We observed a significant decrease in the expression of CD25 (p<0.01) marker and percentage of T-cell subsets like CD4+CD25+ (p<0.001) and CD4+CD25+CD39+ (p<0.05) at the end of intensive phase (IP) as well as in the continuation phase (CP) of ATT. A decrease in CD25 marker expression and percentage of CD4+CD25+ T cell subset showed a positive correlation to sputum conversion both in high and low sputum positive PTB. In eight PTB with cavitary lesions, only CD4+CD25+FoxP3 Treg subset manifested a significant decrease at the end of CP. Thus, results of this study show that CD25 marker and CD4+CD25+ T cells can serve as better markers for monitoring TB treatment efficacy. The Treg subset CD4+CD25+FoxP3 may be useful for prediction of favorable response in PTB with extensive lung lesions. However, these findings have to be evaluated in a larger patient cohort. PMID:29472922

Validation of Manual Muscle Testing and a Subset of Eight Muscles (MMT8) for Adult and Juvenile Idiopathic Inflammatory Myopathies

PubMed Central

Rider, Lisa G.; Koziol, Deloris; Giannini, Edward H.; Jain, Minal S.; Smith, Michaele R.; Whitney-Mahoney, Kristi; Feldman, Brian M.; Wright, Susan J.; Lindsley, Carol B.; Pachman, Lauren M.; Villalba, Maria L.; Lovell, Daniel J.; Bowyer, Suzanne L.; Plotz, Paul H.; Miller, Frederick W.; Hicks, Jeanne E.

2010-01-01

Objective To validate manual muscle testing (MMT) for strength assessment in juvenile and adult dermatomyositis (DM) and polymyositis (PM). Methods Seventy-three children and 45 adult DM/PM patients were assessed at baseline and reevaluated 6–9 months later. We compared Total MMT (a group of 24 proximal, distal, and axial muscles) and Proximal MMT (7 proximal muscle groups) tested bilaterally on a 0–10 scale with 144 subsets of six and 96 subsets of eight muscle groups tested unilaterally. Expert consensus was used to rank the best abbreviated MMT subsets for face validity and ease of assessment. Results The Total, Proximal and best MMT subsets had excellent internal reliability (rs:Total MMT 0.91–0.98), and consistency (Cronbach’s α 0.78–0.97). Inter- and intra-rater reliability were acceptable (Kendall’s W 0.68–0.76; rs 0.84–0.95). MMT subset scores correlated highly with Total and Proximal MMT scores and with the Childhood Myositis Assessment Scale, and correlated moderately with physician global activity, functional disability, magnetic resonance imaging, axial and distal MMT scores and, in adults, with creatine kinase. The standardized response mean for Total MMT was 0.56 in juveniles and 0.75 in adults. Consensus was reached to use a subset of eight muscles (neck flexors, deltoids, biceps, wrist extensors, gluteus maximus and medius, quadriceps and ankle dorsiflexors) that performed as well as the Total and Proximal MMT, and had good face validity and ease of assessment. Conclusions These findings aid in standardizing the use of MMT for assessing strength as an outcome measure for myositis. PMID:20391500

Lectin Ulex europaeus agglutinin I specifically labels a subset of primary afferent fibers which project selectively to the superficial dorsal horn of the spinal cord.

PubMed

Mori, K

1986-02-19

To examine differential carbohydrate expression among different subsets of primary afferent fibers, several fluorescein-isothiocyanate conjugated lectins were used in a histochemical study of the dorsal root ganglion (DRG) and spinal cord of the rabbit. The lectin Ulex europaeus agglutinin I specifically labeled a subset of DRG cells and primary afferent fibers which projected to the superficial laminae of the dorsal horn. These results suggest that specific carbohydrates containing L-fucosyl residue is expressed selectively in small diameter primary afferent fibers which subserve nociception or thermoception.

Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Sivakumar, Shanmugam; Menon, Pradeep A; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

2016-01-01

Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis (PTB), with development of DM pandemic in countries where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co-morbidity is not well understood. In this study, we characterized the frequency of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without coincident diabetes mellitus (PTB-NDM) before, during and after completion of anti-TB treatment. PTB-DM is characterized by diminished frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline and 2 months of anti-TB treatment but not following 6 months of treatment completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant but borderline correlation with fasting blood glucose and glycated hemoglobin levels. Finally, while minor changes in the DC and monocyte compartment were observed at 2 months of treatment, significantly increased frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes were observed at the successful completion of anti-TB treatment. Our data show that coincident diabetes alters the frequencies of innate subset distribution of DC and monocytes in TB-DM co-morbidity and suggests that most of these changes are reversible following anti-TB therapy. PMID:27865391

Efficacy and safety of flavocoxid compared with naproxen in subjects with osteoarthritis of the knee- a subset analysis.

PubMed

Levy, Robert; Khokhlov, Alexander; Kopenkin, Sergey; Bart, Boris; Ermolova, Tatiana; Kantemirova, Raiasa; Mazurov, Vadim; Bell, Marjorie; Caldron, Paul; Pillai, Lakshmi; Burnett, Bruce

2010-12-01

twice-daily flavocoxid, a cyclooxygenase and 5-lipoxygenase inhibitor with potent antioxidant activity of botanical origin, was evaluated for 12 weeks in a randomized, double-blind, active-comparator study against naproxen in 220 subjects with moderate-severe osteoarthritis (OA) of the knee. As previously reported, both groups noted a significant reduction in the signs and symptoms of OA with no detectable differences in efficacy between the groups when the entire intent-to-treat population was considered. This post-hoc analysis compares the efficacy of flavocoxid to naproxen in different subsets of patients, specifically those related to age, gender, and disease severity as reported at baseline for individual response parameters. in the original randomized, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. In this subgroup analysis, primary outcome measures including the Western Ontario and McMaster Universities OA index and subscales, timed walk, and secondary efficacy variables, including investigator global assessment for disease and global response to treatment, subject visual analog scale for discomfort, overall disease activity, global response to treatment, index joint tenderness and mobility, were evaluated for differing trends between the study groups. subset analyses revealed some statistically significant differences and some notable trends in favor of the flavocoxid group. These trends became stronger the longer the subjects continued on therapy. These observations were specifically noted in older subjects (>60 years), males and in subjects with milder disease, particularly those with lower subject global assessment of disease activity and investigator global assessment for disease and faster walking times at baseline. initial analysis of the entire intent-to-treat population revealed that flavocoxid was as effective as naproxen in managing the signs and symptoms of OA of the knee. Detailed analyses of subject subsets demonstrated distinct trends in favor of flavocoxid for specific groups of subjects.

Adaptive servo-ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE-HF.

PubMed

Cowie, Martin R; Woehrle, Holger; Wegscheider, Karl; Vettorazzi, Eik; Lezius, Susanne; Koenig, Wolfgang; Weidemann, Frank; Smith, Gillian; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut

2018-03-01

The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers. In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months. In secondary analyses, data for patients with baseline and 12-month values were evaluated; 312 patients participated in the substudy. The primary endpoint, change in echocardiographically determined left ventricular ejection fraction from baseline to 12 months, did not differ significantly between the ASV and the control groups. There were also no significant between-group differences for changes in left ventricular dimensions, wall thickness, diastolic function or right ventricular dimensions and ejection fraction (echocardiography), and on cMRI (in small patient numbers). Plasma N-terminal pro B-type natriuretic peptide concentration decreased in both groups, and values were similar at 12 months. There were no significant between-group differences in changes in cardiac, renal and systemic inflammation biomarkers. In patients with systolic heart failure and CSA, addition of ASV to guideline-based medical management had no statistically significant effect on cardiac structure and function, or on cardiac biomarkers, renal function and systemic inflammation over 12 months. The increased cardiovascular mortality reported in SERVE-HF may not be related to adverse remodelling or worsening heart failure. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Usability-driven pruning of large ontologies: the case of SNOMED CT

PubMed Central

Boeker, Martin; Illarramendi, Arantza; Schulz, Stefan

2012-01-01

Objectives To study ontology modularization techniques when applied to SNOMED CT in a scenario in which no previous corpus of information exists and to examine if frequency-based filtering using MEDLINE can reduce subset size without discarding relevant concepts. Materials and Methods Subsets were first extracted using four graph-traversal heuristics and one logic-based technique, and were subsequently filtered with frequency information from MEDLINE. Twenty manually coded discharge summaries from cardiology patients were used as signatures and test sets. The coverage, size, and precision of extracted subsets were measured. Results Graph-traversal heuristics provided high coverage (71–96% of terms in the test sets of discharge summaries) at the expense of subset size (17–51% of the size of SNOMED CT). Pre-computed subsets and logic-based techniques extracted small subsets (1%), but coverage was limited (24–55%). Filtering reduced the size of large subsets to 10% while still providing 80% coverage. Discussion Extracting subsets to annotate discharge summaries is challenging when no previous corpus exists. Ontology modularization provides valuable techniques, but the resulting modules grow as signatures spread across subhierarchies, yielding a very low precision. Conclusion Graph-traversal strategies and frequency data from an authoritative source can prune large biomedical ontologies and produce useful subsets that still exhibit acceptable coverage. However, a clinical corpus closer to the specific use case is preferred when available. PMID:22268217

Time-dependent migration of citations through PubMed and OvidSP subsets: a study on a series of simultaneous PubMed and OvidSP searches.

PubMed

Boeker, Martin; Vach, Werner; Motschall, Edith

2013-01-01

To quantitatively describe (1) differences between search results derived at consecutive time points with the PubMed and OvidSP literature search interfaces over a five day interval, and (2) the migration of citations through different subsets to estimate the timeliness of OvidSP. PubMed-Identifiers (PMIDs) of the following subsets were retrieved from PubMed and OvidSP simultaneously (within 8 h) at 11 days in March and April 2010 including 5 consecutive days: as supplied by publisher, in process, PubMed not MEDLINE, and OLDMEDLINE. Search results were compared for difference and intersection sets. The migration of citations on individual level was determined by comparison of corresponding sets over several days. The "in process" set was stable with about 446,000 - 452,000 citations; a small fraction of up to 3 % of the total subsets were in PubMed only and OvidSP only subsets. About 96 % of the ca. 10,500 citations in the OvidSP only subset migrated within 2 days out of the "in process" subset. The database of OvidSP is updated within a period of two days.

Identity and Diversity of Human Peripheral Th and T Regulatory Cells Defined by Single-Cell Mass Cytometry.

PubMed

Kunicki, Matthew A; Amaya Hernandez, Laura C; Davis, Kara L; Bacchetta, Rosa; Roncarolo, Maria-Grazia

2018-01-01

Human CD3 + CD4 + Th cells, FOXP3 + T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3 + CD4 + T cell compartment remains questionable. In this study, we examined CD3 + CD4 + T cell populations by single-cell mass cytometry. We characterize the CD3 + CD4 + Th, Treg, and Tr1 cell populations simultaneously across 23 memory T cell-associated surface and intracellular molecules. High-dimensional analysis identified several new subsets, in addition to the already defined CD3 + CD4 + Th, Treg, and Tr1 cell populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of these subsets share markers previously thought to be selective for Treg, Th1, Th2, Th17, and Tfh cells, including CD194 (CCR4) + FOXP3 + Treg and CD183 (CXCR3) + T-bet + Th17 cell subsets. Unsupervised clustering displayed a phenotypic organization of CD3 + CD4 + T cells that confirmed their diversity but showed interrelation between the different subsets, including similarity between Th1-Th2-Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg cells. In conclusion, the use of single-cell mass cytometry provides a systems-level characterization of CD3 + CD4 + T cells in healthy human blood, which represents an important baseline reference to investigate abnormalities of different subsets in immune-mediated pathologies. Copyright © 2017 by The American Association of Immunologists, Inc.

Precollege Predictors of Incapacitated Rape Among Female Students in Their First Year of College

PubMed Central

Carey, Kate B.; Durney, Sarah E.; Shepardson, Robyn L.; Carey, Michael P.

2015-01-01

Objective: The first year of college is an important transitional period for young adults; it is also a period associated with elevated risk of incapacitated rape (IR) for female students. The goal of this study was to identify prospective risk factors associated with experiencing attempted or completed IR during the first year of college. Method: Using a prospective cohort design, we recruited 483 incoming first-year female students. Participants completed a baseline survey and three follow-up surveys over the next year. At baseline, we assessed precollege alcohol use, marijuana use, sexual behavior, and, for the subset of sexually experienced participants, sex-related alcohol expectancies. At the baseline and all follow-ups, we assessed sexual victimization. Results: Approximately 1 in 6 women (18%) reported IR before entering college, and 15% reported IR during their first year of college. In bivariate analyses, precollege IR history, precollege heavy episodic drinking, number of precollege sexual partners, and sex-related alcohol expectancies (enhancement and disinhibition) predicted first-year IR. In multivariate analyses with the entire sample, only precollege IR (odds ratio = 4.98, p < .001) remained a significant predictor. However, among the subset of sexually experienced participants, both enhancement expectancies and precollege IR predicted IR during the study year. Conclusions: IR during the first year of college is independently associated with a history of IR and with expectancies about alcohol’s enhancement of sexual experience. Alcohol expectancies are a modifiable risk factor that may be a promising target for prevention efforts. PMID:26562590

Army Sustainability Report 2010

DTIC Science & Technology

2011-09-01

a vastly complex concept: it is an organizing principle that factors mission, environment, community and economic benefit into each of its...Report on a minimum of 10 performance indicators, including at least one from each of : economic , social and environmental Report on a minimum...FY09 in a partial performance baseline. It is based on a subset of the economic , environmental and social responsibility performance

Health evaluation of Columbian white-tailed deer on Julia Butler Hansen Refuge for the Columbian white-tailed deer

USGS Publications Warehouse

Creekmore, Terry E.; Glaser, Linda C.

1999-01-01

The objectives of this study were to: (1) gather baseline physiologic data on a subset of the population, (2) evaluate the data to determine the health of the animals sampled, (3) if possible, identify causes of poor health and, ( 4) provide refuge personnel with information that will aid them in managing the population.

Three consecutive days of interval runs to exhaustion affects lymphocyte subset apoptosis and migration.

PubMed

Navalta, James W; Tibana, Ramires Alsamir; Fedor, Elizabeth A; Vieira, Amilton; Prestes, Jonato

2014-01-01

This investigation assessed the lymphocyte subset response to three days of intermittent run exercise to exhaustion. Twelve healthy college-aged males (n = 8) and females (n = 4) (age = 26 ± 4 years; height = 170.2 ± 10 cm; body mass = 75 ± 18 kg) completed an exertion test (maximal running speed and VO2max) and later performed three consecutive days of an intermittent run protocol to exhaustion (30 sec at maximal running speed and 30 sec at half of the maximal running speed). Blood was collected before exercise (PRE) and immediately following the treadmill bout (POST) each day. When the absolute change from baseline was evaluated (i. e., Δ baseline), a significant change in CD4+ and CD8+ for CX3CR1 cells was observed by completion of the third day. Significant changes in both apoptosis and migration were observed following two consecutive days in CD19+ lymphocytes, and the influence of apoptosis persisted following the third day. Given these lymphocyte responses, it is recommended that a rest day be incorporated following two consecutive days of a high-intensity intermittent run program to minimize immune cell modulations and reduce potential susceptibility.

A novel statistical approach shows evidence for multi-system physiological dysregulation during aging.

PubMed

Cohen, Alan A; Milot, Emmanuel; Yong, Jian; Seplaki, Christopher L; Fülöp, Tamàs; Bandeen-Roche, Karen; Fried, Linda P

2013-03-01

Previous studies have identified many biomarkers that are associated with aging and related outcomes, but the relevance of these markers for underlying processes and their relationship to hypothesized systemic dysregulation is not clear. We address this gap by presenting a novel method for measuring dysregulation via the joint distribution of multiple biomarkers and assessing associations of dysregulation with age and mortality. Using longitudinal data from the Women's Health and Aging Study, we selected a 14-marker subset from 63 blood measures: those that diverged from the baseline population mean with age. For the 14 markers and all combinatorial sub-subsets we calculated a multivariate distance called the Mahalanobis distance (MHBD) for all observations, indicating how "strange" each individual's biomarker profile was relative to the baseline population mean. In most models, MHBD correlated positively with age, MHBD increased within individuals over time, and higher MHBD predicted higher risk of subsequent mortality. Predictive power increased as more variables were incorporated into the calculation of MHBD. Biomarkers from multiple systems were implicated. These results support hypotheses of simultaneous dysregulation in multiple systems and confirm the need for longitudinal, multivariate approaches to understanding biomarkers in aging. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

40 CFR 80.595 - How does a small or GPA refiner apply for a motor vehicle diesel fuel volume baseline for the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... for a motor vehicle diesel fuel volume baseline for the purpose of extending their gasoline sulfur... a small or GPA refiner apply for a motor vehicle diesel fuel volume baseline for the purpose of... duration of the GPA standards under § 80.540 must apply for a motor vehicle diesel fuel volume baseline by...

A Survey of Object Oriented Languages in Programming Environments.

DTIC Science & Technology

1987-06-01

subset of natural languages might be more effective , and make the human-computer interface more friendly. 19 .. .. . . -.. -, " ,. o...and complexty of Ada. He meant that the language contained too many features that made it complicated to use effectively . Much of the complexity comes...by sending messages to a class instance. A small subset of the methods in Smalltalk-80 are not expressed in the !-’ Smalhalk-80 programming language

Short-cut Methods versus Rigorous Methods for Performance-evaluation of Distillation Configurations

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

Ramapriya, Gautham Madenoor; Selvarajah, Ajiththaa; Jimenez Cucaita, Luis Eduardo

Here, this study demonstrates the efficacy of a short-cut method such as the Global Minimization Algorithm (GMA), that uses assumptions of ideal mixtures, constant molar overflow (CMO) and pinched columns, in pruning the search-space of distillation column configurations for zeotropic multicomponent separation, to provide a small subset of attractive configurations with low minimum heat duties. The short-cut method, due to its simplifying assumptions, is computationally efficient, yet reliable in identifying the small subset of useful configurations for further detailed process evaluation. This two-tier approach allows expedient search of the configuration space containing hundreds to thousands of candidate configurations for amore » given application.« less

Short-cut Methods versus Rigorous Methods for Performance-evaluation of Distillation Configurations

DOE PAGES

Ramapriya, Gautham Madenoor; Selvarajah, Ajiththaa; Jimenez Cucaita, Luis Eduardo; ...

2018-05-17

Here, this study demonstrates the efficacy of a short-cut method such as the Global Minimization Algorithm (GMA), that uses assumptions of ideal mixtures, constant molar overflow (CMO) and pinched columns, in pruning the search-space of distillation column configurations for zeotropic multicomponent separation, to provide a small subset of attractive configurations with low minimum heat duties. The short-cut method, due to its simplifying assumptions, is computationally efficient, yet reliable in identifying the small subset of useful configurations for further detailed process evaluation. This two-tier approach allows expedient search of the configuration space containing hundreds to thousands of candidate configurations for amore » given application.« less

MMS Multipoint Electric Field Observations of Small-Scale Magnetic Holes

NASA Technical Reports Server (NTRS)

Goodrich, Katherine A.; Ergun, Robert E.; Wilder, Frederick; Burch, James; Torbert, Roy; Khotyaintsev, Yuri; Lindqvist, Per-Arne; Russell, Christopher; Strangeway, Robert; Magnus, Werner

2016-01-01

Small-scale magnetic holes (MHs), local depletions in magnetic field strength, have been observed multiple times in the Earths magnetosphere in the bursty bulk flow (BBF) braking region. This particular subset of MHs has observed scale sizes perpendicular to the background magnetic field (B) less than the ambient ion Larmor radius (p(sib i)). Previous observations by Time History of Events and Macroscale Interactions during Substorms (THEMIS) indicate that this subset of MHs can be supported by a current driven by the E x B drift of electrons. Ions do not participate in the E x B drift due to the small-scale size of the electric field. While in the BBF braking region, during its commissioning phase, the Magnetospheric Multiscale (MMS) spacecraft observed a small-scale MH. The electric field observations taken during this event suggest the presence of electron currents perpendicular to the magnetic field. These observations also suggest that these currents can evolve to smaller spatial scales.

Efficacy, safety, and tolerability of lacosamide in patients with gain-of-function Nav1.7 mutation-related small fiber neuropathy: study protocol of a randomized controlled trial-the LENSS study.

PubMed

de Greef, Bianca T A; Merkies, Ingemar S J; Geerts, Margot; Faber, Catharina G; Hoeijmakers, Janneke G J

2016-06-30

Small fiber neuropathy generally leads to considerable pain and autonomic symptoms. Gain-of-function mutations in the SCN9A- gene, which codes for the Nav1.7 voltage-gated sodium channel, have been reported in small fiber neuropathy, suggesting an underlying genetic basis in a subset of patients. Currently available sodium channel blockers lack selectivity, leading to cardiac and central nervous system side effects. Lacosamide is an anticonvulsant, which blocks Nav1.3, Nav1.7, and Nav1.8, and stabilizes channels in the slow-inactivation state. Since multiple Nav1.7 mutations in small fiber neuropathy showed impaired slow-inactivation, lacosamide might be effective. The Lacosamide-Efficacy-'N'-Safety in Small fiber neuropathy (LENSS) study is a randomized, double-blind, placebo-controlled, crossover trial in patients with SCN9A-associated small fiber neuropathy, with the primary objective to evaluate the efficacy of lacosamide versus placebo. Eligible patients (the aim is to recruit 25) fulfilling the inclusion and exclusion criteria will be randomized to receive lacosamide (200 mg b.i.d.) or placebo during the first double-blinded treatment period (8 weeks), which is preceded by a titration period (3 weeks). The first treatment period will be followed by a tapering period (2 weeks). After a 2-week washout period, patients will crossover to the alternate arm for the second period consisting of an equal titration phase, treatment period, and tapering period. The primary efficacy endpoint will be the proportion of patients demonstrating a 1-point average pain score reduction compared to baseline using the Pain Intensity Numerical Rating Scale. We assume a response rate of approximately 60 % based on the criteria composed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) group for measurement of pain. Patients withdrawing from the study will be considered non- responders. Secondary outcomes will include changes in maximum pain score, the Small Fiber Neuropathy Symptoms Inventory Questionnaire, sleep quality and the quality of life assessment, patients' global impressions of change, and safety and tolerability measurements. Sensitivity analyses will include assessing the proportion of patients having ≥ 2 points average pain improvement compared to the baseline Pain Intensity Numerical Rating Scale scores. This is the first study that will be evaluating the efficacy, safety, and tolerability of lacosamide versus placebo in patients with SCN9A-associated small fiber neuropathy. The findings may increase the knowledge on lacosamide as a potential treatment option in patients with painful neuropathies, considering the central role of Nav1.7 in pain. ClinicalTrials.gov, NCT01911975 . Registered on 13 July 2013.

Subset selective search on the basis of color and preview.

PubMed

Donk, Mieke

2017-01-01

In the preview paradigm observers are presented with one set of elements (the irrelevant set) followed by the addition of a second set among which the target is presented (the relevant set). Search efficiency in such a preview condition has been demonstrated to be higher than that in a full-baseline condition in which both sets are simultaneously presented, suggesting that a preview of the irrelevant set reduces its influence on the search process. However, numbers of irrelevant and relevant elements are typically not independently manipulated. Moreover, subset selective search also occurs when both sets are presented simultaneously but differ in color. The aim of the present study was to investigate how numbers of irrelevant and relevant elements contribute to preview search in the absence and presence of a color difference between subsets. In two experiments it was demonstrated that a preview reduced the influence of the number of irrelevant elements in the absence but not in the presence of a color difference between subsets. In the presence of a color difference, a preview lowered the effect of the number of relevant elements but only when the target was defined by a unique feature within the relevant set (Experiment 1); when the target was defined by a conjunction of features (Experiment 2), search efficiency as a function of the number of relevant elements was not modulated by a preview. Together the results are in line with the idea that subset selective search is based on different simultaneously operating mechanisms.

Discrete Address Beacon System (DABS) Baseline Test and Evaluation.

DTIC Science & Technology

1980-04-01

Organization ReportNo 7. ~/ - 9. PorTorming Organisation Name and Address 10. Work Unit No. (TRALS) Federal Aviation Administration National Aviation...version of the Common International Civil Aviation Organization (ICAO) Data Interchange Network (CIDIN) protocol used in the DABS engineering model. 8. All...grouped into two subsets, one for surveillance data communications and one for Common International Civil Aviation Organization (ICAO) Data Interchange

rhG-CSF in healthy donors: mobilization of peripheral hemopoietic progenitors and effect on peripheral blood leukocytes.

PubMed

Sica, S; Rutella, S; Di Mario, A; Salutari, P; Rumi, C; Ortu la Barbera, E; Etuk, B; Menichella, G; D'Onofrio, G; Leone, G

1996-08-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16 micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG-CSF was administered s.c. for 5 days. No side effects were encountered except for moderate bone pain and lumbago. Mobilization was effective, reaching a peak median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3) colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak values were obtained at a median of 4 days of rhG-CSF and represented, respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007 and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59). Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2-fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1 x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3-fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar changes were observed in lymphocytes collected in leukapheresis product. T helper and T suppressor subsets displayed a similar increase. Thus, besides the anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an unexpected and still unexplained modification of lymphocyte subsets in peripheral blood.

Mapping Changes and Damages in Areas of Conflict: From Archive C-Band SAR Data to New HR X-Band Imagery, Towards the Sentinels

NASA Astrophysics Data System (ADS)

Tapete, Deodato; Cigna, Francesca; Donoghue, Daniel N. M.; Philip, Graham

2015-05-01

On the turn of radar space science with the recent launch of Sentinel-1A, we investigate how to better exploit the opportunities offered by large C-band SAR archives and increasing datasets of HR to VHR X-band data, to map changes and damages in urban and rural areas affected by conflicts. We implement a dual approach coupling multi-interferogram processing and amplitude change detection, to assess the impact of the recent civil war on the city of Homs, Western Syria, and the surrounding semi-arid landscape. More than 280,000 coherent pixels are retrieved from Small BAseline Subset (SBAS) processing of the 8year-long ENVISAT ASAR IS2 archive, to quantify land subsidence due to pre-war water abstraction in rural areas. Damages in Homs are detected by analysing the changes of SAR backscattering (σ0), comparing 3m-resolution StripMap TerraSAR-X pairs from 2009 to 2014. Pre-war alteration is differentiated from war-related damages via operator-driven interpretation of the σ0 patterns.

Additional BCAA-enriched nutrient mixture improves the nutritional condition in cirrhotic patients with hypoalbuminemia despite treatment with regular BCAA granules: A pilot study.

PubMed

Fukui, Aiko; Kawabe, Naoto; Hashimoto, Senju; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Nakaoka, Kazunori; Ohki, Masashi; Takagawa, Yuka; Kamei, Hiroyuki; Yoshioka, Kentaro

2015-07-01

To elucidate the effect of adding branched-chain amino acid (BCAA)-enriched nutrient mixtures in cirrhotic patients with hypoalbuminemia despite the use of BCAA granules. A BCAA-enriched nutrient mixture containing 5.6 g of BCAA and 210 kcal was additionally administered in 40 cirrhotic patients with hypoalbuminemia despite their treatment with BCAA granules containing 12 g of BCAA. Laboratory data were assessed at 6 months before beginning additional therapy, at baseline, and at 6 months after baseline. Serum albumin levels significantly decreased from 6 months before baseline (3.14±0.47 g/dL) to baseline (2.83±0.46 g/dL), despite the treatment with BCAA granules (p<0.001), and tended to increase from baseline to 6 months after baseline (2.95±0.42 g/dL) (p=0.084). In the subset of 23 patients without hepatocellular carcinoma treatments, upper gastrointestinal tract bleeding, or albumin infusion, serum albumin levels significantly increased from baseline (2.93±0.38 g/dL) to 6 months after baseline (3.15±0.34 g/dL) (p=0.014). Additional therapy with BCAA-enriched nutrient mixtures increased serum albumin levels of the cirrhotic patients with hypoalbuminemia despite the treatment with BCAA granules and without hepatocellular carcinoma treatment, upper gastrointestinal tract bleeding, or albumin infusion.

Genetic diversity among wheat accessions from the USDA National Small Grains Collection

USDA-ARS?s Scientific Manuscript database

Accessions of Triticum aestivum subsp. aestivum from the USDA-ARS National Small Grains Collection (NSGC) are a resource for wheat scientists worldwide. The genetic diversity of the wheat core subset, representing approximately 10% of the collection’s 42138 T. aestivum accessions, was examined using...

Personality and Career Success: Concurrent and Longitudinal Relations.

PubMed

Sutin, Angelina R; Costa, Paul T; Miech, Richard; Eaton, William W

2009-03-01

The present research addresses the dynamic transaction between extrinsic (occupational prestige, income) and intrinsic (job satisfaction) career success and the Five-Factor Model of personality. Participants (N = 731) completed a comprehensive measure of personality and reported their job title, annual income, and job satisfaction; a subset of these participants (n = 302) provided the same information approximately 10 years later. Measured concurrently, emotionally stable and conscientious participants reported higher incomes and job satisfaction. Longitudinal analyses revealed that, among younger participants, higher income at baseline predicted decreases in Neuroticism and baseline Extraversion predicted increases in income across the 10 years. Results suggest that the mutual influence of career success and personality is limited to income and occurs early in the career.

Development and use of touch-screen audio computer-assisted self-interviewing in a study of American Indians.

PubMed

Edwards, Sandra L; Slattery, Martha L; Murtaugh, Maureen A; Edwards, Roger L; Bryner, James; Pearson, Mindy; Rogers, Amy; Edwards, Alison M; Tom-Orme, Lillian

2007-06-01

This article describes the development and usability of an audio computer-assisted self-interviewing (ACASI) questionnaire created to collect dietary, physical activity, medical history, and other lifestyle data in a population of American Indians. Study participants were part of a cohort of American Indians living in the southwestern United States. Data were collected between March 2004 and July 2005. Information for evaluating questionnaire usability and acceptability was collected from three different sources: baseline study data, auxiliary background data, and a short questionnaire administered to a subset of study participants. For the subset of participants, 39.6% reported not having used a computer in the past year. The ACASI questionnaires were well accepted: 96.0% of the subset of participants reported finding them enjoyable to use, 97.2% reported that they were easy to use, and 82.6% preferred them for future questionnaires. A lower educational level and infrequent computer use in the past year were predictors of having usability trouble. These results indicate that the ACASI questionnaire is both an acceptable and a preferable mode of data collection in this population.

Validation of the Abdominal Pain Index Using a Revised Scoring Method

PubMed Central

Sherman, Amanda L.; Smith, Craig A.; Walker, Lynn S.

2015-01-01

Objective Evaluate the psychometric properties of child- and parent-report versions of the four-item Abdominal Pain Index (API) in children with functional abdominal pain (FAP) and healthy controls, using a revised scoring method that facilitates comparisons of scores across samples and time. Methods Pediatric patients aged 8–18 years with FAP and controls completed the API at baseline (N = 1,967); a subset of their parents (N = 290) completed the API regarding the child’s pain. Subsets of patients completed follow-up assessments at 2 weeks (N = 231), 3 months (N = 330), and 6 months (N = 107). Subsets of both patients (N = 389) and healthy controls (N = 172) completed a long-term follow-up assessment (mean age at follow-up = 20.21 years, SD = 3.75). Results The API demonstrated good concurrent, discriminant, and construct validity, as well as good internal consistency. Conclusion We conclude that the API, using the revised scoring method, is a useful, reliable, and valid measure of abdominal pain severity. PMID:25617048

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition.

PubMed

Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A

2009-01-27

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

PubMed Central

Mahoney, C L; Choudhury, B; Davies, H; Edkins, S; Greenman, C; Haaften, G van; Mironenko, T; Santarius, T; Stevens, C; Stratton, M R; Futreal, P A

2009-01-01

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies. PMID:19165201

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

PubMed

Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

2016-06-15

Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.

40 CFR 80.250 - How is the small refiner sulfur baseline and volume determined?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 17 2012-07-01 2012-07-01 false How is the small refiner sulfur... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.250 How is the small refiner sulfur baseline and volume determined? (a)(1) The...

40 CFR 80.250 - How is the small refiner sulfur baseline and volume determined?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false How is the small refiner sulfur... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.250 How is the small refiner sulfur baseline and volume determined? (a)(1) The...

40 CFR 80.250 - How is the small refiner sulfur baseline and volume determined?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 17 2014-07-01 2014-07-01 false How is the small refiner sulfur... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.250 How is the small refiner sulfur baseline and volume determined? (a)(1) The...

40 CFR 80.250 - How is the small refiner sulfur baseline and volume determined?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 17 2013-07-01 2013-07-01 false How is the small refiner sulfur... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.250 How is the small refiner sulfur baseline and volume determined? (a)(1) The...

40 CFR 80.250 - How is the small refiner sulfur baseline and volume determined?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false How is the small refiner sulfur... AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Sulfur Hardship Provisions § 80.250 How is the small refiner sulfur baseline and volume determined? (a)(1) The...

Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

PubMed

Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

2017-05-01

The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin.

PubMed

Chamarthi, Bindu; Cincotta, Anthony H

2017-05-01

The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin. The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo). Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p < 0.001) and by -1.13 relative to placebo (p < 0.001). In the high-dose insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p < 0.001) and placebo (p = 0.001) respectively. Secondary analyses of treatment effect at 24 and 52 weeks demonstrated similar influences of B-QR on HbA1c. The fasting plasma glucose (FPG) and TDID changes within each treatment group were not significant. More subjects achieved HbA1c ≤7 at 12 weeks with B-QR relative to placebo (36.4% B-QR vs 0% placebo, Fisher's exact 2-sided p = 0.003 in the entire cohort and 37% vs 0%, 2-sided p = 0.039 in the high-dose insulin subset). B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.

Delayed effects of rhG-CSF mobilization treatment and apheresis on circulating CD34+ and CD34+ Thy-1dim CD38- progenitor cells, and lymphoid subsets in normal stem cell donors for allogeneic transplantation.

PubMed

Körbling, M; Anderlini, P; Durett, A; Maadani, F; Bojko, P; Seong, D; Giralt, S; Khouri, I; Andersson, B; Mehra, R; vanBesien, K; Mirza, N; Przepiorka, D; Champlin, R

1996-12-01

Allogeneic transplantation of peripheral blood progenitor cells (PBPC) is emerging as a new stem cell transplant modality. Rather than undergoing general anesthesia for bone marrow harvest, normal blood stem cell donors are subjected to rhG-CSF mobilization treatment followed by single or multiple apheresis. Whereas the effects of cytokine treatment and apheresis on stem cell peripheralization and collection have been described, little is known about delayed effects of rhG-CSF treatment and apheresis on a normal hematopoietic system, and there are no long-term data that address safety issues. Ten normal, patient-related donors underwent a 3 or 4 day rhG-CSF (filgrastim) treatment (12 micrograms/kg/day) followed by single or tandem apheresis. We monitored peripheral blood (PB) cellularity including CD34+ and lymphoid subsets at baseline, during cytokine treatment, prior to apheresis, and at days 2, 4, 7, 30 and 100 post-apheresis. The PB progenitor cell concentration peak prior to apheresis was followed by a nadir by day 7 and normalized by day 30, with the exception of the most primitive CD34+ Thy-1dim CD38- progenitor subset that reached a nadir by day 30. Lymphoid subsets such as CD3, 4, 8, suppressor cells (CD3+ 4- 8- TCR+ alpha beta), and B cells (CD19+) showed a similar pattern with a nadir concentration by day 7, followed, except for B cells, by a rebound by day 30 and subnormal counts at day 100. The PB concentrations of hemoglobin and platelets dropped mainly due to the apheresis procedure itself, and normalized by day 30. With cytokine treatment, the PB alkaline phosphatase and lactate dehydrogenase concentrations increased 2.2- and 2.8-fold, respectively, over baseline, and returned to normal range by day 30. Based on the preliminary nature of this study, the clinical relevance of these findings is still unclear.

Evaluation of a Faith-Based Culturally Relevant Program for African American Substance Users at Risk for HIV in the Southern United States

ERIC Educational Resources Information Center

MacMaster, Samuel A.; Jones, Jenny L.; Rasch, Randolph F. R.; Crawford, Sharon L.; Thompson, Stephanie; Sanders, Edwin C., II

2007-01-01

Objective: This article provides an evaluation of a federally funded faith-based program that serves African Americans who use heroin and cocaine and are at risk for HIV/AIDS in Nashville, Tennessee. Methods: Data were collected from 163 individuals at baseline and 6- and 12-month follow-up interviews. A subset of participants (n = 51) completed…

Effect of Physical Therapy Students' Clinical Experiences on Clinician Productivity.

PubMed

Pivko, Susan E; Abbruzzese, Laurel D; Duttaroy, Pragati; Hansen, Ruth L; Ryans, Kathryn

2016-01-01

Physical therapy clinical education experiences (CEEs) are difficult to secure, particularly first-level CEEs. Our purpose was to determine 1) what impact student full-time CEEs have on PT clinician productivity and 2) whether there is a productivity difference between first vs final CEEs. Productivity logs, including possible factors impacting productivity, were distributed to clinician-student pairings on first and final CEEs. Two-week baseline data (without a student) were compared to weeks 1 and 6 (with a student) for 31 logs using a 2x4 repeated-measures ANOVA. In a subset of 17 logs for CEEs 8 weeks or longer, a 2x5 repeated-measures ANOVA was performed. There was a significant increase in the number of patients seen and CPT units billed by both levels of CEEs comparing weeks 1 and 6. In the subset of CEEs, 8 weeks or longer, there was a significant increase in the number of patients treated per hour at week 6 and a trend toward a change at week 8 when compared to baseline week A. The factors selected as impacting productivity were census (59%) and staffing (32%). Physical therapy clinician-student pairings showed an overall increase in productivity during both full-time first and final level CEEs.

Training attentional control in older adults

PubMed Central

MacKay-Brandt, Anna

2013-01-01

Recent research has demonstrated benefits for older adults from training attentional control using a variable priority strategy, but the construct validity of the training task and the degree to which benefits of training transfer to other contexts are unclear. The goal of this study was to characterize baseline performance on the training task in a sample of 105 healthy older adults and to test for transfer of training in a subset (n = 21). Training gains after 5 days and extent of transfer was compared to another subset (n = 20) that served as a control group. Baseline performance on the training task was characterized by a two-factor model of working memory and processing speed. Processing speed correlated with the training task. Training gains in speed and accuracy were reliable and robust (ps <.001, η2 = .57 to .90). Transfer to an analogous task was observed (ps <.05, η2 = .10 to .17). The beneficial effect of training did not translate to improved performance on related measures of processing speed. This study highlights the robust effect of training and transfer to a similar context using a variable priority training task. Although processing speed is an important aspect of the training task, training benefit is either related to an untested aspect of the training task or transfer of training is limited to the training context. PMID:21728889

Integration of MODIS data and Short Baseline Subset (SBAS) technique for land subsidence monitoring in Datong, China

NASA Astrophysics Data System (ADS)

Zhao, Chao-ying; Zhang, Qin; Yang, Chengsheng; Zou, Weibao

2011-07-01

Datong is located in the north of Shanxi Province, which is famous for its old-fashioned coal-mining preservation in China. Some serious issues such as land subsidence, ground fissures, mining collapse, and earthquake hazards have occurred over this area for a long time resulting in significant damages to buildings and roads. In order to monitor and mitigate these natural man-made hazards, Short Baseline Subsets (SBAS) InSAR technique with ten Envisat ASAR data is applied to detect the surface deformation over an area of thousands of square kilometers. Then, five MODIS data are used to check the atmospheric effects on InSAR interferograms. Finally, nine nonlinear land subsidence cumulative results during September 2004 and February 2008 are obtained. Based on the deformation data, three kinds of land subsidence are clearly detected, caused by mine extraction, underground water withdrawal and construction of new economic zones, respectively. The annual mean velocity of subsidence can reach 1 to 4 cm/year in different subsidence areas. A newly designed high-speed railway (HSR) with speeds of 350 km/h will cross through the Datong hi-tech zone. Special measures should be taken for the long run of this project. In addition, another two subsidence regions need further investigation to mitigate such hazards.

A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.

PubMed

Oritani, Kenji; Okamoto, Shinichiro; Tauchi, Tetsuzo; Saito, Shigeki; Ohishi, Kohshi; Handa, Hiroshi; Takenaka, Katsuto; Gopalakrishna, Prashanth; Amagasaki, Taro; Ito, Kazuo; Akashi, Koichi

2015-03-01

Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor that has demonstrated rapid and durable improvements in splenomegaly and symptoms and a survival benefit in 2 phase 3 trials in patients with myelofibrosis. Ruxolitinib was well tolerated and effectively reduced splenomegaly and symptom burden in Asian patients with myelofibrosis in the Asian multinational, phase 2 Study A2202. We present a subset analysis of Japanese patients (n = 30) in Study A2202. At data cutoff, 22 patients were ongoing; 8 discontinued, mainly due to adverse events (n = 4). At week 24, 33 % of patients achieved ≥35 % reduction from baseline in spleen volume; 56.0 % achieved ≥50 % reduction from baseline in total symptom score, as measured by the 7-day Myelofibrosis Symptom Assessment Form v2.0. The most common adverse events were anemia (63 %), thrombocytopenia (40 %), nasopharyngitis (37 %), decreased platelet counts (30 %), and diarrhea (30 %). Dose reductions or interruptions due to hemoglobin decreases were more frequent in Japanese patients; no loss of efficacy and no discontinuations due to hematologic abnormalities were observed. Ruxolitinib was well tolerated in Japanese patients and provided substantial reductions in splenomegaly and myelofibrosis-related symptoms similar to those observed in the overall Asian population and phase 3 COMFORT studies.

Design of focused and restrained subsets from extremely large virtual libraries.

PubMed

Jamois, Eric A; Lin, Chien T; Waldman, Marvin

2003-11-01

With the current and ever-growing offering of reagents along with the vast palette of organic reactions, virtual libraries accessible to combinatorial chemists can reach sizes of billions of compounds or more. Extracting practical size subsets for experimentation has remained an essential step in the design of combinatorial libraries. A typical approach to computational library design involves enumeration of structures and properties for the entire virtual library, which may be unpractical for such large libraries. This study describes a new approach termed as on the fly optimization (OTFO) where descriptors are computed as needed within the subset optimization cycle and without intermediate enumeration of structures. Results reported herein highlight the advantages of coupling an ultra-fast descriptor calculation engine to subset optimization capabilities. We also show that enumeration of properties for the entire virtual library may not only be unpractical but also wasteful. Successful design of focused and restrained subsets can be achieved while sampling only a small fraction of the virtual library. We also investigate the stability of the method and compare results obtained from simulated annealing (SA) and genetic algorithms (GA).

Elevated temperatures are associated with stress in rooftop-nesting Common Nighthawk (Chordeiles minor) chicks.

PubMed

Newberry, Gretchen N; Swanson, David L

2018-01-01

Grasslands and riparian forests in southeastern South Dakota have been greatly reduced since historical times, primarily due to conversion to row-crop agriculture. Common Nighthawk ( Chordeiles minor ) nesting habitat includes grasslands, open woodlands and urban rooftops, but nesting sites in southeastern South Dakota are confined to rooftops, as natural nesting habitat is limited. Nighthawks nesting on exposed rooftop habitats may encounter thermal conditions that increase operative temperatures relative to vegetated land cover types. Mean humidity has increased and mean wind speed and cloud cover have decreased during the nighthawk breeding season from 1948 to 2016 in southeastern South Dakota. These changes might contribute to increasing operative temperatures at exposed rooftop nest sites and this could influence chick condition. We studied nest micro-climate and the plasma stress response for 24 rooftop-nesting nighthawk chicks from 17 nests during 2015 and 2016. High humidity prior to blood collection reduced both baseline and stress-induced plasma corticosterone (CORT). In contrast, high maximum temperatures during the day before sampling increased stress-induced CORT. The magnitude of the chick stress response was significantly negatively related to maximum wind speed for the week prior to CORT measurement. Other weather and micro-climate variables were not significant effectors of CORT metrics. Most chicks had low baseline CORT and were able to mount a stress response, but a subset of chicks ( n = 4) showed elevated baseline CORT and a negative association between the magnitude of stress response and ambient temperature. For this subset, mean ambient temperature for the day before sampling was significantly higher (2.3°C) than for chicks with typical baseline CORT levels. These data suggest that regional climate change trends could affect the ability of nighthawk chicks to mount a stress response, which, in turn, might influence the susceptibility of nighthawk chicks to climate change in the Northern Prairie region.

Immune cell response to strenuous resistive breathing: comparison with whole body exercise and the effects of antioxidants

PubMed Central

Karatza, Maria-Helena; Vasileiou, Spyridoula; Katsaounou, Paraskevi; Mastora, Zafeiria

2018-01-01

Background/hypothesis Whole body exercise (WBE) changes lymphocyte subset percentages in peripheral blood. Resistive breathing, a hallmark of diseases of airway obstruction, is a form of exercise for the inspiratory muscles. Strenuous muscle contractions induce oxidative stress that may mediate immune alterations following exercise. We hypothesized that inspiratory resistive breathing (IRB) alters peripheral blood lymphocyte subsets and that oxidative stress mediates lymphocyte subpopulation alterations following both WBE and IRB. Patients and methods Six healthy nonathletes performed two WBE and two IRB sessions for 45 minutes at 70% of VO2 maximum and 70% of maximum inspiratory pressure (Pimax), respectively, before and after the administration of antioxidants (vitamins E, A, and C for 75 days, allopurinol for 30 days, and N-acetylcysteine for 3 days). Blood was drawn at baseline, at the end of each session, and 2 hours into recovery. Lymphocyte subsets were determined by flow cytometry. Results Before antioxidant supplementation at both WBE end and IRB end, the natural killer cell percentage increased, the T helper cell (CD3+ CD4+) percentage was reduced, and the CD4/CD8 ratio was depressed, a response which was abolished by antioxidants only after IRB. Furthermore, at IRB end, antioxidants promoted CD8+ CD38+ and blunted cytotoxic T-cell percentage increase. CD8+ CD45RA+ cell percentage changes were blunted after antioxidant supplementation in both WBE and IRB. Conclusion We conclude that IRB produces (as WBE) changes in peripheral blood lymphocyte subsets and that oxidative stress is a major stimulus predominantly for IRB-induced lymphocyte subset alterations. PMID:29445271

Immune cell response to strenuous resistive breathing: comparison with whole body exercise and the effects of antioxidants.

PubMed

Asimakos, Andreas; Toumpanakis, Dimitrios; Karatza, Maria-Helena; Vasileiou, Spyridoula; Katsaounou, Paraskevi; Mastora, Zafeiria; Vassilakopoulos, Theodoros

2018-01-01

Whole body exercise (WBE) changes lymphocyte subset percentages in peripheral blood. Resistive breathing, a hallmark of diseases of airway obstruction, is a form of exercise for the inspiratory muscles. Strenuous muscle contractions induce oxidative stress that may mediate immune alterations following exercise. We hypothesized that inspiratory resistive breathing (IRB) alters peripheral blood lymphocyte subsets and that oxidative stress mediates lymphocyte subpopulation alterations following both WBE and IRB. Six healthy nonathletes performed two WBE and two IRB sessions for 45 minutes at 70% of VO 2 maximum and 70% of maximum inspiratory pressure (Pi max ), respectively, before and after the administration of antioxidants (vitamins E, A, and C for 75 days, allopurinol for 30 days, and N-acetylcysteine for 3 days). Blood was drawn at baseline, at the end of each session, and 2 hours into recovery. Lymphocyte subsets were determined by flow cytometry. Before antioxidant supplementation at both WBE end and IRB end, the natural killer cell percentage increased, the T helper cell (CD3+ CD4+) percentage was reduced, and the CD4/CD8 ratio was depressed, a response which was abolished by antioxidants only after IRB. Furthermore, at IRB end, antioxidants promoted CD8+ CD38+ and blunted cytotoxic T-cell percentage increase. CD8+ CD45RA+ cell percentage changes were blunted after antioxidant supplementation in both WBE and IRB. We conclude that IRB produces (as WBE) changes in peripheral blood lymphocyte subsets and that oxidative stress is a major stimulus predominantly for IRB-induced lymphocyte subset alterations.

Lifting the Differentiation Embargo.

PubMed

Latif, Anne-Louise; Holyoake, Tessa L

2016-09-22

Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of a novel and scalable clinical decision support intervention to improve venous thromboembolism prophylaxis: a quasi-experimental study.

PubMed

Umscheid, Craig A; Hanish, Asaf; Chittams, Jesse; Weiner, Mark G; Hecht, Todd E H

2012-08-31

Venous thromboembolism (VTE) causes morbidity and mortality in hospitalized patients, and regulators and payors are encouraging the use of systems to prevent them. Here, we examine the effect of a computerized clinical decision support (CDS) intervention implemented across a multi-hospital academic health system on VTE prophylaxis and events. The study included 223,062 inpatients admitted between April 2007 and May 2010, and used administrative and clinical data. The intervention was integrated into a commercial electronic health record (EHR) in an admission orderset used for all admissions. Three time periods were examined: baseline (period 1), and the time after implementation of the first CDS intervention (period 2) and a second iteration (period 3). Providers were prompted to accept or decline prophylaxis based on patient risk. Time series analyses examined the impact of the intervention on VTE prophylaxis during time periods two and three compared to baseline, and a simple pre-post design examined impact on VTE events and bleeds secondary to anticoagulation. VTE prophylaxis and events were also examined in a prespecified surgical subset of our population meeting the public reporting criteria defined by the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator (PSI). Unadjusted analyses suggested that "recommended", "any", and "pharmacologic" prophylaxis increased from baseline to the last study period (27.1% to 51.9%, 56.7% to 78.1%, and 42.0% to 54.4% respectively; p < 0.01 for all comparisons). Results were significant across all hospitals and the health system overall. Interrupted time series analyses suggested that our intervention increased the use of "recommended" and "any" prophylaxis by 7.9% and 9.6% respectively from baseline to time period 2 (p < 0.01 for both comparisons); and 6.6% and 9.6% respectively from baseline to the combined time periods 2 and 3 (p < 0.01 for both comparisons). There were no significant changes in "pharmacologic" prophylaxis in the adjusted model. The overall percent of patients with VTE increased from baseline to the last study period (2.0% to 2.2%; p = 0.03), but an analysis excluding patients with VTE "present on admission" (POA) demonstrated no difference in events (1.3% to 1.3%; p = 0.80). Overall bleeds did not significantly change. An analysis examining VTE prophylaxis and events in a surgical subset of patients defined by the AHRQ PSI demonstrated increased "recommended", "any", and "pharmacologic" prophylaxis from baseline to the last study period (32.3% to 60.0%, 62.8% to 85.7%, and 47.9% to 63.3% respectively; p < 0.01 for all comparisons) as well as reduced VTE events (2.2% to 1.7%; p < 0.01). The CDS intervention was associated with an increase in "recommended" and "any" VTE prophylaxis across the multi-hospital academic health system. The intervention was also associated with increased VTE rates in the overall study population, but a subanalysis using only admissions with appropriate POA documentation suggested no change in VTE rates, and a prespecified analysis of a surgical subset of our sample as defined by the AHRQ PSI for public reporting purposes suggested reduced VTE. This intervention was created in a commonly used commercial EHR and is scalable across institutions with similar systems.

Effectiveness of a novel and scalable clinical decision support intervention to improve venous thromboembolism prophylaxis: a quasi-experimental study

PubMed Central

2012-01-01

Background Venous thromboembolism (VTE) causes morbidity and mortality in hospitalized patients, and regulators and payors are encouraging the use of systems to prevent them. Here, we examine the effect of a computerized clinical decision support (CDS) intervention implemented across a multi-hospital academic health system on VTE prophylaxis and events. Methods The study included 223,062 inpatients admitted between April 2007 and May 2010, and used administrative and clinical data. The intervention was integrated into a commercial electronic health record (EHR) in an admission orderset used for all admissions. Three time periods were examined: baseline (period 1), and the time after implementation of the first CDS intervention (period 2) and a second iteration (period 3). Providers were prompted to accept or decline prophylaxis based on patient risk. Time series analyses examined the impact of the intervention on VTE prophylaxis during time periods two and three compared to baseline, and a simple pre-post design examined impact on VTE events and bleeds secondary to anticoagulation. VTE prophylaxis and events were also examined in a prespecified surgical subset of our population meeting the public reporting criteria defined by the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicator (PSI). Results Unadjusted analyses suggested that “recommended”, “any”, and “pharmacologic” prophylaxis increased from baseline to the last study period (27.1% to 51.9%, 56.7% to 78.1%, and 42.0% to 54.4% respectively; p < 0.01 for all comparisons). Results were significant across all hospitals and the health system overall. Interrupted time series analyses suggested that our intervention increased the use of “recommended” and “any” prophylaxis by 7.9% and 9.6% respectively from baseline to time period 2 (p < 0.01 for both comparisons); and 6.6% and 9.6% respectively from baseline to the combined time periods 2 and 3 (p < 0.01 for both comparisons). There were no significant changes in “pharmacologic” prophylaxis in the adjusted model. The overall percent of patients with VTE increased from baseline to the last study period (2.0% to 2.2%; p = 0.03), but an analysis excluding patients with VTE “present on admission” (POA) demonstrated no difference in events (1.3% to 1.3%; p = 0.80). Overall bleeds did not significantly change. An analysis examining VTE prophylaxis and events in a surgical subset of patients defined by the AHRQ PSI demonstrated increased “recommended”, “any”, and “pharmacologic” prophylaxis from baseline to the last study period (32.3% to 60.0%, 62.8% to 85.7%, and 47.9% to 63.3% respectively; p < 0.01 for all comparisons) as well as reduced VTE events (2.2% to 1.7%; p < 0.01). Conclusions The CDS intervention was associated with an increase in “recommended” and “any” VTE prophylaxis across the multi-hospital academic health system. The intervention was also associated with increased VTE rates in the overall study population, but a subanalysis using only admissions with appropriate POA documentation suggested no change in VTE rates, and a prespecified analysis of a surgical subset of our sample as defined by the AHRQ PSI for public reporting purposes suggested reduced VTE. This intervention was created in a commonly used commercial EHR and is scalable across institutions with similar systems. PMID:22938083

A Metacommunity Framework for Enhancing the Effectiveness of Biological Monitoring Strategies

PubMed Central

Roque, Fabio O.; Cottenie, Karl

2012-01-01

Because of inadequate knowledge and funding, the use of biodiversity indicators is often suggested as a way to support management decisions. Consequently, many studies have analyzed the performance of certain groups as indicator taxa. However, in addition to knowing whether certain groups can adequately represent the biodiversity as a whole, we must also know whether they show similar responses to the main structuring processes affecting biodiversity. Here we present an application of the metacommunity framework for evaluating the effectiveness of biodiversity indicators. Although the metacommunity framework has contributed to a better understanding of biodiversity patterns, there is still limited discussion about its implications for conservation and biomonitoring. We evaluated the effectiveness of indicator taxa in representing spatial variation in macroinvertebrate community composition in Atlantic Forest streams, and the processes that drive this variation. We focused on analyzing whether some groups conform to environmental processes and other groups are more influenced by spatial processes, and on how this can help in deciding which indicator group or groups should be used. We showed that a relatively small subset of taxa from the metacommunity would represent 80% of the variation in community composition shown by the entire metacommunity. Moreover, this subset does not have to be composed of predetermined taxonomic groups, but rather can be defined based on random subsets. We also found that some random subsets composed of a small number of genera performed better in responding to major environmental gradients. There were also random subsets that seemed to be affected by spatial processes, which could indicate important historical processes. We were able to integrate in the same theoretical and practical framework, the selection of biodiversity surrogates, indicators of environmental conditions, and more importantly, an explicit integration of environmental and spatial processes into the selection approach. PMID:22937068

Clinical and dermoscopic stability and volatility of melanocytic nevi in a population-based cohort of children in Framingham school system

PubMed Central

Scope, Alon; Dusza, Stephen W.; Marghoob, Ashfaq A.; Satagopan, Jaya M.; Braga, Casagrande Tavoloni Juliana; Psaty, Estee L.; Weinstock, Martin A.; Oliveria, Susan A.; Bishop, Marilyn; Geller, Alan C.; Halpern, Allan C.

2011-01-01

Nevi are important risk markers of melanoma. The study aim was to describe changes in nevi of children using longitudinal data from a population-based cohort. Overview back photography and dermoscopic imaging of up to 4 index back nevi was performed at age 11 (baseline) and repeated at age 14 (follow-up). Of 443 children (39% females) imaged at baseline, 366 children (39% females) had repeated imaging three year later. At age 14, median back nevus counts increased by 2; 75% of students (n=274) had at least one new back nevus and 28% (n=103) had at least one nevus that disappeared. Of 936 index nevi imaged dermoscopically at baseline and follow-up, 69% (645 nevi) had retained the same dermoscopic classification from baseline evaluation. Only 4% (n=13) of nevi assessed as globular at baseline were classified as reticular at follow-up, and just 3% (n=3) of baseline reticular nevi were classified as globular at follow-up. Of 9 (1%) index nevi that disappeared at follow-up, none showed halo or regression at baseline. In conclusion, the relative stability of dermoscopic pattern of individual nevi in the face of the overall volatility of nevi during adolescence suggests that specific dermoscopic patterns may represent distinct biologic nevus subsets. PMID:21562569

An Active RBSE Framework to Generate Optimal Stimulus Sequences in a BCI for Spelling

NASA Astrophysics Data System (ADS)

Moghadamfalahi, Mohammad; Akcakaya, Murat; Nezamfar, Hooman; Sourati, Jamshid; Erdogmus, Deniz

2017-10-01

A class of brain computer interfaces (BCIs) employs noninvasive recordings of electroencephalography (EEG) signals to enable users with severe speech and motor impairments to interact with their environment and social network. For example, EEG based BCIs for typing popularly utilize event related potentials (ERPs) for inference. Presentation paradigm design in current ERP-based letter by letter typing BCIs typically query the user with an arbitrary subset characters. However, the typing accuracy and also typing speed can potentially be enhanced with more informed subset selection and flash assignment. In this manuscript, we introduce the active recursive Bayesian state estimation (active-RBSE) framework for inference and sequence optimization. Prior to presentation in each iteration, rather than showing a subset of randomly selected characters, the developed framework optimally selects a subset based on a query function. Selected queries are made adaptively specialized for users during each intent detection. Through a simulation-based study, we assess the effect of active-RBSE on the performance of a language-model assisted typing BCI in terms of typing speed and accuracy. To provide a baseline for comparison, we also utilize standard presentation paradigms namely, row and column matrix presentation paradigm and also random rapid serial visual presentation paradigms. The results show that utilization of active-RBSE can enhance the online performance of the system, both in terms of typing accuracy and speed.

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy (ECT)

PubMed Central

Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A.; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J. Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B.; Zorumski, Charles F.; Conway, Charles; Nagele, Peter

2017-01-01

Background While electroconvulsive therapy (ECT) is widely regarded as a life-saving and safe procedure, evidence regarding its effects on myocardial cell injury are sparse. The objective of this investigation was to determine incidence and magnitude of new cardiac troponin elevation after ECT using a novel high-sensitivity cardiac troponin I (hscTnI) assay. Methods This was a prospective cohort study in adult patients undergoing ECT in a single academic center (up to three ECT treatments per patient). The primary outcome was new hscTnI elevation after ECT, defined as an increase of hscTnI >100% after ECT compared to baseline with at least one value above the limit of quantification (10 ng/L). 12-lead ECG and hscTnI values were obtained prior to and 15–30 minutes after ECT; in a subset of patients an additional 2-hour hscTnI value was obtained. Results The final study population was 100 patients and a total of 245 ECT treatment sessions. Eight patients (8/100, 8%) experienced new hscTnI elevation after ECT with a cumulative incidence of 3.7% (9/245 treatments; one patient had two hscTnI elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2/245, 0.8%). Median hscTnI concentrations did not increase significantly after ECT. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of ECT treatments. Conclusions ECT appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with pre-existing cardiovascular risk factors, however, may develop new cardiac troponin elevation after ECT, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia. PMID:28166110

Item response theory analysis of the mechanics baseline test

NASA Astrophysics Data System (ADS)

Cardamone, Caroline N.; Abbott, Jonathan E.; Rayyan, Saif; Seaton, Daniel T.; Pawl, Andrew; Pritchard, David E.

2012-02-01

Item response theory is useful in both the development and evaluation of assessments and in computing standardized measures of student performance. In item response theory, individual parameters (difficulty, discrimination) for each item or question are fit by item response models. These parameters provide a means for evaluating a test and offer a better measure of student skill than a raw test score, because each skill calculation considers not only the number of questions answered correctly, but the individual properties of all questions answered. Here, we present the results from an analysis of the Mechanics Baseline Test given at MIT during 2005-2010. Using the item parameters, we identify questions on the Mechanics Baseline Test that are not effective in discriminating between MIT students of different abilities. We show that a limited subset of the highest quality questions on the Mechanics Baseline Test returns accurate measures of student skill. We compare student skills as determined by item response theory to the more traditional measurement of the raw score and show that a comparable measure of learning gain can be computed.

An exploration of the properties of the CORE problem list subset and how it facilitates the implementation of SNOMED CT

PubMed Central

Xu, Julia

2015-01-01

Objective Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) is the emergent international health terminology standard for encoding clinical information in electronic health records. The CORE Problem List Subset was created to facilitate the terminology’s implementation. This study evaluates the CORE Subset’s coverage and examines its growth pattern as source datasets are being incorporated. Methods Coverage of frequently used terms and the corresponding usage of the covered terms were assessed by “leave-one-out” analysis of the eight datasets constituting the current CORE Subset. The growth pattern was studied using a retrospective experiment, growing the Subset one dataset at a time and examining the relationship between the size of the starting subset and the coverage of frequently used terms in the incoming dataset. Linear regression was used to model that relationship. Results On average, the CORE Subset covered 80.3% of the frequently used terms of the left-out dataset, and the covered terms accounted for 83.7% of term usage. There was a significant positive correlation between the CORE Subset’s size and the coverage of the frequently used terms in an incoming dataset. This implies that the CORE Subset will grow at a progressively slower pace as it gets bigger. Conclusion The CORE Problem List Subset is a useful resource for the implementation of Systematized Nomenclature of Medicine Clinical Terms in electronic health records. It offers good coverage of frequently used terms, which account for a high proportion of term usage. If future datasets are incorporated into the CORE Subset, it is likely that its size will remain small and manageable. PMID:25725003

Personality and Career Success: Concurrent and Longitudinal Relations

PubMed Central

Sutin, Angelina R.; Costa, Paul T.; Miech, Richard; Eaton, William W.

2009-01-01

The present research addresses the dynamic transaction between extrinsic (occupational prestige, income) and intrinsic (job satisfaction) career success and the Five-Factor Model of personality. Participants (N = 731) completed a comprehensive measure of personality and reported their job title, annual income, and job satisfaction; a subset of these participants (n = 302) provided the same information approximately 10 years later. Measured concurrently, emotionally stable and conscientious participants reported higher incomes and job satisfaction. Longitudinal analyses revealed that, among younger participants, higher income at baseline predicted decreases in Neuroticism and baseline Extraversion predicted increases in income across the 10 years. Results suggest that the mutual influence of career success and personality is limited to income and occurs early in the career. PMID:19774106

An endogenous small interfering RNA pathway in Drosophila

PubMed Central

Czech, Benjamin; Malone, Colin D.; Zhou, Rui; Stark, Alexander; Schlingeheyde, Catherine; Dus, Monica; Perrimon, Norbert; Kellis, Manolis; Wohlschlegel, James A.; Sachidanandam, Ravi; Hannon, Gregory J.; Brennecke, Julius

2009-01-01

Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of ~22 nucleotides in length, which arise from structured precursors through the action of Drosha–Pasha and Dicer-1–Loquacious complexes1–7. These join Argonaute-1 to regulate gene expression8,9. A second endogenous small RNA class, the Piwi-interacting RNAs, bind Piwi proteins and suppress transposons10,11. Piwi-interacting RNAs are restricted to the gonad, and at least a subset of these arises by Piwi-catalysed cleavage of single-stranded RNAs12,13. Here we show that Drosophila generates a third small RNA class, endogenous small interfering RNAs, in both gonadal and somatic tissues. Production of these RNAs requires Dicer-2, but a subset depends preferentially on Loquacious1,4,5 rather than the canonical Dicer-2 partner, R2D2 (ref. 14). Endogenous small interfering RNAs arise both from convergent transcription units and from structured genomic loci in a tissue-specific fashion. They predominantly join Argonaute-2 and have the capacity, as a class, to target both protein-coding genes and mobile elements. These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles. PMID:18463631

Changes in inpatient payer-mix and hospitalizations following Medicaid expansion: Evidence from all-capture hospital discharge data.

PubMed

Freedman, Seth; Nikpay, Sayeh; Carroll, Aaron; Simon, Kosali

2017-01-01

The Affordable Care Act resulted in unprecedented reductions in the uninsured population through subsidized private insurance and an expansion of Medicaid. Early estimates from the beginning of 2014 showed that the Medicaid expansion decreased uninsured discharges and increased Medicaid discharges with no change in total discharges. To provide new estimates of the effect of the ACA on discharges for specific conditions. We compared outcomes between states that did and did not expand Medicaid using state-level all-capture discharge data from 2009-2014 for 42 states from the Healthcare Costs and Utilization Project's FastStats database; for a subset of states we used data through 2015. We stratified the analysis by baseline uninsured rates and used difference-in-differences and synthetic control methods to select comparison states with similar baseline characteristics that did not expand Medicaid. Our main outcomes were total and condition-specific hospital discharges per 1,000 population and the share of total discharges by payer. Conditions reported separately in FastStats included maternal, surgical, mental health, injury, and diabetes. The share of uninsured discharges fell in Medicaid expansion states with below (-4.39 percentage points (p.p.), -6.04 --2.73) or above (-7.66 p.p., -9.07 --6.24) median baseline uninsured rates. The share of Medicaid discharges increased in both small (6.42 p.p. 4.22-6.62) and large (10.5 p.p., 8.48-12.5) expansion states. Total and most condition-specific discharges per 1,000 residents did not change in Medicaid expansion states with high or low baseline uninsured rates relative to non-expansion states (0.418, p = 0.225), with one exception: diabetes. Discharges for that condition per 1,000 fell in states with high baseline uninsured rates relative to non-expansion states (-0.038 95% p = 0.027). Early changes in payer mix identified in the first two quarters of 2014 continued through the Medicaid expansion's first year and are distributed across all condition types studied. We found no change in total discharges between Medicaid expansion and non-expansion states, however residents of states that should have been most affected by the Medicaid expansion were less likely to be hospitalized for diabetes.

Numerical algorithms for scatter-to-attenuation reconstruction in PET: empirical comparison of convergence, acceleration, and the effect of subsets.

PubMed

Berker, Yannick; Karp, Joel S; Schulz, Volkmar

2017-09-01

The use of scattered coincidences for attenuation correction of positron emission tomography (PET) data has recently been proposed. For practical applications, convergence speeds require further improvement, yet there exists a trade-off between convergence speed and the risk of non-convergence. In this respect, a maximum-likelihood gradient-ascent (MLGA) algorithm and a two-branch back-projection (2BP), which was previously proposed, were evaluated. MLGA was combined with the Armijo step size rule; and accelerated using conjugate gradients, Nesterov's momentum method, and data subsets of different sizes. In 2BP, we varied the subset size, an important determinant of convergence speed and computational burden. We used three sets of simulation data to evaluate the impact of a spatial scale factor. The Armijo step size allowed 10-fold increased step sizes compared to native MLGA. Conjugate gradients and Nesterov momentum lead to slightly faster, yet non-uniform convergence; improvements were mostly confined to later iterations, possibly due to the non-linearity of the problem. MLGA with data subsets achieved faster, uniform, and predictable convergence, with a speed-up factor equivalent to the number of subsets and no increase in computational burden. By contrast, 2BP computational burden increased linearly with the number of subsets due to repeated evaluation of the objective function, and convergence was limited to the case of many (and therefore small) subsets, which resulted in high computational burden. Possibilities of improving 2BP appear limited. While general-purpose acceleration methods appear insufficient for MLGA, results suggest that data subsets are a promising way of improving MLGA performance.

Denosumab and Bone Metastasis–Free Survival in Men With Nonmetastatic Castration-Resistant Prostate Cancer: Exploratory Analyses by Baseline Prostate-Specific Antigen Doubling Time

PubMed Central

Smith, Matthew R.; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

2013-01-01

Purpose Denosumab, an anti–RANK ligand monoclonal antibody, significantly increases bone metastasis–free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. Patients and Methods A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. Results In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Conclusion Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression. PMID:24043751

Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time.

PubMed

Smith, Matthew R; Saad, Fred; Oudard, Stephane; Shore, Neal; Fizazi, Karim; Sieber, Paul; Tombal, Bertrand; Damiao, Ronaldo; Marx, Gavin; Miller, Kurt; Van Veldhuizen, Peter; Morote, Juan; Ye, Zhishen; Dansey, Roger; Goessl, Carsten

2013-10-20

Denosumab, an anti-RANK ligand monoclonal antibody, significantly increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028) and delays time to first bone metastasis in men with nonmetastatic castration-resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) ≥ 8.0 ng/mL and/or PSA doubling time (PSADT) ≤ 10.0 months. To identify men at greatest risk for bone metastasis or death, we evaluated relationships between PSA and PSADT with BMFS in the placebo group and the efficacy and safety of denosumab in men with PSADT ≤ 10, ≤ 6, and ≤ 4 months. A total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary analysis cutoff was July 2010, when approximately 660 men were anticipated to have developed bone metastases or died. In the placebo group, shorter BMFS was observed as PSADT decreased below 8 months. In analyses by shorter baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2, and 7.5 months among men with PSADT ≤ 10 (HR, 0.84; P = .042), ≤ 6 (HR, 0.77; P = .006), and ≤ 4 months (HR, 0.71; P = .004), respectively. Denosumab also consistently increased time to bone metastasis by PSADT subset. No difference in survival was observed between treatment groups for the overall study population or PSADT subsets. Patients with shorter PSADT are at greater risk for bone metastasis or death. Denosumab consistently improves BMFS in men with shorter PSADT and seems to have the greatest treatment effects in men at high risk for progression.

Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study.

PubMed

Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; Provost, Scott E; Fitzmaurice, Garrett M; McDermott, Katherine A; Srisarajivakul, Emily N; Dodd, Dorian R; Dreifuss, Jessica A; McHugh, R Kathryn; Carroll, Kathleen M

2015-05-01

Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Incorporating High-Frequency Physiologic Data Using Computational Dictionary Learning Improves Prediction of Delayed Cerebral Ischemia Compared to Existing Methods.

PubMed

Megjhani, Murad; Terilli, Kalijah; Frey, Hans-Peter; Velazquez, Angela G; Doyle, Kevin William; Connolly, Edward Sander; Roh, David Jinou; Agarwal, Sachin; Claassen, Jan; Elhadad, Noemie; Park, Soojin

2018-01-01

Accurate prediction of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) can be critical for planning interventions to prevent poor neurological outcome. This paper presents a model using convolution dictionary learning to extract features from physiological data available from bedside monitors. We develop and validate a prediction model for DCI after SAH, demonstrating improved precision over standard methods alone. 488 consecutive SAH admissions from 2006 to 2014 to a tertiary care hospital were included. Models were trained on 80%, while 20% were set aside for validation testing. Modified Fisher Scale was considered the standard grading scale in clinical use; baseline features also analyzed included age, sex, Hunt-Hess, and Glasgow Coma Scales. An unsupervised approach using convolution dictionary learning was used to extract features from physiological time series (systolic blood pressure and diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation). Classifiers (partial least squares and linear and kernel support vector machines) were trained on feature subsets of the derivation dataset. Models were applied to the validation dataset. The performances of the best classifiers on the validation dataset are reported by feature subset. Standard grading scale (mFS): AUC 0.54. Combined demographics and grading scales (baseline features): AUC 0.63. Kernel derived physiologic features: AUC 0.66. Combined baseline and physiologic features with redundant feature reduction: AUC 0.71 on derivation dataset and 0.78 on validation dataset. Current DCI prediction tools rely on admission imaging and are advantageously simple to employ. However, using an agnostic and computationally inexpensive learning approach for high-frequency physiologic time series data, we demonstrated that we could incorporate individual physiologic data to achieve higher classification accuracy.

Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

PubMed Central

Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

2016-01-01

Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

Support for the existence of invertible maps between electronic densities and non-analytic 1-body external potentials in non-relativistic time-dependent quantum mechanics

NASA Astrophysics Data System (ADS)

Mosquera, Martín A.

2017-10-01

Provided the initial state, the Runge-Gross theorem establishes that the time-dependent (TD) external potential of a system of non-relativistic electrons determines uniquely their TD electronic density, and vice versa (up to a constant in the potential). This theorem requires the TD external potential and density to be Taylor-expandable around the initial time of the propagation. This paper presents an extension without this restriction. Given the initial state of the system and evolution of the density due to some TD scalar potential, we show that a perturbative (not necessarily weak) TD potential that induces a non-zero divergence of the external force-density, inside a small spatial subset and immediately after the initial propagation time, will cause a change in the density within that subset, implying that the TD potential uniquely determines the TD density. In this proof, we assume unitary evolution of wavefunctions and first-order differentiability (which does not imply analyticity) in time of the internal and external force-densities, electronic density, current density, and their spatial derivatives over the small spatial subset and short time interval.

The emerging role of ALK inhibitors in the treatment of advanced non-small cell lung cancer.

PubMed

Galetta, Domenico; Rossi, Antonio; Pisconti, Salvatore; Colucci, Giuseppe

2012-04-01

Most NSCLC patients are diagnosed in the advanced stage of the disease. Recently, chemotherapeutic agents have reached a plateau of effectiveness. Increased understanding of cancer biology has revealed several potential therapeutic strategies that have led to marketing of new biologic agents. The echinoderm microtubule-associated protein like-4-anaplastic lymphoma kinase (EML4-ALK) fusion oncogene represents one of the newest molecular targets in NSCLC, identifying a subset of NSCLC patients characterized by distinct clinicopathological features. The available results concerning ALK inhibitors for the treatment of advanced NSCLC patients. An electronic search was used to retrieve the articles addressing this topic. In a pivotal Phase I clinical trial, crizotinib (PF-02341066), a small-molecule ALK inhibitor, demonstrated impressive antitumor activity in the majority of NSCLC patients with ALK fusions. Phase III randomized trials investigating crizotinib in this subgroup of patients are ongoing. If the results from these large international trials confirm the efficacy of crizotinib in the subset of patients, the next few years could see the treatment of advanced NSCLC patients with ALK fusions. Specific inhibitors would realize the so called personalized medicine in subsets of this disease.

The application of cat swarm optimisation algorithm in classifying small loan performance

NASA Astrophysics Data System (ADS)

Kencana, Eka N.; Kiswanti, Nyoman; Sari, Kartika

2017-10-01

It is common for banking system to analyse the feasibility of credit application before its approval. Although this process has been carefully done, there is no warranty that all credits will be repaid smoothly. This study aimed to know the accuracy of Cat Swarm Optimisation (CSO) algorithm in classifying small loans’ performance that is approved by Bank Rakyat Indonesia (BRI), one of several public banks in Indonesia. Data collected from 200 lenders were used in this work. The data matrix consists of 9 independent variables that represent profile of the credit, and one categorical dependent variable reflects credit’s performance. Prior to the analyses, data was divided into two data subset with equal size. Ordinal logistic regression (OLR) procedure is applied for the first subset and gave 3 out of 9 independent variables i.e. the amount of credit, credit’s period, and income per month of lender proved significantly affect credit performance. By using significantly estimated parameters from OLR procedure as the initial values for observations at the second subset, CSO procedure started. This procedure gave 76 percent of classification accuracy of credit performance, slightly better compared to 64 percent resulted from OLR procedure.

Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis

PubMed Central

Mittal, Anuradha; Pachter, Lior; Nelson, J. Lee; Smed, Mette Kiel; Gildengorin, Virginia L.; Zoffmann, Vibeke; Hetland, Merete Lund; Jewell, Nicholas P.; Olsen, Jørn; Jawaheer, Damini

2015-01-01

Background Pregnancy induces drastic biological changes systemically, and has a beneficial effect on some autoimmune conditions such as rheumatoid arthritis (RA). However, specific systemic changes that occur as a result of pregnancy have not been thoroughly examined in healthy women or women with RA. The goal of this study was to identify genes with expression patterns associated with pregnancy, compared to pre-pregnancy as baseline and determine whether those associations are modified by presence of RA. Results In our RNA sequencing (RNA-seq) dataset from 5 healthy women and 20 women with RA, normalized expression levels of 4,710 genes were significantly associated with pregnancy status (pre-pregnancy, first, second and third trimesters) over time, irrespective of presence of RA (False Discovery Rate (FDR)-adjusted p value<0.05). These genes were enriched in pathways spanning multiple systems, as would be expected during pregnancy. A subset of these genes (n = 256) showed greater than two-fold change in expression during pregnancy compared to baseline levels, with distinct temporal trends through pregnancy. Another 98 genes involved in various biological processes including immune regulation exhibited expression patterns that were differentially associated with pregnancy in the presence or absence of RA. Conclusions Our findings support the hypothesis that the maternal immune system plays an active role during pregnancy, and also provide insight into other systemic changes that occur in the maternal transcriptome during pregnancy compared to the pre-pregnancy state. Only a small proportion of genes modulated by pregnancy were influenced by presence of RA in our data. PMID:26683605

Pregnancy-Induced Changes in Systemic Gene Expression among Healthy Women and Women with Rheumatoid Arthritis.

PubMed

Mittal, Anuradha; Pachter, Lior; Nelson, J Lee; Kjærgaard, Hanne; Smed, Mette Kiel; Gildengorin, Virginia L; Zoffmann, Vibeke; Hetland, Merete Lund; Jewell, Nicholas P; Olsen, Jørn; Jawaheer, Damini

2015-01-01

Pregnancy induces drastic biological changes systemically, and has a beneficial effect on some autoimmune conditions such as rheumatoid arthritis (RA). However, specific systemic changes that occur as a result of pregnancy have not been thoroughly examined in healthy women or women with RA. The goal of this study was to identify genes with expression patterns associated with pregnancy, compared to pre-pregnancy as baseline and determine whether those associations are modified by presence of RA. In our RNA sequencing (RNA-seq) dataset from 5 healthy women and 20 women with RA, normalized expression levels of 4,710 genes were significantly associated with pregnancy status (pre-pregnancy, first, second and third trimesters) over time, irrespective of presence of RA (False Discovery Rate (FDR)-adjusted p value<0.05). These genes were enriched in pathways spanning multiple systems, as would be expected during pregnancy. A subset of these genes (n = 256) showed greater than two-fold change in expression during pregnancy compared to baseline levels, with distinct temporal trends through pregnancy. Another 98 genes involved in various biological processes including immune regulation exhibited expression patterns that were differentially associated with pregnancy in the presence or absence of RA. Our findings support the hypothesis that the maternal immune system plays an active role during pregnancy, and also provide insight into other systemic changes that occur in the maternal transcriptome during pregnancy compared to the pre-pregnancy state. Only a small proportion of genes modulated by pregnancy were influenced by presence of RA in our data.

Maintenance of parenteral nutrition volume reduction, without weight loss, after stopping teduglutide in a subset of patients with short bowel syndrome.

PubMed

Compher, Charlene; Gilroy, Richard; Pertkiewicz, Marek; Ziegler, Thomas R; Ratcliffe, Sarah J; Joly, Francisca; Rochling, Fedja; Messing, Bernard

2011-09-01

Teduglutide was discontinued after being tested for ≥ 24 weeks in patients with parenteral nutrition (PN) -dependent short bowel syndrome in a clinical trial for efficacy to reduce PN volume. This study was describes change in body mass index (BMI) and PN volume over 12 months in patients who stopped drug after the clinical trial. Prescribed PN volume, weight, and complications were reported. Patients with stable (NEUT, n = 15) or decreased (DEC, n = 7) PN volume by 12 months after stopping drug (NEUT/DEC, n = 22) were compared to those who had increased PN volume (INC, n = 15). With drug response defined by ≥ 20% reduction from pre-drug PN volume to end of drug therapy, 12 INC and 13 NEUT/DEC patients were drug responders. Eleven of 20 eligible sites reported data for 39 of 53 eligible study participants, with follow-up data for 37. INC patients had shorter colon and less frequently had colon in continuity than NEUT/DEC. BMI was decreased at 3, 6, and 12 months relative to the first off-drug visit in INC patients (P = .001), but not in NEUT/DEC patients. Change in BMI off-drug was predicted by colon and small bowel length, baseline BMI, and on-drug change in PN volume (adjusted R2 = 0.708). Gastrointestinal anatomy, baseline BMI, and PN volume reduction on-drug predicted change in BMI off-drug. Whether this response would be maintained for a longer time or in the context of a challenging clinical situation has not been evaluated.

--No Title--

Science.gov Websites

will be useful, for example, in providing initial and/or lateral boundary conditions for regional reforecasts with various limited-area models. To access a subset of model output, for example a small number

Validation of the Abdominal Pain Index using a revised scoring method.

PubMed

Laird, Kelsey T; Sherman, Amanda L; Smith, Craig A; Walker, Lynn S

2015-06-01

Evaluate the psychometric properties of child- and parent-report versions of the four-item Abdominal Pain Index (API) in children with functional abdominal pain (FAP) and healthy controls, using a revised scoring method that facilitates comparisons of scores across samples and time. Pediatric patients aged 8-18 years with FAP and controls completed the API at baseline (N = 1,967); a subset of their parents (N = 290) completed the API regarding the child's pain. Subsets of patients completed follow-up assessments at 2 weeks (N = 231), 3 months (N = 330), and 6 months (N = 107). Subsets of both patients (N = 389) and healthy controls (N = 172) completed a long-term follow-up assessment (mean age at follow-up = 20.21 years, SD = 3.75). The API demonstrated good concurrent, discriminant, and construct validity, as well as good internal consistency. We conclude that the API, using the revised scoring method, is a useful, reliable, and valid measure of abdominal pain severity. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Elucidating Molecular Motion through Structural and Dynamic Filters of Energy-Minimized Conformer Ensembles

PubMed Central

2015-01-01

Complex RNA structures are constructed from helical segments connected by flexible loops that move spontaneously and in response to binding of small molecule ligands and proteins. Understanding the conformational variability of RNA requires the characterization of the coupled time evolution of interconnected flexible domains. To elucidate the collective molecular motions and explore the conformational landscape of the HIV-1 TAR RNA, we describe a new methodology that utilizes energy-minimized structures generated by the program “Fragment Assembly of RNA with Full-Atom Refinement (FARFAR)”. We apply structural filters in the form of experimental residual dipolar couplings (RDCs) to select a subset of discrete energy-minimized conformers and carry out principal component analyses (PCA) to corroborate the choice of the filtered subset. We use this subset of structures to calculate solution T1 and T1ρ relaxation times for 13C spins in multiple residues in different domains of the molecule using two simulation protocols that we previously published. We match the experimental T1 times to within 2% and the T1ρ times to within less than 10% for helical residues. These results introduce a protocol to construct viable dynamic trajectories for RNA molecules that accord well with experimental NMR data and support the notion that the motions of the helical portions of this small RNA can be described by a relatively small number of discrete conformations exchanging over time scales longer than 1 μs. PMID:24479561

Statistical iterative reconstruction for streak artefact reduction when using multidetector CT to image the dento-alveolar structures.

PubMed

Dong, J; Hayakawa, Y; Kober, C

2014-01-01

When metallic prosthetic appliances and dental fillings exist in the oral cavity, the appearance of metal-induced streak artefacts is not avoidable in CT images. The aim of this study was to develop a method for artefact reduction using the statistical reconstruction on multidetector row CT images. Adjacent CT images often depict similar anatomical structures. Therefore, reconstructed images with weak artefacts were attempted using projection data of an artefact-free image in a neighbouring thin slice. Images with moderate and strong artefacts were continuously processed in sequence by successive iterative restoration where the projection data was generated from the adjacent reconstructed slice. First, the basic maximum likelihood-expectation maximization algorithm was applied. Next, the ordered subset-expectation maximization algorithm was examined. Alternatively, a small region of interest setting was designated. Finally, the general purpose graphic processing unit machine was applied in both situations. The algorithms reduced the metal-induced streak artefacts on multidetector row CT images when the sequential processing method was applied. The ordered subset-expectation maximization and small region of interest reduced the processing duration without apparent detriments. A general-purpose graphic processing unit realized the high performance. A statistical reconstruction method was applied for the streak artefact reduction. The alternative algorithms applied were effective. Both software and hardware tools, such as ordered subset-expectation maximization, small region of interest and general-purpose graphic processing unit achieved fast artefact correction.

A statistical approach to selecting and confirming validation targets in -omics experiments

PubMed Central

2012-01-01

Background Genomic technologies are, by their very nature, designed for hypothesis generation. In some cases, the hypotheses that are generated require that genome scientists confirm findings about specific genes or proteins. But one major advantage of high-throughput technology is that global genetic, genomic, transcriptomic, and proteomic behaviors can be observed. Manual confirmation of every statistically significant genomic result is prohibitively expensive. This has led researchers in genomics to adopt the strategy of confirming only a handful of the most statistically significant results, a small subset chosen for biological interest, or a small random subset. But there is no standard approach for selecting and quantitatively evaluating validation targets. Results Here we present a new statistical method and approach for statistically validating lists of significant results based on confirming only a small random sample. We apply our statistical method to show that the usual practice of confirming only the most statistically significant results does not statistically validate result lists. We analyze an extensively validated RNA-sequencing experiment to show that confirming a random subset can statistically validate entire lists of significant results. Finally, we analyze multiple publicly available microarray experiments to show that statistically validating random samples can both (i) provide evidence to confirm long gene lists and (ii) save thousands of dollars and hundreds of hours of labor over manual validation of each significant result. Conclusions For high-throughput -omics studies, statistical validation is a cost-effective and statistically valid approach to confirming lists of significant results. PMID:22738145

ZINC: A Free Tool to Discover Chemistry for Biology

PubMed Central

2012-01-01

ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org. PMID:22587354

Effect of vitamin D replacement on immunological biomarkers in patients with multiple sclerosis.

PubMed

Mrad, May F; El Ayoubi, Nabil K; Esmerian, Maria O; Kazan, Jalal M; Khoury, Samia J

2017-08-01

We aimed to investigate the immunologic effects of vitamin D replacement in RRMS patients. In a controlled single center study, patients deficient in 25-hydroxyvitamin D (serum level<25ng/ml) received 10,000IU/week cholecalciferol for 3months. Sufficient vitamin D patients (serum level>35ng/ml) were followed for the same period. Assessments were performed at baseline and at 3months. 25-hydroxyvitamin D levels increased significantly from baseline to month-3 in the deficient group after treatment and remained stable in the sufficient group. We observed a decreased interferon-γ (IFNγ) secretion by CD4 + T cells in vitamin D deficient group but not in the sufficient group, and a negative correlation between baseline serum vitamin D and IFNγ production. There was no change in the frequency of T helper or regulatory T cell subsets in either group. Increasing serum levels of 25-hydroxyvitamin D are associated with decreased production of IFNγ by CD4 + T cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Hankin and Reeves' approach to estimating fish abundance in small streams: limitations and alternatives

Treesearch

William L. Thompson

2003-01-01

Hankin and Reeves' (1988) approach to estimating fish abundance in small streams has been applied in stream fish studies across North America. However, their population estimator relies on two key assumptions: (1) removal estimates are equal to the true numbers of fish, and (2) removal estimates are highly correlated with snorkel counts within a subset of sampled...

Circulating Branched-chain Amino Acid Concentrations Are Associated with Obesity and Future Insulin Resistance in Children and Adolescents

PubMed Central

McCormack, Shana E.; Shaham, Oded; McCarthy, Meaghan A.; Deik, Amy A.; Wang, Thomas J.; Gerszten, Robert E.; Clish, Clary B.; Mootha, Vamsi K.; Grinspoon, Steven K.; Fleischman, Amy

2012-01-01

Background Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. Objective To determine whether pediatric obesity is associated with elevations in fasting circulating concentrations of branched-chain amino acids (isoleucine, leucine, and valine), and whether these elevations predict future insulin resistance. Research Design and Methods Sixty-nine healthy subjects, ages 8 to18 years, were enrolled as a cross-sectional cohort. A subset who were pre- or early-pubertal, ages 8 to 13 years, were enrolled in a prospective longitudinal cohort for 18 months (n=17 with complete data). Results Elevations in the concentrations of BCAA’s were significantly associated with BMI Z-score (Spearman’s Rho 0.27, p=0.03) in the cross-sectional cohort. In the subset of subjects followed longitudinally, baseline BCAA concentrations were positively associated with HOMA-IR measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex, and pubertal stage (p=0.046). Conclusions Elevations in the concentrations of circulating branched-chain amino acids are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. PMID:22961720

JAK inhibition induces silencing of T Helper cytokine secretion and a profound reduction in T regulatory cells.

PubMed

Keohane, Clodagh; Kordasti, Shahram; Seidl, Thomas; Perez Abellan, Pilar; Thomas, Nicholas S B; Harrison, Claire N; McLornan, Donal P; Mufti, Ghulam J

2015-10-01

CD4(+) T cells maintain cancer surveillance and immune tolerance. Chronic inflammation has been proposed as a driver of clonal evolution in myeloproliferative neoplasms (MPN), suggesting that T cells play an important role in their pathogenesis. Treatment with JAK inhibitors (JAKi) results in improvements in MPN-associated constitutional symptoms as well as reductions in splenomegaly. However, effects of JAKi on T cells in MPN are not well established and the baseline immune signature remains unclear. We investigated the frequency and function of CD4(+) T cell subsets in 50 MPN patients at baseline as well as during treatment with either ruxolitinib or fedratinib in a subset. We show that CD4(+)  CD127(low)  CD25(high)  FOXP3(+) T regulatory cells are reduced in MPN patients compared to healthy controls and that this decrease is even more pronounced following JAKi therapy. Moreover, we show that after 6 months of treatment the number of T helper (Th)-17 cells increased. We also describe a functional 'silencing' of T helper cells both in vivo and in vitro and a blockade of pro-inflammatory cytokines from these cells. This profound effect of JAKi on T cell function may underlay augmented rates of atypical infections that have been reported with use of these drugs. © 2015 John Wiley & Sons Ltd.

Training attentional control in older adults.

PubMed

Mackay-Brandt, Anna

2011-07-01

Recent research has demonstrated benefits for older adults from training attentional control using a variable priority strategy, but the construct validity of the training task and the degree to which benefits of training transfer to other contexts are unclear. The goal of this study was to characterize baseline performance on the training task in a sample of 105 healthy older adults and to test for transfer of training in a subset (n = 21). Training gains after 5 days and extent of transfer was compared to another subset (n = 20) that served as a control group. Baseline performance on the training task was characterized by a two-factor model of working memory and processing speed. Processing speed correlated with the training task. Training gains in speed and accuracy were reliable and robust (ps <.001, η(2) = .57 to .90). Transfer to an analogous task was observed (ps <.05, η(2) = .10 to .17). The beneficial effect of training did not translate to improved performance on related measures of processing speed. This study highlights the robust effect of training and transfer to a similar context using a variable priority training task. Although processing speed is an important aspect of the training task, training benefit is either related to an untested aspect of the training task or transfer of training is limited to the training context.

Analysis of the Los Angeles Basin ground subsidence with InSAR data by independent component analysis approach

NASA Astrophysics Data System (ADS)

Xu, B.

2017-12-01

Interferometric Synthetic Aperture Radar (InSAR) has the advantages of high spatial resolution which enable measure line of sight (LOS) surface displacements with nearly complete spatial continuity and a satellite's perspective that permits large areas view of Earth's surface quickly and efficiently. However, using InSAR to observe long wavelength and small magnitude deformation signals is still significantly limited by various unmodeled errors sources i.e. atmospheric delays, orbit induced errors, Digital Elevation Model (DEM) errors. Independent component analysis (ICA) is a probabilistic method for separating linear mixed signals generated by different underlying physical processes.The signal sources which form the interferograms are statistically independent both in space and in time, thus, they can be separated by ICA approach.The seismic behavior in the Los Angeles Basin is active and the basin has experienced numerous moderate to large earthquakes since the early Pliocene. Hence, understanding the seismotectonic deformation in the Los Angeles Basin is important for analyzing seismic behavior. Compare with the tectonic deformations, nontectonic deformations due to groundwater and oil extraction may be mainly responsible for the surface deformation in the Los Angeles basin. Using the small baseline subset (SBAS) InSAR method, we extracted the surface deformation time series in the Los Angeles basin with a time span of 7 years (September 27, 2003-September 25,2010). Then, we successfully separate the atmospheric noise from InSAR time series and detect different processes caused by different mechanisms.

Fetal heart rate patterns at 20 to 24 weeks gestation as recorded by fetal electrocardiography

PubMed Central

Hofmeyr, F; Groenewald, CA; Nel, DG; Myers, MM; Fifer, WP; Signore, C; Hankins, GDV; Odendaal, HJ

2014-01-01

Introduction With advancing technology it has become possible to accurately record and assess fetal heart rate (FHR) patterns from gestations as early as 20 weeks. The aim of our study was to describe early patterns of FHR, as recorded by transabdominal fetal electrocardiogram according to the Dawes-Redman criteria. Accordingly, short-term variability, basal heart rate, accelerations and decelerations were quantified at 20-24 weeks gestation among women with uncomplicated pregnancies. Methods This study was conducted in a subset of participants enrolled in a large prospective pregnancy cohort study. Our final data set consisted of 281 recordings of women with good perinatal outcomes that had undergone fetal electrocardiographic assessment as part of the Safe Passage Study. Results The success rate of the recordings was 95.4%. The mean frequency of small and large accelerations was 0.5 and 0.1 per 10 minutes respectively and that of small and large decelerations 0.3 and 0.008 per 10 minutes respectively. The mean and basal heart rates were both equal to 148.0 bpm at a median gestation of 161 days. The mean short term variation was 6.2 (SD 1.4) milliseconds and mean minute range 35.1 (SD 7.1) milliseconds. Conclusion The 20 to 24 week fetus demonstrates FHR patterns with more accelerations and decelerations, as well as higher baseline variability than was anticipated. Information from this study provides an important foundation for further, more detailed, studies of early FHR patterns. PMID:23991757

ERK phosphorylation is predictive of resistance to IGF-1R inhibition in Small Cell Lung Cancer

PubMed Central

Zinn, Rebekah L.; Gardner, Eric E.; Marchionni, Luigi; Murphy, Sara C.; Dobromilskaya, Irina; Hann, Christine L.; Rudin, Charles M.

2013-01-01

New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). IGF-1R inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC, and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways including PI3K-Akt and MAPK. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R and the closely related insulin receptor (IR). Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 < 1 μM. Cell line expression of IGF-1R, IR, IGF-1, IGF-2, IGFBP3, and IGFBP6 did not correlate with sensitivity to OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (p=0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared to mock treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. PMID:23515613

Long-term ground deformation patterns of Bucharest using multi-temporal InSAR and multivariate dynamic analyses: a possible transpressional system?

PubMed Central

Armaş, Iuliana; Mendes, Diana A.; Popa, Răzvan-Gabriel; Gheorghe, Mihaela; Popovici, Diana

2017-01-01

The aim of this exploratory research is to capture spatial evolution patterns in the Bucharest metropolitan area using sets of single polarised synthetic aperture radar (SAR) satellite data and multi-temporal radar interferometry. Three sets of SAR data acquired during the years 1992–2010 from ERS-1/-2 and ENVISAT, and 2011–2014 from TerraSAR-X satellites were used in conjunction with the Small Baseline Subset (SBAS) and persistent scatterers (PS) high-resolution multi-temporal interferometry (InSAR) techniques to provide maps of line-of-sight displacements. The satellite-based remote sensing results were combined with results derived from classical methodologies (i.e., diachronic cartography) and field research to study possible trends in developments over former clay pits, landfill excavation sites, and industrial parks. The ground displacement trend patterns were analysed using several linear and nonlinear models, and techniques. Trends based on the estimated ground displacement are characterised by long-term memory, indicated by low noise Hurst exponents, which in the long-term form interesting attractors. We hypothesize these attractors to be tectonic stress fields generated by transpressional movements. PMID:28252103

Long-term ground deformation patterns of Bucharest using multi-temporal InSAR and multivariate dynamic analyses: a possible transpressional system?

PubMed

Armaş, Iuliana; Mendes, Diana A; Popa, Răzvan-Gabriel; Gheorghe, Mihaela; Popovici, Diana

2017-03-02

The aim of this exploratory research is to capture spatial evolution patterns in the Bucharest metropolitan area using sets of single polarised synthetic aperture radar (SAR) satellite data and multi-temporal radar interferometry. Three sets of SAR data acquired during the years 1992-2010 from ERS-1/-2 and ENVISAT, and 2011-2014 from TerraSAR-X satellites were used in conjunction with the Small Baseline Subset (SBAS) and persistent scatterers (PS) high-resolution multi-temporal interferometry (InSAR) techniques to provide maps of line-of-sight displacements. The satellite-based remote sensing results were combined with results derived from classical methodologies (i.e., diachronic cartography) and field research to study possible trends in developments over former clay pits, landfill excavation sites, and industrial parks. The ground displacement trend patterns were analysed using several linear and nonlinear models, and techniques. Trends based on the estimated ground displacement are characterised by long-term memory, indicated by low noise Hurst exponents, which in the long-term form interesting attractors. We hypothesize these attractors to be tectonic stress fields generated by transpressional movements.

The 2010 slow slip event and secular motion at Kilauea, Hawai`i inferred from TerraSAR-X InSAR data

USGS Publications Warehouse

Chen, Jingyi; Zebker, Howard A.; Segall, Paul; Miklius, Asta

2014-01-01

We present here an Small BAseline Subset (SBAS) algorithm to extract both transient and secular ground deformations on the order of millimeters in the presence of tropospheric noise on the order of centimeters, when the transient is of short duration and known time, and the background deformation is smooth in time. We applied this algorithm to study the 2010 slow slip event as well as the secular motion of Kīlauea's south flank using 49 TerraSAR-X images. We also estimate the tropospheric delay variation relative to a given reference pixel using an InSAR SBAS approach. We compare the InSAR SBAS solution for both ground deformation and tropospheric delays with existing GPS measurements and confirm that the ground deformation signal andtropospheric noise in InSAR data are successfully separated. We observe that the coastal region on the south side of the Hilina Pali moves at a higher background rate than the region north side of the Pali. We also conclude that the 2010 SSE displacement is mainly horizontal and the maximum magnitude of the 2010 SSE vertical component is less than 5 mm.

Stochastic modeling for time series InSAR: with emphasis on atmospheric effects

NASA Astrophysics Data System (ADS)

Cao, Yunmeng; Li, Zhiwei; Wei, Jianchao; Hu, Jun; Duan, Meng; Feng, Guangcai

2018-02-01

Despite the many applications of time series interferometric synthetic aperture radar (TS-InSAR) techniques in geophysical problems, error analysis and assessment have been largely overlooked. Tropospheric propagation error is still the dominant error source of InSAR observations. However, the spatiotemporal variation of atmospheric effects is seldom considered in the present standard TS-InSAR techniques, such as persistent scatterer interferometry and small baseline subset interferometry. The failure to consider the stochastic properties of atmospheric effects not only affects the accuracy of the estimators, but also makes it difficult to assess the uncertainty of the final geophysical results. To address this issue, this paper proposes a network-based variance-covariance estimation method to model the spatiotemporal variation of tropospheric signals, and to estimate the temporal variance-covariance matrix of TS-InSAR observations. The constructed stochastic model is then incorporated into the TS-InSAR estimators both for parameters (e.g., deformation velocity, topography residual) estimation and uncertainty assessment. It is an incremental and positive improvement to the traditional weighted least squares methods to solve the multitemporal InSAR time series. The performance of the proposed method is validated by using both simulated and real datasets.

Spatiotemporal deformation patterns of the Lake Urmia Causeway as characterized by multisensor InSAR analysis.

PubMed

Karimzadeh, Sadra; Matsuoka, Masashi; Ogushi, Fumitaka

2018-04-03

We present deformation patterns in the Lake Urmia Causeway (LUC) in NW Iran based on data collected from four SAR sensors in the form of interferometric synthetic aperture radar (InSAR) time series. Sixty-eight images from Envisat (2004-2008), ALOS-1 (2006-2010), TerraSAR-X (2012-2013) and Sentinel-1 (2015-2017) were acquired, and 227 filtered interferograms were generated using the small baseline subset (SBAS) technique. The rate of line-of-sight (LOS) subsidence of the LUC peaked at 90 mm/year between 2012 and 2013, mainly due to the loss of most of the water in Lake Urmia. Principal component analysis (PCA) was conducted on 200 randomly selected time series of the LUC, and the results are presented in the form of the three major components. The InSAR scores obtained from the PCA were used in a hydro-thermal model to investigate the dynamics of consolidation settlement along the LUC based on detrended water level and temperature data. The results can be used to establish a geodetic network around the LUC to identify more detailed deformation patterns and to help plan future efforts to reduce the possible costs of damage.

Efficacy and safety of etanercept in patients from Latin America, Central Europe and Asia with early non-radiographic axial spondyloarthritis.

PubMed

Wei, James Cheng-Chung; Tsai, Wen-Chan; Citera, Gustavo; Kotak, Sameer; Llamado, Lyndon

2016-11-11

To evaluate etanercept in patients from Latin America, Central/Eastern Europe, and Asia with non-radiographic axial spondyloarthritis (nr-axSpA). A subset analysis was performed on nr-axSpA patients from Argentina, Colombia, the Czech Republic, Hungary, Russia and Taiwan who were enrolled in EMBARK (NCT01258738). Patients received either etanercept 50 mg or placebo once weekly. The primary endpoint was proportion of patients achieving 40% improvement from baseline based on Assessment of SpondyloArthritis International Society (ASAS) criteria. Secondary endpoints included other efficacy assessments, health-related quality of life (HRQoL) and safety. Of the 117 patients in this subset, 59 were treated with etanercept and 58 received placebo. At week 12, numerically greater improvements from baseline were observed for all efficacy endpoints in etanercept-treated patients compared with those receiving placebo. Statistically significant differences between the two treatment groups were observed for proportion of patients achieving ASAS40 (P = 0.0413, at week 8), ASAS5/6 (P = 0.0126), Ankylosing Spondylitis Disease Activity Score - C-reactive protein (CRP) inactive disease (P = 0.0093), Spondyloarthritis Research Consortium of Canada magnetic resonance imaging of sacroiliac joint scores (P = 0.0014), high-sensitivity CRP (P=0.032), and erythrocyte sedimentation rate (P = 0.0082). Statistically significant improvements in the etanercept-treated group compared with placebo group were observed for nocturnal back pain (P = 0.040), total back pain (P = 0.025), physician global assessment of disease (P = 0.023), and Work Productivity and Activity Impairment Questionnaire percent impairment while working (P = 0.047). Adverse events were similar between the two treatment groups. In this subset of patients with nr-axSpA from Latin America, Central/Eastern Europe, and Asia, treatment with etanercept, compared with placebo, resulted in improved disease symptoms and patient HRQoL. Etanercept was well tolerated. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Urinary Bother as a Predictor of Postsurgical Changes in Urinary Function After Robotic Radical Prostatectomy.

PubMed

Murphy, Gregory; Haddock, Peter; Doak, Hoyt; Jackson, Max; Dorin, Ryan; Meraney, Anoop; Kesler, Stuart; Staff, Ilene; Wagner, Joseph R

2015-10-01

To characterize changes in indices of urinary function in prostatectomy patients with presurgical voiding symptoms. A retrospective analysis of our prostate cancer database identified robot-assisted radical prostatectomy patients between April 2007 and December 2011 who completed pre- and postsurgical (24 months) Expanded Prostate Cancer Index Composite-26 surveys. Gleason score, margins, D'Amico risk, prostate-specific antigen, radiotherapy, and nerve-sparing status were tabulated. Survey questions addressed urinary irritation/obstruction, incontinence, and overall bother. Responses were averaged to calculate a urinary sum (US) score. Patients were stratified according to the severity of their baseline urinary bother (UB), and changes in urinary indices determined at 24 months. A total of 737 patients were included. Postsurgical improvement in urinary obstruction, bother, and sum score was related to baseline UB (P <.001). Men with severe baseline bother had the greatest improvement in US (+9.3), whereas those with asymptomatic baseline UB experienced a decline in US (-2.8). All patients experienced a decline in urinary incontinence of 6.3-8.3 that was independent of baseline bother (P = .507). Patients with severe UB experienced positive outcomes, whereas those at asymptomatic baseline experienced negative US outcomes. Negative urinary incontinence outcomes were unrelated to baseline UB. Age, radiotherapy, and nerve-sparing status were not associated with improved UB (P = .029). However, baseline UB was significantly associated with improvement in postsurgical UB (P = .001). Baseline UB is a predictor of postsurgical improvement in urinary function. These data are helpful when counseling a subset of robot-assisted laparoscopic radical prostatectomy patients with severe preoperative urinary symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

Children's binge eating and development of metabolic syndrome.

PubMed

Tanofsky-Kraff, M; Shomaker, L B; Stern, E A; Miller, R; Sebring, N; Dellavalle, D; Yanovski, S Z; Hubbard, V S; Yanovski, J A

2012-07-01

Binge eating predisposes children to excessive weight gain. However, it is unknown if pediatric binge eating predicts other obesity-associated adverse health outcomes. The objective of this study was to investigate the relationship between binge eating and metabolic syndrome (MetS) in children. Children aged 5-12 years at high risk for adult obesity, either because they were overweight/obese when first examined or because their parents were overweight/obese, were recruited from Washington, DC and its suburbs. Children completed a questionnaire assessment of binge eating at baseline and underwent measurements of MetS components at baseline and at a follow-up visit approximately 5 years later. Magnetic resonance imaging was used to measure the visceral adipose tissue (VAT) in a subset. In all, 180 children were studied between July 1996 and August 2010. Baseline self-reported binge eating presence was associated with a 5.33 greater odds of having MetS at follow-up (95% confidence interval (CI): 1.47, 19.27, P=0.01). The association between binge eating and body mass index (BMI) only partially explained changes in MetS components: baseline binge eating predicted higher follow-up triglycerides, even after accounting for baseline triglycerides, baseline BMI, BMI change, sex, race, baseline age and time in study (P = 0.05). Also, adjusting for baseline VAT and demographics, baseline binge eating predicted greater follow-up L(2-3) VAT (P = 0.01). Children's reports of binge eating predicted development of MetS, worsening triglycerides and increased VAT. The excessive weight gain associated with children's binge eating partly explained its adverse metabolic health outcomes. Reported binge eating may represent an early behavioral marker upon which to focus interventions for obesity and MetS.

Transferability of optimally-selected climate models in the quantification of climate change impacts on hydrology

NASA Astrophysics Data System (ADS)

Chen, Jie; Brissette, François P.; Lucas-Picher, Philippe

2016-11-01

Given the ever increasing number of climate change simulations being carried out, it has become impractical to use all of them to cover the uncertainty of climate change impacts. Various methods have been proposed to optimally select subsets of a large ensemble of climate simulations for impact studies. However, the behaviour of optimally-selected subsets of climate simulations for climate change impacts is unknown, since the transfer process from climate projections to the impact study world is usually highly non-linear. Consequently, this study investigates the transferability of optimally-selected subsets of climate simulations in the case of hydrological impacts. Two different methods were used for the optimal selection of subsets of climate scenarios, and both were found to be capable of adequately representing the spread of selected climate model variables contained in the original large ensemble. However, in both cases, the optimal subsets had limited transferability to hydrological impacts. To capture a similar variability in the impact model world, many more simulations have to be used than those that are needed to simply cover variability from the climate model variables' perspective. Overall, both optimal subset selection methods were better than random selection when small subsets were selected from a large ensemble for impact studies. However, as the number of selected simulations increased, random selection often performed better than the two optimal methods. To ensure adequate uncertainty coverage, the results of this study imply that selecting as many climate change simulations as possible is the best avenue. Where this was not possible, the two optimal methods were found to perform adequately.

Effects of Number of Animals Monitored on Representations of Cattle Group Movement Characteristics and Spatial Occupancy

PubMed Central

Liu, Tong; Green, Angela R.; Rodríguez, Luis F.; Ramirez, Brett C.; Shike, Daniel W.

2015-01-01

The number of animals required to represent the collective characteristics of a group remains a concern in animal movement monitoring with GPS. Monitoring a subset of animals from a group instead of all animals can reduce costs and labor; however, incomplete data may cause information losses and inaccuracy in subsequent data analyses. In cattle studies, little work has been conducted to determine the number of cattle within a group needed to be instrumented considering subsequent analyses. Two different groups of cattle (a mixed group of 24 beef cows and heifers, and another group of 8 beef cows) were monitored with GPS collars at 4 min intervals on intensively managed pastures and corn residue fields in 2011. The effects of subset group size on cattle movement characterization and spatial occupancy analysis were evaluated by comparing the results between subset groups and the entire group for a variety of summarization parameters. As expected, more animals yield better results for all parameters. Results show the average group travel speed and daily travel distances are overestimated as subset group size decreases, while the average group radius is underestimated. Accuracy of group centroid locations and group radii are improved linearly as subset group size increases. A kernel density estimation was performed to quantify the spatial occupancy by cattle via GPS location data. Results show animals among the group had high similarity of spatial occupancy. Decisions regarding choosing an appropriate subset group size for monitoring depend on the specific use of data for subsequent analysis: a small subset group may be adequate for identifying areas visited by cattle; larger subset group size (e.g. subset group containing more than 75% of animals) is recommended to achieve better accuracy of group movement characteristics and spatial occupancy for the use of correlating cattle locations with other environmental factors. PMID:25647571

Insights into assessing water quality using taxonomic distinctness based on a small species pool of biofilm-dwelling ciliate fauna in coastal waters of the Yellow Sea, northern China.

PubMed

Zhang, Wei; Liu, Yuanyuan; Warren, Alan; Xu, Henglong

2014-12-15

The aim of this study is to determine the feasibility of using a small species pool from a raw dataset of biofilm-dwelling ciliates for bioassessment based on taxonomic diversity. Samples were collected monthly at four stations within a gradient of environmental stress in coastal waters of the Yellow Sea, northern China from August 2011 to July 2012. A 33-species subset was identified from the raw 137-species dataset using a multivariate method. The spatial patterns of this subset were significantly correlated with the changes in the nutrients and chemical oxygen demand. The taxonomic diversity indices were significantly correlated with nutrients. The pair-wise indices of average taxonomic distinctness (Δ(+)) and the taxonomic distinctness (Λ(+)) showed a clear departure from the expected taxonomic pattern. These findings suggest that this small ciliate assemblage might be used as an adequate species pool for discriminating water quality status based on taxonomic distinctness in marine ecosystems. Copyright © 2014 Elsevier Ltd. All rights reserved.

Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

PubMed

Ghoshal, Uday C; Gwee, Kok-Ann

2017-07-01

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Molecular Analysis of Non-Small Cell Lung Cancer (NSCLC) Identifies Subsets with Different Sensitivity to Insulin like Growth Factor I Receptor (IGF-IR) Inhibition

PubMed Central

Gualberto, Antonio; Dolled-Filhart, Marisa; Gustavson, Mark; Christiansen, Jason; Wang, Yu-Fen; Hixon, Mary L.; Reynolds, Jennifer; McDonald, Sandra; Ang, Agnes; Rimm, David L.; Langer, Corey J.; Blakely, Johnetta; Garland, Linda; Paz-Ares, Luis G.; Karp, Daniel D.; Lee, Adrian V.

2010-01-01

Purpose Identify molecular determinants of sensitivity of NSCLC to anti-insulin like growth factor receptor (IGF-IR) therapy. Experimental Design 216 tumor samples were investigated. 165 consisted of retrospective analyses of banked tissue and an additional 51 were from patients enrolled in a phase 2 study of figitumumab (F), a monoclonal antibody against the IGF-IR, in stage IIIb/IV NSCLC. Biomarkers assessed included IGF-IR, EGFR, IGF-2, IGF-2R, IRS-1, IRS-2, vimentin and E-cadherin. Sub-cellular localization of IRS-1 and phosphorylation levels of MAPK and Akt1 were also analyzed. Results IGF-IR was differentially expressed across histological subtypes (P=0.04), with highest levels observed in squamous cell tumors. Elevated IGF-IR expression was also observed in a small number of squamous cell tumors responding to chemotherapy combined with F (p=0.008). Since no other biomarker/response interaction was observed using classical histological sub-typing, a molecular approach was undertaken to segment NSCLC into mechanism-based subpopulations. Principal component analysis and unsupervised Bayesian clustering identified 3 NSCLC subsets that resembled the steps of the epithelial-to-mesenchymal transition: E-cadherin high/IRS-1 low (Epithelial-like), E-cadherin intermediate/IRS-1 high (Transitional) and E-cadherin low/IRS-1 low (Mesenchymal-like). Several markers of the IGF-IR pathway were over-expressed in the Transitional subset. Furthermore, a higher response rate to the combination of chemotherapy and F was observed in Transitional tumors (71%) compared to those in the Mesenchymal-like subset (32%, p=0.03). Only one Epithelial-like tumor was identified in the phase 2 study, suggesting that advanced NSCLC has undergone significant de-differentiation at diagnosis. Conclusion NSCLC comprises molecular subsets with differential sensitivity to IGF-IR inhibition. PMID:20670944

Clinical evaluation of whole-body oncologic PET with time-of-flight and point-spread function for the hybrid PET/MR system.

PubMed

Shang, Kun; Cui, Bixiao; Ma, Jie; Shuai, Dongmei; Liang, Zhigang; Jansen, Floris; Zhou, Yun; Lu, Jie; Zhao, Guoguang

2017-08-01

Hybrid positron emission tomography/magnetic resonance (PET/MR) imaging is a new multimodality imaging technology that can provide structural and functional information simultaneously. The aim of this study was to investigate the effects of the time-of-flight (TOF) and point-spread function (PSF) on small lesions observed in PET/MR images from clinical patient image sets. This study evaluated 54 small lesions in 14 patients who had undergone 18 F-fluorodeoxyglucose (FDG) PET/MR. Lesions up to 30mm in diameter were included. The PET data were reconstructed with a baseline ordered-subsets expectation-maximization (OSEM) algorithm, OSEM+PSF, OSEM+TOF and OSEM+TOF+PSF. PET image quality and small lesions were visually evaluated and scored by a 3-point scale. A quantitative analysis was then performed using the mean and maximum standardized uptake value (SUV) of the small lesions (SUV mean and SUV max ). The lesions were divided into two groups according to the long-axis diameter and the location respectively and evaluated with each reconstruction algorithm. We also evaluated the background signal by analyzing the SUV liver . OSEM+TOF+PSF provided the highest value and OSEM+TOF or PSF showed a higher value than OSEM for the visual assessment and quantitative analysis. The combination of TOF and PSF increased the SUV mean by 26.6% and the SUV max by 30.0%. The SUV liver was not influenced by PSF or TOF. For the OSEM+TOF+PSF model, the change in SUV mean and SUV max for lesions <10mm in diameter was 31.9% and 35.8%, and 24.5% and 27.6% for lesions 10-30mm in diameter, respectively. The abdominal lesions obtained the higher SUV than those of chest on the images with TOF and/or PSF. Application of TOF and PSF significantly increased the SUV of small lesions in hybrid PET/MR images, potentially improving small lesion detectability. Copyright © 2017 Elsevier B.V. All rights reserved.

A Novel Collection of snRNA-Like Promoters with Tissue-Specific Transcription Properties

PubMed Central

Garritano, Sonia; Gigoni, Arianna; Costa, Delfina; Malatesta, Paolo; Florio, Tullio; Cancedda, Ranieri; Pagano, Aldo

2012-01-01

We recently identified a novel dataset of snRNA-like trascriptional units in the human genome. The investigation of a subset of these elements showed that they play relevant roles in physiology and/or pathology. In this work we expand our collection of small RNAs taking advantage of a newly developed algorithm able to identify genome sequence stretches with RNA polymerase (pol) III type 3 promoter features thus constituting putative pol III binding sites. The bioinformatic analysis of a subset of these elements that map in introns of protein-coding genes in antisense configuration suggest their association with alternative splicing, similarly to other recently characterized small RNAs. Interestingly, the analysis of the transcriptional activity of these novel promoters shows that they are active in a cell-type specific manner, in accordance with the emerging body of evidence of a tissue/cell-specific activity of pol III. PMID:23109855

A novel collection of snRNA-like promoters with tissue-specific transcription properties.

PubMed

Garritano, Sonia; Gigoni, Arianna; Costa, Delfina; Malatesta, Paolo; Florio, Tullio; Cancedda, Ranieri; Pagano, Aldo

2012-01-01

We recently identified a novel dataset of snRNA-like trascriptional units in the human genome. The investigation of a subset of these elements showed that they play relevant roles in physiology and/or pathology. In this work we expand our collection of small RNAs taking advantage of a newly developed algorithm able to identify genome sequence stretches with RNA polymerase (pol) III type 3 promoter features thus constituting putative pol III binding sites. The bioinformatic analysis of a subset of these elements that map in introns of protein-coding genes in antisense configuration suggest their association with alternative splicing, similarly to other recently characterized small RNAs. Interestingly, the analysis of the transcriptional activity of these novel promoters shows that they are active in a cell-type specific manner, in accordance with the emerging body of evidence of a tissue/cell-specific activity of pol III.

Identification of Incident CKD Stage 3 in Research Studies

PubMed Central

Grams, Morgan E.; Rebholz, Casey; MacMahon, Blaithin; Whelton, Seamus; Ballew, Shoshana H.; Selvin, Elizabeth; Wruck, Lisa; Coresh, Josef

2014-01-01

Background In epidemiologic research, incident chronic kidney disease (CKD) is commonly determined by laboratory tests performed at planned study visits. Given the morbidity and mortality associated with CKD, persons with incident disease may be less likely to attend scheduled visits, affecting observed associations. The objective of this study was to quantify loss-to-follow-up by CKD status, and to determine whether supplementation with diagnostic code data improves capture of incident CKD. Study Design Prospective cohort study. Setting & Participants 11,560 participants in the Atherosclerosis Risk in Communities (ARIC) Study underwent continuous surveillance for hospitalizations and death from baseline visit (1996-1999) to follow-up visit (2011-2013). A subset of hospitalizations in Washington County, MD, was used in diagnostic code validation (n=2,540). Predictor Baseline demographics and comorbid conditions. Outcomes Incident CKD stage 3 ascertained by follow-up visit (visit-based definition), or by hospitalization surveillance (hospitalization-based definition). Measurements Visit-based definition: ≥25% decline from baseline estimated glomerular filtration rate to <60 ml/min/1.73 m2 at follow-up visit; hospitalization-based definition: hospitalization CKD diagnostic code. Results Among 11,560 participants, 5,951 attended the follow-up visit, and 9,264 were hospitalized. Never-hospitalized participants were younger, more often female, and had fewer comorbid conditions; 73.5% attended the follow-up visit. Incident CKD stage 3 occurred in 1,172 participants by the visit-based definition (251 were never-hospitalized) and 1,078 participants by the hospitalization-based definition (237 attended the follow-up study visit). The sensitivity of the hospitalization-based CKD definition was 35.5% (95% CI, 31.6%-39.7%); specificity was 95.7% (95% CI, 94.2%-96.8%). Sensitivity was higher with later time period, older participant age, and baseline prevalent diabetes and CKD. Limitations A subset of hospitalizations were used for validation; 15-year gap between study visits. Conclusions The sensitivity of diagnostic code–identified CKD is low and varies by certain factors; however, supplementing a visit-based definition with hospitalization information can increase disease identification during periods of follow-up without study visits. PMID:24726628

Strategies to Improve Activity Recognition Based on Skeletal Tracking: Applying Restrictions Regarding Body Parts and Similarity Boundaries †

PubMed Central

Gutiérrez-López-Franca, Carlos; Hervás, Ramón; Johnson, Esperanza

2018-01-01

This paper aims to improve activity recognition systems based on skeletal tracking through the study of two different strategies (and its combination): (a) specialized body parts analysis and (b) stricter restrictions for the most easily detectable activities. The study was performed using the Extended Body-Angles Algorithm, which is able to analyze activities using only a single key sample. This system allows to select, for each considered activity, which are its relevant joints, which makes it possible to monitor the body of the user selecting only a subset of the same. But this feature of the system has both advantages and disadvantages. As a consequence, in the past we had some difficulties with the recognition of activities that only have a small subset of the joints of the body as relevant. The goal of this work, therefore, is to analyze the effect produced by the application of several strategies on the results of an activity recognition system based on skeletal tracking joint oriented devices. Strategies that we applied with the purpose of improve the recognition rates of the activities with a small subset of relevant joints. Through the results of this work, we aim to give the scientific community some first indications about which considered strategy is better. PMID:29789478

Evaluation of Bias and Variance in Low-count OSEM List Mode Reconstruction

PubMed Central

Jian, Y; Planeta, B; Carson, R E

2016-01-01

Statistical algorithms have been widely used in PET image reconstruction. The maximum likelihood expectation maximization (MLEM) reconstruction has been shown to produce bias in applications where images are reconstructed from a relatively small number of counts. In this study, image bias and variability in low-count OSEM reconstruction are investigated on images reconstructed with MOLAR (motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction) platform. A human brain ([11C]AFM) and a NEMA phantom are used in the simulation and real experiments respectively, for the HRRT and Biograph mCT. Image reconstructions were repeated with different combination of subsets and iterations. Regions of interest (ROIs) were defined on low-activity and high-activity regions to evaluate the bias and noise at matched effective iteration numbers (iterations x subsets). Minimal negative biases and no positive biases were found at moderate count levels and less than 5% negative bias was found using extremely low levels of counts (0.2 M NEC). At any given count level, other factors, such as subset numbers and frame-based scatter correction may introduce small biases (1–5%) in the reconstructed images. The observed bias was substantially lower than that reported in the literature, perhaps due to the use of point spread function and/or other implementation methods in MOLAR. PMID:25479254

Evaluation of bias and variance in low-count OSEM list mode reconstruction

NASA Astrophysics Data System (ADS)

Jian, Y.; Planeta, B.; Carson, R. E.

2015-01-01

Statistical algorithms have been widely used in PET image reconstruction. The maximum likelihood expectation maximization reconstruction has been shown to produce bias in applications where images are reconstructed from a relatively small number of counts. In this study, image bias and variability in low-count OSEM reconstruction are investigated on images reconstructed with MOLAR (motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction) platform. A human brain ([11C]AFM) and a NEMA phantom are used in the simulation and real experiments respectively, for the HRRT and Biograph mCT. Image reconstructions were repeated with different combinations of subsets and iterations. Regions of interest were defined on low-activity and high-activity regions to evaluate the bias and noise at matched effective iteration numbers (iterations × subsets). Minimal negative biases and no positive biases were found at moderate count levels and less than 5% negative bias was found using extremely low levels of counts (0.2 M NEC). At any given count level, other factors, such as subset numbers and frame-based scatter correction may introduce small biases (1-5%) in the reconstructed images. The observed bias was substantially lower than that reported in the literature, perhaps due to the use of point spread function and/or other implementation methods in MOLAR.

Functional analysis of circadian pacemaker neurons in Drosophila melanogaster.

PubMed

Rieger, Dirk; Shafer, Orie Thomas; Tomioka, Kenji; Helfrich-Förster, Charlotte

2006-03-01

The molecular mechanisms of circadian rhythms are well known, but how multiple clocks within one organism generate a structured rhythmic output remains a mystery. Many animals show bimodal activity rhythms with morning (M) and evening (E) activity bouts. One long-standing model assumes that two mutually coupled oscillators underlie these bouts and show different sensitivities to light. Three groups of lateral neurons (LN) and three groups of dorsal neurons govern behavioral rhythmicity of Drosophila. Recent data suggest that two groups of the LN (the ventral subset of the small LN cells and the dorsal subset of LN cells) are plausible candidates for the M and E oscillator, respectively. We provide evidence that these neuronal groups respond differently to light and can be completely desynchronized from one another by constant light, leading to two activity components that free-run with different periods. As expected, a long-period component started from the E activity bout. However, a short-period component originated not exclusively from the morning peak but more prominently from the evening peak. This reveals an interesting deviation from the original Pittendrigh and Daan (1976) model and suggests that a subgroup of the ventral subset of the small LN acts as "main" oscillator controlling M and E activity bouts in Drosophila.

Safe and sensible preprocessing and baseline correction of pupil-size data.

PubMed

Mathôt, Sebastiaan; Fabius, Jasper; Van Heusden, Elle; Van der Stigchel, Stefan

2018-02-01

Measurement of pupil size (pupillometry) has recently gained renewed interest from psychologists, but there is little agreement on how pupil-size data is best analyzed. Here we focus on one aspect of pupillometric analyses: baseline correction, i.e., analyzing changes in pupil size relative to a baseline period. Baseline correction is useful in experiments that investigate the effect of some experimental manipulation on pupil size. In such experiments, baseline correction improves statistical power by taking into account random fluctuations in pupil size over time. However, we show that baseline correction can also distort data if unrealistically small pupil sizes are recorded during the baseline period, which can easily occur due to eye blinks, data loss, or other distortions. Divisive baseline correction (corrected pupil size = pupil size/baseline) is affected more strongly by such distortions than subtractive baseline correction (corrected pupil size = pupil size - baseline). We discuss the role of baseline correction as a part of preprocessing of pupillometric data, and make five recommendations: (1) before baseline correction, perform data preprocessing to mark missing and invalid data, but assume that some distortions will remain in the data; (2) use subtractive baseline correction; (3) visually compare your corrected and uncorrected data; (4) be wary of pupil-size effects that emerge faster than the latency of the pupillary response allows (within ±220 ms after the manipulation that induces the effect); and (5) remove trials on which baseline pupil size is unrealistically small (indicative of blinks and other distortions).

Hubble Parameter and Baryon Acoustic Oscillation Measurement Constraints on the Hubble Constant, the Deviation from the Spatially Flat ΛCDM Model, the Deceleration–Acceleration Transition Redshift, and Spatial Curvature

NASA Astrophysics Data System (ADS)

Yu, Hai; Ratra, Bharat; Wang, Fa-Yin

2018-03-01

We compile a complete collection of reliable Hubble parameter H(z) data to redshift z ≤ 2.36 and use them with the Gaussian Process method to determine continuous H(z) functions for various data subsets. From these continuous H(z)'s, summarizing across the data subsets considered, we find H 0 ∼ 67 ± 4 km s‑1 Mpc‑1, more consistent with the recent lower values determined using a variety of techniques. In most data subsets, we see a cosmological deceleration–acceleration transition at 2σ significance, with the data subsets transition redshifts varying over 0.33< {z}da}< 1.0 at 1σ significance. We find that the flat-ΛCDM model is consistent with the H(z) data to a z of 1.5 to 2.0, depending on data subset considered, with 2σ deviations from flat-ΛCDM above this redshift range. Using the continuous H(z) with baryon acoustic oscillation distance-redshift observations, we constrain the current spatial curvature density parameter to be {{{Ω }}}K0=-0.03+/- 0.21, consistent with a flat universe, but the large error bar does not rule out small values of spatial curvature that are now under debate.

The dead do not lie: using skeletal remains for rapid assessment of historical small-mammal community baselines

PubMed Central

Terry, Rebecca C.

2010-01-01

Conservation and restoration efforts are often hindered by a lack of historical baselines that pre-date intense anthropogenic environmental change. In this paper I document that natural accumulations of skeletal remains represent a potential source of high-quality data on the historical composition and structure of small-mammal communities. I do so by assessing the fidelity of modern, decadal and centennial-scale time-averaged samples of skeletal remains (concentrated by raptor predation) to the living small-mammal communities from which they are derived. To test the power of skeletal remains to reveal baseline shifts, I employ the design of a natural experiment, comparing two taphonomically similar Great Basin cave localities in areas where anthropogenic land-use practices have diverged within the last century. I find relative stasis at the undisturbed site, but document rapid restructuring of the small-mammal community at the site subjected to recent disturbance. I independently validate this result using historical trapping records to show that dead remains accurately capture both the magnitude and direction of this baseline shift. Surveys of skeletal remains therefore provide a simple, powerful and rapid alternative approach for gaining insight into the historical structure and dynamics of modern small-mammal communities. PMID:20031992

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Gagnon, J; Hong, Y; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-03-01

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

Stereoacuity in children with anisometropic amblyopia.

PubMed

Wallace, David K; Lazar, Elizabeth L; Melia, Michele; Birch, Eileen E; Holmes, Jonathan M; Hopkins, Kristine B; Kraker, Raymond T; Kulp, Marjean T; Pang, Yi; Repka, Michael X; Tamkins, Susanna M; Weise, Katherine K

2011-10-01

To determine factors associated with pretreatment and posttreatment stereoacuity in subjects with moderate anisometropic amblyopia. Data for subjects enrolled in seven studies conducted by the Pediatric Eye Disease Investigator Group were pooled. The sample included 633 subjects aged 3 to <18 years with anisometropic amblyopia, no heterotropia observed by cover test, and baseline amblyopic eye acuity of 20/100 or better. A subset included 248 subjects who were treated with patching or Bangerter filters and had stereoacuity testing at both the baseline and outcome examinations. Multivariate regression models identified factors associated with baseline stereoacuity and with outcome stereoacuity as measured by the Randot Preschool Stereoacuity test. Better baseline stereoacuity was associated with better baseline amblyopic eye acuity (P < 0.001), less anisometropia (P = 0.03), and anisometropia due to astigmatism alone (P < 0.001). Better outcome stereoacuity was associated with better baseline stereoacuity (P < 0.001) and better amblyopic eye acuity at outcome (P < 0.001). Among 48 subjects whose amblyopic eye visual acuity at outcome was 20/25 or better and within one line of the fellow eye, stereoacuity was worse than that of children with normal vision of the same age. In children with anisometropic amblyopia of 20/40 to 20/100 inclusive, better posttreatment stereoacuity is associated with better baseline stereoacuity and better posttreatment amblyopic eye acuity. Even if their visual acuity deficit resolves, many children with anisometropic amblyopia have stereoacuity worse than that of nonamblyopic children of the same age. Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Candidate Sequence Variants and Fetal Hemoglobin in Children with Sickle Cell Disease Treated with Hydroxyurea

PubMed Central

Green, Nancy S.; Ender, Katherine L.; Pashankar, Farzana; Driscoll, Catherine; Giardina, Patricia J.; Mullen, Craig A.; Clark, Lorraine N.; Manwani, Deepa; Crotty, Jennifer; Kisselev, Sergey; Neville, Kathleen A.; Hoppe, Carolyn; Barral, Sandra

2013-01-01

Background Fetal hemoglobin level is a heritable complex trait that strongly correlates swith the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to induction of fetal hemoglobin. Methodology/Principal Findings In a multi-site observational analysis of children with sickle cell disease, candidate single nucleotide polymorphisms associated with baseline fetal hemoglobin levels in adult sickle cell disease were examined in children at baseline and induced by hydroxyurea therapy. For baseline levels, single marker analysis demonstrated significant association with BCL11A and the beta and epsilon globin loci (HBB and HBE, respectively), with an additive attributable variance from these loci of 23%. Among a subset of children on hydroxyurea, baseline fetal hemoglobin levels explained 33% of the variance in induced levels. The variant in HBE accounted for an additional 13% of the variance in induced levels, while variants in the HBB and BCL11A loci did not contribute beyond baseline levels. Conclusions/Significance These findings clarify the overlap between baseline and hydroxyurea-induced fetal hemoglobin levels in pediatric disease. Studies assessing influences of specific sequence variants in these and other genetic loci in larger populations and in unusual hydroxyurea responders are needed to further understand the maintenance and therapeutic induction of fetal hemoglobin in pediatric sickle cell disease. PMID:23409025

Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double-blind randomized clinical trial.

PubMed

Baughman, Robert P; Judson, Marc A; Lower, Elyse E; Drent, Marjolein; Costabel, Ulrich; Flavin, Susan; Lo, Kim Hung; Barnathan, Elliot S

2016-01-15

Limited evidence exists demonstrating an effective treatment for chronic cutaneous sarcoidosis. To determine infliximab's effectiveness in sarcoidosis. We conducted a subset analysis from a randomized, double-blind, placebo-controlled trial for chronic pulmonary sarcoidosis to determine infliximab's effectiveness. Patients with chronic cutaneous sarcoidosis received infliximab (3 or 5 mg/kg) or placebo over 24 weeks. Of 138 patients, the subset analysis evaluated 17 patients with chronic facial and another 9 patients with nonfacial skin involvement. The SASI evaluated lesions for degree of erythema, desquamation, induration, and percentage of area involved. Facial and nonfacial lesions were scored in a blinded manner. Among 5 placebo-treated and 12 infliximab-treated patients, an improvement was observed with infliximab versus placebo in change from baseline to weeks 12 and 24 in desquamation (P<0.005) and induration (P<0.01) at week 24. Erythema, percentage of area involved and the evaluation of paired photographs did not reveal significant differences. Sample size; more extensive disease in placebo patients; chronic therapy upon enrollment; lung as primary organ of sarcoidosis involvement; limited investigator experience with SASI. Infliximab appears to be a beneficial treatment for chronic cutaneous sarcoidosis. The SASI scoring system demonstrated significant improvement versus placebo in lesion desquamation and induration.

Nutritional Factors and Preservation of C-Peptide in Youth With Recently Diagnosed Type 1 Diabetes

PubMed Central

Mayer-Davis, Elizabeth J.; Dabelea, Dana; Crandell, Jamie L.; Crume, Tessa; D’Agostino, Ralph B.; Dolan, Lawrence; King, Irena B.; Lawrence, Jean M.; Norris, Jill M.; Pihoker, Catherine; The, Natalie

2013-01-01

OBJECTIVE To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Included were 1,316 youth with autoantibody-positive type 1 diabetes who participated in the SEARCH for Diabetes in Youth study (baseline disease duration, 9.9 months; SD, 6.3). Nutritional exposures included breastfeeding and age at introduction of complementary foods, baseline plasma long-chain omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin D, vitamin E, and, from a baseline food frequency questionnaire, estimated intake of the branched-chain amino acid leucine and total carbohydrate. Multiple linear regression models were conducted to relate each nutritional factor to baseline FCP adjusted for demographics, disease-related factors, and other confounders. Prospective analyses included the subset of participants with preserved β-cell function at baseline (baseline FCP ≥0.23 ng/mL) with additional adjustment for baseline FCP and time (mean follow-up, 24.3 months; SD, 8.2; n = 656). FCP concentration was analyzed as log(FCP). RESULTS In adjusted prospective analyses, baseline EPA (P = 0.02), EPA plus DHA (P = 0.03), and leucine (P = 0.03) were each associated positively and significantly with FCP at follow-up. Vitamin D was unexpectedly inversely associated with FCP (P = 0.002). CONCLUSIONS Increased intake of branched-chain amino acids and long-chain omega-3 fatty acids may support preservation of β-cell function. This represents a new direction for research to improve prognosis for type 1 diabetes. PMID:23801797

Clinical and neurocognitive course in early-onset psychosis: a longitudinal study of adolescents with schizophrenia-spectrum disorders*

PubMed Central

Wozniak, Jeffrey R.; Block, Erin E.; White, Tonya; Jensen, Jonathan B.; Schulz, S. Charles

2017-01-01

Aim Adolescents with psychotic disorders show deficits in IQ, attention, learning and memory, executive functioning, and processing speed that are related to important clinical variables including negative symptoms, adaptive functioning and academics. Previous studies have reported relatively consistent deficits with varying relationships to illness status and symptoms. The goals of this study were to examine these relationships in a larger sample at baseline, and also to examine the longitudinal course of these deficits in a smaller subset of adolescents. Method Thirty-six subjects, aged 10 to 17 years, were included at baseline. All had Diagnostic and Statistical Manual-Fourth Edition diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder and psychosis – not otherwise specified, as determined by Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children structured interviews. Patients were administered a neuropsychological battery, and Positive and Negative Syndrome Scale ratings were completed at baseline and again at 1 year (n = 14). Most participants were inpatients at baseline, and 13 of 14were on atypical antipsychotic medication during both sessions. Results At baseline, the patients demonstrated impairments in working memory, processing speed, executive function and verbal learning. No significant cognitive change was detected at 1-year follow-up. In contrast, clinical symptoms were variable across 1 year, with an improvement in positive symptoms at 1 year. No relationships between clinical and cognitive symptoms were observed, with the exception of baseline IQ predicting negative symptoms at 1 year. Conclusions Young patients with schizophrenia-spectrum disorders displayed neurocognitive impairments at baseline. Despite measurable fluctuations in clinical symptoms over the year, no significant changes were measured in cognition. Lower IQ at baseline was predictive of more negative symptoms at 1 year. PMID:21352150

Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab.

PubMed

Chaput, N; Lepage, P; Coutzac, C; Soularue, E; Le Roux, K; Monot, C; Boselli, L; Routier, E; Cassard, L; Collins, M; Vaysse, T; Marthey, L; Eggermont, A; Asvatourian, V; Lanoy, E; Mateus, C; Robert, C; Carbonnel, F

2017-06-01

Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. Twenty-six patients with MM treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing at baseline and before each ipilimumab infusion. Patients were further clustered based on microbiota patterns. Peripheral blood lymphocytes immunophenotypes were studied in parallel. A distinct baseline gut microbiota composition was associated with both clinical response and colitis. Compared with patients whose baseline microbiota was driven by Bacteroides (cluster B, n = 10), patients whose baseline microbiota was enriched with Faecalibacterium genus and other Firmicutes (cluster A, n = 12) had longer progression-free survival (P = 0.0039) and overall survival (P = 0.051). Most of the baseline colitis-associated phylotypes were related to Firmicutes (e.g. relatives of Faecalibacterium prausnitzii and Gemmiger formicilis), whereas no colitis-related phylotypes were assigned to Bacteroidetes. A low proportion of peripheral blood regulatory T cells was associated with cluster A, long-term clinical benefit and colitis. Ipilimumab led to a higher inducible T-cell COStimulator induction on CD4+ T cells and to a higher increase in serum CD25 in patients who belonged to Faecalibacterium-driven cluster A. Baseline gut microbiota enriched with Faecalibacterium and other Firmicutes is associated with beneficial clinical response to ipilimumab and more frequent occurrence of ipilimumab-induced colitis. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Nutritional factors and preservation of C-peptide in youth with recently diagnosed type 1 diabetes: SEARCH Nutrition Ancillary Study.

PubMed

Mayer-Davis, Elizabeth J; Dabelea, Dana; Crandell, Jamie L; Crume, Tessa; D'Agostino, Ralph B; Dolan, Lawrence; King, Irena B; Lawrence, Jean M; Norris, Jill M; Pihoker, Catherine; The, Natalie

2013-07-01

To test the novel hypothesis that nutritional factors previously associated with type 1 diabetes etiology or with insulin secretion are prospectively associated with fasting C-peptide (FCP) concentration among youth recently diagnosed with type 1 diabetes. Included were 1,316 youth with autoantibody-positive type 1 diabetes who participated in the SEARCH for Diabetes in Youth study (baseline disease duration, 9.9 months; SD, 6.3). Nutritional exposures included breastfeeding and age at introduction of complementary foods, baseline plasma long-chain omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), vitamin D, vitamin E, and, from a baseline food frequency questionnaire, estimated intake of the branched-chain amino acid leucine and total carbohydrate. Multiple linear regression models were conducted to relate each nutritional factor to baseline FCP adjusted for demographics, disease-related factors, and other confounders. Prospective analyses included the subset of participants with preserved β-cell function at baseline (baseline FCP ≥0.23 ng/mL) with additional adjustment for baseline FCP and time (mean follow-up, 24.3 months; SD, 8.2; n = 656). FCP concentration was analyzed as log(FCP). In adjusted prospective analyses, baseline EPA (P = 0.02), EPA plus DHA (P = 0.03), and leucine (P = 0.03) were each associated positively and significantly with FCP at follow-up. Vitamin D was unexpectedly inversely associated with FCP (P = 0.002). Increased intake of branched-chain amino acids and long-chain omega-3 fatty acids may support preservation of β-cell function. This represents a new direction for research to improve prognosis for type 1 diabetes.

A GeoNode-Based Multiscale Platform For Management, Visualization And Integration Of DInSAR Data With Different Geospatial Information Sources

NASA Astrophysics Data System (ADS)

Buonanno, Sabatino; Fusco, Adele; Zeni, Giovanni; Manunta, Michele; Lanari, Riccardo

2017-04-01

This work describes the implementation of an efficient system for managing, viewing, analyzing and updating remotely sensed data, with special reference to Differential Interferometric Synthetic Aperture Radar (DInSAR) data. The DInSAR products measure Earth surface deformation both in space and time, producing deformation maps and time series[1,2]. The use of these data in research or operational contexts requires tools that have to handle temporal and spatial variability with high efficiency. For this aim we present an implementation based on Spatial Data Infrastructure (SDI) for data integration, management and interchange, by using standard protocols[3]. SDI tools provide access to static datasets that operate only with spatial variability . In this paper we use the open source project GeoNode as framework to extend SDI infrastructure functionalities to ingest very efficiently DInSAR deformation maps and deformation time series. GeoNode allows to realize comprehensive and distributed infrastructure, following the standards of the Open Geospatial Consortium, Inc. - OGC, for remote sensing data management, analysis and integration [4,5]. In the current paper we explain the methodology used for manage the data complexity and data integration using the opens source project GeoNode. The solution presented in this work for the ingestion of DinSAR products is a very promising starting point for future developments of the OGC compliant implementation of a semi-automatic remote sensing data processing chain . [1] Berardino, P., Fornaro, G., Lanari, R., & Sansosti, E. (2002). A new Algorithm for Surface Deformation Monitoring based on Small Baseline Differential SAR Interferograms. IEEE Transactions on Geoscience and Remote Sensing, 40, 11, pp. 2375-2383. [2] Lanari R., F. Casu, M. Manzo, G. Zeni,, P. Berardino, M. Manunta and A. Pepe (2007), An overview of the Small Baseline Subset Algorithm: a DInSAR Technique for Surface Deformation Analysis, P. Appl. Geophys., 164, doi: 10.1007/s00024-007-0192-9. [3] Nebert, D.D. (ed). 2000. Developing Spatial data Infrastructures: The SDI Cookbook. [4] Geonode (www.geonode.org) [5] Kolodziej, k. (ed). 2004. OGC OpenGIS Web Map Server Cookbook. Open Geospatial Consortium, 1.0.2 edition.

Generation of deformation time series from SAR data sequences in areas affected by large dynamics: insights from Sierra Negra caldera, Galápagos Islands

NASA Astrophysics Data System (ADS)

Casu, Francesco; Manconi, Andrea; Pepe, Antonio; Lanari, Riccardo

2010-05-01

Differential Synthetic Aperture Radar Interferometry (DInSAR) is a remote sensing technique that allows producing spatially dense deformation maps of the Earth surface, with centimeter accuracy. To this end, the phase difference of SAR image pairs acquired before and after a deformation episode is properly exploited. This technique, originally applied to investigate single deformation events, has been further extended to analyze the temporal evolution of the deformation field through the generation of displacement time-series. A well-established approach is represented by the Small BAseline Subset (SBAS) technique (Berardino et al., 2002), whose capability to analyze deformation events at low and full spatial resolution has largely been demonstrated. However, in areas where large and/or rapid deformation phenomena occur, the exploitation of the differential interferograms, thus also of the displacement time-series, can be strongly limited by the presence of significant misregistration errors and/or very high fringe rates, making unfeasible the phase unwrapping step. In this work, we propose advances on the generation of deformation time-series in areas affected by large deformation dynamics. We present an extension of the amplitude-based Pixel-Offset analyses by applying the SBAS strategy, in order to move from the investigation of single (large) deformation events to that of dynamic phenomena. The above-mentioned method has been tested on an ENVISAT SAR data archive (Track 61, Frames 7173-7191) related to the Galapagos Islands, focusing on Sierra Negra caldera (Galapagos Islands), an active volcanic area often characterized by large and rapid deformation events leading to severe image misregistration effects (Yun et al., 2007). Moreover, we present a cross-validation of the retrieved deformation estimates comparing our results to continuous GPS measurements and to synthetic deformation obtained by independently modeling the interferometric phase information when available. References: P. Berardino et al., (2002), A new algorithm for Surface Deformation Monitoring based on Small Baseline Differential SAR Interferograms, IEEE Transactions on Geoscience and Remote Sensing, vol. 40, 11, pp. 2375-2383. S-H. Yun et al., (2007), Interferogram formation in the presence of complex and large deformation, Geophys. Res. Lett., vol. 34, L12305.

Impact of a provincial asthma guidelines continuing medical education project: The Ontario Asthma Plan of Action’s Provider Education in Asthma Care Project

PubMed Central

Lougheed, M Diane; Moosa, Dilshad; Finlayson, Shelagh; Hopman, Wilma M; Quinn, Mallory; Szpiro, Kim; Reisman, Joseph

2007-01-01

BACKGROUND: The Ontario Ministry of Health and Long-Term Care funded the Ontario Lung Association to develop and implement a continuing medical education program to promote implementation of the Canadian asthma guidelines in primary care. OBJECTIVES: To determine baseline knowledge, preferred learning format, satisfaction with the program and reported impact on practice patterns. METHODS: A 3 h workshop was developed that combined didactic presentations and small group case discussions. Outcome measures included a workshop evaluation, baseline assessment of asthma management knowledge and three-month postreflective evaluations. RESULTS: One hundred thirty-seven workshops were delivered to 2783 primary care providers (1313 physicians, 1470 allied health) between September 2002 and March 2005. Of the 2133 participants, 1007 physicians and 1126 allied health professionals submitted workshop evaluations. Most (98%) of the attendees indicated they would recommend the workshop to a colleague. The majority preferred the combination of didactic lecture plus interactive case discussions. A subset of physicians provided consent to use these data for research (n=298 pediatric and 288 adult needs assessments; n=349 postreflective evaluations). Important needs identified included appropriate medication for chronic asthma and development of written action plans. On the postreflective evaluations, 88.7% remained very satisfied, 95.5% reported increased confidence, 91.9% reported an influence on practice and 67.2% reported using a written action plan. CONCLUSIONS: This continuing medical education program addresses identified needs of primary care providers. Participants reported improvements in asthma care, including prescribing practices, use of spirometry and written action plans. Similar programs should be considered as part of multifaceted asthma guidelines dissemination and implementation initiatives in other provinces and nationally. PMID:17372639

Anesthetic management of patients undergoing extra-anatomic renal bypass surgery for renovascular hypertension.

PubMed

Kumar, Bhupesh; Sinha, Prabhat Kumar; Unnikrishnan, M

2011-01-01

Renal artery disease is the most common cause for surgically curable form of hypertension. In a small subset of patients with severe aortic disease where the aorta is not suitable for endovascular technique and to provide an arterial inflow, an extra-anatomic renal bypass surgery (EARBS) is an option. Anesthetic management of such procedures has not been described so far in the literature. We retrospectively analyzed the anesthetic techniques used in all patients who underwent EARBS between February 1998 and June 2008 at this institute. We also further analyzed data concerning blood pressure (BP) control and renal function response following surgery as outcome variable measures. A total of 11 patients underwent EARBS during this period. Five received oral clonidine with premedication. During laryngoscopy, esmolol was used in 4 patients, while lignocaine was used in remaining 7 patients. Of 11 patients, 7 showed significant hemodynamic response to laryngoscopy and intubation; among these, one had oral clonidine with premedicant, and 6 received lignocaine just before laryngoscopy. Intravenous vasodilators were used to maintain target BP within 20% of baseline during perioperative period. All patients received renal protective measures. During follow-up, 10% were considered cured, 70% had improved BP response, while 20% failed to show improvement in BP response. Renal functions improved in 54.5%, remain unchanged in 36.5%, and worsened in 9% of patients. Use of clonidine during premedication and esmolol before laryngoscopy were beneficial in attenuating hemodynamic response to laryngoscopy, while use of vasodilators to maintain target BP within 20% of baseline, and routine use of renal protective measures appear to be promising in patients undergoing EARBS.

Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study.

PubMed

Hess, Lisa M; Huang, Helen Q; Hanlon, Alexandra L; Robinson, William R; Johnson, Rhonda; Chambers, Setsuko K; Mannel, Robert S; Puls, Larry; Davidson, Susan A; Method, Michael; Lele, Shashikant; Havrilesky, Laura; Nelson, Tina; Alberts, David S

2015-12-01

Changes in cognitive function have been identified in and reported by many cancer survivors. These changes have the potential to impact patient quality of life and functional ability. This prospective longitudinal study was designed to quantify the incidence of change in cognitive function in newly diagnosed ovarian cancer patients throughout and following primary chemotherapy. Eligible patients had newly diagnosed, untreated ovarian cancer and had planned to receive chemotherapy. Web-based and patient reported cognitive assessments and quality of life questionnaires were conducted prior to chemotherapy, prior to cycle four, after cycle six, and six months after completion of primary therapy. Two-hundred-thirty-one evaluable patients entered this study between May 2010 and October 2011. At the cycle 4 time point, 25.2% (55/218) of patients exhibited cognitive impairment in at least one domain. At the post-cycle 6 and 6-month follow up time points, 21.1% (44/208) and 17.8% (30/169) of patients, respectively, demonstrated impairment in at least one domain of cognitive function. There were statistically significant, but clinically small, improvements in processing speed (p<0.001) and attention (p<0.001) but not in motor response time (p=0.066), from baseline through the six-month follow up time period. This was a large, prospective study designed to measure cognitive function in ovarian cancer. A subset of patients had evidence of cognitive decline from baseline during chemotherapy treatment in this study as measured by the web-based assessment; however, changes were generally limited to no more than one domain. Copyright © 2015 Elsevier Inc. All rights reserved.

Variability in baseline laboratory measurements of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Ladwig, R; Vigo, A; Fedeli, L M G; Chambless, L E; Bensenor, I; Schmidt, M I; Vidigal, P G; Castilhos, C D; Duncan, B B

2016-08-01

Multi-center epidemiological studies must ascertain that their measurements are accurate and reliable. For laboratory measurements, reliability can be assessed through investigation of reproducibility of measurements in the same individual. In this paper, we present results from the quality control analysis of the baseline laboratory measurements from the ELSA-Brasil study. The study enrolled 15,105 civil servants at 6 research centers in 3 regions of Brazil between 2008-2010, with multiple biochemical analytes being measured at a central laboratory. Quality control was ascertained through standard laboratory evaluation of intra- and inter-assay variability and test-retest analysis in a subset of randomly chosen participants. An additional sample of urine or blood was collected from these participants, and these samples were handled in the same manner as the original ones, locally and at the central laboratory. Reliability was assessed with the intraclass correlation coefficient (ICC), estimated through a random effects model. Coefficients of variation (CV) and Bland-Altman plots were additionally used to assess measurement variability. Laboratory intra and inter-assay CVs varied from 0.86% to 7.77%. From test-retest analyses, the ICCs were high for the majority of the analytes. Notably lower ICCs were observed for serum sodium (ICC=0.50; 95%CI=0.31-0.65) and serum potassium (ICC=0.73; 95%CI=0.60-0.83), due to the small biological range of these analytes. The CVs ranged from 1 to 14%. The Bland-Altman plots confirmed these results. The quality control analyses showed that the collection, processing and measurement protocols utilized in the ELSA-Brasil produced reliable biochemical measurements.

Liver dysfunction after chemotherapy in lymphoma patients infected with hepatitis C.

PubMed

Dizdar, Omer; Tapan, Umit; Aksoy, Sercan; Harputluoglu, Hakan; Kilickap, Saadettin; Barista, Ibrahim

2008-05-01

Reactivation of hepatitis B virus (HBV) infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented complication. However, data on the consequence of chemotherapy on the course of hepatitis C virus (HCV) infection in HCV+ patients have been controversial. Here, we review the current knowledge about the complications related to HCV in lymphoma patients receiving chemotherapy/immunosuppressive therapy. Although less frequent than HBV, these complications occur in a subset of patients with mortality rates up to 45%. Therefore, baseline screening for HBV and HCV before initiation of chemotherapy is crucial. High-risk patients having chronic active hepatitis, high baseline HCV viral load, HBV co-infection and receiving cytotoxic drugs, corticosteroids and rituximab (particularly if combined) should be closely monitored for serum transaminase, bilirubin and HCV RNA levels.

Investigating Evolutionary Conservation of Dendritic Cell Subset Identity and Functions

PubMed Central

Vu Manh, Thien-Phong; Bertho, Nicolas; Hosmalin, Anne; Schwartz-Cornil, Isabelle; Dalod, Marc

2015-01-01

Dendritic cells (DCs) were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T-cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks, and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization, and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation, and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes, and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types, organs, and species. PMID:26082777

Satellite Level 3 & 4 Data Subsetting at NASA GES DISC

NASA Technical Reports Server (NTRS)

Huwe, Paul; Su, Jian; Loeser, Carlee; Ostrenga, Dana; Rui, Hualan; Vollmer, Bruce

2017-01-01

Earth Science data are available in many file formats (NetCDF, HDF, GRB, etc.) and in a wide range of sizes, from kilobytes to gigabytes. These properties have become a challenge to users if they are not familiar with these formats or only want a small region of interest (ROI) from a specific dataset. At NASA Goddard Earth Sciences Data and Information Services Center (GES DISC), we have developed and implemented a multipurpose subset service to ease user access to Earth Science data. Our Level 3 & 4 Regridder is capable of subsetting across multiple parameters (spatially, temporally, by level, and by variable) as well as having additional beneficial features (temporal means, regridding to target grids, and file conversion to other data formats). In this presentation, we will demonstrate how users can use this service to better access only the data they need in the form they require.

Satellite Level 3 & 4 Data Subsetting at NASA GES DISC

NASA Astrophysics Data System (ADS)

Huwe, P.; Su, J.; Loeser, C. F.; Ostrenga, D.; Rui, H.; Vollmer, B.

2017-12-01

Earth Science data are available in many file formats (NetCDF, HDF, GRB, etc.) and in a wide range of sizes, from kilobytes to gigabytes. These properties have become a challenge to users if they are not familiar with these formats or only want a small region of interest (ROI) from a specific dataset. At NASA Goddard Earth Sciences Data and Information Services Center (GES DISC), we have developed and implemented a multipurpose subset service to ease user access to Earth Science data. Our Level 3 & 4 Regridder is capable of subsetting across multiple parameters (spatially, temporally, by level, and by variable) as well as having additional beneficial features (temporal means, regridding to target grids, and file conversion to other data formats). In this presentation, we will demonstrate how users can use this service to better access only the data they need in the form they require.

Earth Observatory Satellite system definition study. Report 5: System design and specifications. Volume 1: Baseline system description

NASA Technical Reports Server (NTRS)

1974-01-01

A system baseline design oriented to the requirements of the next generation of Earth Observatory Satellite missions is presented. The first mission (EOS-A) is envisioned as a two-fold mission which (1) provides a continuum of data of the type being supplied by ERTS for the emerging operational applications and also (2) expands the research and development activities for future instrumentation and analysis techniques. The baseline system specifically satisfies the requirements of this first mission. However, EOS-A is expected to be the first of a series of earth observation missions. Thus the baseline design has been developed so as to accommodate these latter missions effectively as the transition is made from conventional, expendable launch vehicles and spacecraft to the Shuttle Space Transportation System era. Further, a subset of alternative missions requirements including Seasat, SEOS, SMM and MSS-5 have been analyzed to verify that the spacecraft design to serve a multi-mission role is economically sound. A key feature of the baseline system design is the concept of a modular observatory system whose elements are compatible with varying levels of launch vehicle capability. The design configuration can be used with either the Delta or Titan launch vehicles and will adapt readily to the space shuttle when that system becomes available in the early 1980's.

Identification of mission sensitivities for high-power electric propulsion systems

NASA Technical Reports Server (NTRS)

Frisbee, Robert H.; Moeller, Robert C.

2005-01-01

This paper presents the results of mission analyses that expose various mission performance sensitivities and system advantages of the ALFA technology for a small but representative subset of nuclear electric propulsion (NEP) missions considered under NASA's Project Prometheus.

Effect of atelectasis changes on tissue mass and dose during lung radiotherapy.

PubMed

Guy, Christopher L; Weiss, Elisabeth; Jan, Nuzhat; Reshko, Leonid B; Christensen, Gary E; Hugo, Geoffrey D

2016-11-01

To characterize mass and density changes of lung parenchyma in non-small cell lung cancer (NSCLC) patients following midtreatment resolution of atelectasis and to quantify the impact this large geometric change has on normal tissue dose. Baseline and midtreatment CT images and contours were obtained for 18 NSCLC patients with atelectasis. Patients were classified based on atelectasis volume reduction between the two scans as having either full, partial, or no resolution. Relative mass and density changes from baseline to midtreatment were calculated based on voxel intensity and volume for each lung lobe. Patients also had clinical treatment plans available which were used to assess changes in normal tissue dose constraints from baseline to midtreatment. The midtreatment image was rigidly aligned with the baseline scan in two ways: (1) bony anatomy and (2) carina. Treatment parameters (beam apertures, weights, angles, monitor units, etc.) were transferred to each image. Then, dose was recalculated. Typical IMRT dose constraints were evaluated on all images, and the changes from baseline to each midtreatment image were investigated. Atelectatic lobes experienced mean (stdev) mass changes of -2.8% (36.6%), -24.4% (33.0%), and -9.2% (17.5%) and density changes of -66.0% (6.4%), -25.6% (13.6%), and -17.0% (21.1%) for full, partial, and no resolution, respectively. Means (stdev) of dose changes to spinal cord D max , esophagus D mean , and lungs D mean were 0.67 (2.99), 0.99 (2.69), and 0.50 Gy (2.05 Gy), respectively, for bone alignment and 0.14 (1.80), 0.77 (2.95), and 0.06 Gy (1.71 Gy) for carina alignment. Dose increases with bone alignment up to 10.93, 7.92, and 5.69 Gy were found for maximum spinal cord, mean esophagus, and mean lung doses, respectively, with carina alignment yielding similar values. 44% and 22% of patients had at least one metric change by at least 5 Gy (dose metrics) or 5% (volume metrics) for bone and carina alignments, respectively. Investigation of GTV coverage showed mean (stdev) changes in V Rx , D max , and D min of -5.5% (13.5%), 2.5% (4.2%), and 0.8% (8.9%), respectively, for bone alignment with similar results for carina alignment. Resolution of atelectasis caused mass and density decreases, on average, and introduced substantial changes in normal tissue dose metrics in a subset of the patient cohort.

Effect of atelectasis changes on tissue mass and dose during lung radiotherapy

PubMed Central

Guy, Christopher L.; Weiss, Elisabeth; Jan, Nuzhat; Reshko, Leonid B.; Christensen, Gary E.; Hugo, Geoffrey D.

2016-01-01

Purpose: To characterize mass and density changes of lung parenchyma in non-small cell lung cancer (NSCLC) patients following midtreatment resolution of atelectasis and to quantify the impact this large geometric change has on normal tissue dose. Methods: Baseline and midtreatment CT images and contours were obtained for 18 NSCLC patients with atelectasis. Patients were classified based on atelectasis volume reduction between the two scans as having either full, partial, or no resolution. Relative mass and density changes from baseline to midtreatment were calculated based on voxel intensity and volume for each lung lobe. Patients also had clinical treatment plans available which were used to assess changes in normal tissue dose constraints from baseline to midtreatment. The midtreatment image was rigidly aligned with the baseline scan in two ways: (1) bony anatomy and (2) carina. Treatment parameters (beam apertures, weights, angles, monitor units, etc.) were transferred to each image. Then, dose was recalculated. Typical IMRT dose constraints were evaluated on all images, and the changes from baseline to each midtreatment image were investigated. Results: Atelectatic lobes experienced mean (stdev) mass changes of −2.8% (36.6%), −24.4% (33.0%), and −9.2% (17.5%) and density changes of −66.0% (6.4%), −25.6% (13.6%), and −17.0% (21.1%) for full, partial, and no resolution, respectively. Means (stdev) of dose changes to spinal cord Dmax, esophagus Dmean, and lungs Dmean were 0.67 (2.99), 0.99 (2.69), and 0.50 Gy (2.05 Gy), respectively, for bone alignment and 0.14 (1.80), 0.77 (2.95), and 0.06 Gy (1.71 Gy) for carina alignment. Dose increases with bone alignment up to 10.93, 7.92, and 5.69 Gy were found for maximum spinal cord, mean esophagus, and mean lung doses, respectively, with carina alignment yielding similar values. 44% and 22% of patients had at least one metric change by at least 5 Gy (dose metrics) or 5% (volume metrics) for bone and carina alignments, respectively. Investigation of GTV coverage showed mean (stdev) changes in VRx, Dmax, and Dmin of −5.5% (13.5%), 2.5% (4.2%), and 0.8% (8.9%), respectively, for bone alignment with similar results for carina alignment. Conclusions: Resolution of atelectasis caused mass and density decreases, on average, and introduced substantial changes in normal tissue dose metrics in a subset of the patient cohort. PMID:27806593

A candidate anti-HIV reservoir compound, auranofin, exerts a selective ‘anti-memory' effect by exploiting the baseline oxidative status of lymphocytes

PubMed Central

Chirullo, B; Sgarbanti, R; Limongi, D; Shytaj, I L; Alvarez, D; Das, B; Boe, A; DaFonseca, S; Chomont, N; Liotta, L; III Petricoin, E; Norelli, S; Pelosi, E; Garaci, E; Savarino, A; Palamara, A T

2013-01-01

Central memory (TCM) and transitional memory (TTM) CD4+ T cells are known to be the major cellular reservoirs for HIV, as these cells can harbor a transcriptionally silent form of viral DNA that is not targeted by either the immune system or current antiretroviral drug regimens. In the present study, we explored the molecular bases of the anti-HIV reservoir effects of auranofin (AF), a pro-oxidant gold-based drug and a candidate compound for a cure of AIDS. We here show that TCM and TTM lymphocytes have lower baseline antioxidant defenses as compared with their naive counterpart. These differences are mirrored by the effects exerted by AF on T-lymphocytes: AF was able to exert a pro-differentiating and pro-apoptotic effect, which was more pronounced in the memory subsets. AF induced an early activation of the p38 mitogen-activated protein kinase (p38 MAPK) followed by mitochondrial depolarization and a final burst in intracellular peroxides. The pro-differentiating effect was characterized by a downregulation of the CD27 marker expression. Interestingly, AF-induced apoptosis was inhibited by pyruvate, a well-known peroxide scavenger, but pyruvate did not inhibit the pro-differentiating effect of AF, indicating that the pro-apoptotic and pro-differentiating effects involve different pathways. In conclusion, our results demonstrate that AF selectively targets the TCM/TTM lymphocyte subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell death pathways. PMID:24309931

Removal of irrelevant information from working memory: sometimes fast, sometimes slow, and sometimes not at all.

PubMed

Oberauer, Klaus

2018-03-12

To function properly, working memory must be rapidly updated. Updating requires the removal of information no longer relevant. I present six experiments designed to explore the boundary conditions and the time course of removal. A condition in which three out of six memory items can be removed was compared to two baseline conditions in which either three or six items were encoded and maintained in working memory. The time for removal was varied. In experiment 1, in the removal condition, a distinct subset of three words was cued to be irrelevant after encoding all six words. With longer removal time, response times in the removal condition approximated those in the set-size 3 baseline, but accuracies stayed at the set-size 6 level. In experiment 2, in which a random subset of three words was cued as irrelevant, there was no evidence for removal. Experiments 3 and 4 showed that when each item is cued as relevant or irrelevant after its encoding, irrelevant items can be removed rapidly and completely. Experiments 5 and 6 showed that complete removal was no longer possible when words had to be processed before being cued as irrelevant. The pattern of findings can be explained by distinguishing two forms of removal: deactivation removes working-memory contents from the set of competitors for retrieval; unbinding contents from their contexts removes them from working memory entirely, so that they also cease to compete for limited capacity. © 2018 New York Academy of Sciences.

"Small" data in a big data world: archiving terrestrial ecology data at ORNL DAAC

NASA Astrophysics Data System (ADS)

Santhana Vannan, S. K.; Beaty, T.; Boyer, A.; Deb, D.; Hook, L.; Shrestha, R.; Thornton, M.; Virdi, M.; Wei, Y.; Wright, D.

2016-12-01

The Oak Ridge National Laboratory Distributed Active Archive Center (ORNL DAAC http://daac.ornl.gov), a NASA-funded data center, archives a diverse collection of terrestrial biogeochemistry and ecological dynamics observations and models in support of NASA's Earth Science program. The ORNL DAAC has been addressing the increasing challenge of publishing diverse small data products into an online archive while dealing with the enhanced need for integration and availability of these data to address big science questions. This paper will show examples of "small" diverse data holdings - ranging from the Daymet model output data to site-based soil moisture observation data. We define "small" by the data volume of these data products compared to petabyte scale observations. We will highlight the use of tools and services for visualizing diverse data holdings and subsetting services such as the MODIS land products subsets tool (at ORNL DAAC) that provides big MODIS data in small chunks. Digital Object Identifiers (DOI) and data citations have enhanced the availability of data. The challenge faced by data publishers now is to deal with the increased number of publishable data products and most importantly the difficulties of publishing small diverse data products into an online archive. This paper will also present our experiences designing a data curation system for these types of data. The characteristics of these data will be examined and their scientific value will be demonstrated via data citation metrics. We will present case studies of leveraging specialized tools and services that have enabled small data sets to realize their "big" scientific potential. Overall, we will provide a holistic view of the challenges and potential of small diverse terrestrial ecology data sets from data curation to distribution.

Complex segregation analysis of blood pressure and heart rate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Pérusse, L; Borecki, I B; Gagnon, J; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-05-01

Complex segregation analysis of baseline resting blood pressure (BP) and heart rate (HR) and their responses to training (post-training minus baseline) were performed in a sample of 482 individuals from 99 white families who participated in the HERITAGE Family Study. Resting BP and HR were measured at baseline and after a 20-week training program. Baseline resting BP and HR were age-adjusted and age-BMI-adjusted, and the responses to training were age-adjusted and age-baseline-adjusted, within four gender-by-generation groups. This study also analyzed the responses to training in two subsets of families: (1) the so-called "high" subsample, 45 families (216 individuals) with at least one member whose baseline resting BP is in the high end of the normal BP range (the upper 95th percentile: systolic BP [SBP] > or = 135 or diastolic BP [DBP] > or = 80 mm Hg); and (2) the so-called "nonhigh" subsample, the 54 remaining families (266 individuals). Baseline resting SBP was influenced by a multifactorial component (23%), which was independent of body mass index (BMI). Baseline resting DBP was influenced by a putative recessive locus, which accounted for 31% of the variance. In addition to the major gene effect, which may impact BMI as well, baseline resting DBP was also influenced by a multifactorial component (29%). Baseline resting HR was influenced by a putative dominant locus independent of BMI, which accounted for 31% of the variance. For the responses to training, no familiality was found in the whole sample or in the nonhigh subsample. However, in the high subsample, resting SBP response to training was influenced by a putative recessive locus, which accounted for 44% of the variance. No familiality was found for resting DBP response to training. Resting HR response to training was influenced by a major effect (accounting for 35% of the variance), with an ambiguous transmission from parents to offspring.

Statistical analysis for validating ACO-KNN algorithm as feature selection in sentiment analysis

NASA Astrophysics Data System (ADS)

Ahmad, Siti Rohaidah; Yusop, Nurhafizah Moziyana Mohd; Bakar, Azuraliza Abu; Yaakub, Mohd Ridzwan

2017-10-01

This research paper aims to propose a hybrid of ant colony optimization (ACO) and k-nearest neighbor (KNN) algorithms as feature selections for selecting and choosing relevant features from customer review datasets. Information gain (IG), genetic algorithm (GA), and rough set attribute reduction (RSAR) were used as baseline algorithms in a performance comparison with the proposed algorithm. This paper will also discuss the significance test, which was used to evaluate the performance differences between the ACO-KNN, IG-GA, and IG-RSAR algorithms. This study evaluated the performance of the ACO-KNN algorithm using precision, recall, and F-score, which were validated using the parametric statistical significance tests. The evaluation process has statistically proven that this ACO-KNN algorithm has been significantly improved compared to the baseline algorithms. The evaluation process has statistically proven that this ACO-KNN algorithm has been significantly improved compared to the baseline algorithms. In addition, the experimental results have proven that the ACO-KNN can be used as a feature selection technique in sentiment analysis to obtain quality, optimal feature subset that can represent the actual data in customer review data.

Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

PubMed

McCormack, S E; Shaham, O; McCarthy, M A; Deik, A A; Wang, T J; Gerszten, R E; Clish, C B; Mootha, V K; Grinspoon, S K; Fleischman, A

2013-02-01

What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease.

PubMed

Kastenbauer, U; Wolf, E; Kollan, C; Hamouda, O; Bogner, J R

2009-06-18

There is only little data on immune reconstitution in antiretroviral naive AIDS-patients with toxoplasmosis. The observation of several cases with reduced increase of CD4-cells upon start of antiretroviral treatment (ART) prompted us to investigate the topic using the ClinSurv cohort. 17 German HIV treatment centers contribute to ClinSurv, a multicentre observational cohort under the auspices of the Robert Koch Institute. We retrospectively selected all antiretroviral-naive patients with toxoplasmic encephalitis (TE) and - as comparator group - with pneumocystosis (PCP) between January 1999 and December 2005. A total of 257 patients were included in the analysis, 61 with TE and 196 with PCP. Demographic baseline data showed differences with regard to gender, transmission group, and baseline CD4 superset+ counts (60.9 vs. 44.7/microl, p = 0.022). After ART-initiation the increase in CD4 superset+ lymphocytes was lower in the TE- versus the PCP-group in the first, second and fourth three-month-period (74.4 vs. 120.3/microl, p = 0.006; 96.6 vs. 136.2/microl, p = 0.021; 156.5 vs. 211.5/microl, p = 0.013). Viral load (VL) was higher in the PCP-group at baseline (4.46 log subset10cop/ml vs. 5.00 log subset10cop/ml, p = 0.008), while virological success of ART was equal. Our data show for the first time that the average CD4 superset+ T-cell increase of patients with toxoplasmosis is impaired compared to PCP-patients. Most clinicians would not be prepared to discontinue follow-up TE-therapy unless CD4 superset+ counts of 200/microl are reached. Explanation for our finding might be the myelosuppressive side effect of pyrimethamine, possible interactions of toxoplasmosis therapy with ART, or an unknown direct biological influence of toxoplasmosis on immune restoration.

Otoacoustic emissions versus audiometry in monitoring hearing loss after long-term noise exposure - a systematic review.

PubMed

Helleman, Hiske W; Eising, Hilde; Limpens, Jacqueline; Dreschler, Wouter A

2018-03-15

Objectives The objective of this systematic review was to compare otoacoustic emissions (OAE) with audiometry in their effectiveness to monitor effects of long-term noise exposure on hearing. Methods We conducted a systematic search of MEDLINE, Embase and the non-MEDLINE subset of PubMed up to March 2016 to identify longitudinal studies on effects of noise exposure on hearing as determined by both audiometry and OAE. Results This review comprised 13 articles, with 30-350 subjects in the longitudinal analysis. A meta-analysis could not be performed because the studies were very heterogeneous in terms of measurement paradigms, follow-up time, age of included subjects, inclusion of data points, outcome parameters and method of analysis. Overall there seemed to be small changes in both audiometry and OAE over time. Individual shifts were detected by both methods but a congruent pattern could not be observed. Some studies found that initial abnormal or low-level emissions might predict future hearing loss but at the cost of low specificity due to a high number of false positives. Other studies could not find such predictive value. Conclusions The reported heterogeneity in the studies calls for more uniformity in including, reporting and analyzing longitudinal data for audiometry and OAE. For the overall results, both methods showed small changes from baseline towards a deterioration in hearing. OAE could not reliably detect threshold shifts at individual level. With respect to the predictive value of OAE, the evidence was not conclusive and studies were not in agreement. The reported predictors had low specificity.

Assessment of the generalization of learned image reconstruction and the potential for transfer learning.

PubMed

Knoll, Florian; Hammernik, Kerstin; Kobler, Erich; Pock, Thomas; Recht, Michael P; Sodickson, Daniel K

2018-05-17

Although deep learning has shown great promise for MR image reconstruction, an open question regarding the success of this approach is the robustness in the case of deviations between training and test data. The goal of this study is to assess the influence of image contrast, SNR, and image content on the generalization of learned image reconstruction, and to demonstrate the potential for transfer learning. Reconstructions were trained from undersampled data using data sets with varying SNR, sampling pattern, image contrast, and synthetic data generated from a public image database. The performance of the trained reconstructions was evaluated on 10 in vivo patient knee MRI acquisitions from 2 different pulse sequences that were not used during training. Transfer learning was evaluated by fine-tuning baseline trainings from synthetic data with a small subset of in vivo MR training data. Deviations in SNR between training and testing led to substantial decreases in reconstruction image quality, whereas image contrast was less relevant. Trainings from heterogeneous training data generalized well toward the test data with a range of acquisition parameters. Trainings from synthetic, non-MR image data showed residual aliasing artifacts, which could be removed by transfer learning-inspired fine-tuning. This study presents insights into the generalization ability of learned image reconstruction with respect to deviations in the acquisition settings between training and testing. It also provides an outlook for the potential of transfer learning to fine-tune trainings to a particular target application using only a small number of training cases. © 2018 International Society for Magnetic Resonance in Medicine.

"Effects of a Web-Based Intervention on Family Functioning Following Pediatric Traumatic Brain Injury"

PubMed Central

Minich, Nori; Taylor, H. Gerry; Kirkwood, Michael; Brown, Tanya Maines; Stancin, Terry; Wade, Shari L

2015-01-01

Objective Investigate effectiveness of an online Counselor-Assisted Problem-Solving (CAPS) intervention on family functioning after traumatic brain injury (TBI). Methods Participants were randomized to CAPS (n = 65) or internet resource comparison (IRC; n = 67). CAPS is a counselor-assisted web-based program. IRC was given access to online resources. Outcomes were examined 6 months, 12 months, and 18 months after baseline. Injury severity, age, and SES were examined as moderators. Results A main effect of time was noted for teen-reported conflict and parent-reported problem solving. CAPS had decreased parent-reported conflict and a reduction in parental effective communication. Effects were specific to subsets of the sample. Conclusions CAPS, a family-based problem-solving intervention designed to address problem behaviors, had modest effects on some aspects of family functioning, when compared to IRC. Effects were generally limited to subsets of the families and were not evident across all follow-up assessments. PMID:26461100

Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data.

PubMed

Wang, Shuaiqun; Aorigele; Kong, Wei; Zeng, Weiming; Hong, Xiaomin

2016-01-01

Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes.

Hybrid Binary Imperialist Competition Algorithm and Tabu Search Approach for Feature Selection Using Gene Expression Data

PubMed Central

Aorigele; Zeng, Weiming; Hong, Xiaomin

2016-01-01

Gene expression data composed of thousands of genes play an important role in classification platforms and disease diagnosis. Hence, it is vital to select a small subset of salient features over a large number of gene expression data. Lately, many researchers devote themselves to feature selection using diverse computational intelligence methods. However, in the progress of selecting informative genes, many computational methods face difficulties in selecting small subsets for cancer classification due to the huge number of genes (high dimension) compared to the small number of samples, noisy genes, and irrelevant genes. In this paper, we propose a new hybrid algorithm HICATS incorporating imperialist competition algorithm (ICA) which performs global search and tabu search (TS) that conducts fine-tuned search. In order to verify the performance of the proposed algorithm HICATS, we have tested it on 10 well-known benchmark gene expression classification datasets with dimensions varying from 2308 to 12600. The performance of our proposed method proved to be superior to other related works including the conventional version of binary optimization algorithm in terms of classification accuracy and the number of selected genes. PMID:27579323

The aeolian wind tunnel

NASA Technical Reports Server (NTRS)

Iversen, J. D.

1991-01-01

The aeolian wind tunnel is a special case of a larger subset of the wind tunnel family which is designed to simulate the atmospheric surface layer winds to small scale (a member of this larger subset is usually called an atmospheric boundary layer wind tunnel or environmental wind tunnel). The atmospheric boundary layer wind tunnel is designed to simulate, as closely as possible, the mean velocity and turbulence that occur naturally in the atmospheric boundary layer (defined as the lowest portion of the atmosphere, of the order of 500 m, in which the winds are most greatly affected by surface roughness and topography). The aeolian wind tunnel is used for two purposes: to simulate the physics of the saltation process and to model at small scale the erosional and depositional processes associated with topographic surface features. For purposes of studying aeolian effects on the surface of Mars and Venus as well as on Earth, the aeolian wind tunnel continues to prove to be a useful tool for estimating wind speeds necessary to move small particles on the three planets as well as to determine the effects of topography on the evolution of aeolian features such as wind streaks and dune patterns.

The association between adolescents' depressive symptoms, maternal negative affect, and family relationships in Hong Kong: cross-sectional and longitudinal findings.

PubMed

Leung, Sharron S K; Stewart, Sunita M; Wong, Joy P S; Ho, Daniel S Y; Fong, Daniel Y T; Lam, T H

2009-10-01

This study investigated the bidirectional relationships of adolescents' and maternal mood, and the moderating effect by gender and perceived family relationships on these relationships. Data were obtained from 626 adolescent-mother dyads and follow-up data were collected one year later from a subset. Adolescents reported their depressive symptoms, and their mothers reported their negative affect. Adolescents described their perception of family relationships. Maternal negative affect and adolescents' depressive symptoms were significantly correlated at baseline. This association was moderated by gender and family relationships. The association was stronger in mother-daughter compared to mother-son dyads. In families where relationships were reported to be poor, adolescent depressive symptoms were uniformly high, regardless of maternal negative affect. However, in families where relationships were good, maternal negative affect was associated with higher adolescents' depressive symptoms. In longitudinal analyses, adolescents' mood at baseline was found to relate to maternal negative affect at follow-up. Family relationships at baseline were also associated with adolescents' depressive symptoms at follow-up. However, there was no prediction from maternal negative affect at baseline to adolescents' depressive symptoms at follow-up. Gender and quality of family relationships did not moderate the longitudinal relationships between adolescents' depressive symptoms and maternal negative affect in either direction.

VizieR Online Data Catalog: Optically Bright extragalactic Radio Sources II (Petrov, 2013)

NASA Astrophysics Data System (ADS)

Petrov, L.

2014-06-01

The first VLBI (Very Long Baseline Interferometry) observing campaign in 2007 resulted in the detection of 398 targets with the European VLBI Network (EVN; Bourda et al., 2010, cat. J/A+A/520/A113). During the second observing campaign, a subset of 105 sources detected in the previous campaign was observed (Bourda et al., 2011, cat. J/A+A/526/A102). Their positions were derived by Petrov (2011, cat. J/AJ/142/105) and formed the OBRS-1 (Optically Bright extragalactic Radio Sources) catalog. The remaining sources were observed in the third campaign, called OBRS-2. During the OBRS-2 campaign, there were three observing sessions with 10 VLBA (Very Long Baseline Array) stations and 5-6 EVN stations from this list: EFLSBERG, MEDICINA, ONSALA60, YEBES40M, DSS63, HARTRAO, and NOTO. Observations were made on 2010 Mar 23 (session ID gc034a), on 2011 Nov 8 (gc034bcd), and on 2011 Mar 15 (gc034ef). The OBRS-2 catalog presents precise positions of the 295 extragalactic radio sources as well as median correlated flux densities at 8.4 and 2.2GHz at baseline lengths shorter than 900km and at baseline lengths longer than 5000km. (1 data file).

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study.

PubMed

Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B; Zorumski, Charles F; Conway, Charles; Nagele, Peter

2017-04-01

While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new cardiac troponin elevation after electroconvulsive therapy, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia.

Assessing a mini-application as a performance proxy for a finite element method engineering application

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

Lin, Paul T.; Heroux, Michael A.; Barrett, Richard F.

The performance of a large-scale, production-quality science and engineering application (‘app’) is often dominated by a small subset of the code. Even within that subset, computational and data access patterns are often repeated, so that an even smaller portion can represent the performance-impacting features. If application developers, parallel computing experts, and computer architects can together identify this representative subset and then develop a small mini-application (‘miniapp’) that can capture these primary performance characteristics, then this miniapp can be used to both improve the performance of the app as well as provide a tool for co-design for the high-performance computing community.more » However, a critical question is whether a miniapp can effectively capture key performance behavior of an app. This study provides a comparison of an implicit finite element semiconductor device modeling app on unstructured meshes with an implicit finite element miniapp on unstructured meshes. The goal is to assess whether the miniapp is predictive of the performance of the app. Finally, single compute node performance will be compared, as well as scaling up to 16,000 cores. Results indicate that the miniapp can be reasonably predictive of the performance characteristics of the app for a single iteration of the solver on a single compute node.« less

Assessing a mini-application as a performance proxy for a finite element method engineering application

DOE PAGES

Lin, Paul T.; Heroux, Michael A.; Barrett, Richard F.; ...

2015-07-30

The performance of a large-scale, production-quality science and engineering application (‘app’) is often dominated by a small subset of the code. Even within that subset, computational and data access patterns are often repeated, so that an even smaller portion can represent the performance-impacting features. If application developers, parallel computing experts, and computer architects can together identify this representative subset and then develop a small mini-application (‘miniapp’) that can capture these primary performance characteristics, then this miniapp can be used to both improve the performance of the app as well as provide a tool for co-design for the high-performance computing community.more » However, a critical question is whether a miniapp can effectively capture key performance behavior of an app. This study provides a comparison of an implicit finite element semiconductor device modeling app on unstructured meshes with an implicit finite element miniapp on unstructured meshes. The goal is to assess whether the miniapp is predictive of the performance of the app. Finally, single compute node performance will be compared, as well as scaling up to 16,000 cores. Results indicate that the miniapp can be reasonably predictive of the performance characteristics of the app for a single iteration of the solver on a single compute node.« less

Multiple regression based imputation for individualizing template human model from a small number of measured dimensions.

PubMed

Nohara, Ryuki; Endo, Yui; Murai, Akihiko; Takemura, Hiroshi; Kouchi, Makiko; Tada, Mitsunori

2016-08-01

Individual human models are usually created by direct 3D scanning or deforming a template model according to the measured dimensions. In this paper, we propose a method to estimate all the necessary dimensions (full set) for the human model individualization from a small number of measured dimensions (subset) and human dimension database. For this purpose, we solved multiple regression equation from the dimension database given full set dimensions as the objective variable and subset dimensions as the explanatory variables. Thus, the full set dimensions are obtained by simply multiplying the subset dimensions to the coefficient matrix of the regression equation. We verified the accuracy of our method by imputing hand, foot, and whole body dimensions from their dimension database. The leave-one-out cross validation is employed in this evaluation. The mean absolute errors (MAE) between the measured and the estimated dimensions computed from 4 dimensions (hand length, breadth, middle finger breadth at proximal, and middle finger depth at proximal) in the hand, 2 dimensions (foot length, breadth, and lateral malleolus height) in the foot, and 1 dimension (height) and weight in the whole body are computed. The average MAE of non-measured dimensions were 4.58% in the hand, 4.42% in the foot, and 3.54% in the whole body, while that of measured dimensions were 0.00%.

High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease.

PubMed

Palacios, Florencia; Moreno, Pilar; Morande, Pablo; Abreu, Cecilia; Correa, Agustín; Porro, Valentina; Landoni, Ana Ines; Gabus, Raul; Giordano, Mirta; Dighiero, Guillermo; Pritsch, Otto; Oppezzo, Pablo

2010-06-03

Interaction of chronic lymphocytic leukemia (CLL) B cells with tissue microenvironment has been suggested to favor disease progression by promoting malignant B-cell growth. Previous work has shown expression in peripheral blood (PB) of CLL B cells of activation-induced cytidine deaminase (AID) among CLL patients with an unmutated (UM) profile of immunoglobulin genes and with ongoing class switch recombination (CSR) process. Because AID expression results from interaction with activated tissue microenvironment, we speculated whether the small subset with ongoing CSR is responsible for high levels of AID expression and could be derived from this particular microenvironment. In this work, we quantified AID expression and ongoing CSR in PB of 50 CLL patients and characterized the expression of different molecules related to microenvironment interaction. Our results show that among UM patients (1) high AID expression is restricted to the subpopulation of tumoral cells ongoing CSR; (2) this small subset expresses high levels of proliferation, antiapoptotic and progression markers (Ki-67, c-myc, Bcl-2, CD49d, and CCL3/4 chemokines). Overall, this work outlines the importance of a cellular subset in PB of UM CLL patients with a poor clinical outcome, high AID levels, and ongoing CSR, whose presence might be a hallmark of a recent contact with the microenvironment.

Nonuniform update for sparse target recovery in fluorescence molecular tomography accelerated by ordered subsets.

PubMed

Zhu, Dianwen; Li, Changqing

2014-12-01

Fluorescence molecular tomography (FMT) is a promising imaging modality and has been actively studied in the past two decades since it can locate the specific tumor position three-dimensionally in small animals. However, it remains a challenging task to obtain fast, robust and accurate reconstruction of fluorescent probe distribution in small animals due to the large computational burden, the noisy measurement and the ill-posed nature of the inverse problem. In this paper we propose a nonuniform preconditioning method in combination with L (1) regularization and ordered subsets technique (NUMOS) to take care of the different updating needs at different pixels, to enhance sparsity and suppress noise, and to further boost convergence of approximate solutions for fluorescence molecular tomography. Using both simulated data and phantom experiment, we found that the proposed nonuniform updating method outperforms its popular uniform counterpart by obtaining a more localized, less noisy, more accurate image. The computational cost was greatly reduced as well. The ordered subset (OS) technique provided additional 5 times and 3 times speed enhancements for simulation and phantom experiments, respectively, without degrading image qualities. When compared with the popular L (1) algorithms such as iterative soft-thresholding algorithm (ISTA) and Fast iterative soft-thresholding algorithm (FISTA) algorithms, NUMOS also outperforms them by obtaining a better image in much shorter period of time.

Multiple Acquisition InSAR Analysis: Persistent Scatterer and Small Baseline Approaches

NASA Astrophysics Data System (ADS)

Hooper, A.

2006-12-01

InSAR techniques that process data from multiple acquisitions enable us to form time series of deformation and also allow us to reduce error terms present in single interferograms. There are currently two broad categories of methods that deal with multiple images: persistent scatterer methods and small baseline methods. The persistent scatterer approach relies on identifying pixels whose scattering properties vary little with time and look angle. Pixels that are dominated by a singular scatterer best meet these criteria; therefore, images are processed at full resolution to both increase the chance of there being only one dominant scatterer present, and to reduce the contribution from other scatterers within each pixel. In images where most pixels contain multiple scatterers of similar strength, even at the highest possible resolution, the persistent scatterer approach is less optimal, as the scattering characteristics of these pixels vary substantially with look angle. In this case, an approach that interferes only pairs of images for which the difference in look angle is small makes better sense, and resolution can be sacrificed to reduce the effects of the look angle difference by band-pass filtering. This is the small baseline approach. Existing small baseline methods depend on forming a series of multilooked interferograms and unwrapping each one individually. This approach fails to take advantage of two of the benefits of processing multiple acquisitions, however, which are usually embodied in persistent scatterer methods: the ability to find and extract the phase for single-look pixels with good signal-to-noise ratio that are surrounded by noisy pixels, and the ability to unwrap more robustly in three dimensions, the third dimension being that of time. We have developed, therefore, a new small baseline method to select individual single-look pixels that behave coherently in time, so that isolated stable pixels may be found. After correction for various error terms, the phase values of the selected pixels are unwrapped using a new three-dimensional algorithm. We apply our small baseline method to an area in southern Iceland that includes Katla and Eyjafjallajökull volcanoes, and retrieve a time series of deformation that shows transient deformation due to intrusion of magma beneath Eyjafjallajökull. We also process the data using the Stanford method for persistent scatterers (StaMPS) for comparison.

The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome.

PubMed

Baris, Hatice Ezgi; Baris, Safa; Karakoc-Aydiner, Elif; Gokce, Ibrahim; Yildiz, Nurdan; Cicekkoku, Dilek; Ogulur, Ismail; Ozen, Ahmet; Alpay, Harika; Barlan, Isil

2016-05-01

The severity and duration of immunosuppression caused by corticosteroids (CSs) usage have not been extensively studied. We aimed to investigate the effects of CSs on the various compartments of immune system in relation to timing of initiation and persistence of therapy. Pediatric patients with idiopathic nephrotic syndrome (NS) treated with 2 mg/kg/day prednisolone and healthy control (HC) were enrolled. Blood samples were drawn for immunologic analyses at baseline and at the first and second weeks and first, second, and third months of CS therapy in addition to first and second weeks and first, second, and third months of discontinuation. Fourteen patients (M/F, 7/7) between 1 and 8 years old were evaluated. Untreated NS exhibited high absolute lymphocyte count (ALC)(p = 0.010), absolute CD3(+) T cells (p = 0.020) and absolute CD8(+) T cells (p = 0.006) compared to HC. Suppression in ALC was observed and nadir value was noted at first month of therapy compared to baseline (p = 0.002). The CD4(+) (p = 0.036) and CD8(+) T cell (p = 0.013) counts decreased significantly at the first week of treatment compared to baseline. While baseline B cell counts was indifferent from HC, gradually increased in 2 weeks of CS initiation and decreased during the treatment with a statistical significance compared to HC (p = 0.010). However, after cessation of CS, B cell counts continued to decline and found to be significantly different than baseline at first week (p = 0.008) and at third month (p = 0.040). Apart from baseline lymphocyte subset changing observed in untreated NS patients, our data implies that T cells were suppressed very early in the CS treatment. Interestingly, depressed B cell counts were detected later but persisted even after CS cessation. Due to early decrease in T cells, it would be beneficial to assume the patients as immunosuppressed at the very beginning of CS treatment to avoid infections. • Corticosteroids (CSs) are widely used for a variety of diseases including nephrotic syndrome, which is related with complex immune disturbance including T and B cells dysfunctions. • CSs induce neutrophilic leukocytosis concomitant with lymphopenia and eosinopenia leading to immunosupression. What is New: • T cell subsets and proliferation are susceptible to CSs more than B cells; however, the reversibility is faster with dose reduction in CS. • The change of B cells and B cell subtypes (CD27 (+) memory) shows prolonged effect of CSs on B cells which may alter antibody production even after 3 months of CSs cessation.

Associations of Adolescent Emotional and Loss of Control Eating with 1-year Changes in Disordered Eating, Weight and Adiposity

PubMed Central

Stojek, Monika M. K.; Tanofsky-Kraff, Marian; Shomaker, Lauren B.; Kelly, Nichole R.; Thompson, Katherine A.; Mehari, Rim D.; Marwitz, Shannon E.; Demidowich, Andrew P.; Galescu, Ovidiu A.; Brady, Sheila M.; Yanovski, Susan Z.; Yanovski, Jack A.

2016-01-01

Objective Adolescent emotional-eating, referring to eating in response to negative affective states, is frequently reported by those with loss of control (LOC) eating. Although LOC eating has been shown to predict exacerbated disordered eating and excess weight/adiposity gain, the extent to which emotional-eating, either alone or in combination with LOC, predicts adverse outcomes has not been determined. Thus, we examined associations of baseline emotional-eating with changes in disordered eating, BMI, and adiposity over 1-year, and to what degree the presence or absence of baseline LOC moderated these associations. Methods 189 non-treatment-seeking youth (15.4±1.4y; 66% female; 67% non-Hispanic White, 38% overweight [BMI ≥85th %ile]) completed the emotional-eating Scale for Children/Adolescents and the Eating Disorder Examination interview at baseline and again at 1-year. Air displacement plethysmography assessed adiposity at both time points. Results Baseline emotional-eating alone was not significantly associated with the development of objective binge eating or changes in disordered eating attitudes, BMI or adiposity 1-year later. However, baseline emotional-eating interacted with the presence of baseline LOC in the prediction of 1-year outcomes. Among adolescents with LOC eating, greater baseline emotional-eating was related to increased disordered eating attitudes (p=.03), BMI (p=.04), and adiposity (p=.04) at 1-year, after correcting for false discovery rate. Discussion Emotional-eating among youth also reporting LOC was associated with adverse outcomes over 1-year. Adolescents who report both behaviors may represent a subset of individuals at especially high risk for exacerbated disordered eating and excess weight gain. PMID:27753140

Small intracerebral hemorrhages have a low spot sign prevalence and are less likely to expand.

PubMed

Dowlatshahi, Dar; Yogendrakumar, Vignan; Aviv, Richard I; Rodriguez-Luna, David; Molina, Carlos A; Silva, Yolanda; Dzialowski, Imanuel; Czlonkowska, Anna; Boulanger, Jean-Martin; Lum, Cheemun; Gubitz, Gord; Padma, Vasantha; Roy, Jayanta; Kase, Carlos S; Bhatia, Rohit; Hill, Michael D; Demchuk, Andrew M

2016-02-01

Hematoma expansion is a major predictor of morbidity and mortality after intracerebral hemorrhage (ICH). Both baseline hematoma volume and the CT-angiogram (CTA) spot sign predict hematoma expansion. Because the CTA spot sign may represent foci of active hemorrhage, we hypothesized that patients with smaller baseline hematoma volumes are less likely to be spot sign positive, and therefore less likely to expand. We sought to validate our prior finding that small hematomas are unlikely to expand, and to determine the relationship between baseline hematoma volume, spot sign status, and risk of hematoma expansion. Data were from the prospective PREDICT ICH study. Patients presenting within 6 h of symptom onset with completed baseline CT, CTA, and follow-up CT were included. Baseline hematoma volume was categorized a priori (<3 mL, 3-10 mL, 10-20 mL, >20 mL). The primary outcome was significant hematoma expansion (≥6 mL, ≥12.5 mL or ≥33%) and secondary outcomes were early neurological worsening, good clinical outcome (modified Rankin Scale 0-3), and mortality at 90 days. Among 315 patients meeting the inclusion criteria, baseline hematoma volume category predicted absolute hematoma expansion (p < 0.001), spot sign prevalence (p < 0.001), early neurologic worsening (p = 0.002), clinical outcome (p < 0.001), and mortality (p < 0.001). Very small hematomas (<3 mL) were unlikely to be spot positive (7.7%), unlikely to expand (2.6%), and were associated with a 73% chance of good clinical outcome. Spot sign appeared to be most predictive of expansion in the 3-10 mL baseline hematoma volume category. Very small hematomas are unlikely to expand and have a low spot sign prevalence. Hemostatic therapy trials may be best targeted at hemorrhages >3 mL in volume. © 2016 World Stroke Organization.

Undocumented Immigrants in Higher Education: A Preliminary Analysis

ERIC Educational Resources Information Center

Garcia, Lisa D.; Tierney, William G.

2011-01-01

Background/Context: Undocumented immigrant postsecondary students are an understudied group on American campuses. The authors suggest that increased national attention on the topic of undocumented immigration warrants an in-depth study of a small subset of the larger undocumented population--college students. Purpose/Objective/Research…

Single-neuron labeling with inducible cre-mediated knockout in transgenic mice

PubMed Central

Young, Paul; Qiu, Li; Wang, Dongqing; Zhao, Shengli; Gross, James; Feng, Guoping

2011-01-01

To facilitate functional analysis of neuronal connectivity in a mammalian nervous system tightly packed with billions of cells, we developed a new technique that allows inducible genetic manipulations within fluorescently labeled single neurons in mice. We term this technique SLICK for Single-neuron Labeling with Inducible Cre-mediated Knockout. SLICK is achieved by co-expressing a drug-inducible form of cre recombinase and a fluorescent protein within the same small subsets of neurons. Thus, SLICK combines the powerful cre recombinase system for conditional genetic manipulation and the fluorescent labeling of single neurons for imaging. We demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we apply SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals. More broadly, these studies demonstrate a cre-LoxP compatible system for dissecting gene functions in single identifiable neurons. PMID:18454144

Predicting Treatment Outcomes and Responder Subsets in Scleroderma-related Interstitial Lung Disease

PubMed Central

Roth, Michael D.; Tseng, Chi-Hong; Clements, Philip J.; Furst, Daniel E.; Tashkin, Donald P.; Goldin, Jonathan G.; Khanna, Dinesh; Kleerup, Eric C.; Li, Ning; Elashoff, David; Elashoff, Robert E.

2014-01-01

Objectives To identify baseline characteristics of patients with Scleroderma-Related Interstitial Lung Disease (SSc-ILD) which predict the most favorable response to a 12-month treatment with oral cyclophosphamide (CYC). Methods Regression analyses were retrospectively applied to the Scleroderma Lung Study data in order to identify baseline characteristics that correlated with the absolute change in %-predicted Forced Vital Capacity (FVC) and the placebo-adjusted change in %-predicted FVC over time (the CYC treatment effect). Results Completion of the CYC arm of the Scleroderma Lung Study was associated with a placebo-adjusted improvement in %-predicted FVC of 2.11% at 12 months which increased to 4.16% when patients were followed for another 6 months (p=0.014). Multivariate regression analyses identified the maximal severity of reticular infiltrates on baseline high-resolution computerized tomography (HRCT), the modified Rodnan Skin Score (mRSS), and Mahler's Baseline Dyspnea Index (BDI) as independent correlates of treatment response. When patients were stratified based on whether 50% or more of any lung zone was involved by reticular infiltrates on HRCT and/or the presence of a mRSS of at least 23, a subgroup emerged with an average CYC treatment effect of 4.73% at 12 months and 9.81% at 18 months (p<0.001). Conversely, there was no treatment effect (−0.58%) in patients with less severe HRCT findings and a lower mRSS. Conclusions A retrospective analysis of the Scleroderma Lung Study identified the severity of reticular infiltrates on baseline HRCT and the baseline mRSS as patient features that might predict responsiveness to CYC therapy. PMID:21547897

High Resolution Deformation Time Series Estimation for Distributed Scatterers Using Terrasar-X Data

NASA Astrophysics Data System (ADS)

Goel, K.; Adam, N.

2012-07-01

In recent years, several SAR satellites such as TerraSAR-X, COSMO-SkyMed and Radarsat-2 have been launched. These satellites provide high resolution data suitable for sophisticated interferometric applications. With shorter repeat cycles, smaller orbital tubes and higher bandwidth of the satellites; deformation time series analysis of distributed scatterers (DSs) is now supported by a practical data basis. Techniques for exploiting DSs in non-urban (rural) areas include the Small Baseline Subset Algorithm (SBAS). However, it involves spatial phase unwrapping, and phase unwrapping errors are typically encountered in rural areas and are difficult to detect. In addition, the SBAS technique involves a rectangular multilooking of the differential interferograms to reduce phase noise, resulting in a loss of resolution and superposition of different objects on ground. In this paper, we introduce a new approach for deformation monitoring with a focus on DSs, wherein, there is no need to unwrap the differential interferograms and the deformation is mapped at object resolution. It is based on a robust object adaptive parameter estimation using single look differential interferograms, where, the local tilts of deformation velocity and local slopes of residual DEM in range and azimuth directions are estimated. We present here the technical details and a processing example of this newly developed algorithm.

Land subsidence in Tianjin for 2015 to 2016 revealed by the analysis of Sentinel-1A with SBAS-InSAR

NASA Astrophysics Data System (ADS)

Guo, Jiming; Hu, Jiyuan; Li, Bing; Zhou, Lv; Wang, Wei

2017-04-01

It has been suggested that Tianjin, China, has significant land subsidence due to excessive extraction of water. Although it is presently under control, the land subsidence around Tianjin suburbs in recent years should not be ignored. However, existing research work on land subsidence is based on traditional synthetic aperture radar satellite images in which the research time spans are mainly before 2012. An advanced time-series method, namely small baselines subset (SBAS) technique, is applied to a total of 27 Sentinel-1A images over Tianjin acquired between May 31, 2015, and May 13, 2016, to derive the subsidence magnitude and distribution of Tianjin. Furthermore, the overall and quantitative validations of SBAS-derived results are implemented. First, the overall subsidence distribution derived by SBAS is compared with the annual report of land subsidence in Tianjin 2015, which shows the same subsidence trend and distribution. Then, 44 benchmarks and 2 continuously operating reference station datasets, i.e., CH01 and XQYY, are processed to provide a specific validation of SBAS-derived results of Sentinel-1A. Finally, through investigation, an interpretation from two aspects of groundwater extraction and geological structures of the surrounding Wangqingtuo settlement funnel area is given.

Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial.

PubMed

Schiffmann, Raphael; Bichet, Daniel G; Jovanovic, Ana; Hughes, Derralynn A; Giugliani, Roberto; Feldt-Rasmussen, Ulla; Shankar, Suma P; Barisoni, Laura; Colvin, Robert B; Jennette, J Charles; Holdbrook, Fred; Mulberg, Andrew; Castelli, Jeffrey P; Skuban, Nina; Barth, Jay A; Nicholls, Kathleen

2018-04-27

Fabry disease is frequently characterized by gastrointestinal symptoms, including diarrhea. Migalastat is an orally-administered small molecule approved to treat the symptoms of Fabry disease in patients with amenable mutations. We evaluated minimal clinically important differences (MCID) in diarrhea based on the corresponding domain of the patient-reported Gastrointestinal Symptom Rating Scale (GSRS) in patients with Fabry disease and amenable mutations (N = 50) treated with migalastat 150 mg every other day or placebo during the phase 3 FACETS trial (NCT00925301). After 6 months, significantly more patients receiving migalastat versus placebo experienced improvement in diarrhea based on a MCID of 0.33 (43% vs 11%; p = .02), including the subset with baseline diarrhea (71% vs 20%; p = .02). A decline in kidney peritubular capillary globotriaosylceramide inclusions correlated with diarrhea improvement; patients with a reduction > 0.1 were 5.6 times more likely to have an improvement in diarrhea than those without (p = .031). Migalastat was associated with a clinically meaningful improvement in diarrhea in patients with Fabry disease and amenable mutations. Reductions in kidney globotriaosylceramide may be a useful surrogate endpoint to predict clinical benefit with migalastat in patients with Fabry disease. NCT00925301 ; June 19, 2009.

Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis.

PubMed

Chakravarty, Eliza F; Martyanov, Viktor; Fiorentino, David; Wood, Tammara A; Haddon, David James; Jarrell, Justin Ansel; Utz, Paul J; Genovese, Mark C; Whitfield, Michael L; Chung, Lorinda

2015-06-13

Systemic sclerosis is an autoimmune disease characterized by inflammation and fibrosis of the skin and internal organs. We sought to assess the clinical and molecular effects associated with response to intravenous abatacept in patients with diffuse cutaneous systemic. Adult diffuse cutaneous systemic sclerosis patients were randomized in a 2:1 double-blinded fashion to receive abatacept or placebo over 24 weeks. Primary outcomes were safety and the change in modified Rodnan Skin Score (mRSS) at week 24 compared with baseline. Improvers were defined as patients with a decrease in mRSS of ≥30% post-treatment compared to baseline. Skin biopsies were obtained for differential gene expression and pathway enrichment analyses and intrinsic gene expression subset assignment. Ten subjects were randomized to abatacept (n = 7) or placebo (n = 3). Disease duration from first non-Raynaud's symptom was significantly longer (8.8 ± 3.8 years vs. 2.4 ± 1.6 years, p = 0.004) and median mRSS was higher (30 vs. 22, p = 0.05) in the placebo compared to abatacept group. Adverse events were similar in the two groups. Five out of seven patients (71%) randomized to abatacept and one out of three patients (33%) randomized to placebo experienced ≥30% improvement in skin score. Subjects receiving abatacept showed a trend toward improvement in mRSS at week 24 (-8.6 ± 7.5, p = 0.0625) while those in the placebo group did not (-2.3 ± 15, p = 0.75). After adjusting for disease duration, mRSS significantly improved in the abatacept compared with the placebo group (abatacept vs. placebo mRSS decrease estimate -9.8, 95% confidence interval -16.7 to -3.0, p = 0.0114). In the abatacept group, the patients in the inflammatory intrinsic subset showed a trend toward greater improvement in skin score at 24 weeks compared with the patients in the normal-like intrinsic subset (-13.5 ± 3.1 vs. -4.5 ± 6.4, p = 0.067). Abatacept resulted in decreased CD28 co-stimulatory gene expression in improvers consistent with its mechanism of action. Improvers mapped to the inflammatory intrinsic subset and showed decreased gene expression in inflammatory pathways, while non-improver and placebos showed stable or reverse gene expression over 24 weeks. Clinical improvement following abatacept therapy was associated with modulation of inflammatory pathways in skin. ClinicalTrials.gov NCT00442611. Registered 1 March 2007.

Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers.

PubMed

Fesseha, Betiel K; Abularrage, Christopher J; Hines, Kathryn F; Sherman, Ronald; Frost, Priscilla; Langan, Susan; Canner, Joseph; Likes, Kendall C; Hosseini, Sayed M; Jack, Gwendolyne; Hicks, Caitlin W; Yalamanchi, Swaytha; Mathioudakis, Nestoras

2018-04-16

This study evaluated the association between hemoglobin A 1c (A1C) and wound outcomes in patients with diabetic foot ulcers (DFUs). We conducted a retrospective analysis of an ongoing prospective, clinic-based study of patients with DFUs treated at an academic institution during a 4.7-year period. Data from 270 participants and 584 wounds were included in the analysis. Cox proportional hazards regression was used to assess the incidence of wound healing at any follow-up time in relation to categories of baseline A1C and the incidence of long-term (≥90 days) wound healing in relation to tertiles of nadir A1C change and mean A1C change from baseline, adjusted for potential confounders. Baseline A1C was not associated with wound healing in univariate or fully adjusted models. Compared with a nadir A1C change from baseline of -0.29 to 0.0 (tertile 2), a nadir A1C change of 0.09 to 2.4 (tertile 3) was positively associated with long-term wound healing in the subset of participants with baseline A1C <7.5% (hazard ratio [HR], 2.07; 95% CI, 1.08-4.00), but no association with wound healing was seen with the mean A1C change from baseline in this group. Neither nadir A1C change nor mean A1C change were associated with long-term wound healing in participants with baseline A1C ≥7.5%. There does not appear to be a clinically meaningful association between baseline or prospective A1C and wound healing in patients with DFUs. The paradoxical finding of accelerated wound healing and increase in A1C in participants with better baseline glycemic control requires confirmation in further studies. © 2018 by the American Diabetes Association.

Radiographic estimation in seropositive and seronegative rheumatoid arthritis

PubMed Central

Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kërliu, Suzana; Rexhepi, Mjellma

2011-01-01

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups. PMID:21875421

Radiographic estimation in seropositive and seronegative rheumatoid arthritis.

PubMed

Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kërliu, Suzana; Rexhepi, Mjellma

2011-08-01

Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups.

Reduction in CD4 central memory T-cell subset in costimulation modulator abatacept-treated patients with recent-onset type 1 diabetes is associated with slower C-peptide decline.

PubMed

Orban, Tihamer; Beam, Craig A; Xu, Ping; Moore, Keith; Jiang, Qi; Deng, Jun; Muller, Sarah; Gottlieb, Peter; Spain, Lisa; Peakman, Mark

2014-10-01

We previously reported that continuous 24-month costimulation blockade by abatacept significantly slows the decline of β-cell function after diagnosis of type 1 diabetes. In a mechanistic extension of that study, we evaluated peripheral blood immune cell subsets (CD4, CD8-naive, memory and activated subsets, myeloid and plasmacytoid dendritic cells, monocytes, B lymphocytes, CD4(+)CD25(high) regulatory T cells, and invariant NK T cells) by flow cytometry at baseline and 3, 6, 12, 24, and 30 months after treatment initiation to discover biomarkers of therapeutic effect. Using multivariable analysis and lagging of longitudinally measured variables, we made the novel observation in the placebo group that an increase in central memory (CM) CD4 T cells (CD4(+)CD45R0(+)CD62L(+)) during a preceding visit was significantly associated with C-peptide decline at the subsequent visit. These changes were significantly affected by abatacept treatment, which drove the peripheral contraction of CM CD4 T cells and the expansion of naive (CD45R0(-)CD62L(+)) CD4 T cells in association with a significantly slower rate of C-peptide decline. The findings show that the quantification of CM CD4 T cells can provide a surrogate immune marker for C-peptide decline after the diagnosis of type 1 diabetes and that costimulation blockade may exert its beneficial therapeutic effect via modulation of this subset. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A combined multi-interferogram algorithm for high resolution DEM reconstruction over deformed regions with TerraSAR-X data

NASA Astrophysics Data System (ADS)

Zhao, Chaoying; Qu, Feifei; Zhang, Qin; Zhu, Wu

2012-10-01

The accuracy of DEM generated with interferometric synthetic aperture radar (InSAR) technique mostly depends on phase unwrapping errors, atmospheric effects, baseline errors and phase noise. The first term is more serious if the high-resolution TerraSAR-X data over urban regions and mountainous regions are applied. In addition, the deformation effect cannot be neglected if the study regions are suffering from surface deformation within the SAR acquisition dates. In this paper, several measures have been taken to generate high resolution DEM over urban regions and mountainous regions with TerraSAR data. The SAR interferometric pairs are divided into two subsets: (a) DEM subsets and (b) deformation subsets. These two interferometric sets serve to generate DEM and deformation, respectively. The external DEM is applied to assist the phase unwrapping with "remove-restore" procedure. The deformation phase is re-scaled and subtracted from each DEM observations. Lastly, the stochastic errors including atmospheric effects and phase noise are suppressed by averaging heights from several interferograms with weights. Six TerraSAR-X data are applied to generate a 6-m-resolution DEM over Xi'an, China using these procedures. Both discrete GPS heights and local high resolution and high precision DEM data are applied to calibrate the DEM generated with our algorithm, and around 4.1 m precision is achieved.

Approximation of reliability of direct genomic breeding values

USDA-ARS?s Scientific Manuscript database

Two methods to efficiently approximate theoretical genomic reliabilities are presented. The first method is based on the direct inverse of the left hand side (LHS) of mixed model equations. It uses the genomic relationship matrix for a small subset of individuals with the highest genomic relationshi...

Drinking Level Versus Drinking Pattern and Cigarette Smoking Among Older Adults.

PubMed

Holahan, Charles J; Brennan, Penny L; Schutte, Kathleen K; Holahan, Carole K; Hixon, J Gregory; Moos, Rudolf H

2018-04-01

There is a lack of research on the role of alcohol consumption in cigarette smoking among older adults, and the few studies on alcohol use and smoking with older adults have failed to distinguish between average level and pattern of drinking as predictors of smoking. The main purpose of this study was to examine the independent contributions of average level versus pattern of drinking as predictors of cigarette smoking among older adults. A subsidiary purpose was to examine the link between continued smoking and mortality among older smokers. We investigated average level and pattern of drinking as predictors of current smoking among 1,151 older adults at baseline and of continued smoking and mortality among the subset of 276 baseline smokers tracked across 20 years. We used multiple linear and logistic regression analyses and, to test mediation, bias-corrected bootstrap confidence intervals. A high level of average drinking and a pattern of episodic heavy drinking were concurrently associated with smoking at baseline. However, only episodic heavy drinking was prospectively linked to continued smoking among baseline smokers. Continued smoking among baseline smokers increased the odds of 20-year mortality and provided an indirect pathway through which heavy episodic drinking related to mortality. Smokers who misuse alcohol are a challenging population for smoking cessation efforts. Older adults who concurrently misuse alcohol and smoke cigarettes provide a unique target for public health interventions. Copyright © 2018 by the Research Society on Alcoholism.

Reversal of Glaucoma Hemifield Test Results and Visual Field Features in Glaucoma.

PubMed

Wang, Mengyu; Pasquale, Louis R; Shen, Lucy Q; Boland, Michael V; Wellik, Sarah R; De Moraes, Carlos Gustavo; Myers, Jonathan S; Wang, Hui; Baniasadi, Neda; Li, Dian; Silva, Rafaella Nascimento E; Bex, Peter J; Elze, Tobias

2018-03-01

To develop a visual field (VF) feature model to predict the reversal of glaucoma hemifield test (GHT) results to within normal limits (WNL) after 2 consecutive outside normal limits (ONL) results. Retrospective cohort study. Visual fields of 44 503 eyes from 26 130 participants. Eyes with 3 or more consecutive reliable VFs measured with the Humphrey Field Analyzer (Swedish interactive threshold algorithm standard 24-2) were included. Eyes with ONL GHT results for the 2 baseline VFs were selected. We extracted 3 categories of VF features from the baseline tests: (1) VF global indices (mean deviation [MD] and pattern standard deviation), (2) mismatch between baseline VFs, and (3) VF loss patterns (archetypes). Logistic regression was applied to predict the GHT results reversal. Cross-validation was applied to evaluate the model on testing data by the area under the receiver operating characteristic curve (AUC). We ascertained clinical glaucoma status on a patient subset (n = 97) to determine the usefulness of our model. Predictive models for GHT results reversal using VF features. For the 16 604 eyes with 2 initial ONL results, the prevalence of a subsequent WNL result increased from 0.1% for MD < -12 dB to 13.8% for MD ≥-3 dB. Compared with models with VF global indices, the AUC of predictive models increased from 0.669 (MD ≥-3 dB) and 0.697 (-6 dB ≤ MD < -3 dB) to 0.770 and 0.820, respectively, by adding VF mismatch features and computationally derived VF archetypes (P < 0.001 for both). The GHT results reversal was associated with a large mismatch between baseline VFs. Moreover, the GHT results reversal was associated more with VF archetypes of nonglaucomatous loss, severe widespread loss, and lens rim artifacts. For a subset of 97 eyes, using our model to predict absence of glaucoma based on clinical evidence after 2 ONL results yielded significantly better prediction accuracy (87.7%; P < 0.001) than predicting GHT results reversal (68.8%) with a prescribed specificity 67.7%. Using VF features may predict the GHT results reversal to WNL after 2 consecutive ONL results. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Dynamics of T-cell subsets and their relationship with oral and systemic opportunistic infections in HIV/AIDS patients during the first year of HAART in Guangxi, China.

PubMed

Zhang, Linlin; Huang, Yuxiao; Liu, Zhenmin; Liu, Wei; Qin, Qi; Tao, Renchuan

2015-07-01

To analyze the dynamic changes in Th1, Th2, Tc1, and Tc2 of HIV/AIDS patients during the first year of highly active antiretroviral therapy (HAART) and to explore their relationship with oral and systemic opportunistic infections, a cohort study was carried out among HIV/AIDS patients in Guangxi, China. Ninety HIV/AIDS patients and 30 healthy controls (HC) were included. The enrolled HIV/AIDS patients were examined at baseline and after 3, 6, and 12 months of HAART. On each visit, oral and systemic opportunistic infections were recorded, oral Candida load and plasma viral load (VL) were counted, differential T-cell counts and flow cytometric analysis of T-cell subsets were performed. During the first year of HAART, the total number of opportunistic infections decreased steadily with the change in oral candidiasis (OC) most representatively. A significant Th1→Th2 switch (Th1/Th2 ratio 0.23 ± 0.12, HC 1.45 ± 0.38) and slight Tc1→Tc2 shift (Tc1/Tc2 ratio 0.93 ± 0.29, HC 1.13 ± 0.33) were found at baseline, and both received slow mitigation after HAART. LgCFU and clinical OC were correlated positively with both LgVL and clinical stage (P < 0.05) at baseline. LgCFU was also correlated positively with clinical stage at all four time points (P < 0.05). In multiple factor analysis, Th1 was confirmed to be correlated negatively with LgVL (Std.B = -0.295, P = 0.025) and LgCFU (Std.B = -0.227, P < 0.001) at baseline. After HAART, LgCFU and clinical stage were only correlated negatively with CD4 when all factors were included. These results suggest that oral candidiasis and oral Candida load could be useful clinical markers in the evaluation of HIV/AIDS patients. Th1 may play an important role against oral and systemic opportunistic infections. Tc1 and Tc2 both showed positive roles in the control of viremia without HAART. J. Med. Virol. 87:1158-1167, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Frequency and distribution of incidental findings deemed appropriate for S modifier designation on low-dose CT in a lung cancer screening program.

PubMed

Reiter, Michael J; Nemesure, Allison; Madu, Ezemonye; Reagan, Lisa; Plank, April

2018-06-01

To describe the frequency, distribution and reporting patterns of incidental findings receiving the Lung-RADS S modifier on low-dose chest computed tomography (CT) among lung cancer screening participants. This retrospective investigation included 581 individuals who received baseline low-dose chest CT for lung cancer screening between October 2013 and June 2017 at a single center. Incidental findings resulting in assignment of Lung-RADS S modifier were recorded as were incidental abnormalities detailed within the body of the radiology report only. A subset of 60 randomly selected CTs was reviewed by a second (blinded) radiologist to evaluate inter-rater variability of Lung-RADS reporting. A total of 261 (45%) participants received the Lung-RADS S modifier on baseline CT with 369 incidental findings indicated as potentially clinically significant. Coronary artery calcification was most commonly reported, accounting for 182 of the 369 (49%) findings. An additional 141 incidentalomas of the same types as these 369 findings were described in reports but were not labelled with the S modifier. Therefore, as high as 69% (402 of 581) of participants could have received the S modifier if reporting was uniform. Inter-radiologist concordance of S modifier reporting in a subset of 60 participants was poor (42% agreement, kappa = 0.2). Incidental findings are commonly identified on chest CT for lung cancer screening, yet reporting of the S modifier within Lung-RADS is inconsistent. Specific guidelines are necessary to better define potentially clinically significant abnormalities and to improve reporting uniformity. Copyright © 2018 Elsevier B.V. All rights reserved.

Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression.

PubMed

Connolly, Colm G; Ho, Tiffany C; Blom, Eva Henje; LeWinn, Kaja Z; Sacchet, Matthew D; Tymofiyeva, Olga; Simmons, Alan N; Yang, Tony T

2017-01-01

The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents. We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24). Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later. Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized. Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time. Copyright © 2016 Elsevier B.V. All rights reserved.

Identifying cut points for biomarker defined subset effects in clinical trials with survival endpoints.

PubMed

He, Pei

2014-07-01

The advancements in biotechnology and genetics lead to an increasing research interest in personalized medicine, where a patient's genetic profile or biological traits contribute to choosing the most effective treatment for the patient. The process starts with finding a specific biomarker among all possible candidates that can best predict the treatment effect. After a biomarker is chosen, identifying a cut point of the biomarker value that splits the patients into treatment effective and non-effective subgroups becomes an important scientific problem. Numerous methods have been proposed to validate the predictive marker and select the appropriate cut points either prospectively or retrospectively using clinical trial data. In trials with survival outcomes, the current practice applies an interaction testing procedure and chooses the cut point that minimizes the p-values for the tests. Such method assumes independence between the baseline hazard and biomarker value. In reality, however, this assumption is often violated, as the chosen biomarker might also be prognostic in addition to its predictive nature for treatment effect. In this paper we propose a block-wise estimation and a sequential testing approach to identify the cut point in biomarkers that can group the patients into subsets based on their distinct treatment outcomes without assuming independence between the biomarker and baseline hazard. Numerical results based on simulated survival data show that the proposed method could pinpoint accurately the cut points in biomarker values that separate the patient subpopulations into subgroups with distinctive treatment outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Sample size determination for bibliographic retrieval studies

PubMed Central

Yao, Xiaomei; Wilczynski, Nancy L; Walter, Stephen D; Haynes, R Brian

2008-01-01

Background Research for developing search strategies to retrieve high-quality clinical journal articles from MEDLINE is expensive and time-consuming. The objective of this study was to determine the minimal number of high-quality articles in a journal subset that would need to be hand-searched to update or create new MEDLINE search strategies for treatment, diagnosis, and prognosis studies. Methods The desired width of the 95% confidence intervals (W) for the lowest sensitivity among existing search strategies was used to calculate the number of high-quality articles needed to reliably update search strategies. New search strategies were derived in journal subsets formed by 2 approaches: random sampling of journals and top journals (having the most high-quality articles). The new strategies were tested in both the original large journal database and in a low-yielding journal (having few high-quality articles) subset. Results For treatment studies, if W was 10% or less for the lowest sensitivity among our existing search strategies, a subset of 15 randomly selected journals or 2 top journals were adequate for updating search strategies, based on each approach having at least 99 high-quality articles. The new strategies derived in 15 randomly selected journals or 2 top journals performed well in the original large journal database. Nevertheless, the new search strategies developed using the random sampling approach performed better than those developed using the top journal approach in a low-yielding journal subset. For studies of diagnosis and prognosis, no journal subset had enough high-quality articles to achieve the expected W (10%). Conclusion The approach of randomly sampling a small subset of journals that includes sufficient high-quality articles is an efficient way to update or create search strategies for high-quality articles on therapy in MEDLINE. The concentrations of diagnosis and prognosis articles are too low for this approach. PMID:18823538

A SOAP Web Service for accessing MODIS land product subsets

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

SanthanaVannan, Suresh K; Cook, Robert B; Pan, Jerry Yun

2011-01-01

Remote sensing data from satellites have provided valuable information on the state of the earth for several decades. Since March 2000, the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor on board NASA s Terra and Aqua satellites have been providing estimates of several land parameters useful in understanding earth system processes at global, continental, and regional scales. However, the HDF-EOS file format, specialized software needed to process the HDF-EOS files, data volume, and the high spatial and temporal resolution of MODIS data make it difficult for users wanting to extract small but valuable amounts of information from the MODIS record. Tomore » overcome this usability issue, the NASA-funded Distributed Active Archive Center (DAAC) for Biogeochemical Dynamics at Oak Ridge National Laboratory (ORNL) developed a Web service that provides subsets of MODIS land products using Simple Object Access Protocol (SOAP). The ORNL DAAC MODIS subsetting Web service is a unique way of serving satellite data that exploits a fairly established and popular Internet protocol to allow users access to massive amounts of remote sensing data. The Web service provides MODIS land product subsets up to 201 x 201 km in a non-proprietary comma delimited text file format. Users can programmatically query the Web service to extract MODIS land parameters for real time data integration into models, decision support tools or connect to workflow software. Information regarding the MODIS SOAP subsetting Web service is available on the World Wide Web (WWW) at http://daac.ornl.gov/modiswebservice.« less

40 CFR 80.285 - Who may generate credits under the ABT program?

Code of Federal Regulations, 2010 CFR

2010-07-01

... who produce gasoline from crude oil, and are: (i) Refiners who establish a sulfur baseline under § 80.295 for a refinery; (ii) Foreign refiners for refineries with an approved baseline under § 80.94, or refineries with baselines established in accordance with § 80.290(d); or (iii) Small refiners for any...

Asteroid-Deepsky Appulses in 2018

NASA Astrophysics Data System (ADS)

Warner, Brian D.

2018-01-01

The following list is a very small subset of the results of a search for asteroid-deepsky appulses for 2018, presenting only the highlights for the year based on close approaches of brighter asteroids to brighter DSOs. The complete set of predictions is available at http://www.minorplanet.info/ObsGuides/Appulses/DSOAppulses.htm

Associations between marine phytoplankton and symptoms of illness among recreational beachgoers in Puerto Rico, 2009

EPA Science Inventory

While phytoplankton generally have crucial roles in marine ecosystems, a small subset can release toxins and produce harmful algal blooms (HABs). HABs can be a threat to human health as symptoms from exposure range from neurological impairment to gastrointestinal (GI), dermal, a...

An Assessment of the Dimensionality of SAT-Mathematical.

ERIC Educational Resources Information Center

Lawrence, Ida M.; Dorans, Neil J.

Six editions of Scholastic Aptitude Test-Mathematical (SAT-M) were factor analyzed using confirmatory and exploratory methods. Confirmatory factor analyses (using the LISREL VI program) were conducted on correlation matrices among item parcels--sums of scores on a small subset of items. Item parcels were constructed to yield correlation matrices…

Decoding the ecological function of accessory genome

USDA-ARS?s Scientific Manuscript database

Shiga toxin-producing Escherichia coli O157:H7 primarily resides in cattle asymptomatically, and can be transmitted to humans through food. A study by Lupolova et al applied a machine-learning approach to complex pan-genome information and predicted that only a small subset of bovine isolates have t...

Capillary Electrophoretic Technologies for Single Cell Metabolomics

ERIC Educational Resources Information Center

Lapainis, Theodore E.

2009-01-01

Understanding the functioning of the brain is hindered by a lack of knowledge of the full complement of neurotransmitters and neuromodulatory compounds. Single cell measurements aid in the discovery of neurotransmitters used by small subsets of neurons that would be diluted below detection limits or masked by ubiquitous compounds when working with…

2009 ESTCP UXO Discrimination Study, San Luis Obispo, CA

DTIC Science & Technology

2010-11-01

SUPERVISED LEARNING . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.5 ACTIVE LEARNING . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8...PERFORMANCE . . . . . . . . . . . . . . . . 29 7.2 ACTIVE LEARNING CLASSIFICATION PERFORMANCE . . . . . . . . . . . 30 8 COST ASSESSMENT 32 9... learning on EM61-array and TEMTADS data. During active learning , SIG started with no a priori labeled data, and acquired labels for a small subset that

Combination Therapy Targeting BCL6 and Phospho-STAT3 Defeats Intratumor Heterogeneity in a Subset of Non-Small Cell Lung Cancers. | Office of Cancer Genomics

Cancer.gov

Oncogene-specific changes in cellular signaling have been widely observed in lung cancer. Here, we investigated how these alterations could affect signaling heterogeneity and suggest novel therapeutic strategies. We compared signaling changes across six human bronchial epithelial cell (HBEC) strains that were systematically transformed with various combinations of TP53, KRAS, and MYC-oncogenic alterations commonly found in non-small cell lung cancer (NSCLC).

General proactive interference and the N450 response.

PubMed

Tays, William J; Dywan, Jane; Segalowitz, Sidney J

2009-10-25

Strategic repetition of verbal stimuli can effectively produce proactive interference (PI) effects in the Sternberg working memory task. Unique fronto-cortical activation to PI-eliciting letter probes has been interpreted as reflecting brain responses to PI. However, the use of only a small set of stimuli (e.g., letters and digits) requires constant repetition of stimuli in both PI and baseline trials, potentially creating a general PI effect in all conditions. We used event-related potentials to examine general PI effects by contrasting the interference-related frontal N450 response in two Sternberg tasks using a small versus large set size. We found that the N450 response differed significantly from baseline during the small set-size task only for response-conflict PI trials but not when PI was created solely from stimulus repetition. During the large set-size task N450 responses in both the familiarity-based and response-conflict PI conditions differed from baseline but not from each other. We conclude that the general stimulus repetition inherent in small set-size conditions can mask effects of familiarity-based PI and complicate the interpretation of any associated neural response.

ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer.

PubMed

Zinn, Rebekah L; Gardner, Eric E; Marchionni, Luigi; Murphy, Sara C; Dobromilskaya, Irina; Hann, Christine L; Rudin, Charles M

2013-06-01

New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways, including phosphatidylinositol-3-kinase-Akt and mitogen-activated protein kinase. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R, and the closely related insulin receptor. Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 < 1 μmol/L. Cell line expression of IGF-1R, IR, IGF-1, IGF-2, IGFBP3, and IGFBP6 did not correlate with sensitivity to OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (P = 0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell-cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared with mock-treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. ©2013 AACR

Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals

PubMed Central

Werchan, Chelsey A.; Rosenfield, David; Ritz, Thomas

2018-01-01

Background and objective Nitric oxide (NO) plays an important role in the airways’ innate immune response, and the fraction of exhaled NO at a flow rate of 50mL per second (FENO50) has been utilized to capture NO. Deficits in NO are linked to loss of bronchoprotective effects in airway challenges and predict symptoms of respiratory infection. While beetroot juice supplements have been proposed to enhance exercise performance by increasing dietary nitrate consumption, few studies have examined the impact of beetroot juice or nitrate supplementation on airway NO in contexts beyond an exercise challenge, which we know influences FENO50. Methods We therefore examined the influence of a beetroot juice supplement on FENO50 in healthy males and females (n = 38) during periods of rest and in normoxic conditions. FENO50, heart rate, blood pressure, and state affect were measured at baseline, 45 minutes, and 90 minutes following ingestion of 70ml beetroot juice (6.5 mmol nitrate). Identical procedures were followed with ingestion of 70ml of water on a control day. Results After beetroot consumption, average values of the natural log of FENO50 (lnFENO50) increased by 21.3% (Cohen’s d = 1.54, p < .001) 45 minutes after consumption and by 20.3% (Cohen’s d = 1.45, p < .001) 90 min after consumption. On the other hand, only very small increases in FENO50 were observed after consumption of the control liquid (less than 1% increase). A small subset (n = 4) of participants completed an extended protocol lasting over 3 hours, where elevated levels of FENO50 persisted. No significant changes in cardiovascular measures were observed with this small single dose of beetroot juice. Conclusion As NO serves a key role in innate immunity, future research is needed to explore the potential clinical utility of beetroot and dietary nitrate to elevate FENO50 and prevent respiratory infection. PMID:29370244

Availability of illicit tobacco in small retail outlets before and after the implementation of Australian plain packaging legislation.

PubMed

Scollo, Michelle; Bayly, Megan; Wakefield, Melanie

2015-03-01

We aimed to assess change in the availability of illicit tobacco in small mixed business retail outlets following the December 2012 introduction of plain packaging in Australia. 303 small retail outlets were visited in June and September 2012 (baseline months), and in December 2012 and February, April and July 2013. Fieldworkers requested a particular low-cost brand of cigarettes and then pressed the retailer for an 'even cheaper' brand. The cheapest pack of cigarettes offered was purchased and later examined to assess any divergence from prescribed Australian packaging regulations. The price paid was compared with tax liability and recommended retail price for the particular brand and pack size. In a sub-set of 179 stores, fieldworkers then asked the retailer about availability of unbranded (chop-chop) tobacco. Thirteen (2.2%) of 598 packs purchased pre-plain packaging were either non-compliant with Australian health warnings and/or suspiciously priced. Four packs (1.3%) of 297 met either or both criteria in the December implementation month, and five (0.6%) of 878 did so in the three collection months following implementation. Chop-chop was offered upon enquiry on 0.6% (n=2) of 338 occasions prior to implementation, 0.6% (n=1) of 170 occasions in the December 2012 implementation month, and 0.6% (n=3) of 514 occasions postimplementation. The likelihood of a 'positive' response (either an offer to sell or information about where unbranded tobacco may be purchased) did not differ across preimplementation, during-implementation and postimplementation waves. Overall, packs judged likely to be illicit were sold in response to requests for cheapest available packs on fewer than one percent of occasions. Offers to sell unbranded tobacco were rare. No change in availability of illicit tobacco was observed following implementation of plain packaging. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A regulator's view of comparative effectiveness research.

PubMed

Temple, Robert

2012-02-01

'Comparative effectiveness' is the current enthusiasm, and for good reason. After knowing a treatment works, the most critical question is how it compares with alternatives. Comparative studies are not commonly conducted by drug companies and they represent a significant methodological challenge. Comparative data could include evidence of overall superiority to an alternative or advantages in identifiable subsets, for example, people who do not respond to or tolerate alternatives, or members of a genetic subset and could also include convincing evidence that there is little difference between two treatments. To describe regulations, guidance, and Food and Drug Administration experience related to studies of comparative effectiveness, including approaches to showing superiority and problems encountered in showing similarity. Review of Food and Drug Administration regulations and guidance and experience with showing superiority and similarity, particularly related to randomized trials and epidemiologic studies. Methods exist, and they have been successful for showing overall superiority of one drug over another, advantages in specific population subsets. Efforts to show true equivalence face problems of definition and very large sample sizes needed to rule out small differences. There is need for further discussion of what is meant by similarity or equivalence of two treatments. Comparative studies are challenging because differences between effective therapies are likely to be small and can be detected reliably only in randomized trials, often large ones. Despite the difficulties, comparative trials have been successful and we clearly would like to see more of them.

Dysexecutive versus amnestic Alzheimer disease subgroups: analysis of demographic, genetic, and vascular factors.

PubMed

Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Manly, Jennifer J; Mayeux, Richard

2013-01-01

The objective of this study was to compare the demographic and vascular characteristics and APOE genotypes of a dysexecutive subgroup of Alzheimer disease (AD) with an amnestic subgroup of AD early in the disease course. A total of 2224 participants from the National Alzheimer's Coordinating Center database who carried a diagnosis of mild cognitive impairment (n=1188) or mild AD (clinical dementia rating ≤1) (n=1036) were included in this study. A subset of the mild cognitive impairment (n=61) and mild AD (n=79) participants underwent an autopsy. A dysexecutive subgroup (n=587) was defined as having executive performance >1 SD worse than memory performance, and an amnestic subgroup (n=549) was defined conversely. Among the autopsy subset, the odds of an AD pathologic diagnosis were compared in the 2 subgroups. The demographics, APOE[Latin Small Letter Open E]4 status, and vascular risk factors were compared in the 2 subgroups. Among the autopsy subset, the odds of having an AD pathologic diagnosis did not differ between the dysexecutive and amnestic subgroups. Under an additive model, participants in the dysexecutive subgroup possessed the APOE[Latin Small Letter Open E]4 allele less frequently compared with those in the amnestic subgroup. The dysexecutive subgroup had a history of hypertension less frequently compared with the amnestic subgroup. These distinct characteristics add to accumulating evidence that a dysexecutive subgroup of AD may have a unique underlying pathophysiology.

Quantitative assessment model for gastric cancer screening

PubMed Central

Chen, Kun; Yu, Wei-Ping; Song, Liang; Zhu, Yi-Min

2005-01-01

AIM: To set up a mathematic model for gastric cancer screening and to evaluate its function in mass screening for gastric cancer. METHODS: A case control study was carried on in 66 patients and 198 normal people, then the risk and protective factors of gastric cancer were determined, including heavy manual work, foods such as small yellow-fin tuna, dried small shrimps, squills, crabs, mothers suffering from gastric diseases, spouse alive, use of refrigerators and hot food, etc. According to some principles and methods of probability and fuzzy mathematics, a quantitative assessment model was established as follows: first, we selected some factors significant in statistics, and calculated weight coefficient for each one by two different methods; second, population space was divided into gastric cancer fuzzy subset and non gastric cancer fuzzy subset, then a mathematic model for each subset was established, we got a mathematic expression of attribute degree (AD). RESULTS: Based on the data of 63 patients and 693 normal people, AD of each subject was calculated. Considering the sensitivity and specificity, the thresholds of AD values calculated were configured with 0.20 and 0.17, respectively. According to these thresholds, the sensitivity and specificity of the quantitative model were about 69% and 63%. Moreover, statistical test showed that the identification outcomes of these two different calculation methods were identical (P>0.05). CONCLUSION: The validity of this method is satisfactory. It is convenient, feasible, economic and can be used to determine individual and population risks of gastric cancer. PMID:15655813

Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer.

PubMed

Le, Xiuning; Antony, Rajee; Razavi, Pedram; Treacy, Daniel J; Luo, Flora; Ghandi, Mahmoud; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose; Garraway, Levi A

2016-10-01

PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. Cancer Discov; 6(10); 1134-47. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

PubMed

Tietze, Julia K; Angelova, Daniela; Heppt, Markus V; Ruzicka, Thomas; Berking, Carola

2017-07-01

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56 dim and CD56 bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56 dim NK cells, whereas the baseline levels of CD56 bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56 dim and CD56 bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56 dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56 bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56 dim NK cells as well as normal baseline levels of CD56 bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56 dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56 bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56 dim and CD56 bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

CXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver

PubMed Central

Stegmann, Kerstin A.; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J.; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R.; Kennedy, Patrick; Maini, Mala K.

2016-01-01

Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p < 0.0001). Human hepatic CXCR6+ NK had an immature phenotype (predominantly CD56brightCD16−CD57−), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6− fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bethiEomeslo(CXCR6−) and T-betloEomeshi(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bethiEomeslo, suggesting its lineage was closer to CXCR6− peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-betloEomeshi NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity. PMID:27210614

CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.

PubMed

Stegmann, Kerstin A; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R; Kennedy, Patrick; Maini, Mala K

2016-05-23

Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p < 0.0001). Human hepatic CXCR6+ NK had an immature phenotype (predominantly CD56(bright)CD16-CD57-), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6- fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bet(hi)Eomes(lo)(CXCR6-) and T-bet(lo)Eomes(hi)(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bet(hi)Eomes(lo), suggesting its lineage was closer to CXCR6- peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-bet(lo)Eomes(hi) NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.

Mixed input to olfactory glomeruli from two subsets of ciliated sensory neurons does not impede relay neuron specificity in the crucian carp.

PubMed

Hansson, Kenth-Arne; Døving, Kjell B; Skjeldal, Frode M

2015-10-01

The consensus view of olfactory processing is that the axons of receptor-specific primary olfactory sensory neurons (OSNs) converge to a small subset of glomeruli, thus preserving the odour identity before the olfactory information is processed in higher brain centres. In the present study, we show that two different subsets of ciliated OSNs with different odorant specificities converge to the same glomeruli. In order to stain different ciliated OSNs in the crucian carp Carassius carassius we used two different chemical odorants, a bile salt and a purported alarm substance, together with fluorescent dextrans. The dye is transported within the axons and stains glomeruli in the olfactory bulb. Interestingly, the axons from the ciliated OSNs co-converge to the same glomeruli. Despite intermingled innervation of glomeruli, axons and terminal fields from the two different subsets of ciliated OSNs remained mono-coloured. By 4-6 days after staining, the dye was transported trans-synaptically to separately stained axons of relay neurons. These findings demonstrate that specificity of the primary neurons is retained in the olfactory pathways despite mixed innervation of the olfactory glomeruli. The results are discussed in relation to the emerging concepts about non-mammalian glomeruli. © 2015. Published by The Company of Biologists Ltd.

Selection-Fusion Approach for Classification of Datasets with Missing Values

PubMed Central

Ghannad-Rezaie, Mostafa; Soltanian-Zadeh, Hamid; Ying, Hao; Dong, Ming

2010-01-01

This paper proposes a new approach based on missing value pattern discovery for classifying incomplete data. This approach is particularly designed for classification of datasets with a small number of samples and a high percentage of missing values where available missing value treatment approaches do not usually work well. Based on the pattern of the missing values, the proposed approach finds subsets of samples for which most of the features are available and trains a classifier for each subset. Then, it combines the outputs of the classifiers. Subset selection is translated into a clustering problem, allowing derivation of a mathematical framework for it. A trade off is established between the computational complexity (number of subsets) and the accuracy of the overall classifier. To deal with this trade off, a numerical criterion is proposed for the prediction of the overall performance. The proposed method is applied to seven datasets from the popular University of California, Irvine data mining archive and an epilepsy dataset from Henry Ford Hospital, Detroit, Michigan (total of eight datasets). Experimental results show that classification accuracy of the proposed method is superior to those of the widely used multiple imputations method and four other methods. They also show that the level of superiority depends on the pattern and percentage of missing values. PMID:20212921

Predicting early cognitive decline in newly-diagnosed Parkinson's patients: A practical model.

PubMed

Hogue, Olivia; Fernandez, Hubert H; Floden, Darlene P

2018-06-19

To create a multivariable model to predict early cognitive decline among de novo patients with Parkinson's disease, using brief, inexpensive assessments that are easily incorporated into clinical flow. Data for 351 drug-naïve patients diagnosed with idiopathic Parkinson's disease were obtained from the Parkinson's Progression Markers Initiative. Baseline demographic, disease history, motor, and non-motor features were considered as candidate predictors. Best subsets selection was used to determine the multivariable baseline symptom profile that most accurately predicted individual cognitive decline within three years. Eleven per cent of the sample experienced cognitive decline. The final logistic regression model predicting decline included five baseline variables: verbal memory retention, right-sided bradykinesia, years of education, subjective report of cognitive impairment, and REM behavior disorder. Model discrimination was good (optimism-adjusted concordance index = .749). The associated nomogram provides a tool to determine individual patient risk of meaningful cognitive change in the early stages of the disease. Through the consideration of easily-implemented or routinely-gathered assessments, we have identified a multidimensional baseline profile and created a convenient, inexpensive tool to predict cognitive decline in the earliest stages of Parkinson's disease. The use of this tool would generate prediction at the individual level, allowing clinicians to tailor medical management for each patient and identify at-risk patients for clinical trials aimed at disease modifying therapies. Copyright © 2018. Published by Elsevier Ltd.

Descriptive Analysis of a Baseline Concussion Battery Among U.S. Service Academy Members: Results from the Concussion Assessment, Research, and Education (CARE) Consortium.

PubMed

O'Connor, Kathryn L; Dain Allred, C; Cameron, Kenneth L; Campbell, Darren E; D'Lauro, Christopher J; Houston, Megan N; Johnson, Brian R; Kelly, Tim F; McGinty, Gerald; O'Donnell, Patrick G; Peck, Karen Y; Svoboda, Steven J; Pasquina, Paul; McAllister, Thomas; McCrea, Michael; Broglio, Steven P

2018-03-28

The prevalence and possible long-term consequences of concussion remain an increasing concern to the U.S. military, particularly as it pertains to maintaining a medically ready force. Baseline testing is being used both in the civilian and military domains to assess concussion injury and recovery. Accurate interpretation of these baseline assessments requires one to consider other influencing factors not related to concussion. To date, there is limited understanding, especially within the military, of what factors influence normative test performance. Given the significant physical and mental demands placed on service academy members (SAM), and their relatively high risk for concussion, it is important to describe demographics and normative profile of SAMs. Furthermore, the absence of available baseline normative data on female and non-varsity SAMs makes interpretation of post-injury assessments challenging. Understanding how individuals perform at baseline, given their unique individual characteristics (e.g., concussion history, sex, competition level), will inform post-concussion assessment and management. Thus, the primary aim of this manuscript is to characterize the SAM population and determine normative values on a concussion baseline testing battery. All data were collected as part of the Concussion Assessment, Research and Education (CARE) Consortium. The baseline test battery included a post-concussion symptom checklist (Sport Concussion Assessment Tool (SCAT), psychological health screening inventory (Brief Symptom Inventory (BSI-18) and neurocognitive evaluation (ImPACT), Balance Error Scoring System (BESS), and Standardized Assessment of Concussion (SAC). Linear regression models were used to examine differences across sexes, competition levels, and varsity contact levels while controlling for academy, freshman status, race, and previous concussion. Zero inflated negative binomial models estimated symptom scores due to the high frequency of zero scores. Significant, but small, sex effects were observed on the ImPACT visual memory task. While, females performed worse than males (p < 0.0001, pη2 = 0.01), these differences were small and not larger than the effects of the covariates. A similar pattern was observed for competition level on the SAC. There was a small, but significant difference across competition level. SAMs participating in varsity athletics did significantly worse on the SAC compared to SAMs participating in club or intramural athletics (all p's < 0.001, η2 = 0.01). When examining symptom reporting, males were more than two times as likely to report zero symptoms on the SCAT or BSI-18. Intramural SAMs had the highest number of symptoms and severity compared to varsity SAMs (p < 0.0001, Cohen's d < 0.2). Contact level was not associated with SCAT or BSI-18 symptoms among varsity SAMs. Notably, the significant differences across competition level on SCAT and BSI-18 were sub-clinical and had small effect sizes. The current analyses provide the first baseline concussion battery normative data among SAMs. While statistically significant differences may be observed on baseline tests, the effect sizes for competition and contact levels are very small, indicating that differences are likely not clinically meaningful at baseline. Identifying baseline differences and significant covariates is important for future concussion-related analyses to inform concussion evaluations for all athlete levels.

One year outcome of boys with Duchenne muscular dystrophy using the Bayley-III scales of infant and toddler development.

PubMed

Connolly, Anne M; Florence, Julaine M; Cradock, Mary M; Eagle, Michelle; Flanigan, Kevin M; McDonald, Craig M; Karachunski, Peter I; Darras, Basil T; Bushby, Kate; Malkus, Elizabeth C; Golumbek, Paul T; Zaidman, Craig M; Miller, J Philip; Mendell, Jerry R

2014-06-01

The pathogenesis of Duchenne muscular dystrophy starts before birth. Despite this, clinical trials exclude young boys because traditional outcome measures rely on cooperation. We recently used the Bayley-III Scales of Infant and Toddler Development to study 24 infants and boys with Duchenne muscular dystrophy. Clinical evaluators at six centers were trained and certified to perform the Bayley-III. Here, we report 6- and 12-month follow-up of two subsets of these boys. Nineteen boys (1.9 ± 0.8 years) were assessed at baseline and 6 months. Twelve boys (1.5 ± 0.8 years) were assessed at baseline, 6, and 12 months. Gross motor scores were lower at baseline compared with published controls (6.2 ± 1.7; normal 10 ± 3; P < 0.0001) and revealed a further declining trend to 5.7 ± 1.7 (P = 0.20) at 6 months. Repeated measures analysis of the 12 boys monitored for 12 months revealed that gross motor scores, again low at baseline (6.6 ± 1.7; P < 0.0001), declined at 6 months (5.9 ± 1.8) and further at 12 months (5.3 ± 2.0) (P = 0.11). Cognitive and language scores were lower at baseline compared with normal children (range, P = 0.002-<0.0001) and did not change significantly at 6 or 12 months (range, P = 0.89-0.09). Fine motor skills, also low at baseline, improved >1 year (P = 0.05). Development can reliably be measured in infants and young boys with Duchenne muscular dystrophy across time using the Bayley-III. Power calculations using these data reveal that motor development may be used as an outcome measure. Copyright © 2014 Elsevier Inc. All rights reserved.

Prioritizing sites for conservation based on similarity to historical baselines and feasibility of protection.

PubMed

Popejoy, Traci; Randklev, Charles R; Neeson, Thomas M; Vaughn, Caryn C

2018-05-08

The shifting baseline syndrome concept advocates for the use of historical knowledge to inform conservation baselines, but does not address the feasibility of restoring sites to those baselines. In many regions, conservation feasibility varies among sites due to differences in resource availability, statutory power, and land-owner participation. We use zooarchaeological records to identify a historical baseline of the freshwater mussel community's composition before Euro-American influence at a river-reach scale. We evaluate how the community reference position and the feasibility of conservation might enable identification of sites where conservation actions would preserve historically representative communities and be likely to succeed. We first present a conceptual model that incorporates community information and landscape factors to link the best conservation areas to potential cost and conservation benefits. Using fuzzy ordination, we identify modern mussel beds that are most like the historical baseline. We then quantify the housing density and land use near each reach to estimate feasibility of habitat restoration. Using our conceptual framework, we identify reaches that have high conservation value (i.e., reaches that contain the best mussel beds) and where restoration actions would be most likely to succeed. Reaches above Lake Belton in central Texas, U.S.A. were most similar in species composition and relative abundance to zooarchaeological sites. A subset of these mussel beds occurred in locations where conservation actions appear to be most feasible. This study demonstrates how to use zooarchaeological data (biodiversity data often readily available) and estimates of conservation feasibility to inform conservation priorities at a local spatial scale. This article is protected by copyright. All rights reserved.

Phase 1 of the First Solar Small Power System Experiment (experimental System No. 1). Volume 3: Appendix E - N

NASA Technical Reports Server (NTRS)

Clark, T. B. (Editor)

1979-01-01

The design of a solar electric power plant for a small community is reported. Topics covered include: (1) control configurations and interface requirements for the baseline power system; (2) annual small power system output; (3) energy requirements for operation of the collectors and control building; (4) life cycle costs and reliability predictions; (5) thermal conductivities and costs of receiver insulation materials; (6) transient thermal modelling for the baseline receiver/thermal transport system under normal and inclement operating conditions; (7) high temperature use of sodium; (8) shading in a field of parabolic collectors; and (9) buffer storage materials.

A first attempt at few coils and low-coverage resistive wall mode stabilization of EXTRAP T2R

NASA Astrophysics Data System (ADS)

Olofsson, K. Erik J.; Brunsell, Per R.; Drake, James R.; Frassinetti, Lorenzo

2012-09-01

The reversed-field pinch features resistive-shell-type instabilities at any (vanishing and finite) plasma pressure. An attempt to stabilize the full spectrum of these modes using both (i) incomplete coverage and (ii) few coils is presented. Two empirically derived model-based control algorithms are compared with a baseline guaranteed suboptimal intelligent-shell-type (IS) feedback. Experimental stabilization could not be achieved for the coil array subset sizes considered by this first study. But the model-based controllers appear to significantly outperform the decentralized IS method.

Association analysis of whole genome sequencing data accounting for longitudinal and family designs.

PubMed

Hu, Yijuan; Hui, Qin; Sun, Yan V

2014-01-01

Using the whole genome sequencing data and the simulated longitudinal phenotypes for 849 pedigree-based individuals from Genetic Analysis Workshop 18, we investigated various approaches to detecting the association of rare and common variants with blood pressure traits. We compared three strategies for longitudinal data: (a) using the baseline measurement only, (b) using the average from multiple visits, and (c) using all individual measurements. We also compared the power of using all of the pedigree-based data and the unrelated subset. The analyses were performed without knowledge of the underlying simulating model.

Imaging skeletal muscle volume, density, and FDG uptake before and after induction therapy for non-small cell lung cancer.

PubMed

Goncalves, M D; Taylor, S; Halpenny, D F; Schwitzer, E; Gandelman, S; Jackson, J; Lukose, A; Plodkowski, A J; Tan, K S; Dunphy, M; Jones, L W; Downey, R J

2018-05-01

To assess whether changes in body composition could be assessed serially using conventional thoracic computed tomography (CT) and positron-emission tomography (PET)/CT imaging in patients receiving induction chemotherapy for non-small cell lung cancer (NSCLC). CT-based skeletal muscle volume and density were measured retrospectively from thoracic and lumbar segment CT images from 88 patients with newly diagnosed and untreated NSCLC before and after induction chemotherapy. Skeletal muscle 2-[ 18 F]-fluoro-2-deoxy-d-glucose (FDG) uptake was measured from PET/CT images from a subset of patients (n=42). Comparisons of each metric before and after induction chemotherapy were conducted using the non-parametric Wilcoxon signed-rank test for paired data. The association between clinical factors and percentage change in muscle volume was examined using univariate linear regression models, with adjustment for baseline muscle volume. Following induction chemotherapy, thoracic (-3.3%, p=0.0005) and lumbar (-2.6%, p=0.0101) skeletal muscle volume were reduced (adiposity remained unchanged). The proportion of skeletal muscle with a density <0 HU increased (7.9%, p<0.0001), reflecting a decrease in skeletal muscle density and skeletal muscle FDG uptake increased (10.4-31%, p<0.05). No imaging biomarkers were correlated with overall survival. Changes in body composition can be measured from routine thoracic imaging. During chemotherapy skeletal muscle volume and metabolism are altered; however, there was no impact on survival in this retrospective series, and further validation in prospective, well-controlled studies are required. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Rapid Ice Loss at Vatnajokull,Iceland Since Late 1990s Constrained by Synthetic Aperture Radar Interferometry

NASA Astrophysics Data System (ADS)

Zhao, W.; Amelung, F.; Dixon, T. H.; Wdowinski, S.

2012-12-01

Synthetic aperture radar interferometry time series is applied over Vatnajokull, Iceland by using 15 years ERS data. Ice loss at Vatnajokull accelerates since late 1990s especially after 21th century. Clear uplift signal due to ice mass loss is detected. The rebound signal is generally linear and increases a little bit after 2000. The relative annual velocity (GPS station 7485 as reference) is about 12 mm/yr at the ice cap edge, which matches the previous studies using GPS. The standard deviation compared to 11 GPS stations in this area is about 2 mm/yr. A relative-value modeling method ignoring the effect of viscous flow is chosen assuming elastic half space earth. The final ice loss estimation - 83 cm/yr - matches the climatology model with ground observations. Small Baseline Subsets is applied for time series analysis. Orbit error coupling with long wavelength phase trend due to horizontal plate motion is removed based on a second polynomial model. For simplicity, we do not consider atmospheric delay in this area because of no complex topography and small-scale turbulence is eliminated well after long-term average when calculating the annual mean velocity. Some unwrapping error still exits because of low coherence. Other uncertainties can be the basic assumption of ice loss pattern and spatial variation of the elastic parameters. It is the first time we apply InSAR time series for ice mass balance study and provide detailed error and uncertainty analysis. The successful of this application proves InSAR as an option for mass balance study and it is also important for validation of different ice loss estimation techniques.

Mapping ground surface deformation using temporarily coherent point SAR interferometry: Application to Los Angeles Basin

USGS Publications Warehouse

Zhang, L.; Lu, Zhong; Ding, X.; Jung, H.-S.; Feng, G.; Lee, C.-W.

2012-01-01

Multi-temporal interferometric synthetic aperture radar (InSAR) is an effective tool to detect long-term seismotectonic motions by reducing the atmospheric artifacts, thereby providing more precise deformation signal. The commonly used approaches such as persistent scatterer InSAR (PSInSAR) and small baseline subset (SBAS) algorithms need to resolve the phase ambiguities in interferogram stacks either by searching a predefined solution space or by sparse phase unwrapping methods; however the efficiency and the success of phase unwrapping cannot be guaranteed. We present here an alternative approach – temporarily coherent point (TCP) InSAR (TCPInSAR) – to estimate the long term deformation rate without the need of phase unwrapping. The proposed approach has a series of innovations including TCP identification, TCP network and TCP least squares estimator. We apply the proposed method to the Los Angeles Basin in southern California where structurally active faults are believed capable of generating damaging earthquakes. The analysis is based on 55 interferograms from 32 ERS-1/2 images acquired during Oct. 1995 and Dec. 2000. To evaluate the performance of TCPInSAR on a small set of observations, a test with half of interferometric pairs is also performed. The retrieved TCPInSAR measurements have been validated by a comparison with GPS observations from Southern California Integrated GPS Network. Our result presents a similar deformation pattern as shown in past InSAR studies but with a smaller average standard deviation (4.6 mm) compared with GPS observations, indicating that TCPInSAR is a promising alternative for efficiently mapping ground deformation even from a relatively smaller set of interferograms.

The landscape of precision cancer medicine clinical trials in the United States.

PubMed

Roper, Nitin; Stensland, Kristian D; Hendricks, Ryan; Galsky, Matthew D

2015-05-01

Advances in tumor biology and multiplex genomic analysis have ushered in the era of precision cancer medicine. Little is currently known, however, about the landscape of prospective "precision cancer medicine" clinical trials in the U.S. We identified all adult interventional cancer trials registered on ClinicalTrials.gov between September 2005 and May 2013. Trials were classified as "precision cancer medicine" if a genomic alteration in a predefined set of 88 genes was required for enrollment. Baseline characteristics were ascertained for each trial. Of the initial 18,797 trials identified, 9094 (48%) were eligible for inclusion: 684 (8%) were classified as precision cancer medicine trials and 8410 (92%) were non-precision cancer medicine trials. Compared with non-precision cancer medicine trials, precision cancer medicine trials were significantly more likely to be phase II [RR 1.19 (1.10-1.29), p<0.001], multi-center [RR 1.18 (1.11-1.26), p<0.001], open-label [RR 1.04 (1.02-1.07), p=0.005] and involve breast [RR 4.03 (3.49-4.52), p<0.001], colorectal [RR 1.62 (1.22-2.14), p=0.002] and skin [RR 1.98 (1.55-2.54), p<0.001] cancers. Precision medicine trials required 38 unique genomic alterations for enrollment. The proportion of precision cancer medicine trials compared to the total number of trials increased from 3% in 2006 to 16% in 2013. The proportion of adult cancer clinical trials in the U.S. requiring a genomic alteration for enrollment has increased substantially over the past several years. However, such trials still represent a small minority of studies performed within the cancer clinical trials enterprise and include a small subset of putatively "actionable" alterations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficient one-cycle affinity selection of binding proteins or peptides specific for a small-molecule using a T7 phage display pool.

PubMed

Takakusagi, Yoichi; Kuramochi, Kouji; Takagi, Manami; Kusayanagi, Tomoe; Manita, Daisuke; Ozawa, Hiroko; Iwakiri, Kanako; Takakusagi, Kaori; Miyano, Yuka; Nakazaki, Atsuo; Kobayashi, Susumu; Sugawara, Fumio; Sakaguchi, Kengo

2008-11-15

Here, we report an efficient one-cycle affinity selection using a natural-protein or random-peptide T7 phage pool for identification of binding proteins or peptides specific for small-molecules. The screening procedure involved a cuvette type 27-MHz quartz-crystal microbalance (QCM) apparatus with introduction of self-assembled monolayer (SAM) for a specific small-molecule immobilization on the gold electrode surface of a sensor chip. Using this apparatus, we attempted an affinity selection of proteins or peptides against synthetic ligand for FK506-binding protein (SLF) or irinotecan (Iri, CPT-11). An affinity selection using SLF-SAM and a natural-protein T7 phage pool successfully detected FK506-binding protein 12 (FKBP12)-displaying T7 phage after an interaction time of only 10 min. Extensive exploration of time-consuming wash and/or elution conditions together with several rounds of selection was not required. Furthermore, in the selection using a 15-mer random-peptide T7 phage pool and subsequent analysis utilizing receptor ligand contact (RELIC) software, a subset of SLF-selected peptides clearly pinpointed several amino-acid residues within the binding site of FKBP12. Likewise, a subset of Iri-selected peptides pinpointed part of the positive amino-acid region of residues from the Iri-binding site of the well-known direct targets, acetylcholinesterase (AChE) and carboxylesterase (CE). Our findings demonstrate the effectiveness of this method and general applicability for a wide range of small-molecules.

BILLIARDS: Baseline Instrumented Lithology Lander, Inspector and Asteroid Redirection Demonstration System

NASA Technical Reports Server (NTRS)

Marcus, Matthew; Sloane, Joshua; Ortiz, Oliver; Barbee, Brent

2015-01-01

BILLIARDS Baseline Instrumented Lithology Lander, Inspector, and Asteroid Redirection Demonstration System Proposed demonstration mission for Billiard-Ball concept Select asteroid pair with natural close approach to minimize cost and complexity Primary Objectives Rendezvous with a small (10m), near Earth (alpha) asteroid Maneuver the alpha asteroid to a collision with a 100m (beta) asteroid Produce a detectable deflection or disruption of the beta asteroid Secondary objectives Contribute knowledge of asteroid composition and characteristics Contribute knowledge of small-body formation Opportunity for international collaboration

Deformation Time-Series of the Lost-Hills Oil Field using a Multi-Baseline Interferometric SAR Inversion Algorithm with Finite Difference Smoothing Constraints

NASA Astrophysics Data System (ADS)

Werner, C. L.; Wegmüller, U.; Strozzi, T.

2012-12-01

The Lost-Hills oil field located in Kern County,California ranks sixth in total remaining reserves in California. Hundreds of densely packed wells characterize the field with one well every 5000 to 20000 square meters. Subsidence due to oil extraction can be grater than 10 cm/year and is highly variable both in space and time. The RADARSAT-1 SAR satellite collected data over this area with a 24-day repeat during a 2 year period spanning 2002-2004. Relatively high interferometric correlation makes this an excellent region for development and test of deformation time-series inversion algorithms. Errors in deformation time series derived from a stack of differential interferograms are primarily due to errors in the digital terrain model, interferometric baselines, variability in tropospheric delay, thermal noise and phase unwrapping errors. Particularly challenging is separation of non-linear deformation from variations in troposphere delay and phase unwrapping errors. In our algorithm a subset of interferometric pairs is selected from a set of N radar acquisitions based on criteria of connectivity, time interval, and perpendicular baseline. When possible, the subset consists of temporally connected interferograms, otherwise the different groups of interferograms are selected to overlap in time. The maximum time interval is constrained to be less than a threshold value to minimize phase gradients due to deformation as well as minimize temporal decorrelation. Large baselines are also avoided to minimize the consequence of DEM errors on the interferometric phase. Based on an extension of the SVD based inversion described by Lee et al. ( USGS Professional Paper 1769), Schmidt and Burgmann (JGR, 2003), and the earlier work of Berardino (TGRS, 2002), our algorithm combines estimation of the DEM height error with a set of finite difference smoothing constraints. A set of linear equations are formulated for each spatial point that are functions of the deformation velocities during the time intervals spanned by the interferogram and a DEM height correction. The sensitivity of the phase to the height correction depends on the length of the perpendicular baseline of each interferogram. This design matrix is augmented with a set of additional weighted constraints on the acceleration that penalize rapid velocity variations. The weighting factor γ can be varied from 0 (no smoothing) to a large values (> 10) that yield an essentially linear time-series solution. The factor can be tuned to take into account a priori knowledge of the deformation non-linearity. The difference between the time-series solution and the unconstrained time-series can be interpreted as due to a combination of tropospheric path delay and baseline error. Spatial smoothing of the residual phase leads to an improved atmospheric model that can be fed back into the model and iterated. Our analysis shows non-linear deformation related to changes in the oil extraction as well as local height corrections improving on the low resolution 3 arc-sec SRTM DEM.

Teaching Leadership to Undergraduates: Lessons from U.S. Military Colleges

ERIC Educational Resources Information Center

West, Clifford

2012-01-01

Military colleges and service academies are a small and unique subset of the U.S. schools offering undergraduate degrees. With missions of preparing young men and women for serving and leading in perilous circumstances, what lessons, regarding developing leadership skills in young people, can be transferred to traditional schools? This paper…

77 FR 31806 - Changes to Implement Micro Entity Status for Paying Patent Fees

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... legislative history of 35 U.S.C. 123 is clear that it is directed to a subset of small entities, namely... history do not, for example, contemplate a for-profit, large entity applicant becoming a ``micro entity... across government agencies and identified goals designed to promote innovation; (8) considered approaches...

An Undergraduate Survey Course on Asynchronous Sequential Logic, Ladder Logic, and Fuzzy Logic

ERIC Educational Resources Information Center

Foster, D. L.

2012-01-01

For a basic foundation in computer engineering, universities traditionally teach synchronous sequential circuit design, using discrete gates or field programmable gate arrays, and a microcomputers course that includes basic I/O processing. These courses, though critical, expose students to only a small subset of tools. At co-op schools like…

Environmental Asbestos Assessment Manual: Superfund Method for the Determination of Asbestos in Ambient Air, Part 1: Method

EPA Science Inventory

This is a sampling and analysis method for the determination of asbestos in air. Samples are analyzed by transmission electron microscopy (TEM). Although a small subset of samples are to be prepared using a direct procedure, the majority of samples analyzed using this method wil...

Clinical Psychology Ph.D. Program Rankings: Evaluating Eminence on Faculty Publications and Citations

ERIC Educational Resources Information Center

Matson, Johnny L.; Malone, Carrie J.; Gonzalez, Melissa L.; McClure, David R.; Laud, Rinita B.; Minshawi, Noha F.

2005-01-01

Program rankings and their visibility have taken on greater and greater significance. Rarely is the accuracy of these rankings, which are typically based on a small subset of university faculty impressions, questioned. This paper presents a more comprehensive survey method based on quantifiable measures of faculty publications and citations. The…

The importance of assessing climate change vulnerability to address species conservation

Treesearch

Karen E. Bagne; Megan M. Friggens; Sharon J. Coe; Deborah M. Finch

2014-01-01

Species conservation often prioritizes attention on a small subset of "special status" species at high risk of extinction, but actions based on current lists of special status species may not effectively moderate biodiversity loss if climate change alters threats. Assessments of climate change vulnerability may provide a method to enhance identification of...

Development and Validation of the Star Properties Concept Inventory

ERIC Educational Resources Information Center

Bailey, Janelle M.; Johnson, Bruce; Prather, Edward E.; Slater, Timothy F.

2012-01-01

Concept inventories (CIs)--typically multiple-choice instruments that focus on a single or small subset of closely related topics--have been used in science education for more than a decade. This paper describes the development and validation of a new CI for astronomy, the "Star Properties Concept Inventory" (SPCI). Questions cover the areas of…

Planning Guide for Career Academies

ERIC Educational Resources Information Center

Dayton, Charles

2010-01-01

A career academy is a small learning community within a high school, which selects a subset of students and teachers for a two-, three-, or four-year period. Students enter through a voluntary process; they must apply and be accepted, with parental knowledge and support. A career academy involves teachers from different subjects working together…

Variation in geographic access to specialist inpatient hospices in England and Wales.

PubMed

Gatrell, Anthony C; Wood, D Justin

2012-07-01

We seek to map and describe variation in geographic access to the set of 189 specialist adult inpatient hospices in England and Wales. Using almost 35,000 small Census areas (Local Super Output Areas: LSOAs) as our units of analysis, the locations of hospices, and estimated drive times from LSOAs to hospices we construct an accessibility 'score' for each LSOA, for England and Wales as a whole. Data on cancer mortality are used as a proxy for the 'demand' for hospice care and we then identify that subset of small areas in which accessibility (service supply) is relatively poor yet the potential 'demand' for hospice services is above average. That subset is then filtered according to the deprivation score for each LSOA, in order to identify those LSOAs which are also above average in terms of deprivation. While urban areas are relatively well served, large parts of England and Wales have poor access to hospices, and there is a risk that the needs of those living in relatively deprived areas may be unmet. Copyright © 2012 Elsevier Ltd. All rights reserved.

Developing a radiomics framework for classifying non-small cell lung carcinoma subtypes

NASA Astrophysics Data System (ADS)

Yu, Dongdong; Zang, Yali; Dong, Di; Zhou, Mu; Gevaert, Olivier; Fang, Mengjie; Shi, Jingyun; Tian, Jie

2017-03-01

Patient-targeted treatment of non-small cell lung carcinoma (NSCLC) has been well documented according to the histologic subtypes over the past decade. In parallel, recent development of quantitative image biomarkers has recently been highlighted as important diagnostic tools to facilitate histological subtype classification. In this study, we present a radiomics analysis that classifies the adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). We extract 52-dimensional, CT-based features (7 statistical features and 45 image texture features) to represent each nodule. We evaluate our approach on a clinical dataset including 324 ADCs and 110 SqCCs patients with CT image scans. Classification of these features is performed with four different machine-learning classifiers including Support Vector Machines with Radial Basis Function kernel (RBF-SVM), Random forest (RF), K-nearest neighbor (KNN), and RUSBoost algorithms. To improve the classifiers' performance, optimal feature subset is selected from the original feature set by using an iterative forward inclusion and backward eliminating algorithm. Extensive experimental results demonstrate that radiomics features achieve encouraging classification results on both complete feature set (AUC=0.89) and optimal feature subset (AUC=0.91).

Small Engine Component Technology (SECT) study

NASA Technical Reports Server (NTRS)

Singh, B.

1986-01-01

Small advanced (450 to 850 pounds thrust, 2002 to 3781 N) gas turbine engines were studied for a subsonic strategic cruise missile application, using projected year 2000 technology. An aircraft, mission characteristics, and baseline (state-of-the-art) engine were defined to evaluate technology benefits. Engine performance and configuration analyses were performed for two and three spool turbofan and propfan engine concepts. Mission and Life Cycle Cost (LCC) analyses were performed in which the candidate engines were compared to the baseline engines over a prescribed mission. The advanced technology engines reduced system LCC up to 41 percent relative to the baseline engine. Critical aerodynamic, materials, and mechanical systems turbine engine technologies were identified and program plans were defined for each identified critical technology.

Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database

PubMed Central

Rajasuriar, Reena; Gouillou, Maelenn; Spelman, Tim; Read, Tim; Hoy, Jennifer; Law, Matthew; Cameron, Paul U.; Petoumenos, Kathy; Lewin, Sharon R.

2011-01-01

Background A small but significant number of patients do not achieve CD4 T-cell counts >500cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART. Methods Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500cells/µl, HIV RNA<500copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500cells/µl and >200cells/µl. Results 501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32–47) years and 236 (130–350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3–10) years. Most patients (80%) achieved CD4 T-cell counts >500cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001). Conclusion The time taken to achieve a CD4 T-cell count >500cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500cells/µl. PMID:21674057

Approach to Non-Neutropenic Fever in Pediatric Oncology Patients-A Single Institution Study.

PubMed

Ali, Bilal Abou; Hirmas, Nader; Tamim, Hani; Merabi, Zeina; Hanna-Wakim, Rima; Muwakkit, Samar; Abboud, Miguel; Solh, Hassan El; Saab, Raya

2015-12-01

Pediatric oncology patients with fever, even when not neutropenic, are known to be at an increased risk of bloodstream infections. However, there are no standard guidelines for management of fever in non-neutropenic patients, resulting in variability in practice across institutions. We retrospectively analyzed the clinical characteristics, management, and outcome of all febrile non-neutropenic episodes in pediatric oncology patients at a single institution over the two-year period 2011-2012, to identify predictors of bloodstream infections. We assessed the efficacy of a uniform approach to outpatient management of a defined subset of patients at low risk of invasive infections. A total of 254 episodes in 83 patients were identified. All patients had implanted central venous catheters (port). Sixty-two episodes (24%) were triaged as high-risk and admitted for inpatient management; five (8%) had positive blood cultures. The remaining 192 episodes were triaged as low risk and managed with once daily outpatient intravenous ceftriaxone; three (1.6%) were associated with bacteremia, and 10% required eventual inpatient management. Of all the factors analyzed, only signs of sepsis (lethargy, chills, hypotension) were associated with positive bloodstream infection. Treatment of a defined subset of patients with outpatient intravenous ceftriaxone was safe and effective. Signs of sepsis were the only factor significantly associated with bloodstream infection. This study provides a baseline for future prospective studies assessing the safety of withholding antibiotics in this subset of patients. © 2015 Wiley Periodicals, Inc.

CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease.

PubMed

Kadivar, Mohammad; Petersson, Julia; Svensson, Lena; Marsal, Jan

2016-12-15

γδ T cells have been attributed a wide variety of functions, which in some cases may appear as contradictory. To better understand the enigmatic biology of γδ T cells it is crucial to define the constituting subpopulations. γδ T cells have previously been categorized into two subpopulations: CD8αα + and CD8 - cells. In this study we have defined and characterized a novel subset of human γδ T-cells expressing CD8αβ. These CD8αβ + γδ T cells differed from the previously described γδ T cell subsets in several aspects, including the degree of enrichment within the gut mucosa, the activation status in blood, the type of TCRδ variant used in blood, and small but significant differences in their response to IL-2 stimulation. Furthermore, the novel subset expressed cytotoxic mediators and CD69, and produced IFN-γ and TNF-α. In patients with active inflammatory bowel disease the mucosal frequencies of CD8αβ + γδ T cells were significantly lower as compared with healthy controls, correlated negatively with the degree of disease activity, and increased to normal levels as a result of anti-TNF-α therapy. In conclusion, our results demonstrate that CD8αβ + γδ T cells constitute a novel lymphocyte subset, which is strongly enriched within the gut and may play an important role in gut homeostasis and mucosal healing in inflammatory bowel disease. Copyright © 2016 by The American Association of Immunologists, Inc.

Occupational exposure to formaldehyde and alterations in lymphocyte subsets

PubMed Central

Hosgood, H. Dean; Zhang, Luoping; Tang, Xiaojiang; Vermeulen, Roel; Hao, Zhenyue; Shen, Min; Qiu, Chuangyi; Ge, Yichen; Hua, Ming; Ji, Zhiying; Li, Senhua; Xiong, Jun; Reiss, Boris; Liu, Songwang; Xin, Kerry X.; Azuma, Mariko; Xie, Yuxuan; Freeman, Laura Beane; Ruan, Xiaolin; Guo, Weihong; Galvan, Noe; Blair, Aaron; Li, Laiyu; Huang, Hanlin; Smith, Martyn T.; Rothman, Nathaniel; Lan, Qing

2012-01-01

Background Formaldehyde is used in many occupational settings, most notably in manufacturing, health care, and embalming. Formaldehyde has been classified as a human carcinogen, but its mechanism of action remains uncertain. Methods We carried out a cross-sectional study of 43 formaldehyde exposed-workers and 51 unexposed age and sex-matched controls in Guangdong, China to study formaldehyde’s early biologic effects. To follow-up our previous report that the total lymphocyte count was decreased in formaldehyde-exposed workers compared to controls, we evaluated each major lymphocyte subset (i.e., CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and B cells) and T cell lymphocyte subset (CD4+ naïve and memory T cells, CD8+ naïve and memory T cells, and regulatory T cells). Linear regression of each subset was used to test for differences between exposed workers and controls, adjusting for potential confounders. Results Total NK cell and T cell counts were about 24% (p=0.037) and 16% (p=0.0042) lower, respectively, among exposed workers. Among certain T cell subsets, decreased counts among exposed workers were observed for CD8+ T cells (p=0.026), CD8+ effector memory T cells (p=0.018), and regulatory T cells (CD4+FoxP3+: p=0.04; CD25+FoxP3+: p=0.008). Conclusions Formaldehyde exposed-workers experienced decreased counts of NK cells, regulatory T cells, and CD8+ effector memory T cells; however, due to the small sample size these findings need to be confirmed in larger studies. PMID:22767408

Terahertz imaging with compressed sensing and phase retrieval.

PubMed

Chan, Wai Lam; Moravec, Matthew L; Baraniuk, Richard G; Mittleman, Daniel M

2008-05-01

We describe a novel, high-speed pulsed terahertz (THz) Fourier imaging system based on compressed sensing (CS), a new signal processing theory, which allows image reconstruction with fewer samples than traditionally required. Using CS, we successfully reconstruct a 64 x 64 image of an object with pixel size 1.4 mm using a randomly chosen subset of the 4096 pixels, which defines the image in the Fourier plane, and observe improved reconstruction quality when we apply phase correction. For our chosen image, only about 12% of the pixels are required for reassembling the image. In combination with phase retrieval, our system has the capability to reconstruct images with only a small subset of Fourier amplitude measurements and thus has potential application in THz imaging with cw sources.

Wind Information Uplink to Aircraft Performing Interval Management Operations

NASA Technical Reports Server (NTRS)

Ahmad, Nashat; Barmore, Bryan; Swieringa, Kurt

2015-01-01

The accuracy of the wind information used to generate trajectories for aircraft performing Interval Management (IM) operations is critical to the success of an IM operation. There are two main forms of uncertainty in the wind information used by the Flight Deck Interval Management (FIM) equipment. The first is the accuracy of the forecast modeling done by the weather provider. The second is that only a small subset of the forecast data can be uplinked to the aircraft for use by the FIM equipment, resulting in loss of additional information. This study focuses on what subset of forecast data, such as the number and location of the points where the wind is sampled should be made available to uplink to the aircraft.

The CXCL16-CXCR6 chemokine axis in glial tumors.

PubMed

Hattermann, Kirsten; Held-Feindt, Janka; Ludwig, Andreas; Mentlein, Rolf

2013-07-15

Since chemokines and their receptors play a pivotal role in tumors, we investigated the CXCL16-CXCR6-axis in human astroglial tumors. The transmembrane chemokine CXCL16 is heavily expressed by tumor, microglial and endothelial cells in situ and in vitro. In contrast, the receptor CXCR6 is restricted in glioblastomas to a small subset of proliferating cells positive for the stem-cell markers Musashi, Nanog, Sox2 and Oct4. In particular, the vast majority (about 90%) of Musashi-positive cells stained also for CXCR6. Thus, CXCL16 is highly expressed by glial tumor and stroma cells whereas CXCR6 defines a subset of cells with stem cell character. Copyright © 2013 Elsevier B.V. All rights reserved.

Schizophrenia classification using functional network features

NASA Astrophysics Data System (ADS)

Rish, Irina; Cecchi, Guillermo A.; Heuton, Kyle

2012-03-01

This paper focuses on discovering statistical biomarkers (features) that are predictive of schizophrenia, with a particular focus on topological properties of fMRI functional networks. We consider several network properties, such as node (voxel) strength, clustering coefficients, local efficiency, as well as just a subset of pairwise correlations. While all types of features demonstrate highly significant statistical differences in several brain areas, and close to 80% classification accuracy, the most remarkable results of 93% accuracy are achieved by using a small subset of only a dozen of most-informative (lowest p-value) correlation features. Our results suggest that voxel-level correlations and functional network features derived from them are highly informative about schizophrenia and can be used as statistical biomarkers for the disease.

Characterization of the CD4+ and CD8+ tumor infiltrating lymphocytes propagated with bispecific monoclonal antibodies.

PubMed

Wong, J T; Pinto, C E; Gifford, J D; Kurnick, J T; Kradin, R L

1989-11-15

To study the CD4+ and CD8+ tumor infiltrating lymphocytes (TIL) in the antitumor response, we propagated these subsets directly from tumor tissues with anti-CD3:anti-CD8 (CD3,8) and anti-CD3:anti-CD4 (CD3,4) bispecific mAb (BSMAB). CD3,8 BSMAB cause selective cytolysis of CD8+ lymphocytes by bridging the CD8 molecules of target lymphocytes to the CD3 molecular complex of cytolytic T lymphocytes with concurrent activation and proliferation of residual CD3+CD4+ T lymphocytes. Similarly, CD3,4 BSMAB cause selective lysis of CD4+ lymphocytes whereas concurrently activating the residual CD3+CD8+ T cells. Small tumor fragments from four malignant melanoma and three renal cell carcinoma patients were cultured in medium containing CD3,8 + IL-2, CD3,4 + IL-2, or IL-2 alone. CD3,8 led to selective propagation of the CD4+ TIL whereas CD3,4 led to selective propagation of the CD8+ TIL from each of the tumors. The phenotypes of the TIL subset cultures were generally stable when assayed over a 1 to 3 months period and after further expansion with anti-CD3 mAb or lectins. Specific 51Cr release of labeled target cells that were bridged to the CD3 molecular complexes of TIL suggested that both CD4+ and CD8+ TIL cultures have the capacity of mediating cytolysis via their Ti/CD3 TCR complexes. In addition, both CD4+ and CD8+ TIL cultures from most patients caused substantial (greater than 20%) lysis of the NK-sensitive K562 cell line. The majority of CD4+ but not CD8+ TIL cultures also produced substantial lysis of the NK-resistant Daudi cell line. Lysis of the autologous tumor by the TIL subsets was assessed in two patients with malignant melanoma. The CD8+ TIL from one tumor demonstrated cytotoxic activity against the autologous tumor but negligible lysis of allogeneic melanoma targets. In conclusion, immunocompetent CD4+ and CD8+ TIL subsets can be isolated and expanded directly from small tumor fragments of malignant melanoma and renal cell carcinoma using BSMAB. The resultant TIL subsets can be further expanded for detailed studies or for adoptive immunotherapy.

Histomorphometric characteristics of immune cells in small intestine of pigs perorally immunized with vaccine candidate F18ac nonenterotoxigenic E. coli strain.

PubMed

Kovšca Janjatović, A; Lacković, G; Božić, F; Spoljarić, D; Popović, M; Valpotić, H; Vijtiuk, N; Pavičić, Z; Valpotić, I

2009-12-29

Colidiarrhea and colienterotoxemia caused by F4(+) and/or F18(+) enterotoxigenic E. coli (ETEC) strains are the most prevalent infections of suckling and weaned pigs. Here we tested the immunogenicity and protective effectiveness of attenuated F18ac(+) non-ETEC vaccine candidate strain against challenge infection with F4ac(+) ETEC strain by quantitative phenotypic analysis of small intestinal leukocyte subsets in weaned pigs.We also evaluated levamisole as an immune response modifier (IRM) and its adjuvanticity when given in the combination with the experimental vaccine. The pigs were parenterally immunized with either levamisole (at days -2, -1 and 0) or with levamisole and perorally given F18ac(+) non-ETEC strain (at day 0), and challenged with F4ac(+) ETEC strain 7 days later.At day 13 the pigs were euthanatized and sampled for immunohistological/histomorphometrical analyses. Lymphoid CD3(+), CD45RA(+), CD45RC(+), CD21(+), IgA(+) and myeloid SWC3(+) cell subsets were identified in jejunal and ileal epithelium, lamina propria and Peyer's patches using the avidin-biotin complex method, and their numbers were determined by computer-assisted histomorphometry. Quantitative immunophenotypic analyses showed that levamisole treated pigs had highly increased numbers of jejunal CD3(+), CD45RC(+) and SWC3(+) cells (p<0.05) as compared to those recorded in nontreated control pigs.In the ileum of these pigs we have recorded that only CD21(+) cells were significantly increased (p<0.01). The pigs that were treated with levamisole adjuvanted experimental vaccine had significantly increased numbers of all tested cell subsets in both segments of the small intestine. It was concluded that levamisole adjuvanted F18ac(+) non-ETEC vaccine was a requirement for the elicitation of protective gut immunity in this model; nonspecific immunization with levamisole was less effective, but confirmed its potential as an IRM.

A time series deformation estimation in the NW Himalayas using SBAS InSAR technique

NASA Astrophysics Data System (ADS)

Kumar, V.; Venkataraman, G.

2012-12-01

A time series land deformation studies in north western Himalayan region has been presented in this study. Synthetic aperture radar (SAR) interferometry (InSAR) is an important tool for measuring the land displacement caused by different geological processes [1]. Frequent spatial and temporal decorrelation in the Himalayan region is a strong impediment in precise deformation estimation using conventional interferometric SAR approach. In such cases, advanced DInSAR approaches PSInSAR as well as Small base line subset (SBAS) can be used to estimate earth surface deformation. The SBAS technique [2] is a DInSAR approach which uses a twelve or more number of repeat SAR acquisitions in different combinations of a properly chosen data (subsets) for generation of DInSAR interferograms using two pass interferometric approach. Finally it leads to the generation of mean deformation velocity maps and displacement time series. Herein, SBAS algorithm has been used for time series deformation estimation in the NW Himalayan region. ENVISAT ASAR IS2 swath data from 2003 to 2008 have been used for quantifying slow deformation. Himalayan region is a very active tectonic belt and active orogeny play a significant role in land deformation process [3]. Geomorphology in the region is unique and reacts to the climate change adversely bringing with land slides and subsidence. Settlements on the hill slopes are prone to land slides, landslips, rockslides and soil creep. These hazardous features have hampered the over all progress of the region as they obstruct the roads and flow of traffic, break communication, block flowing water in stream and create temporary reservoirs and also bring down lot of soil cover and thus add enormous silt and gravel to the streams. It has been observed that average deformation varies from -30.0 mm/year to 10 mm/year in the NW Himalayan region . References [1] Massonnet, D., Feigl, K.L.,Rossi, M. and Adragna, F. (1994) Radar interferometry mapping of deformation in the year after the Landers earthquake. Nature 1994, 369, 227-230. [2] Berardino, P., Fornaro, G., Lanari, R., Sansosti, E. (2002). A new algorithm for surface deformation Monitoring based on Small Baseline Differential SAR Interferograms. IEEE Transactions on Geoscience and Remote Sensing, 40 (11), 2375-2383. [3] GEOLOGICAL SURVEY OF INDIA (GSI), (1999) Inventory of the Himalayan glaciers. Special publication, vol. 34, pp. 165-168. [4] Chen, C.W., and Zebker, H. A., (2000). Network approaches to two-dimensional phase unwrapping: intractability and two new algorithms. Journal of the Optical Society of America, A, 17, 401-414.

Small pulmonary nodules in baseline and incidence screening rounds of low-dose CT lung cancer screening

PubMed Central

Walter, Joan E.; Oudkerk, Matthijs

2017-01-01

Currently, lung cancer screening by low-dose computed tomography (LDCT) is widely recommended for high-risk individuals by US guidelines, but there still is an ongoing debate concerning respective recommendations for European countries. Nevertheless, the available data regarding pulmonary nodules released by lung cancer screening studies could improve future screening guidelines, as well as the clinical practice of incidentally detected pulmonary nodules on routine CT scans. Most lung cancer screening trials present results for baseline and incidence screening rounds separately, clustering pulmonary nodules initially found at baseline screening and newly detected pulmonary nodules after baseline screening together. This approach does not appreciate possible differences among pulmonary nodules detected at baseline and firstly detected at incidence screening rounds and is heavily influenced by methodological differences of the respective screening trials. This review intends to create a basis for assessing non-calcified pulmonary nodules detected during LDCT lung cancer screening in a more clinical relevant manner. The aim is to present data of non-calcified pulmonary baseline nodules and new non-calcified pulmonary incident nodules without clustering them together, thereby also simplifying translation to the clinical practice of incidentally detected pulmonary nodules. Small pulmonary nodules newly detected at incidence screening rounds of LDCT lung cancer screening may possess a greater lung cancer probability than pulmonary baseline nodules at a smaller size, which is essential for the development of new guidelines. PMID:28331823

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

PubMed Central

Myers, Amy J.; Jarvela, Jessica; Flynn, JoAnne; Rutledge, Tara; Bonfield, Tracey

2016-01-01

Immune cells of the distal airways serve as “first responders” of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection. A simple gating strategy effectively defined BAL T-cell and phagocyte populations in both species. BAL from Mtb-naive humans and macaques showed similar differential cell counts. BAL T cells of macaques were composed of fewer CD4+cells but more CD8+ and CD4+CD8+ double-positive cells than were BAL T cells of humans. The most common mononuclear phagocyte population in BAL of both species displayed coexpression of HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying only some of these markers were observed as well. Macaques with LTBI displayed a marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques, the prevalence of specific mononuclear phagocyte subsets in baseline BAL correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active disease). Overall, these findings demonstrate the comparability of studies of pulmonary immunity to Mtb in humans and macaques. They also indicate a previously undescribed complexity of airway mononuclear phagocyte populations that suggests further lines of investigation relevant to understanding the mechanisms of both protection from and susceptibility to the development of active tuberculosis within the lung. PMID:27509488

A Comparison of Clinical Outcomes for Diabetic and Nondiabetic Patients Following Directional Atherectomy in the DEFINITIVE LE Claudicant Cohort.

PubMed

Garcia, Lawrence A; Jaff, Michael R; Rocha-Singh, Krishna J; Zeller, Thomas; Bosarge, Christopher; Kamat, Suraj; McKinsey, James F

2015-10-01

To report a subset analysis that evaluated the hypothesis that directional atherectomy for peripheral artery disease in diabetic claudicants has noninferior primary patency at 12 months compared with nondiabetic claudicants. DEFINITIVE LE, a US/European multicenter study, assessed the effectiveness of directional atherectomy using SilverHawk/TurboHawk systems for treatment of peripheral artery disease in the superficial femoral, popliteal, and infrapopliteal arteries. Of the 800 patients enrolled in the study, only the 598 claudicant patients (mean age 69.5±10.4 years; 336 men) who were classified at baseline as Rutherford category 1-3 were eligible for this subset analysis. Of these, 46.8% (280/598) had diabetes. Follow-up to 12 months included duplex ultrasound examination, functional assessments, and adverse event evaluations. Independent angiographic and duplex ultrasound core laboratories assessed primary patency and secondary endpoints; a clinical events committee adjudicated adverse events. Although diabetics had significantly more baseline comorbidities, 12-month primary patency (77.0%) was no different than for nondiabetics (77.9%; superiority p=0.98; noninferiority p<0.001) across all anatomic territories treated. Freedom from clinically driven target lesion revascularization was no different between diabetics (83.8%) and nondiabetics (87.5%) overall (p=0.19) or by lesion locations. Secondary clinical outcomes (Rutherford category, ankle-brachial index, and walking impairment) improved at 12 months for both diabetics and nondiabetics. Noninferior 12-month patency rates demonstrate that directional atherectomy is an effective treatment in diabetic as well as nondiabetic claudicants. Directional atherectomy remains an attractive treatment option, improving luminal diameters without stents, which preserves future treatment options for both diabetic and nondiabetic patients with progressive, diffuse vascular disease. © The Author(s) 2015.

Effects of Subthalamic Stimulation on Olfactory Function in Parkinson Disease.

PubMed

Cury, Rubens Gisbert; Carvalho, Margarete de Jesus; Lasteros, Fernando Jeyson Lopez; Dias, Alice Estevo; Dos Santos Ghilardi, Maria Gabriela; Paiva, Anderson Rodrigues Brandão; Coutinho, Artur Martins; Buchpiguel, Carlos Alberto; Teixeira, Manoel J; Barbosa, Egberto Reis; Fonoff, Erich Talamoni

2018-06-01

Olfactory dysfunction is a nonmotor symptom of Parkinson disease (PD) associated with reduction in quality of life. There is no evidence on whether improvements in olfaction after subthalamic deep brain stimulation (STN-DBS) may be directly attributable to motor improvement or whether this reflects a direct effect of DBS on olfactory brain areas. The aim of the present study was to evaluate the effect of DBS on olfactory function in PD, as well as to explore the correlation between these changes and changes in motor symptoms and brain metabolism. Thirty-two patients with PD were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. Primary outcome was the change in olfactory function (Sniffin' Sticks odor-identification test [SST]) after surgery among the patients with hyposmia at baseline. Secondary outcomes included the relationship between motor outcomes and olfactory changes and [ 18 F]fluorodeoxyglucose-positron emission tomography analysis between subgroups with improvement versus no improvement of smell. STN-DBS improved SST after surgery (preoperative SST, median 7.3 ± 2.4 vs. postoperative SST, median 8.2 ± 2.1; P = 0.045) in a subset of patients among 29 of 32 patients who presented with hyposmia at baseline. The improvement in SST was correlated with DBS response (r = 0.424; P = 0.035). There was also an increase in glucose metabolism in the midbrain, cerebellum, and right frontal lobe in patients with SST improvement (P < 0.001). STN-DBS improves odor identification in a subset of patients with PD. Motor improvement together with changes in the brain metabolism may be linked to this improvement. Copyright © 2018 Elsevier Inc. All rights reserved.

Body Mass Index and Physical Activity at Different Ages and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study

PubMed Central

Hofmann, Jonathan N.; Moore, Steven C.; Lim, Unhee; Park, Yikyung; Baris, Dalsu; Hollenbeck, Albert R.; Matthews, Charles E.; Gibson, Todd M.; Hartge, Patricia; Purdue, Mark P.

2013-01-01

Several studies have reported an increased risk of multiple myeloma associated with excess body weight. We investigated the risk of multiple myeloma in relation to separate measures of adiposity and energy balance at different ages in the National Institutes of Health-AARP Diet and Health Study, a large prospective cohort study in the United States. Participants completed a baseline questionnaire (1995–1996; n = 485,049), and a subset of participants completed a second questionnaire (1996–1997; n = 305,618) in which we solicited more detailed exposure information. Hazard ratios and 95% confidence intervals were estimated for the risk of multiple myeloma (overall, n = 813; subset, n = 489) in relation to several measures of obesity and leisure time physical activity. Multiple myeloma risk was associated with increasing body mass index (BMI) at cohort entry (per 5-kg/m2 increase, hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00, 1.22); similar associations were observed for BMI at age 50 years (HR = 1.14, 95% CI: 1.02, 1.28), age 35 years (HR = 1.20, 95% CI: 1.05, 1.36), and age 18 years (HR = 1.13, 95% CI: 0.98, 1.32) without adjustment for baseline BMI. Risk of multiple myeloma was not associated with physical activity level at any age. These findings support the hypothesis that excess body weight, both in early adulthood and later in life, is a risk factor for multiple myeloma and suggest that maintaining a healthy body weight throughout life may reduce multiple myeloma risk. PMID:23543160

Associations of Parity, Breastfeeding, and Fractures in the Women's Health Observational Study.

PubMed

Crandall, Carolyn J; Liu, Jingmin; Cauley, Jane; Newcomb, Polly A; Manson, JoAnn E; Vitolins, Mara Z; Jacobson, Lisette T; Rykman, Kelli K; Stefanick, Marcia L

2017-07-01

To examine associations of several aspects of parity and history of lactation with incident hip fractures and clinical fractures and, in a subset of women, with bone mineral density. In this observational study, we analyzed data from 93,676 postmenopausal women participating in the Women's Health Initiative Observational Study and all bone density data from the subset of participants who underwent bone density testing at three clinical centers. At baseline, participants were aged 50-79 years. Using Cox proportional hazards regression analysis, we examined associations of fracture incidence and bone density with several aspects of parity (number of pregnancies, age at first pregnancy lasting 6 months or greater, and number of pregnancies lasting 6 months or greater) and breastfeeding (number of episodes of breastfeeding for at least 1 month, number of children breastfed, age when first breastfed, age when last breastfed, total number of months breastfed). The mean baseline age (standard deviation) of participants was 64 (±7.4) years (mean follow-up 7.9 years). During follow-up, the incident rate of hip fracture was 1.27%. Ten percent of participants were nulligravid. In fully adjusted models, number of pregnancies, parity, age at first birth, number of children breastfed, age at first breastfeeding, age at last breastfeeding, and total duration of breastfeeding were not statistically significantly associated with hip fracture incidence. There were no consistent associations of parity or lactation characteristics with overall clinical fracture risk or bone density. However, compared with never breastfeeding, a history of breastfeeding for at least 1 month was associated with a decreased risk of hip fracture (yes compared with no, hazard ratio 0.84, 95% confidence interval 0.73-0.98). Patterns of parity and history of lactation were largely unrelated to fracture risk or bone density.

Employing individual measures of baseline glucocorticoids as population-level conservation biomarkers: considering within-individual variation in a breeding passerine

PubMed Central

Madliger, Christine L; Love, Oliver P

2016-01-01

Abstract Labile physiological variables, such as stress hormones [i.e. glucocorticoids (GCs)], allow individuals to react to perturbations in their environment and may therefore reflect the effect of disturbances or positive conservation initiatives in advance of population-level demographic measures. Although the application of GCs as conservation biomarkers has been of extensive interest, few studies have explicitly investigated whether baseline GC concentrations respond to disturbances consistently across individuals. However, confirmation of consistent responses is of paramount importance to assessing the ease of use of GCs in natural systems and to making valid interpretations regarding population-level change (or lack of change) in GC concentrations. We investigated whether free-ranging female tree swallows (Tachycineta bicolor) display individually specific changes in baseline glucocorticoid concentrations naturally over the breeding season (from incubation to offspring provisioning) and in response to a manipulation of foraging profitability (representing a decrease in access to food resources). We show that baseline GC concentrations are repeatable within individuals over reproduction in natural conditions. However, in response to a reduction in foraging ability, baseline GC concentrations increase at the population level but are not repeatable within individuals, indicating a high level of within-individual variation. Overall, we suggest that baseline GCs measured on a subset of individuals may not provide a representative indication of responses to environmental change at the population level, and multiple within-individual measures may be necessary to determine the fitness correlates of GC concentrations. Further validation should be completed across a variety of taxa and life-history stages. Moving beyond a traditional cross-sectional approach by incorporating repeated-measures methods will be necessary to assess the suitability of baseline GCs as biomarkers of environmental change and population persistence, particularly from a logistical and ease-of-use perspective for conservation managers. PMID:27757239

Autonomous and controlled motivation for eating disorders treatment: baseline predictors and relationship to treatment outcome.

PubMed

Carter, Jacqueline C; Kelly, Allison C

2015-03-01

This study aimed to identify baseline predictors of autonomous and controlled motivation for treatment (ACMT) in a transdiagnostic eating disorder sample, and to examine whether ACMT at baseline predicted change in eating disorder psychopathology during treatment. Participants were 97 individuals who met DSM-IV-TR criteria for an eating disorder and were admitted to a specialized intensive treatment programme. Self-report measures of eating disorder psychopathology, ACMT, and various psychosocial variables were completed at the start of treatment. A subset of these measures was completed again after 3, 6, 9, and 12 weeks of treatment. Multiple regression analyses showed that baseline autonomous motivation was higher among patients who reported more self-compassion and more received social support, whereas the only baseline predictor of controlled motivation was shame. Multilevel modelling revealed that higher baseline autonomous motivation predicted faster decreases in global eating disorder psychopathology, whereas the level of controlled motivation at baseline did not. The current findings suggest that developing interventions designed to foster autonomous motivation specifically and employing autonomy supportive strategies may be important to improving eating disorders treatment outcome. The findings of this study suggest that developing motivational interventions that focus specifically on enhancing autonomous motivation for change may be important for promoting eating disorder recovery. Our results lend support for the use of autonomy supportive strategies to strengthen personally meaningful reasons to achieve freely chosen change goals in order to enhance treatment for eating disorders. One study limitation is that there were no follow-up assessments beyond the 12-week study and we therefore do not know whether the relationships that we observed persisted after treatment. Another limitation is that this was a correlational study and it is therefore important to be cautious about making causal conclusions when interpreting the results. © 2014 The British Psychological Society.

A retrospective study of proteinuria in dogs receiving toceranib phosphate.

PubMed

Piscoya, Sindy L; Hume, Kelly R; Balkman, Cheryl E

2018-06-01

The incidence of proteinuria in humans receiving tyrosine kinase inhibitors has been well-documented. Reports of proteinuria with this class of drugs are limited in veterinary medicine. This retrospective study describes the incidence, severity, and progression of proteinuria in 55 dogs treated with toceranib phosphate, with or without concurrent glucocorticoid or NSAID (non-steroidal anti-inflammatory drug). Six dogs were proteinuric at baseline. Twelve of the 49 dogs that were not proteinuric at baseline developed proteinuria while receiving toceranib phosphate. Median urine protein:creatinine (UPC) ratio when proteinuria developed was 0.75 (range: 0.6 to 4.9). There was no association with intermittent glucocorticoid or NSAID use and development of proteinuria ( P = 0.5 and P = 0.7, respectively). Overall duration of toceranib phosphate treatment ranged from 70 to 802 days in proteinuric dogs and 28 to 1285 days in non-proteinuric dogs. Our results indicate a subset of dogs receiving toceranib phosphate may develop proteinuria; careful monitoring with serial UPCs is recommended.

Baseline well inventory and groundwater-quality data from a potential shale gas resource area in parts of Lee and Chatham Counties, North Carolina, October 2011-August 2012

USGS Publications Warehouse

Chapman, Melinda J.; Gurley, Laura N.; Fitzgerald, Sharon A.

2014-01-01

Records were obtained for 305 wells and 1 spring in northwestern Lee and southeastern Chatham counties, North Carolina. Well depths ranged from 26 to 720 feet and yields ranged from 0.25 to 100 gallons per minute. A subset of 56 wells and 1 spring were sampled for baseline groundwaterquality constituents including the following: major ions; dissolved metals; nutrients; dissolved gases (including methane); volatile and semivolatile organic compounds; glycols; isotopes of strontium, radium, methane (if sufficient concentration), and water; and dissolved organic and inorganic carbon. Dissolved methane gas concentrations were low, ranging from less than 0.00007 (lowest reporting level) to 0.48 milligrams per liter. Concentrations of nitrate, boron, iron, manganese, sulfate, chloride, total dissolved solids, and measurements of pH exceeded federal and state drinking water standards in a few samples. Iron and manganese concentrations exceeded the secondary (aesthetic) drinking water standard in approximately 35 to 37 percent of the samples.

The Subset Sum game.

PubMed

Darmann, Andreas; Nicosia, Gaia; Pferschy, Ulrich; Schauer, Joachim

2014-03-16

In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an [Formula: see text]-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem.

The Subset Sum game☆

PubMed Central

Darmann, Andreas; Nicosia, Gaia; Pferschy, Ulrich; Schauer, Joachim

2014-01-01

In this work we address a game theoretic variant of the Subset Sum problem, in which two decision makers (agents/players) compete for the usage of a common resource represented by a knapsack capacity. Each agent owns a set of integer weighted items and wants to maximize the total weight of its own items included in the knapsack. The solution is built as follows: Each agent, in turn, selects one of its items (not previously selected) and includes it in the knapsack if there is enough capacity. The process ends when the remaining capacity is too small for including any item left. We look at the problem from a single agent point of view and show that finding an optimal sequence of items to select is an NP-hard problem. Therefore we propose two natural heuristic strategies and analyze their worst-case performance when (1) the opponent is able to play optimally and (2) the opponent adopts a greedy strategy. From a centralized perspective we observe that some known results on the approximation of the classical Subset Sum can be effectively adapted to the multi-agent version of the problem. PMID:25844012

The Monitoring and Spatial-Temporal Evolution Characteristic Analysis for Land Subsidence in Beijing

NASA Astrophysics Data System (ADS)

Zhou, Q.; Zhao, W.; Yu, J.

2018-05-01

At present the land subsidence has been the main geological disaster in the plain area of China, and became one of the most serious disaster that restrict the social and economic sustainable development, it also is an important content in the project of national geographic conditions monitoring. With the development of economy and society, Beijing as the capital of China has experienced significant population growth in the last few decades which led to over-exploitation of the ground water to meet the water demand of more than 20 million inhabitants, especially in the urban region with high population density. However, the rainfall and surface runoff can't satisfy the need of aquifer recharge that product the land subsidence. As China's political center and a metropolis, there are a lot of large constructions, underground traffic projects and complicated municipal pipeline network, and Beijing is also an important traffic hub for national railway and highway network, all of them would be threatened by the land subsidence disaster. In this article the author used twenty ENVISAT Synthetic Aperture Radar (SAR) images acquired in 2008 June-2010 August and ten TerraSAR images acquired in 2011 June-2012 September were processed with Small Baseline Subset SAR Interferometry (SBAS-InSAR) techniques, to investigate spatial and temporal patterns of land subsidence in the urban area of Beijing.

N-acetyl cysteine add-on treatment for bipolar II disorder: a subgroup analysis of a randomized placebo-controlled trial.

PubMed

Magalhães, P V; Dean, O M; Bush, A I; Copolov, D L; Malhi, G S; Kohlmann, K; Jeavons, S; Schapkaitz, I; Anderson-Hunt, M; Berk, M

2011-03-01

The evidence base for the pharmacological treatment of bipolar II disorder is limited. In bipolar disorder, there is evidence for glutathione depletion and increased oxidative stress, as well as dysregulation of glutamate; N-acetyl cysteine (NAC) has effects on both of these systems. Add-on NAC has been shown to have a significant benefit on depressive symptoms in a randomized placebo-controlled trial. In this report, we explore the effects of this compound in a subset of patients with bipolar II disorder from that trial. Individuals were randomized to NAC or placebo in addition to treatment as usual, in a double-blind fashion. Mood and functional outcomes were assessed up to 24 weeks of treatment. Fourteen individuals were available for this report, seven in each group. Six people achieved full remission of both depressive and manic symptoms in the NAC group; this was true for only two people in the placebo group (χ(2)=4.67, p=0.031). Subgroup analyses in a small subsample of patients. Not all participants had elevated depression scores at baseline. Notwithstanding all the limitations that subgroup analysis of trials carry, this data could serve as a hypothesis-generating stimulus for further clinical trials of pharmacologic treatment for bipolar II depression. Copyright © 2010 Elsevier B.V. All rights reserved.

Ground deformation monitoring using RADARSAT-2 DInSAR-MSBAS at the Aquistore CO2 storage site in Saskatchewan (Canada)

NASA Astrophysics Data System (ADS)

Czarnogorska, M.; Samsonov, S.; White, D.

2014-11-01

The research objectives of the Aquistore CO2 storage project are to design, adapt, and test non-seismic monitoring methods for measurement, and verification of CO2 storage, and to integrate data to determine subsurface fluid distributions, pressure changes and associated surface deformation. Aquistore site is located near Estevan in Southern Saskatchewan on the South flank of the Souris River and west of the Boundary Dam Power Station and the historical part of Estevan coal mine in southeastern Saskatchewan, Canada. Several monitoring techniques were employed in the study area including advanced satellite Differential Interferometric Synthetic Aperture Radar (DInSAR) technique, GPS, tiltmeters and piezometers. The targeted CO2 injection zones are within the Winnipeg and Deadwood formations located at > 3000 m depth. An array of monitoring techniques was employed in the study area including advanced satellite Differential Interferometric Synthetic Aperture Radar (DInSAR) with established corner reflectors, GPS, tiltmeters and piezometers stations. We used airborne LIDAR data for topographic phase estimation, and DInSAR product geocoding. Ground deformation maps have been calculated using Multidimensional Small Baseline Subset (MSBAS) methodology from 134 RADARSAT-2 images, from five different beams, acquired during 20120612-20140706. We computed and interpreted nine time series for selected places. MSBAS results indicate slow ground deformation up to 1 cm/year not related to CO2 injection but caused by various natural and anthropogenic causes.

Completing the gaps in Kilauea's Father's Day InSAR displacement signature with ScanSAR

NASA Astrophysics Data System (ADS)

Bertran Ortiz, A.; Pepe, A.; Lanari, R.; Lundgren, P.; Rosen, P. A.

2009-12-01

Currently there are gaps in the known displacement signature obtained with InSAR at Kilauea between 2002 and 2009. InSAR data can be richer than GPS because of denser spatial cover. However, to better model rapidly varying and non-steady geophysical events InSAR is limited because of its less dense time observations of the area under study. The ScanSAR mode currently available in several satellites mitigates this effect because the satellite may illuminate a given area more than once within an orbit cycle. The Kilauea displacement graph below from Instituto per Il Rilevamento Electromagnetico dell'Ambiente (IREA) is a cut in space of the displacement signature obtained from a time series of several stripmap-to-stripmap interferograms. It shows that critical information is missing, especially between 2006 and 2007. The displacement is expected to be non-linear judging from the 2007-2008 displacement signature, thus simple interpolation would not suffice. The gap can be filled by incorporating Envisat stripmap-to-ScanSAR interferograms available during that time period. We propose leveraging JPL's new ROI-PAC ScanSAR module to create stripmap-to-ScanSAR interferograms. The new interferograms will be added to the stripmap ones in order to extend the existing stripmap time series generated by using the Small BAseline Subset (SBAS) technique. At AGU we will present denser graphs that better capture Kilauea's displacement between 2003 and 2009.

Analysis of deformation patterns through advanced DINSAR techniques in Istanbul megacity

NASA Astrophysics Data System (ADS)

Balik Sanli, F.; Calò, F.; Abdikan, S.; Pepe, A.; Gorum, T.

2014-09-01

As result of the Turkey's economic growth and heavy migration processes from rural areas, Istanbul has experienced a high urbanization rate, with severe impacts on the environment in terms of natural resources pressure, land-cover changes and uncontrolled sprawl. As a consequence, the city became extremely vulnerable to natural and man-made hazards, inducing ground deformation phenomena that threaten buildings and infrastructures and often cause significant socio-economic losses. Therefore, the detection and monitoring of such deformation patterns is of primary importance for hazard and risk assessment as well as for the design and implementation of effective mitigation strategies. Aim of this work is to analyze the spatial distribution and temporal evolution of deformations affecting the Istanbul metropolitan area, by exploiting advanced Differential SAR Interferometry (DInSAR) techniques. In particular, we apply the Small BAseline Subset (SBAS) approach to a dataset of 43 TerraSAR-X images acquired, between November 2010 and June 2012, along descending orbits with an 11-day revisit time and a 3 m × 3 m spatial resolution. The SBAS processing allowed us to remotely detect and monitor subsidence patterns over all the urban area as well as to provide detailed information at the scale of the single building. Such SBAS measurements, effectively integrated with ground-based monitoring data and thematic maps, allows to explore the relationship between the detected deformation phenomena and urbanization, contributing to improve the urban planning and management.

Land Subsidence Monitoring by InSAR Time Series Technique Derived From ALOS-2 PALSAR-2 over Surabaya City, Indonesia

NASA Astrophysics Data System (ADS)

Aditiya, A.; Takeuchi, W.; Aoki, Y.

2017-12-01

Surabaya is the second largest city in Indonesia and the capital of East Java Province with rapid population and industrialization. The impact of urbanization in the big city can suffer potential disasters either nature or anthropogenic such as land subsidence and flood. The pattern of land subsidence need to be mapped for the purposes of planning and structuring the city as well as taking appropriate policy in anticipating and mitigating the impact. This research has used interferometric Synthetic Aperture Radar (InSAR) Small Baseline Subset (SBAS) technique and applied time series analysis to investigate land subsidence occured. The technique includes the process of focusing the SAR data, incorporating the precise orbit, generating interferogram and phase unwrapping using SNAPHU algorithms. The results showed land subsidence has been detected during 2014-2017 over Surabaya city area using ALOS-2/PALSAR-2 images data. These results reveal the subsidence has observed in several area in Surabaya in particular northern part reach up to ∼2 cm/year. The fastest subsidence occurs in highly populated areas suffer vulnerable to flooding and sea level rise impact. In urban areas we found a correlation between land subsidence with residential or industrial land use. It concludes that land subsidence is mainly caused by ground water consumption for industrial and residential use respectively.

Extreme temperature trends in major cropping systems and their relation to agricultural land use change

NASA Astrophysics Data System (ADS)

Mueller, N. D.; Butler, E. E.; McKinnon, K. A.; Rhines, A. N.; Tingley, M.; Siebert, S.; Holbrook, N. M.; Huybers, P. J.

2015-12-01

High temperature extremes during the growing season can reduce agricultural production. At the same time, agricultural practices can modify temperatures by altering the surface energy budget. Here we investigate growing season climate trends in major cropping systems and their relationship with agricultural land use change. In the US Midwest, 100-year trends exhibit a transition towards more favorable conditions, with cooler summer temperature extremes and increased precipitation. Statistically significant correspondence is found between the cooling pattern and trends in cropland intensification, as well as with trends towards greater irrigated land over a small subset of the domain. Land conversion to cropland, often considered an important influence on historical temperatures, is not significantly associated with cooling. We suggest that cooling is primarily associated with agricultural intensification increasing the potential for evapotranspiration, consistent with our finding that cooling trends are greatest for the highest temperature percentiles, and that increased evapotranspiration generally leads to greater precipitation. Temperatures over rainfed croplands show no cooling trend during drought conditions, consistent with evapotranspiration requiring adequate soil moisture, and implying that modern drought events feature greater warming as baseline cooler temperatures revert to historically high extremes. Preliminary results indicate these relationships between temperature extremes, irrigation, and intensification are also observed in other major summer cropping systems, including northeast China, Argentina, and the Canadian Prairies.

Strategic larval decision-making in a bivoltine butterfly.

PubMed

Friberg, Magne; Dahlerus, Josefin; Wiklund, Christer

2012-07-01

In temperate areas, insect larvae must decide between entering winter diapause or developing directly and reproducing in the same season. Long daylength and high temperature promote direct development, which is generally associated with a higher growth rate. In this work, we investigated whether the larval pathway decision precedes the adjustment of growth rate (state-independent), or whether the pathway decision is conditional on the individual's growth rate (state-dependent), in the butterfly Pieris napi. This species typically makes the pathway decision in the penultimate instar. We measured growth rate throughout larval development under two daylengths: slightly shorter and slightly longer than the critical daylength. Results indicate that the pathway decision can be both state-independent and state-dependent; under the shorter daylength condition, most larvae entered diapause, and direct development was chosen exclusively by a small subset of larvae showing the highest growth rates already in the early instars; under the longer daylength condition, most larvae developed directly, and the diapause pathway was chosen exclusively by a small subset of slow-growing individuals. Among the remainder, the choice of pathway was independent of the early growth rate; larvae entering diapause under the short daylength grew as fast as or faster than the direct developers under the longer daylength in the early instars, whereas the direct developers grew faster than the diapausers only in the ultimate instar. Hence, the pathway decision was state-dependent in a subset with a very high or very low growth rate, whereas the decision was state-independent in the majority of the larvae, which made the growth rate adjustment downstream from the pathway decision.

Interseismic Deformation along the Red River Fault from InSAR Measurements

NASA Astrophysics Data System (ADS)

Chen, J.; Li, Z.; Clarke, P. J.

2017-12-01

The Red River Fault (RRF) zone is a profound geological discontinuity separating South China from Indochina. Right lateral movements along this >900 km fault are considered to accommodate the extrusion of SE China. Crustal deformation monitoring at high resolution is the key to understand the present-day mode of deformation in this zone and its interaction with the adjacent regions. This is the first study to measure the interseismic deformation of the entire fault with ALOS-1/2 and Sentinel-1 observations. Nine ascending tracks of ALOS-1 data between 2007 and 2011 are collected from the Alaska Satellite Facility (ASF), four descending tracks of Sentinel-1 data are acquired every 24 days since October 2014, and ALOS-2 data are being systematically acquired since 2014. The long wavelength (L-band) of ALOS-1/2 and short temporal baseline of Sentinel-1 ensure good coherence to overcome the limitations of heavy vegetation and variable climate in the region. Stacks of interferograms are generated by our automatic processing chain based on the InSAR Scientific Computing Environment (ISCE) software, ionospheric errors are estimated and corrected using the split-spectrum method (Fattahi et al., IEEE Trans. Geosci. Remote Sens., 2017) and the tropospheric delays are calibrated using the Generic Atmospheric Correction Online Service for InSAR (GACOS: http://ceg-research.ncl.ac.uk/v2/gacos) with high-resolution ECMWF products (Yu et al., J. Geophys. Res., 2017). Time series analysis is performed to determine the interseismic deformation rate of the RRF using the in-house InSAR time series with atmospheric estimation model (InSAR TS + AEM) package based on the Small Baseline Subset (SBAS) algorithm. Our results reveal the decrease of slip rate from north to south. We map the interseismic strain rate field to characterize the deformation patterns and seismic hazard throughout the RRF zone.

The effects of mindfulness-based stress reduction on objective and subjective sleep parameters in women with breast cancer: a randomized controlled trial.

PubMed

Lengacher, Cecile A; Reich, Richard R; Paterson, Carly L; Jim, Heather S; Ramesar, Sophia; Alinat, Carissa B; Budhrani, Pinky H; Farias, Jerrica R; Shelton, Melissa M; Moscoso, Manolete S; Park, Jong Y; Kip, Kevin E

2015-04-01

The purpose of this study was to investigate the effects of mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)) on multiple measures of objective and subjective sleep parameters among breast cancer survivors (BCS). Data were collected using a two-armed randomized controlled design among BCS enrolled in either a 6-week MBSR(BC) program or a usual care (UC) group with a 12-week follow-up. The present analysis is a subset of the larger parent trial (ClinicalTrials.gov Identifier: NCT01177124). Seventy-nine BCS participants (mean age 57 years), stages 0-III, were randomly assigned to either the formal (in-class) 6-week MBSR(BC) program or UC. Subjective sleep parameters (SSP) (i.e., sleep diaries and the Pittsburgh Sleep Quality Index (PSQI)) and objective sleep parameters (OSP) (i.e., actigraphy) were measured at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) or UC program. Results showed indications of a positive effect of MBSR(BC) on OSP at 12 weeks on sleep efficiency (78.2% MBSR(BC) group versus 74.6% UC group, p = 0.04), percent of sleep time (81.0% MBSR(BC) group versus 77.4% UC group, p = 0.02), and less number waking bouts (93.5 in MBSR(BC) group versus 118.6 in the UC group, p < 0.01). Small nonsignificant improvements were found in SSP in the MBSR(BC) group from baseline to 6 weeks (PSQI total score, p = 0.09). No significant relationship was observed between minutes of MBSR(BC) practice and SSP or OSP. These data suggest that MBSR(BC) may be an efficacious treatment to improve objective and subjective sleep parameters in BCS. Copyright © 2014 John Wiley & Sons, Ltd.

Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease.

PubMed

Coric, Vladimir; van Dyck, Christopher H; Salloway, Stephen; Andreasen, Niels; Brody, Mark; Richter, Ralph W; Soininen, Hilkka; Thein, Stephen; Shiovitz, Thomas; Pilcher, Gary; Colby, Susan; Rollin, Linda; Dockens, Randy; Pachai, Chahin; Portelius, Erik; Andreasson, Ulf; Blennow, Kaj; Soares, Holly; Albright, Charles; Feldman, Howard H; Berman, Robert M

2012-11-01

To assess the safety, tolerability, and pharmacokinetic and pharmacodynamic effects of the -secretase inhibitor avagacestat in patients with mild to moderate Alzheimer disease (AD). Randomized, double-blind, placebo-controlled,24-week phase 2 study. Global, multicenter trial. A total of 209 outpatients with mild to moderate AD were randomized into the double-blind treatment phase. The median age of the patients was 75 years,58.9% were APOE ε4 carriers, and baseline measures of disease severity were similar among groups. Avagacestat, 25, 50, 100, or 125 mg daily,or placebo administered orally daily. Safety and tolerability of avagacestat. Discontinuation rates for the 25-mg and 50-mg doses of avagacestat were comparable with placebo but were higher in the 100-mg and 125-mg dose groups.Trends for worsening cognition, as measured by change from baseline Alzheimer Disease Assessment Scale cognitive subscale score, were observed in the 100-mg and125-mg dose groups. Treatment-emergent serious adverse events were similar across placebo and treatment groups. The most common reason for discontinuation was adverse events, predominantly gastrointestinal anddermatologic. Other adverse events occurring more frequentlyin patients undergoing treatment included reversibleglycosuria (without associated serum glucose changes), nonmelanoma skin cancer, and asymptomaticmagnetic resonance imaging findings. Exploratory cerebrospinal fluid amyloid isoforms and tau biomarker analysis demonstrated dose-dependent but not statistically significant reductions in a small subset of patients. Avagacestat dosed at 25 and 50 mg daily was relatively well tolerated and had low discontinuation rates. The 100-mg and 125-mg dose arms were poorly tolerated with trends for cognitive worsening. Exploratory cerebrospinal fluid biomarker substudies provide preliminary support for -secretase target engagement,but additional studies are warranted to better characterize pharmacodynamic effects at the 25- and 50-mg doses.This study establishes an acceptable safety and tolerability dose range for future avagacestat studies in AD. clinicaltrials.gov Identifier: NCT00810147

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

PubMed

Bancroft, Elizabeth K; Saya, Sibel; Page, Elizabeth C; Myhill, Kathryn; Thomas, Sarah; Pope, Jennifer; Chamberlain, Anthony; Hart, Rachel; Glover, Wayne; Cook, Jackie; Rosario, Derek J; Helfand, Brian T; Hutten Selkirk, Christina; Davidson, Rosemarie; Longmuir, Mark; Eccles, Diana M; Gadea, Neus; Brewer, Carole; Barwell, Julian; Salinas, Monica; Greenhalgh, Lynn; Tischkowitz, Marc; Henderson, Alex; Evans, David Gareth; Buys, Saundra S; Eeles, Rosalind A; Aaronson, Neil K

2018-05-26

To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening. © 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Optical imaging of the ventral medullary surface of developing kittens during ventilatory challenges.

PubMed

Gozal, D; Dong, X W; Rector, D M; Harper, R K; Harper, R M

1996-01-01

We used large-array optical recording procedures to examine maturation of regional neural activity within the ventral medullary surface (VMS) of anaesthetized kittens during graded hypercapnic and hypoxic challenges. The VMS was exposed through a ventral surgical approach in 10, 20, 30, and 45-day-old kittens and in adult cats under sodium pentobarbital anaesthesia. Arterial pressure, costal diaphragmatic EMG, and ECG were continuously monitored. A coherent image conduit with 12 mu fibre resolution was attached to a charge-coupled-device camera and positioned over the VMS. Reflected 660 nm light was digitized continuously at 2-s intervals during a baseline period, hyperoxic hypercapnia, (3, 5, and 10% CO2 in O2), and poikylocapnic hypoxia (6%, 9%, and 12% O2 in N2), and recovery. Sixty to seventy-five images within each epoch were averaged, and subtracted from baseline. Regional differences within the image were determined by ANOVA procedures (alpha = 0.05). During hypercapnia, an overall decrease in neural activity (increase in scattered light) occurred, which was marginally age-dependent. By 30 days, regional bidirectional reflectance changes in response to CO2 emerged in a small proportion of animals, and were similar to adult responses. Hypoxia induced a dose- and age-dependent decrease in overall scattered light. Transient "on" and "off" responses were common under both ventilatory stimuli. In 20-30-day kittens, marked rebound responses in reflectance accompanied cessation of hypoxic stimuli; such patterns were absent at other ages. At 30 days, a caudal-rostral bidirectionality in response to mild hypoxia (12% O2) began to emerge in a subset of animals. We conclude that dose-dependent response to ventilatory stimuli occur in the VMS at all post-natal ages of the kitten; however, in hypoxia, the magnitude of the overall reflectance changes is diminished relative to adult patterns. Rebound responses to hypoxia are present at particular ages, and older kittens begin to show a topographical organization of neural activation.

Choosing non-redundant representative subsets of protein sequence data sets using submodular optimization.

PubMed

Libbrecht, Maxwell W; Bilmes, Jeffrey A; Noble, William Stafford

2018-04-01

Selecting a non-redundant representative subset of sequences is a common step in many bioinformatics workflows, such as the creation of non-redundant training sets for sequence and structural models or selection of "operational taxonomic units" from metagenomics data. Previous methods for this task, such as CD-HIT, PISCES, and UCLUST, apply a heuristic threshold-based algorithm that has no theoretical guarantees. We propose a new approach based on submodular optimization. Submodular optimization, a discrete analogue to continuous convex optimization, has been used with great success for other representative set selection problems. We demonstrate that the submodular optimization approach results in representative protein sequence subsets with greater structural diversity than sets chosen by existing methods, using as a gold standard the SCOPe library of protein domain structures. In this setting, submodular optimization consistently yields protein sequence subsets that include more SCOPe domain families than sets of the same size selected by competing approaches. We also show how the optimization framework allows us to design a mixture objective function that performs well for both large and small representative sets. The framework we describe is the best possible in polynomial time (under some assumptions), and it is flexible and intuitive because it applies a suite of generic methods to optimize one of a variety of objective functions. © 2018 Wiley Periodicals, Inc.

Structural Studies on Intact Clostridium botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

DTIC Science & Technology

2009-02-01

compounds via virtual screening. These compounds include small molecules – transition state analogues and benzimidazoles . Since there is a commonality in...Crystal structure of BoNT/E has been determined helping us to understand the faster action of BoNT/E compared to BoNT/A. • A subset of benzimidazole

Cantor Groups

ERIC Educational Resources Information Center

Mathes, Ben; Dow, Chris; Livshits, Leo

2011-01-01

The Cantor subset of the unit interval [0, 1) is "large" in cardinality and also "large" algebraically, that is, the smallest subgroup of [0, 1) generated by the Cantor set (using addition mod 1 as the group operation) is the whole of [0, 1). In this paper, we show how to construct Cantor-like sets which are "large" in cardinality but "small"…

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

Bannon, Michael J.

The dopamine transporter (DAT) is a plasma membrane transport protein expressed exclusively within a small subset of CNS neurons. It plays a crucial role in controlling dopamine-mediated neurotransmission and a number of associated behaviors. This review focuses on recent data elucidating the role of the dopamine transporter in neurotoxicity and a number of CNS disorders, including Parkinson disease, drug abuse, and attention deficit hyperactivity disorder (ADHD)

Breaching the Last Frontier: Dignity and the Toileting Issue for Persons with Multiple and Severe Disabilities

ERIC Educational Resources Information Center

Pivato, Emma

2009-01-01

Although much has been written about the normalization and social inclusion of persons with developmental disabilities over the past 50 years, a small subset of this population has remained largely overlooked--individuals who are quadriplegic, non-verbal and who also have additional disabilities, including cognitive impairment. The present project…

Selecting climate change scenarios using impact-relevant sensitivities

Treesearch

Julie A. Vano; John B. Kim; David E. Rupp; Philip W. Mote

2015-01-01

Climate impact studies often require the selection of a small number of climate scenarios. Ideally, a subset would have simulations that both (1) appropriately represent the range of possible futures for the variable/s most important to the impact under investigation and (2) come from global climate models (GCMs) that provide plausible results for future climate in the...

Identifying Tumor Progenitor Cells | Center for Cancer Research

Cancer.gov

All cells within a tumor are not identical. In fact, only a small subset appears to be capable of actually generating the tumor. These tumor-initiating cells tend to resemble normal stem cells, which have the unique ability to give rise to differentiated cells while simultaneously producing additional undifferentiated stem cells. Most chemotherapeutics affect the bulk of a

Analysis of the Phlebiopsis gigantea Genome, Transcriptome and Secretome Provides Insight into Its Pioneer Colonization Strategies of Wood

Treesearch

Chiaki Hori; Takuya Ishida; Kiyohiko Igarashi; Masahiro Samejima; Hitoshi Suzuki; Emma Master; Patricia Ferreira; Francisco J. Ruiz-Duenas; Benjamin Held; Paulo Canessa; Luis F. Larrondo; Monika Schmoll; Irina S. Druzhinina; Christian P. Kubicek; Jill A. Gaskell; Phil Kersten; Franz St. John; Jeremy Glasner; Grzegorz Sabat; Sandra Splinter Bondurant; Khajamohiddin Syed; Jagjit Yadav; Anthony C. Mgbeahuruike; Andriy Kovalchuk; Fred O. Asiegbu; Gerald Lackner; Dirk Hoffmeister; Jorge Recoret; Ana Gutierrez; Hui Sun; Erika Lindquist; Kerrie Barry; Robert Riley; Igor V. Grigoriev; Bernard Henrissat; Ursula Kues; Randy M. Berka; Angel T. Martinez; Sarah F. Covert; Robert A. Blanchette; Daniel Cullen

2014-01-01

Collectively classified as white-rot fungi, certain basidiomycetes efficiently degrade the major structural polymers of wood cell walls. A small subset of these Agaricomycetes, exemplified by Phlebiopsis gigantea, is capable of colonizing freshly exposed conifer sapwood despite its high content of extractives, which retards the establishment of other...

Phase 1 of the First Solar Small Power System Experiment (experimental System No. 1). Volume 2: Appendix A - D

NASA Technical Reports Server (NTRS)

Clark, T. B. (Editor)

1979-01-01

Recommended conceptual designs for the baseline solar concentrator and electrical subsystems are defined, and trade offs that were evaluated to arrive at the baseline systems are presented. In addition, the developmental history of the Stirling engine is reviewed, the U4 configuration is described, and a Stirling engine heat pipe system is evaluated for solar application where sodium vapor is used as the heat source. An organic Rankine cycle engine is also evaluated for solar small power system application.

Use of internal control T-cell populations in the flow cytometric evaluation for T-cell neoplasms.

PubMed

Hunt, Alicia M; Shallenberger, Wendy; Ten Eyck, Stephen P; Craig, Fiona E

2016-09-01

Flow cytometry is an important tool for identification of neoplastic T-cells, but immunophenotypic abnormalities are often subtle and must be distinguished from nonneoplastic subsets. Use of internal control (IC) T-cells in the evaluation for T-cell neoplasms was explored, both as a quality measure and as a reference for evaluating abnormal antigen expression. All peripheral blood specimens (3-month period), or those containing abnormal T-cells (29-month period), stained with CD45 V500, CD2 V450, CD3 PE-Cy7, CD7 PE, CD4 Per-CP-Cy5.5, CD8 APC-H7, CD56 APC, CD16&57 FITC, were evaluated. IC T-cells were identified (DIVA, BD Biosciences) and median fluorescence intensity (MFI) recorded. Selected files were merged and reference templates generated (Infinicyt, Cytognos). IC T-cells were present in all specimens, including those with abnormal T-cells, but subsets were less well-represented. IC T-cell CD3 MFI differed between instruments (p = 0.0007) and subsets (p < 0.001), but not specimen categories, and served as a longitudinal process control. Merged files highlighted small unusual IC-T subsets: CD2+(dim) (0.25% total), CD2- (0.03% total). An IC reference template highlighted neoplastic T-cells, but was limited by staining variability (IC CD3 MFI reference samples different from test (p = 0.003)). IC T-cells present in the majority of specimens can serve as positive and longitudinal process controls. Use of IC T-cells as an internal reference is limited by variable representation of subsets. Analysis of merged IC T-cells from previously analyzed patient samples can alert the interpreter to less-well-recognized non-neoplastic subsets. However, application of a merged file IC reference template was limited by staining variability. © 2016 Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Assessment of local GNSS baselines at co-location sites

NASA Astrophysics Data System (ADS)

Herrera Pinzón, Iván; Rothacher, Markus

2018-01-01

As one of the major contributors to the realisation of the International Terrestrial Reference System (ITRS), the Global Navigation Satellite Systems (GNSS) are prone to suffer from irregularities and discontinuities in time series. While often associated with hardware/software changes and the influence of the local environment, these discrepancies constitute a major threat for ITRS realisations. Co-located GNSS at fundamental sites, with two or more available instruments, provide the opportunity to mitigate their influence while improving the accuracy of estimated positions by examining data breaks, local biases, deformations, time-dependent variations and the comparison of GNSS baselines with existing local tie measurements. With the use of co-located GNSS data from a subset sites of the International GNSS Service network, this paper discusses a global multi-year analysis with the aim of delivering homogeneous time series of coordinates to analyse system-specific error sources in the local baselines. Results based on the comparison of different GNSS-based solutions with the local survey ties show discrepancies of up to 10 mm despite GNSS coordinate repeatabilities at the sub-mm level. The discrepancies are especially large for the solutions using the ionosphere-free linear combination and estimating tropospheric zenith delays, thus corresponding to the processing strategy used for global solutions. Snow on the antennas causes further problems and seasonal variations of the station coordinates. These demonstrate the need for a permanent high-quality monitoring of the effects present in the short GNSS baselines at fundamental sites.

Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps.

PubMed

Maki, Kevin C; Palacios, Orsolya M; Bell, Marjorie; Toth, Peter P

Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results. The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk. A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses. Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%-29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I 2  ≤ 15.5%, P > .05) for the primary and subset analyses. LC-OM3 supplementation is associated with a modest reduction in cardiac death. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Nucleotide supplementation and the growth of term small for gestational age infants.

PubMed Central

Cosgrove, M.; Davies, D. P.; Jenkins, H. R.

1996-01-01

A double blind randomised controlled trial in small for gestational age (SGA) infants, whose intestinal mucosa was shown to be functionally impaired as a result of intrauterine undernutrition, was carried out to investigate the hypothesis that nucleotide supplementation of a milk formula could improve catchup growth. Anthropometric data were collected on 74 infants, 39 randomly allocated to the nucleotide supplemented group (group N) and 35 to a standard formula group (group S). From study entry to 2 months of age, infants in group N had significantly higher mean rates of weight gain (106.3 compared with 94.7 g/kg baseline weight/week) and length gain (21.8 v 19.7 mm/m baseline length/week). Over the whole six months for which the trial formula was provided group N had significantly higher mean rates of gain of weight (80.1 compared with 71.8 g/kg baseline weight/week), length (16.2 compared with 15.0 mm/m baseline length/week), and head circumference (11.8 compared with 10.8 mm/m baseline head circumference/week). Catchup growth in SGA infants is therefore improved by nucleotide supplementation of infant formula. PMID:8777659

Analysis of baseline gene expression levels from ...

EPA Pesticide Factsheets

The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in gene expression. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selectiv

Post-exertion neurocognitive test failure among student-athletes following concussion.

PubMed

McGrath, Neal; Dinn, Wayne M; Collins, Michael W; Lovell, Mark R; Elbin, R J; Kontos, Anthony P

2013-01-01

The purpose of the present study was to examine post-exertion (PE) neurocognitive performance among student-athletes following concussion who were asymptomatic and returned to baseline normal neurocognitive test levels at rest. This study examined the neurocognitive performance of a sub-set of student-athletes who 'failed' to perform at baseline levels of neurocognitive function, i.e. exhibited downward reliable change index (RCI) alterations following a moderate exertional protocol during recovery from concussion. A retrospective records review was carried out of Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) and neuropsychological consultation data among athletes with sports-related concussion from a network of 22 schools and one junior hockey programme. Fifty-four student-athletes met inclusion criteria and participated in the study. A total of 27.7% of concussed student-athletes who were symptom-free and returned to baseline on ImPACT at rest (i.e. no longer demonstrated performance deficits on neurocognitive tests) exhibited cognitive decline following moderate physical exertion. The PE cognitive changes were not simply general performance effects, but significant changes in memory ability in the presence of intact processing speed functions. The PE-Pass and PE-Fail groups did not, however, differ on post-concussive symptoms or concussion history. Clinicians' return-to-play evaluation protocols should include post-exertional computerized neurocognitive testing.

Feasibility of conducting a randomised controlled trial of a cookstove intervention in rural Malawi

PubMed Central

Kachidiku, J.; Banda, H.; Kapanga, M.; Doyle, J. V.; Banda, E.; Fox, C.; Gordon, S. B.; Mortimer, K.

2014-01-01

BACKGROUND: Exposure to household air pollution (HAP) causes 4 million deaths annually, and strategies to reduce HAP exposure are urgently required. OBJECTIVE: To evaluate the acceptability and feasibility of conducting a trial of a cookstove intervention in rural Malawi. DESIGN: Non-smoking women were randomised to continuing to use an open fire (control) or to using a wood-burning clay cookstove (intervention). Symptom burden, oxygen saturation and exhaled carbon monoxide (eCO) were assessed at baseline and 7-day follow-up. A subset of women underwent HAP exposure monitoring. RESULTS: Of 51 women recruited, 50 (98%) completed the main study. The methodology was acceptable to participants. Headache, back pain and cough were the most commonly reported symptoms at baseline and follow-up. Median eCO was within normal limits, but with a difference of 0.5 parts per million (ppm) in median change of eCO from baseline to follow-up seen between the two groups (P ∙ 0.035). The peak ambient CO concentration detected was 150 ppm. CONCLUSION: This study suggests that a large cookstove intervention trial in Malawi would be feasible with careful community sensitisation. Monitoring exposure to HAP is challenging, and further studies evaluating potential biomarkers of exposure, including eCO, should be undertaken. PMID:24429320

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

PubMed

Robertson, A Gordon; Kim, Jaegil; Al-Ahmadie, Hikmat; Bellmunt, Joaquim; Guo, Guangwu; Cherniack, Andrew D; Hinoue, Toshinori; Laird, Peter W; Hoadley, Katherine A; Akbani, Rehan; Castro, Mauro A A; Gibb, Ewan A; Kanchi, Rupa S; Gordenin, Dmitry A; Shukla, Sachet A; Sanchez-Vega, Francisco; Hansel, Donna E; Czerniak, Bogdan A; Reuter, Victor E; Su, Xiaoping; de Sa Carvalho, Benilton; Chagas, Vinicius S; Mungall, Karen L; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Lu, Yiling; Klimczak, Leszek J; Zhang, Jiexin; Choo, Caleb; Ojesina, Akinyemi I; Bullman, Susan; Leraas, Kristen M; Lichtenberg, Tara M; Wu, Catherine J; Schultz, Nicholaus; Getz, Gad; Meyerson, Matthew; Mills, Gordon B; McConkey, David J; Weinstein, John N; Kwiatkowski, David J; Lerner, Seth P

2017-10-19

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Compact cancer biomarkers discovery using a swarm intelligence feature selection algorithm.

PubMed

Martinez, Emmanuel; Alvarez, Mario Moises; Trevino, Victor

2010-08-01

Biomarker discovery is a typical application from functional genomics. Due to the large number of genes studied simultaneously in microarray data, feature selection is a key step. Swarm intelligence has emerged as a solution for the feature selection problem. However, swarm intelligence settings for feature selection fail to select small features subsets. We have proposed a swarm intelligence feature selection algorithm based on the initialization and update of only a subset of particles in the swarm. In this study, we tested our algorithm in 11 microarray datasets for brain, leukemia, lung, prostate, and others. We show that the proposed swarm intelligence algorithm successfully increase the classification accuracy and decrease the number of selected features compared to other swarm intelligence methods. Copyright © 2010 Elsevier Ltd. All rights reserved.

Method and system of filtering and recommending documents

DOEpatents

Patton, Robert M.; Potok, Thomas E.

2016-02-09

Disclosed is a method and system for discovering documents using a computer and providing a small set of the most relevant documents to the attention of a human observer. Using the method, the computer obtains a seed document from the user and generates a seed document vector using term frequency-inverse corpus frequency weighting. A keyword index for a plurality of source documents can be compared with the weighted terms of the seed document vector. The comparison is then filtered to reduce the number of documents, which define an initial subset of the source documents. Initial subset vectors are generated and compared to the seed document vector to obtain a similarity value for each comparison. Based on the similarity value, the method then recommends one or more of the source documents.

Dense mesh sampling for video-based facial animation

NASA Astrophysics Data System (ADS)

Peszor, Damian; Wojciechowska, Marzena

2016-06-01

The paper describes an approach for selection of feature points on three-dimensional, triangle mesh obtained using various techniques from several video footages. This approach has a dual purpose. First, it allows to minimize the data stored for the purpose of facial animation, so that instead of storing position of each vertex in each frame, one could store only a small subset of vertices for each frame and calculate positions of others based on the subset. Second purpose is to select feature points that could be used for anthropometry-based retargeting of recorded mimicry to another model, with sampling density beyond that which can be achieved using marker-based performance capture techniques. Developed approach was successfully tested on artificial models, models constructed using structured light scanner, and models constructed from video footages using stereophotogrammetry.

Gingival transcriptome patterns during induction and resolution of experimental gingivitis in humans.

PubMed

Offenbacher, Steven; Barros, Silvana P; Paquette, David W; Winston, J Leslie; Biesbrock, Aaron R; Thomason, Ryan G; Gibb, Roger D; Fulmer, Andy W; Tiesman, Jay P; Juhlin, Kenton D; Wang, Shuo L; Reichling, Tim D; Chen, Ker-Sang; Ho, Begonia

2009-12-01

To our knowledge, changes in the patterns of whole-transcriptome gene expression that occur during the induction and resolution of experimental gingivitis in humans were not previously explored using bioinformatic tools. Gingival biopsy samples collected from 14 subjects during a 28-day stent-induced experimental gingivitis model, followed by treatment, and resolution at days 28 through 35 were analyzed using gene-expression arrays. Biopsy samples were collected at different sites within each subject at baseline (day 0), at the peak of gingivitis (day 28), and at resolution (day 35) and processed using whole-transcriptome gene-expression arrays. Gene-expression data were analyzed to identify biologic themes and pathways associated with changes in gene-expression profiles that occur during the induction and resolution of experimental gingivitis using bioinformatic tools. During disease induction and resolution, the dominant expression pathway was the immune response, with 131 immune response genes significantly up- or downregulated during induction, during resolution, or during both at P <0.05. During induction, there was significant transient increase in the expression of inflammatory and oxidative stress mediators, including interleukin (IL)-1 alpha (IL1A), IL-1 beta (IL1B), IL8, RANTES, colony stimulating factor 3 (CSF3), and superoxide dismutase 2 (SOD2), and a decreased expression of IP10, interferon inducible T-cell alpha chemoattractant (ITAC), matrix metalloproteinase 10 (MMP10), and beta 4 defensin (DEFB4). These genes reversed expression patterns upon resolution in parallel with the reversal of gingival inflammation. A relatively small subset (11.9%) of the immune response genes analyzed by array was transiently activated in response to biofilm overgrowth, suggesting a degree of specificity in the transcriptome-expression response. The fact that this same subset demonstrates a reversal in expression patterns during clinical resolution implicates these genes as being critical for maintaining tissue homeostasis at the biofilm-gingival interface. In addition to the immune response pathway as the dominant response theme, new candidate genes and pathways were identified as being selectively modulated in experimental gingivitis, including neural processes, epithelial defenses, angiogenesis, and wound healing.

Multinational Prospective Study of Patient-Reported Outcomes After Prostate Radiation Therapy: Detailed Assessment of Rectal Bleeding

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

Lee, Jae Y.; Daignault-Newton, Stephanie; Heath, Gerard

Purpose: The new short Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) patient-reported health-related quality of life (HRQOL) tool has removed the rectal bleeding question from the previous much longer version, EPIC-26. Herein, we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospective multicenter cohorts. Methods and Materials: In a prospective multicenter test cohort (n=865), EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011. A second prospective multicenter cohort (n=442) was used for independent validation. A repeated-effects model was used to predictmore » the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores. Results: Two years after radiation therapy, 91% of patients were free of bleeding, and only 2.6% reported bothersome bleeding problems. Correlations between EPIC-26 and EPIC-CP bowel scores were very high (r{sup 2}=0.90-0.96) and were statistically improved with the addition of rectal bleeding information (r{sup 2}=0.94-0.98). Considering all patients, only 0.2% of patients in the test cohort and 0.7% in the validation cohort reported bothersome bleeding and had clinically relevant HRQOL changes missed with EPIC-CP. However, of the 2.6% (n=17) of men with bothersome rectal bleeding in the test cohort, EPIC-CP failed to capture 1 patient (6%) as experiencing meaningful declines in bowel HRQOL. Conclusions: Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding, and <1% of patients experience bothersome bleeding and are not captured by EPIC-CP as having meaningful HRQOL declines after radiation therapy. However, in the small subset of patients with bothersome rectal bleeding, the longer EPIC-26 should strongly be considered, given its superior performance in this patient subset.« less

Weight loss is coupled with improvements to affective state in obese participants engaged in behavior change therapy based on incremental, self-selected "small changes".

PubMed

Paxman, Jenny R; Hall, Anna C; Harden, Charlotte J; O'Keeffe, Jean; Simper, Trevor N

2011-05-01

The aim of this study was to investigate the effects of a group behavior change intervention involving self-selected, contextualized, and mediated goal setting on anthropometric, affective, and dietary markers of health. It was hypothesized that the intervention would elicit changes consistent with accepted health recommendations for obese individuals. A rolling program of 12-week "Small Changes" interventions during 24 months recruited 71 participants; each program accommodated 10 to 13 adults (body mass index [BMI] ≥ 30 kg/m²). Fifty-eight participants completed Small Changes. Repeated measures were made at baseline, 6 and 12 weeks. Anthropometric measures included height and weight (to calculate BMI), body composition, waist circumference, and blood pressure. Affective state was monitored using relevant validated questionnaires. Dietary assessment used 3-day household measures food diaries with Schofield equations to monitor underreporting. Relevant blood measures were recorded throughout. Across the measurement period, Small Changes elicited a significant reduction in body weight (baseline, 102.95 ± 15.47 vs 12 weeks 100.09 ± 16.01 kg, P < .0005), coupled with associated significant improvements in BMI, body fat percentage, and waist circumference measures. There were additional significant positive changes in measures of affective state including general well-being (baseline, 58.92 ± 21.22 vs 12 weeks 78.04 ± 14.60, P < .0005) and total mood disturbance (baseline, 31.19 ± 34.03 vs 12 weeks 2.67 ± 24.96, P < .0005). Dietary changes that occurred were largely consistent with evidenced-based recommendations for weight management and included significant reductions in total energy intake and in fat and saturated fat as a proportion of energy. The Small Changes approach can elicit a range of health-orientated benefits for obese participants, and although further work is needed to ascertain the longevity of such effects, the outcomes from Small Changes are likely to help inform health professionals when framing the future of weight management. Long-term follow-up of Small Changes is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

Detection of small subendocardial infarction using speckle tracking echocardiography in a rat model.

PubMed

Bachner-Hinenzon, Noa; Shlomo, Liron; Khamis, Hanan; Ertracht, Offir; Vered, Zvi; Malka, Assaf; Binah, Ofer; Adam, Dan

2016-10-01

It is challenging to detect small nontransmural infarcts visually or automatically. As it is important to detect myocardial infarction (MI) at early stages, we tested the hypothesis that small nontransmural MI can be detected using speckle tracking echocardiography (STE) at the acute stage. Minimal nontransmural infarcts were induced in 18 rats by causing recurrent ischemia-reperfusion of the left anterior descending (LAD) coronary artery, followed by a 30-min ligation and by reperfusion. A week later, the scar size was measured by histological analysis. Each rat underwent three echocardiography measurements: at baseline, 1 day post-MI, and 1 week post-MI. To measure the peak circumferential strain (CS), peak systolic CS, radial strain (RS), and time-to-peak (TTP) of the CS, short-axis view of the apex was analyzed by a STE program. The TTP was normalized by the duration of the heart cycle to create percent change of heart cycle. Histological analysis after 1 week showed scar size of 4±6% at the anterior wall. At 24 h post-MI, the peak CS, peak systolic CS, and RS were reduced compared to baseline at the anterior wall due to the MI, and at the adjacent segments-the anterior septum and lateral wall, due to stunning (P<.05). However, only the anterior wall, the genuine damaged segment, showed prolonged TTP vs baseline (baseline 36%, 24 h 48%, P<.05). The TTP of the CS can distinguish between regions adjacent to MI (stunned or tethered) and MI, even in small nontransmural infarcts. © 2016, Wiley Periodicals, Inc.

Rate of Decay in Proportion of Condom Protected Sex Acts among Adolescents Following Participation in an HIV Risk-Reduction Intervention

PubMed Central

DiClemente, Ralph J.; Brown, Jennifer L.; Sales, Jessica M.; Rose, Eve S.

2013-01-01

Objective HIV risk-reduction interventions have demonstrated efficacy in enhancing the proportion of condom protected sex acts (CPS) among diverse populations. While post-intervention exposure increases in CPS are often observed, there is scant empirical data quantifying decay of intervention efficacy (declines in CPS following cessation of the intervention among participants reporting an initial post-intervention increase in CPS). Thus, the objective of this study was to quantify the rate of decay in intervention efficacy over a 24-month follow-up. Design African-American adolescent females (ages 14–20; N = 349) completed a baseline ACASI, participated in an HIV risk-reduction intervention, and were assessed at 6-month intervals for 24-months post-intervention. Intervention efficacy was conceptualized as an increase in participants’ CPS relative to baseline. Methods Analyses focused on the subset of participants who reported an initial increase in CPS from baseline to the 6-month post-intervention assessment (n = 121) to quantify the rate of decay in intervention efficacy over a 24-month follow-up period. Results CPS increased markedly from baseline to 6-month follow-up assessment. However, from 6- to 12-months, a marked decline in CPS was observed. Further CPS declines, though not statistically significant, were observed from 12- to 18-months and 18- to 24-months. Cumulative reductions in CPS over the entire 24-month follow-up resulted in no statistical difference between baseline and 24-month follow-up; indicative of a non-significant intervention effect at 24-month assessment. Conclusions Innovative post-intervention optimization strategies are needed to minimize CPS decay over protracted time periods by reinforcing, sustaining, and potentially amplifying initial gains in condom use. PMID:23673893

Long-term immunologic and virologic responses on raltegravir-containing regimens among ART-experienced participants in the HIV Outpatient Study

PubMed Central

Buchacz, Kate; Wiegand, Ryan; Armon, Carl; Chmiel, Joan S.; Wood, Kathleen; Brooks, John T.; Palella, Frank J.

2015-01-01

Objectives Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data exist on long-term outcomes in routine HIV care. Methods We studied ART-experienced HIV outpatient study (HOPS) participants seen at 10 US HIV-specialty clinics during 2007–2011. We identified patients who started (baseline date) either continuous ≥30 days of RAL-containing or RAL-sparing ART, and used propensity score (PS) matching methods to account for baseline clinical and demographic differences. We used Kaplan–Meier methods and log-rank tests for the matched subsets to evaluate probability of death, achieving HIV RNA <50 copies/ml, and CD4 cell count (CD4) increase of ≥50 cells mm−3 during follow-up. Results Among 784 RAL-exposed and 1062 RAL-unexposed patients, 472 from each group were matched by PS. At baseline, the 472 RAL-exposed patients (mean nadir CD4, 205 cells mm−3; mean baseline CD4, 460 cells mm−3; HIV RNA <50 copies ml−1 in 61%; mean years on prescribed ART, 7.5) were similar to RAL unexposed. During a mean follow-up of over 3 years, mortality rates and immunologic and virologic trajectories did not differ between the two groups. Among patients with detectable baseline HIV RNA levels, 76% of RAL-exposed and 63% of RAL-unexposed achieved HIV RNA <50 copies ml−1 (P=0.51); 69 and 58%, respectively, achieved a CD4 increase ≥50 cells mm−3 (P=0.70). Discussion In our large cohort of US ART-experienced patients with a wide spectrum of clinical history, similar outcomes were observed when prescribed RAL containing versus other contemporary ART. PMID:26126549

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.

PubMed

Corlier, Fabian; Hafzalla, George; Faskowitz, Joshua; Kuller, Lewis H; Becker, James T; Lopez, Oscar L; Thompson, Paul M; Braskie, Meredith N

2018-05-15

Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline. Copyright © 2018 Elsevier Inc. All rights reserved.

Mechanistic correlates of clinical responses to omalizumab in the setting of oral immunotherapy for milk allergy.

PubMed

Frischmeyer-Guerrerio, Pamela A; Masilamani, Madhan; Gu, Wenjuan; Brittain, Erica; Wood, Robert; Kim, Jennifer; Nadeau, Kari; Jarvinen, Kirsi M; Grishin, Alexander; Lindblad, Robert; Sampson, Hugh A

2017-10-01

In our recent clinical trial, the addition of omalizumab to oral immunotherapy (OIT) for milk allergy improved safety, but no significant clinical benefit was detected. We sought to investigate mechanisms by which omalizumab modulates immunity in the context of OIT and to identify baseline biomarkers that predict subgroups of patients most likely to benefit from omalizumab. Blood was obtained at baseline and multiple time points during a placebo-controlled trial of OIT for milk allergy in which subjects were randomized to receive omalizumab or placebo. Immunologic outcomes included measurement of basophil CD63 expression and histamine release and casein-specific CD4 + regulatory T-cell proliferation. Biomarkers were analyzed in relationship to measurements of safety and efficacy. Milk-induced basophil CD63 expression was transiently reduced in whole blood samples from both omalizumab- and placebo-treated subjects. However, IgE-dependent histamine release increased in washed cell preparations from omalizumab- but not placebo-treated subjects. No increase in regulatory T-cell frequency was evident in either group. Subjects with lower rates of adverse reactions, regardless of arm, experienced better clinical outcomes. Pre-OIT basophil reactivity positively associated with occurrence of symptoms during OIT, whereas the baseline milk IgE/total IgE ratio correlated with the likelihood of achieving sustained unresponsiveness. A combination of baseline basophil and serologic biomarkers defined a subset of patients in which adjunctive therapy with omalizumab was associated with attainment of sustained unresponsiveness and a reduction in adverse reactions. Combining omalizumab therapy with milk OIT led to distinct alterations in basophil reactivity but not T-cell responses. Baseline biomarkers can identify subjects most likely to benefit from adjunctive therapy with omalizumab. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

The relation of digital vascular function to cardiovascular risk factors in African-Americans using digital tonometry: the Jackson Heart Study.

PubMed

McClendon, Eric E; Musani, Solomon K; Samdarshi, Tandaw E; Khaire, Sushant; Stokes, Donny; Hamburg, Naomi M; Sheffy, Koby; Mitchell, Gary F; Taylor, Herman R; Benjamin, Emelia J; Fox, Ervin R

2017-06-01

Digital vascular tone and function, as measured by peripheral arterial tonometry (PAT), are associated with cardiovascular risk and events in non-Hispanic whites. There are limited data on relations between PAT and cardiovascular risk in African-Americans. PAT was performed on a subset of Jackson Heart Study participants using a fingertip tonometry device. Resting digital vascular tone was assessed as baseline pulse amplitude. Hyperemic vascular response to 5 minutes of ischemia was expressed as the PAT ratio (hyperemic/baseline amplitude ratio). Peripheral augmentation index (AI), a measure of relative wave reflection, also was estimated. The association of baseline pulse amplitude (PA), PAT ratio, and AI to risk factors was assessed using stepwise multivariable models. The study sample consisted of 837 participants from the Jackson Heart Study (mean age, 54 ± 11 years; 61% women). In stepwise multivariable regression models, baseline pulse amplitude was related to male sex, body mass index, and diastolic blood pressure (BP), accounting for 16% of the total variability of the baseline pulse amplitude. Age, male sex, systolic BP, diastolic BP, antihypertensive medication, and prevalent cardiovascular disease contributed to 11% of the total variability of the PAT ratio. Risk factors (primarily age, sex, and heart rate) explained 47% of the total variability of the AI. We confirmed in our cohort of African-Americans, a significant relation between digital vascular tone and function measured by PAT and multiple traditional cardiovascular risk factors. Further studies are warranted to investigate the utility of these measurements in predicting clinical outcomes in African-Americans. Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Infantile Accountability: When Big Data Meet Small Children

ERIC Educational Resources Information Center

Wrigley, Terry; Wormwell, Louise

2016-01-01

This article examines a government attempt to impose testing of 4-year-olds as a baseline against which to "hold primary schools accountable" for children's subsequent progress. It examines the various forms of baseline testing in this experiment and analyses the misleading claims made for the "predictive validity" of baseline…

Cognitive Performance as Predictor and Outcome of Adolescent Bariatric Surgery: A Nonrandomized Pilot Study.

PubMed

Mackey, Eleanor R; Jacobs, Marni; Nadler, Evan P; Olson, Alexandra; Pearce, Alaina; Cherry, J Bradley C; Magge, Sheela N; Mietus-Snyer, Michele; Vaidya, Chandan

2018-05-16

Evidence in adults suggests that improvements in cognitive performance may follow weight loss resulting from bariatric surgery, and baseline cognitive performance may be associated with weight loss following surgery. This has not been evaluated in adolescents. Participants were 38 adolescents of age 14-21 years composed of three groups: (1) 12 adolescents with severe obesity who received vertical sleeve gastrectomy during the study (VSG); (2) 14 adolescents with severe obesity who were wait-listed for VSG (WL); and (3) 12 healthy weight controls (HC). Participants completed testing of visual memory, verbal memory, and executive functioning at baseline (T1), which occurred presurgery for the VSG group, and approximately 4 months after baseline (T2). Body mass index (BMI) was assessed at T1, T2, and additionally at 6 months following VSG for the adolescents who received surgery. Although there was evidence of greater improvement for the VSG as compared with WL and HC groups in visual and verbal memory, group differences did not reach significance and effect sizes were small (η2 < 0.01). There was a significant positive association between indices of baseline executive functioning and excess BMI loss at 6 months postsurgery. This small pilot study showed no significant differences by group in cognitive performance post-VSG. There was a significant association of baseline cognitive performance with weight loss outcomes. Given the very preliminary nature of these results in a small sample, future research should examine these relationships in a larger sample and evaluate mechanisms of these associations (e.g., insulin resistance, sleep, physical activity).

Advanced System Design Requirements for Large and Small Fixed-wing Aerial Application Systems for Agriculture

NASA Technical Reports Server (NTRS)

Hinely, J. T., Jr.; Boyles, R. Q., Jr.

1979-01-01

Several candidate aircraft configurations were defined over the range of 1000 to 10,000 pounds payload and evaluated over a broad spectrum of agricultural missions. From these studies, baseline design points were selected at 3200 pounds payload for the small aircraft and 7500 pounds for the large aircraft. The small baseline aircraft utilizes a single turboprop powerplant while the large aircraft utilizes two turboprop powerplants. These configurations were optimized for wing loading, aspect ratio, and power loading to provide the best mission economics in representative missions. Wing loading of 20 lb/sq ft was selected for the small aircraft and 25 lb/sq ft for the large aircraft. Aspect ratio of 8 was selected for both aircraft. It was found that a 10% reduction in engine power from the original configurations provided improved mission economics for both aircraft by reducing the cost of the turboprop. Refined configurations incorporate a 675 HP engine in the small aircraft and two 688 HP engines in the large aircraft.

A fuzzy-based data transformation for feature extraction to increase classification performance with small medical data sets.

PubMed

Li, Der-Chiang; Liu, Chiao-Wen; Hu, Susan C

2011-05-01

Medical data sets are usually small and have very high dimensionality. Too many attributes will make the analysis less efficient and will not necessarily increase accuracy, while too few data will decrease the modeling stability. Consequently, the main objective of this study is to extract the optimal subset of features to increase analytical performance when the data set is small. This paper proposes a fuzzy-based non-linear transformation method to extend classification related information from the original data attribute values for a small data set. Based on the new transformed data set, this study applies principal component analysis (PCA) to extract the optimal subset of features. Finally, we use the transformed data with these optimal features as the input data for a learning tool, a support vector machine (SVM). Six medical data sets: Pima Indians' diabetes, Wisconsin diagnostic breast cancer, Parkinson disease, echocardiogram, BUPA liver disorders dataset, and bladder cancer cases in Taiwan, are employed to illustrate the approach presented in this paper. This research uses the t-test to evaluate the classification accuracy for a single data set; and uses the Friedman test to show the proposed method is better than other methods over the multiple data sets. The experiment results indicate that the proposed method has better classification performance than either PCA or kernel principal component analysis (KPCA) when the data set is small, and suggest creating new purpose-related information to improve the analysis performance. This paper has shown that feature extraction is important as a function of feature selection for efficient data analysis. When the data set is small, using the fuzzy-based transformation method presented in this work to increase the information available produces better results than the PCA and KPCA approaches. Copyright © 2011 Elsevier B.V. All rights reserved.

Stability analysis of geomagnetic baseline data obtained at Cheongyang observatory in Korea

NASA Astrophysics Data System (ADS)

Amran, Shakirah M.; Kim, Wan-Seop; Cho, Heh Ree; Park, Po Gyu

2017-07-01

The stability of baselines produced by Cheongyang (CYG) observatory from the period of 2014 to 2016 is analysed. Step heights of higher than 5 nT were found in H and Z components in 2014 and 2015 due to magnetic noise in the absolute-measurement hut. In addition, a periodic modulation behaviour observed in the H and Z baseline curves was related to annual temperature variation of about 20 °C in the fluxgate magnetometer hut. Improvement in data quality was evidenced by a small dispersion between successive measurements from June 2015 to the end of 2016. Moreover, the baseline was also improved by correcting the discontinuity in the H and Z baselines.

In Living Memory: The Dying Art of Learning Poetry and a Case for Revival

ERIC Educational Resources Information Center

Pullinger, Debbie

2012-01-01

This article considers the practice of learning poems and the value of poetry in the memory, and emerges from the Cambridge Poetry Teaching Project, a small-scale research study co-ordinated through the Faculty of Education at the University of Cambridge. Drawing on the subset of findings in relation to learning and memory, the essay locates the…

75 FR 67642 - Investment of Customer Funds and Funds Held in an Account for Foreign Futures and Foreign Options...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-03

...), Investment Company Institute (ICI), MF Global Inc. (MF Global), National Futures Association (NFA), Newedge... Global, Newedge and FC Stone. CME asserted that only ``a small subset of the complete list of Regulation... today address the elimination of credit ratings from Regulations 1.49 and 4.24 and the removal of...

A first look at measurement error on FIA plots using blind plots in the Pacific Northwest

Treesearch

Susanna Melson; David Azuma; Jeremy S. Fried

2002-01-01

Measurement error in the Forest Inventory and Analysis work of the Pacific Northwest Station was estimated with a recently implemented blind plot measurement protocol. A small subset of plots was revisited by a crew having limited knowledge of the first crew's measurements. This preliminary analysis of the first 18 months' blind plot data indicates that...

Strengthening Ties: The Case for Building a Social Policy Centered on Families

ERIC Educational Resources Information Center

Longman, Phillip; Mundy, Liza; Black, Rachel; Bornfreund, Laura; Byrum, Greta; Cramer, Reid; Gangadharan, Seeta Peña; Guernsey, Lisa; Lieberman, Abbie; Lynn, Barry; McCarthy, Mary Alice

2015-01-01

Most of the social and economic policies in the U.S. do not explicitly address or take into account the growing importance of families as sources of human capital and determinants of individual success. Even the small subsets of programs that we conventionally frame as part of "family policy" are often based on long-defunct assumptions…

Critical Pedagogy in the Twenty-First Century: A New Generation of Scholars. Critical Constructions: Studies on Education and Society

ERIC Educational Resources Information Center

Malott, Curry Stephenson, Ed.; Porfilio, Bradley, Ed.

2011-01-01

This book simultaneously provides multiple analyses of critical pedagogy in the twenty-first century while showcasing the scholarship of this new generation of critical scholar-educators. Needless to say, the writers herein represent just a small subset of a much larger movement for critical transformation and a more humane, less Eurocentric, less…

Recent Innovations in Small-N Designs for Research and Practice in "Professional School Counseling"

ERIC Educational Resources Information Center

McDougall, Dennis; Smith, Douglas

2006-01-01

This article illustrates an innovative small-N research design that researchers and practitioners can use to investigate questions of interest in "professional school counseling." The distributed criterion (DC) design integrates elements of three classic small-N research designs--the changing criterion, reversal, and multiple baseline. The DC…

Pre-seizure architecture of the local connections of the epileptic focus examined via graph-theory.

PubMed

Vecchio, Fabrizio; Miraglia, Francesca; Vollono, Catello; Fuggetta, Filomena; Bramanti, Placido; Cioni, Beatrice; Rossini, Paolo Maria

2016-10-01

Epilepsy is characterized by unpredictable and sudden paroxysmal neuronal firing occurrences and sometimes evolving in clinically evident seizure. To predict seizure event, small-world characteristic in nine minutes before seizure, divided in three 3-min periods (T0, T1, T2) were investigated. Intracerebral recordings were obtained from 10 patients with drug resistant focal epilepsy examined by means of stereotactically implanted electrodes; analysis was focused in a period of low spiking (Baseline) and during two seizures. Networks' architecture is undirected and weighted. Electrodes' contacts close to epileptic focus are the vertices, edges are weighted by mscohere (=magnitude squared coherence). Differences were observed between Baseline and T1 and between Baseline and T2 in theta band; and between Baseline and T1, Baseline and T2, and near-significant difference between T0 and T2 in Alpha 2 band. Moreover, an intra-band index was computed for small worldness as difference between Theta and Alpha 2. It was found a growing index trend from Baseline to T2. Cortical network features a specific pre-seizure architecture which could predict the incoming epileptic seizure. Through this study future researches could investigate brain connectivity modifications approximating a clinical seizure also in order to address a preventive therapy. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Logistic regression trees for initial selection of interesting loci in case-control studies

PubMed Central

Nickolov, Radoslav Z; Milanov, Valentin B

2007-01-01

Modern genetic epidemiology faces the challenge of dealing with hundreds of thousands of genetic markers. The selection of a small initial subset of interesting markers for further investigation can greatly facilitate genetic studies. In this contribution we suggest the use of a logistic regression tree algorithm known as logistic tree with unbiased selection. Using the simulated data provided for Genetic Analysis Workshop 15, we show how this algorithm, with incorporation of multifactor dimensionality reduction method, can reduce an initial large pool of markers to a small set that includes the interesting markers with high probability. PMID:18466557

Interpersonal maladjustment as predictor of mothers' response to a relational parenting intervention.

PubMed

Suchman, Nancy E; McMahon, Thomas J; Luthar, Suniya S

2004-09-01

In previous work, Luthar and Suchman (2000, Development & Psychopathology, 12, 235) reported results of a randomized clinical trial testing the efficacy of the Relational Psychotherapy Mothers' Group (RPMG) for methadone-maintained mothers. In this extension, we examined maternal interpersonal maladjustment as a predictor of differential response to RPMG versus standard drug counseling (DC). We predicted that RPMG mothers with high levels of interpersonal maladjustment would improve on parent-child relationship indices, whereas DC mothers with high levels of interpersonal maladjustment would show no improvement. Fifty-two mothers enrolled in the study completed baseline, post-treatment and 6-month followup assessments and a subset of 24 "target" children between the ages of 7 and 16 completed measures on mothers' parenting. As predicted, results of hierarchical regression analyses indicated moderate interpersonal maladjustment x treatment interaction effects for all parenting outcomes at post-treatment and for a subset of outcomes at followup. Plotted interactions confirmed predictions that, as maternal interpersonal maladjustment increased, parenting problems improved for RPMG mothers and remained the same or worsened for DC mothers. Results indicate the potential value of interpersonally oriented interventions for substance-abusing mothers and their children.

Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study.

PubMed

Carr, Brian I; Pancoska, Petr; Branch, Robert A

2009-12-24

967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis.

Alcohol Misuse and Psychological Resilience among U.S. Iraq and Afghanistan Era Veteran Military Personnel

PubMed Central

Green, Kimberly T.; Beckham, Jean C.; Youssef, Nagy; Elbogen, Eric B.

2013-01-01

Objective The present study sought to investigate the longitudinal effects of psychological resilience against alcohol misuse adjusting for socio-demographic factors, trauma-related variables, and self-reported history of alcohol abuse. Methodology Data were from National Post-Deployment Adjustment Study (NPDAS) participants who completed both a baseline and one-year follow-up survey (N=1090). Survey questionnaires measured combat exposure, probable posttraumatic stress disorder (PTSD), psychological resilience, and alcohol misuse, all of which were measured at two discrete time periods (baseline and one-year follow-up). Baseline resilience and change in resilience (increased or decreased) were utilized as independent variables in separate models evaluating alcohol misuse at the one-year follow-up. Results Multiple linear regression analyses controlled for age, gender, level of educational attainment, combat exposure, PTSD symptom severity, and self-reported alcohol abuse. Accounting for these covariates, findings revealed that lower baseline resilience, younger age, male gender, and self-reported alcohol abuse were related to alcohol misuse at the one-year follow-up. A separate regression analysis, adjusting for the same covariates, revealed a relationship between change in resilience (from baseline to the one-year follow-up) and alcohol misuse at the one-year follow-up. The regression model evaluating these variables in a subset of the sample in which all the participants had been deployed to Iraq and/or Afghanistan was consistent with findings involving the overall era sample. Finally, logistic regression analyses of the one-year follow-up data yielded similar results to the baseline and resilience change models. Conclusions These findings suggest that increased psychological resilience is inversely related to alcohol misuse and is protective against alcohol misuse over time. Additionally, it supports the conceptualization of resilience as a process which evolves over time. Moreover, our results underscore the importance of assessing resilience as part of alcohol use screening for preventing alcohol misuse in Iraq and Afghanistan era military veterans. PMID:24090625

Depression severity in electroconvulsive therapy (ECT) versus pharmacotherapy trials.

PubMed

Kellner, Charles H; Kaicher, David C; Banerjee, Hiya; Knapp, Rebecca G; Shapiro, Rachael J; Briggs, Mimi C; Pasculli, Rosa M; Popeo, Dennis M; Ahle, Gabriella M; Liebman, Lauren S

2015-03-01

We sought to compare the level of severity of depressive symptoms on entry into electroconvulsive therapy (ECT) clinical trials versus pharmacotherapy clinical trials. English-language MEDLINE/PubMed publication databases were searched for ECT literature (search terms: ECT, electroconvulsive therapy, depression, and Hamilton) for clinical trials in which depressed patients had baseline Hamilton Rating Scale for Depression (HRSD) scores. For comparison, we used a convenience sample of 7 large pharmacotherapy trials in major depression (N = 3677). The search included articles from 1960 to 2011. We included 100 studies that met the following criteria: ECT trial for depression, patients adequately characterized by diagnosis at baseline, and patients rated at baseline by 15-item HRSD (HRSD15), HRSD17, HRSD21, HRSD24, or HRSD28, with mean (SD) and sample size (n) reported. For the comparator pharmacotherapy trials, we chose to use a subset of the studies (excluding one study of minor depression) in the widely publicized meta-analysis of Fournier et al, as well as the STAR*D study and one additional study by Shelton et al. This provided 7 studies of major depression using HRSD17 (total N = 3677). Data extracted included number of subjects and baseline and final HRSD scores, with mean (SD) values. Of 100 ECT studies, 56 studies (N = 2243) used the HRSD17 version. The mean baseline HRSD17 score in the ECT trials was 27.6, the mean in the pharmacotherapy trials was 21.94, a statistically, and clinically, significant difference. In a subanalysis of the 16 ECT studies that used the HRSD24 version, the mean baseline score was 32.2. This selective literature review confirms that patients who entered ECT clinical trials were more severely ill than those who entered the selected comparator pharmacotherapy trials. Such data highlight the critical role of ECT in the treatment of severe and treatment-resistant mood disorders.

Effects of Dorzolamide on Retinal and Choroidal Blood Flow in the DBA/2J Mouse Model of Glaucoma

PubMed Central

Chandra, Saurav; Muir, Eric R.; Deo, Kaiwalya; Kiel, Jeffrey W.; Duong, Timothy Q.

2016-01-01

Purpose To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma. Methods Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice under isoflurane anesthesia using magnetic resonance imaging. Ocular blood flow was measured at baseline, and 1 and 2 hours after topical dorzolamide. Intraocular pressure was measured using a rebound tonometer in a subset of animals at the same time points. Results Baseline IOP in the 4-month-old DBA/2J mice and C57BL/6 mice was not significantly different (P > 0.05), and IOP in both groups was less than in the 9-month-old DBA/2J mice (P < 0.05 for both). Compared to baseline, dorzolamide reduced IOP at 1 and 2 hours after dorzolamide in the 4- (P < 0.05) and 9-month-old (P < 0.01) DBA/2J mice, but not in the C57BL/6J mice (P > 0.05). Baseline retinal blood flow was lower in the 4-month and 9-month-old DBA/2J mice compared with the 4-month-old C57BL/6J mice (P < 0.05). Baseline choroidal blood flow in the 9-month-old DBA/2J mice was less than in the C57BL/6J mice (P < 0.05). Compared with baseline, both retinal and choroidal blood flow increased at 1-hour post-dorzolamide and remained elevated 2 hours later in the 9-month-old DBA/2J mice (P < 0.05). Conclusions Dorzolamide lowers IOP and raises retinal and choroidal blood flow in older DBA/2J mice, consistent with the study hypothesis. PMID:26934140

Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

PubMed

West, Howard

2017-09-01

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

Monoclonal antibodies targeting non-small cell lung cancer stem-like cells by multipotent cancer stem cell monoclonal antibody library.

PubMed

Cao, Kaiyue; Pan, Yunzhi; Yu, Long; Shu, Xiong; Yang, Jing; Sun, Linxin; Sun, Lichao; Yang, Zhihua; Ran, Yuliang

2017-02-01

Cancer stem cells (CSCs) are a rare subset of cancer cells that play a significant role in cancer initiation, spreading, and recurrence. In this study, a subpopulation of lung cancer stem-like cells (LCSLCs) was identified from non-small cell lung carcinoma cell lines, SPCA-1 and A549, using serum-free suspension sphere-forming culture method. A monoclonal antibody library was constructed using immunized BLAB/c mice with the multipotent CSC cell line T3A-A3. Flow cytometry analysis showed that 33 mAbs targeted antigens can be enriched in sphere cells compared with the parental cells of SPCA-1 and A549 cell lines. Then, we performed functional antibody screening including sphere-forming inhibiting and invasion inhibiting assay. The results showed that two antibodies, 12C7 and 9B8, notably suppressed the self-renewal and invasion of LCSLCs. Fluorescence-activated cell sorting (FACs) found that the positive cells recognized by mAbs, 12C7 or 9B8, displayed features of LCSLCs. Interestingly, we found that these two antibodies recognized different subsets of cells and their combination effect was superior to the individual effect both in vitro and in vivo. Tissue microarrays were applied to detect the expression of the antigens targeted by these two antibodies. The positive expression of 12C7 and 9B8 targeted antigen was 84.4 and 82.5%, respectively, which was significantly higher than that in the non-tumor lung tissues. In conclusion, we screened two potential therapeutic antibodies that target different subsets of LCSLCs.

Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients.

PubMed

Denardo, Scott J; Vock, David M; Schmalfuss, Carsten M; Young, Gregory D; Tcheng, James E; O'Connor, Christopher M

2016-07-01

Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta-Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (P<0.01); elevated baseline PCWP and decreased CI after contrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P≤0.02). In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and decreased CI after contrast merit greatest concern. © 2016 American Heart Association, Inc.

Multiclass cancer classification using a feature subset-based ensemble from microRNA expression profiles.

PubMed

Piao, Yongjun; Piao, Minghao; Ryu, Keun Ho

2017-01-01

Cancer classification has been a crucial topic of research in cancer treatment. In the last decade, messenger RNA (mRNA) expression profiles have been widely used to classify different types of cancers. With the discovery of a new class of small non-coding RNAs; known as microRNAs (miRNAs), various studies have shown that the expression patterns of miRNA can also accurately classify human cancers. Therefore, there is a great demand for the development of machine learning approaches to accurately classify various types of cancers using miRNA expression data. In this article, we propose a feature subset-based ensemble method in which each model is learned from a different projection of the original feature space to classify multiple cancers. In our method, the feature relevance and redundancy are considered to generate multiple feature subsets, the base classifiers are learned from each independent miRNA subset, and the average posterior probability is used to combine the base classifiers. To test the performance of our method, we used bead-based and sequence-based miRNA expression datasets and conducted 10-fold and leave-one-out cross validations. The experimental results show that the proposed method yields good results and has higher prediction accuracy than popular ensemble methods. The Java program and source code of the proposed method and the datasets in the experiments are freely available at https://sourceforge.net/projects/mirna-ensemble/. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enantioselectivity in Candida antarctica lipase B: A molecular dynamics study

PubMed Central

Raza, Sami; Fransson, Linda; Hult, Karl

2001-01-01

A major problem in predicting the enantioselectivity of an enzyme toward substrate molecules is that even high selectivity toward one substrate enantiomer over the other corresponds to a very small difference in free energy. However, total free energies in enzyme-substrate systems are very large and fluctuate significantly because of general protein motion. Candida antarctica lipase B (CALB), a serine hydrolase, displays enantioselectivity toward secondary alcohols. Here, we present a modeling study where the aim has been to develop a molecular dynamics-based methodology for the prediction of enantioselectivity in CALB. The substrates modeled (seven in total) were 3-methyl-2-butanol with various aliphatic carboxylic acids and also 2-butanol, as well as 3,3-dimethyl-2-butanol with octanoic acid. The tetrahedral reaction intermediate was used as a model of the transition state. Investigative analyses were performed on ensembles of nonminimized structures and focused on the potential energies of a number of subsets within the modeled systems to determine which specific regions are important for the prediction of enantioselectivity. One category of subset was based on atoms that make up the core structural elements of the transition state. We considered that a more favorable energetic conformation of such a subset should relate to a greater likelihood for catalysis to occur, thus reflecting higher selectivity. The results of this study conveyed that the use of this type of subset was viable for the analysis of structural ensembles and yielded good predictions of enantioselectivity. PMID:11266619

Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4+ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

PubMed Central

Veazey, Ronald S.; Tham, Irene C.; Mansfield, Keith G.; DeMaria, MaryAnn; Forand, Amy E.; Shvetz, Daniel E.; Chalifoux, Laura V.; Sehgal, Prabhat K.; Lackner, Andrew A.

2000-01-01

It has recently been shown that rapid and profound CD4+ T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4+ T cells, namely, those having both a highly and/or acutely activated (CD69+ CD38+ HLA-DR+) and memory (CD45RA− Leu8−) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4+ T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4+ T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4+ T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4+ T cells in vivo. PMID:10590091

Mipomersen preferentially reduces small low-density lipoprotein particle number in patients with hypercholesterolemia.

PubMed

Santos, Raul D; Raal, Frederick J; Donovan, Joanne M; Cromwell, William C

2015-01-01

Because of variability in lipoprotein cholesterol content, low-density lipoprotein (LDL) cholesterol frequently underrepresents or overrepresents the number of LDL particles. Mipomersen is an antisense oligonucleotide that reduces hepatic production of apolipoprotein B-100, the sole apolipoprotein of LDL. To characterize the effects of mipomersen on lipoprotein particle numbers as well as subclass distribution using nuclear magnetic resonance (NMR) spectroscopy. We compared the tertiary results for the direct measurement of LDL particle numbers by NMR among 4 placebo-controlled, phase 3 studies of mipomersen that had similar study designs but different patient populations: homozygous familial hypercholesterolemia (HoFH), severe hypercholesterolemia, heterozygous familial hypercholesterolemia with established coronary artery disease, or hypercholesterolemia with high risk for coronary heart disease (HC-CHD). HoFH patients had the highest median total LDL particles at baseline compared with HC-CHD patients, who had the lowest. At baseline, the HoFH population uniquely had a greater mean percentage of large LDL particles (placebo, 60.2%; mipomersen, 54.9%) compared with small LDL particles (placebo, 33.1%; mipomersen, 38.9%). In all 4 studies, mipomersen was associated with greater reductions from baseline in the concentrations of small LDL particles compared with those of large LDL particles, and both total LDL particles and small LDL particles were statistically significantly reduced. Mipomersen consistently reduced all LDL particle numbers and preferentially reduced the concentration of small LDL particles in all 4 phase 3 studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

PubMed Central

Chia, Puey Ling; Mitchell, Paul; Dobrovic, Alexander; John, Thomas

2014-01-01

Improved understanding of molecular drivers of carcinogenesis has led to significant progress in the management of lung cancer. Patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangements constitute about 4%–5% of all NSCLC patients. ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment. There are now several newer ALK inhibitors, with the next generation of agents targeting resistance mutations. In this review, we will discuss the prevalence and clinical characteristics of ALK+ lung cancer, current treatment options, and future directions in the management of this subset of NSCLC patients. PMID:25429239

A snoRNA modulates mRNA 3′ end processing and regulates the expression of a subset of mRNAs

PubMed Central

Huang, Chunliu; Shi, Junjie; Guo, Yibin; Huang, Weijun; Huang, Shanshan; Ming, Siqi; Wu, Xingui; Zhang, Rui; Ding, Junjun; Zhao, Wei; Jia, Jie; Huang, Xi; Xiang, Andy Peng

2017-01-01

Abstract mRNA 3′ end processing is an essential step in gene expression. It is well established that canonical eukaryotic pre-mRNA 3′ processing is carried out within a macromolecular machinery consisting of dozens of trans-acting proteins. However, it is unknown whether RNAs play any role in this process. Unexpectedly, we found that a subset of small nucleolar RNAs (snoRNAs) are associated with the mammalian mRNA 3′ processing complex. These snoRNAs primarily interact with Fip1, a component of cleavage and polyadenylation specificity factor (CPSF). We have functionally characterized one of these snoRNAs and our results demonstrated that the U/A-rich SNORD50A inhibits mRNA 3′ processing by blocking the Fip1-poly(A) site (PAS) interaction. Consistently, SNORD50A depletion altered the Fip1–RNA interaction landscape and changed the alternative polyadenylation (APA) profiles and/or transcript levels of a subset of genes. Taken together, our data revealed a novel function for snoRNAs and provided the first evidence that non-coding RNAs may play an important role in regulating mRNA 3′ processing. PMID:28911119

Stability and Agreement of a Microtransducer and an Air-Filled Balloon Esophageal Catheter in the Monitoring of Esophageal Pressure.

PubMed

Augusto, Renan Maloni; Albuquerque, André Luis Pereira; Jaeger, Thomas; de Carvalho, Carlos Roberto Ribeiro; Caruso, Pedro

2017-02-01

The use of esophageal catheters with microtransducer promises advantages over traditional catheters with air-filled balloons. However, performance comparisons between these 2 types of catheters are scarce and incomplete. A catheter with a 9.5-cm air-filled balloon at the distal tip and a catheter with a microtransducer mounted within a flexible silicone rubber were tested in vitro and in vivo. In vitro, the response times of both catheters were compared, and the drift of the baseline pressure of the microtransducer catheter was evaluated over a 6-h period. In vivo, 11 healthy volunteers had both catheters inserted, and the drift of the baseline esophageal pressure was measured over a 3-h period. Also, the correlation and agreement of the baseline and changes in the esophageal pressure of both catheters were evaluated. In vitro, the microtransducer catheter had a response time significantly higher (262 × 114 Hz, P < .01) and a good pressure stability, with a mean baseline pressure drift of 1.4 cm H 2 O. In vivo, both catheters presented a small and similar baseline esophageal pressure drift (P = 0.08). For measurements of baseline and changes in esophageal pressure, the correlation and agreement between the catheters were poor, with a large bias between them. The catheter with the microtransducer had a small baseline pressure drift, similar to the air-filled balloon catheter. The low agreement between the catheters does not allow the microtransducer catheter to be used as a surrogate for the traditional air-filled balloon catheter. Copyright © 2017 by Daedalus Enterprises.

Lacunar Infarcts, but Not Perivascular Spaces, Are Predictors of Cognitive Decline in Cerebral Small-Vessel Disease

PubMed Central

Trippier, Sarah; Lawrence, Andrew J.; Lambert, Christian; Zeestraten, Eva; Williams, Owen A.; Patel, Bhavini; Morris, Robin G.; Barrick, Thomas R.; MacKinnon, Andrew D.; Markus, Hugh S.

2018-01-01

Background and Purpose— Cerebral small-vessel disease is a major cause of cognitive impairment. Perivascular spaces (PvS) occur in small-vessel disease, but their relationship to cognitive impairment remains uncertain. One reason may be difficulty in distinguishing between lacunes and PvS. We determined the relationship between baseline PvS score and PvS volume with change in cognition over a 5-year follow-up. We compared this to the relationship between baseline lacune count and total lacune volume with cognition. In addition, we examined change in PvS volume over time. Methods— Data from the prospective SCANS study (St Georges Cognition and Neuroimaging in Stroke) of patients with symptomatic lacunar stroke and confluent leukoaraiosis were used (n=121). Multimodal magnetic resonance imaging was performed annually for 3 years and neuropsychological testing annually for 5 years. Lacunes were manually identified and distinguished from PvS. PvS were rated using a validated visual rating scale, and PvS volumes calculated using T1-weighted images. Linear mixed-effect models were used to determine the impact of PvS and lacunes on cognition. Results— Baseline PvS scores or volumes showed no association with cognitive indices. No change was detectable in PvS volumes over the 3 years. In contrast, baseline lacunes associated with all cognitive indices and predicted cognitive decline over the 5-year follow-up. Conclusions— Although a feature of small-vessel disease, PvS are not a predictor of cognitive decline, in contrast to lacunes. This study highlights the importance of carefully differentiating between lacunes and PvS in studies investigating vascular cognitive impairment. PMID:29438074

DNA-based immunotherapy for HPV-associated head and neck cancer.

PubMed

Aggarwal, Charu

2016-10-01

Squamous cell carcinoma of the head and neck (SCCHN) accounts for 3% of all cancers. Most patients present with locally advanced disease, where multimodality therapies are used with curative intent. Despite favorable early local treatment results, about one third of the patients will eventually develop metastatic disease. Immunotherapy offers a novel therapeutic strategy beyond cytotoxic chemotherapy, with initial approvals in melanoma and non-small-cell lung cancer. HPV-associated SCCHN is a distinct subset, with unique epidemiology and treatment outcomes. Both subsets of SCCHN (HPV-related or not) are particularly favorable for immunotherapy, as immune evasion and dysregulation have been shown to play a key role in the initiation and progression of disease. This review focuses on the latest developments in immunotherapy in SCCHN, with a particular focus on DNA-based approaches including vaccine and adoptive cellular therapies.

Mapping the Medical Literature for High Quality Studies and Reviews for Age-specific Clinical Specialties

PubMed Central

Stevens, Adrienne L.; Wilczynski, Nancy L.; McKibbon, K. Ann; Haynes, R. Brian

2001-01-01

Objective: To identify a journal subset that publishes reports of high quality studies and reviews relating to age-specific clinical specialties, such as pediatrics and geriatrics. Design: Handsearch of 172 journals using explicit criteria to determine methodologic quality for generating evidence for clinical practice. Main outcome measure: Frequency of high quality articles and their top yielding journals. Results: Between 17% and 33% of articles published in age-specific specialties are of high quality for clinical use. Top yielding journals for the specialties ranged from 16 to 130. Conclusion: Handsearch of the clinical literature for the year 2000 reveals that high quality articles for some age-specific specialties are concentrated in a small subset of journals (eg, obstetrics), whereas articles for other specialties are widely scattered among a large number of journals (eg, adult medicine).

Measurement-Device-Independent Approach to Entanglement Measures

NASA Astrophysics Data System (ADS)

Shahandeh, Farid; Hall, Michael J. W.; Ralph, Timothy C.

2017-04-01

Within the context of semiquantum nonlocal games, the trust can be removed from the measurement devices in an entanglement-detection procedure. Here, we show that a similar approach can be taken to quantify the amount of entanglement. To be specific, first, we show that in this context, a small subset of semiquantum nonlocal games is necessary and sufficient for entanglement detection in the local operations and classical communication paradigm. Second, we prove that the maximum payoff for these games is a universal measure of entanglement which is convex and continuous. Third, we show that for the quantification of negative-partial-transpose entanglement, this subset can be further reduced down to a single arbitrary element. Importantly, our measure is measurement device independent by construction and operationally accessible. Finally, our approach straightforwardly extends to quantify the entanglement within any partitioning of multipartite quantum states.

Taking the Measure of Massive Stars and their Environments with the CHARA Array Long-baseline Interferometer

NASA Astrophysics Data System (ADS)

Gies, Douglas R.

2017-11-01

Most massive stars are so distant that their angular diameters are too small for direct resolution. However, the observational situation is now much more favorable, thanks to new opportunities available with optical/IR long-baseline interferometry. The Georgia State University Center for High Angular Resolution Astronomy Array at Mount Wilson Observatory is a six-telescope instrument with a maximum baseline of 330 meters, which is capable of resolving stellar disks with diameters as small as 0.2 milliarcsec. The distant stars are no longer out of range, and many kinds of investigations are possible. Here we summarize a number of studies involving angular diameter measurements and effective temperature estimates for OB stars, binary and multiple stars (including the σ Orionis system), and outflows in Luminous Blue Variables. An enlarged visitors program will begin in 2017 that will open many opportunities for new programs in high angular resolution astronomy.

Current trends in small vocabulary speech recognition for equipment control

NASA Astrophysics Data System (ADS)

Doukas, Nikolaos; Bardis, Nikolaos G.

2017-09-01

Speech recognition systems allow human - machine communication to acquire an intuitive nature that approaches the simplicity of inter - human communication. Small vocabulary speech recognition is a subset of the overall speech recognition problem, where only a small number of words need to be recognized. Speaker independent small vocabulary recognition can find significant applications in field equipment used by military personnel. Such equipment may typically be controlled by a small number of commands that need to be given quickly and accurately, under conditions where delicate manual operations are difficult to achieve. This type of application could hence significantly benefit by the use of robust voice operated control components, as they would facilitate the interaction with their users and render it much more reliable in times of crisis. This paper presents current challenges involved in attaining efficient and robust small vocabulary speech recognition. These challenges concern feature selection, classification techniques, speaker diversity and noise effects. A state machine approach is presented that facilitates the voice guidance of different equipment in a variety of situations.

Chemical, Biological, and Radiological (CBR) Contamination Survivability, Small Items of Equipment

DTIC Science & Technology

2012-06-22

thickness (number of coats), paint condition, and surface cleanliness (mud, grease, and other). j. Pretest (baseline) and posttest (30 days after...survivability testing of small items of mission-essential (ME) Army materiel. Small items, for example , include personal gear, small arms, radios...their effects. An example would be the age of the paint on the surface (aged, new, etc.). f. The only current mechanism for converting agent mass

AKAP localizes in a specific subset of TRPV1 and CaV1.2 positive nociceptive rat DRG neurons

PubMed Central

Brandao, Katherine E.; Dell’Acqua, Mark L.; Levinson, Simon R.

2016-01-01

Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and phosphatases by the scaffolding A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 has been implicated in inflammatory pain by targeting PKA and PKC to the TRPV1 channel in peripheral sensory neurons, thus lowering threshold for activation by multiple inflammatory reagents. However, the expression pattern of AKAP79/150 in peripheral sensory neurons is unknown. In this study we use immunofluorescence microscopy to identify in DRG sections the peripheral neuron subtypes that express the rodent isoform AKAP150, as well as the subcellular distribution of AKAP150 and its potential target ion channels. We found that AKAP150 is predominantly expressed in a subset of small DRG sensory neurons where it is localized at the plasma membrane of the soma, axon initial segment and small fibers. The majority of these neurons is peripherin positive and produces c-fibers, though a small portion produces Aδ-fibers. Furthermore, we demonstrate that AKAP79/150 colocalizes with TRPV1 and CaV1.2 in the soma and axon initial segment. Thus AKAP150 is expressed in small, nociceptive DRG neurons where it is targeted to membrane regions and where it may play a role in the modulation of ion channel phosphorylation states required for hyperalgesia. PMID:21674494

Evaluating the Efficacy of a Short Aging Simulation Workshop for an Interdisciplinary Group of Health-Care Employees at a Veterans Affairs Medical Center

ERIC Educational Resources Information Center

Halpin, Sean N.

2015-01-01

Several interventions aimed at increasing positive attitudes towards older adults among health-care professionals have been introduced. These interventions tend to focus on a small subset of clinical employees, ignoring other clinical and nonclinical hospital staff. The objective of this study was to evaluate the efficacy of a short aging…

Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for Prader-Willi Syndrome

USDA-ARS?s Scientific Manuscript database

Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has been identified as the major contributor to PWS symptoms. The Snord116 deletion (Snord116del) mouse model manifested a subset of PWS symptoms ...

Structural Studies on Intact Clostridium botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

DTIC Science & Technology

2008-02-01

via virtual screening. These compounds include small molecules – transition state analogues and benzimidazoles . We have determined the crystal...project period. It has been established that benzimidazole compounds are good zinc chealators and since botulinum neurotoxin catalytic domains are zinc...endopeptidases we first selected a subset of compounds containing benzimidazole moieties. We pulled out nearly 9000 compound containing both

An Exploration of Autonetnography as an eResearch Methodology to Examine Learning and Teaching Scholarship in Networked Learning

ERIC Educational Resources Information Center

Howard, Lyz

2016-01-01

As an experienced face-to-face teacher, working in a small Crown Dependency with no Higher Education Institute (HEI) to call its own, the subsequent geographical and professional isolation in the context of Networked Learning (NL), as a sub-set of eLearning, calls for innovative ways in which to develop self-reliant methods of professional…

On the existence and uniqueness of minima and maxima on spheres of the integral functional of the calculus of variations

NASA Astrophysics Data System (ADS)

Ricceri, Biagio

2006-12-01

Given a bounded domain [Omega][subset of]Rn, we prove that if is a C1 function whose gradient is Lipschitzian in Rn+1 and non-zero at 0, then, for each r>0 small enough, the restriction of the integral functional to the sphere has a unique global minimum and a unique global maximum.

Impact of epidermal leaf mining by the aspen leaf miner (Phyllocnistis populiella) on the growth, physiology, and leaf longevity of quaking aspen.

Treesearch

Diane L. Wagner; Linda DeFoliart; Patricia Doak; Jenny Schneiderheinze

2008-01-01

The aspen leaf miner, Phyllocnistis populiella, feeds on the contents of epidermal cells on both top (adaxial) and bottom (abaxial) surfaces of quaking aspen leaves, leaving the photosynthetic tissue of the mesophyll intact. This type of feeding is taxonomically restricted to a small subset of leaf mining insects but can cause widespread plant...

A pilot investigation of the Motivation Behaviors Checklist (MBC): An observational rating scale of effort towards testing for baseline sports-concussion assessment.

PubMed

Rabinowitz, Amanda R; Merritt, Victoria; Arnett, Peter A

2016-08-01

Baseline neuropsychological testing is commonly used in the management of sports-related concussion. However, underperformance due to poor effort could lead to invalid conclusions regarding postconcussion cognitive decline. We designed the Motivation Behaviors Checklist (MBC) as an observational rating scale to assess effort towards baseline neuropsychological testing. Here we present preliminary data in support of its reliability and validity. MBC items were generated based on the consensus of a panel of graduate students, undergraduates, and a clinical neuropsychologist who conduct neuropsychological evaluations for a sports concussion management program. A total of 261 college athletes were administered a standard neuropsychological test battery in addition to the MBC. A subset of evaluations (n= 101) was videotape and viewed by a second rater. Exploratory factor analysis (EFA) was used to refine the scale, and reliability and validity were evaluated. EFA revealed that the MBC items represent four latent factors-Complaints, Poor Focus, Psychomotor Agitation, and Impulsivity. Reliability analyses demonstrated that the MBC has good inter-rater reliability (intraclass correlation coefficient, ICC = .767) and internal consistency (α = .839). The construct validity of the MBC is supported by large correlations with examiners' ratings of effort (ρ = -.623) and medium-sized relationships with cognitive performance and self-ratings of effort (|ρ| between .263 and .345). Discriminant validity was supported by nonsignificant correlations with measures of depression and postconcussion symptoms (ρ = .056 and .082, respectively). These findings provide preliminary evidence that the MBC could be a useful adjunct to baseline neuropsychological evaluations for sports-concussion management.

Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program.

PubMed

Ceglia, Lisa; Nelson, Jason; Ware, James; Alysandratos, Konstantinos-Dionysios; Bray, George A; Garganta, Cheryl; Nathan, David M; Hu, Frank B; Dawson-Hughes, Bess; Pittas, Anastassios G

2017-02-01

We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in prediabetes and sought to estimate the impact of adiposity on these associations. The study was conducted in the placebo (n = 1082) and intensive lifestyle (n = 1079) groups of the Diabetes Prevention Program (DPP), a multicenter trial to prevent type 2 diabetes in adults with prediabetes. Weight and 25OHD were measured at baseline, month 6, years 1 and 2. In a subset (n = 584), visceral (VAT) and subcutaneous (SAT) adiposity were assessed by computed tomography at baseline and year 1. In cross-sectional analyses, baseline body weight, total fat, VAT, and SAT were inversely associated with plasma 25OHD concentration after multivariable adjustment. VAT accounted for 40 % [95 % CI 11, 69] of the association of body weight with plasma 25OHD concentration. There was no significant contribution by total fat or SAT. Two-year changes in plasma 25OHD concentration varied inversely with changes in body weight (p < 0.0001). One-year changes in total fat, VAT, or SAT were not significant mediators of the association between change in plasma 25OHD concentration and body weight. Our study found an inverse association between body weight and plasma 25OHD concentration at baseline and over a 2-year period in adults with prediabetes. These findings in the DPP, a weight loss intervention study, raise the possibility that weight loss increases plasma 25OHD concentration. Whether adiposity mediates this association remains inconclusive.

Lasting depression in corticomotor excitability associated with local scalp cooling.

PubMed

Tremblay, François; Remaud, Anthony; Mekonnen, Abeye; Gholami-Boroujeny, Shiva; Racine, Karl-Édouard; Bolic, Miodrag

2015-07-23

In this study, we investigated the effect of local scalp cooling on corticomotor excitability with transcranial magnetic simulation (TMS). Participants (healthy male adults, n=12) were first assessed with TMS to derive baseline measure of excitability from motor evoked potentials (MEPs) using the right first dorsal interosseous as the target muscle. Then, local cooling was induced on the right hemi-scalp (upper frontal region ∼ 15 cm(2)) by means of a cold wrap. The cooling was maintained for 10-15 min to get a decrease of at least 10°C from baseline temperature. In the post-cooling period, both scalp temperature and MEPs were reassessed at specific time intervals (i.e., T0, T10, T20 and T30 min). Scalp surface temperatures dropped on average by 12.5°C from baseline at T0 (p<0.001) with partial recovery at T10 (p<0.05) and full recovery at T20. Parallel analysis of post-cooling variations in MEP amplitude revealed significant reductions relative to baseline at T0, T10 and T20. No concurrent change in MEP latency was observed. A secondary control experiment was performed in a subset of participants (n=5) to account for the mild discomfort associated with the wrapping procedure without the cooling agent. Results showed no effect on any of the dependent variables (temperature, MEP amplitude and latency). To our knowledge, this report provides the first neurophysiological evidence linking changes in scalp temperature with lasting changes in corticomotor excitability. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial

PubMed Central

Wang, Ying; Tong, Lili; Pak, Youngju; Andalibi, Ali; LaPage, Janine A.; Adler, Sharon G.

2016-01-01

Background We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline’s biological effects. Methods Design: Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance > 30 mL/min; proteinuria ≥ 1.0 g/day; Age ≥30 years; BP <150/95 mm Hg; intolerant of/at maximum RAASi dose. Protocol. 3-wk screening; Baseline randomization; Urine and blood measures at months 1, 2, 4, and Month 6 study completion. Urine interleukin-6 (IL-6) and osteoprotegerin were measured in a subset. Primary outcome. Natural log of urine protein/creatinine (ln U P:Cr) ratio at Month 6 vs Baseline. Results 30 patients completed the study. The 15% decline in U P: Cr in minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92) was not significant (p = 0.27). Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03) and osteoprotegerin/Cr (p = 0.046) decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect. Conclusions Although the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study. Trial Registration Clinicaltrials.gov NCT01779089 PMID:27019421

Changes in Dietary Patterns from Childhood to Adolescence and Associated Body Adiposity Status

PubMed Central

Bellisle, France

2017-01-01

The aims of this study were to identify cross-sectional dietary patterns (DPs) in a representative sample of 7–10-year-old schoolchildren, to examine how scores for these DPs tracked over a time period of five years (from age 7–10 years to 12–15 years), and to investigate longitudinal associations between changes in DPs scores and changes in BMI (Body Mass Index) z-scores. Children aged 7–10-years were examined in 2007 (n = 1158) and a subset of the sample participated in a follow-up in 2012 (n = 458). Factor analysis (FA) was applied to derive DPs at baseline. The change in DP from childhood to adolescence was analyzed by comparing factor scores using the complete cases, in which factor loadings were the ones evaluated at baseline. Associations of BMI change with DP change were assessed by multivariate linear regression. At baseline, four DP were identified that explained 47.9% of the food intake variance. On average, the factor scores of “DP II” (salty snacks, French fries, fast-food, sugary beverages) decreased in follow-up, while no changes were observed for “DP I” (rice, cooked beans, beef/poultry, leafy vegetables), “DP III” (fruits, cooked and leafy vegetables, fruit juices, pasta, milk, cheese), and “DP IV” (milk, coffee with milk, cheese, breads/biscuits). No significant linear association was shown between changes in BMI z-scores and changes in DP scores from childhood to adolescence. In conclusion, three out of four DP scores identified at baseline tracked slightly in adolescence. PMID:28984828

Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program

PubMed Central

CEGLIA, LISA; NELSON, JASON; WARE, JAMES; ALYSANDRATOS, KONSTANTINOS-DIONYSIOS; BRAY, GEORGE A.; GARGANTA, CHERYL; NATHAN, DAVID M.; HU, FRANK B; DAWSON-HUGHES, BESS; PITTAS, ANASTASSIOS G.

2016-01-01

Objective We examined associations between body weight and plasma 25-hydroxyvitamin D concentration (25OHD) in pre-diabetes and sought to estimate the impact of adiposity on these associations. Methods The study was conducted in the placebo (n=1,082) and intensive lifestyle (n=1,079) groups of the Diabetes Prevention Program (DPP), a multicenter trial to prevent type 2 diabetes in adults with pre-diabetes. Weight and 25OHD were measured at baseline, month 6, years 1 and 2. In a subset (n=584), visceral [VAT] and subcutaneous [SAT] adiposity were assessed by computed tomography at baseline and year 1. Results In cross-sectional analyses, baseline body weight, total fat, VAT, and SAT were inversely associated with plasma 25OHD concentration after multivariable adjustment. VAT accounted for 40% [95% CI 11, 69] of the association of body weight with plasma 25OHD concentration. There was no significant contribution by total fat or SAT. Two-year changes in plasma 25OHD concentration varied inversely with changes in body weight (p<0.0001). One-year changes in total fat, VAT, or SAT were not significant mediators of the association between change in plasma 25OHD concentration and body weight. Conclusion Our study found an inverse association between body weight and plasma 25OHD concentration at baseline and over a 2-year period in adults with pre-diabetes. These findings in the DPP, a weight loss intervention study, raise the possibility that weight loss increases plasma 25OHD concentration. Whether adiposity mediates this association remains inconclusive. PMID:26525562

Haemodynamic and anatomic progression of aortic stenosis.

PubMed

Nguyen, Virginia; Cimadevilla, Claire; Estellat, Candice; Codogno, Isabelle; Huart, Virginie; Benessiano, Joelle; Duval, Xavier; Pibarot, Philippe; Clavel, Marie Annick; Enriquez-Sarano, Maurice; Vahanian, Alec; Messika-Zeitoun, David

2015-06-01

Aortic valve stenosis (AS) is a progressive disease, but the impact of baseline AS haemodynamic or anatomic severity on AS progression remains unclear. In 149 patients (104 mild AS, 36 moderate AS and 9 severe AS) enrolled in 2 ongoing prospective cohorts (COFRASA/GENERAC), we evaluated AS haemodynamic severity at baseline and yearly, thereafter, using echocardiography (mean pressure gradient (MPG)) and AS anatomic severity using CT (degree of aortic valve calcification (AVC)). After a mean follow-up of 2.9±1.0 years, mean MGP increased from 22±11 to 30±16 mm Hg (+3±3 mm Hg/year), and mean AVC from 1108±891 to 1640±1251 AU (arbitrary units) (+188±176 AU/year). Progression of AS was strongly related to baseline haemodynamic severity (+2±3 mm Hg/year in mild AS, +4±3 mm Hg/year in moderate AS and +5±5 mm Hg/year in severe AS (p=0.01)), and baseline haemodynamic severity was an independent predictor of haemodynamic progression (p=0.0003). Annualised haemodynamic and anatomic progression rates were significantly correlated (r=0.55, p<0.0001), but AVC progression rate was also significantly associated with baseline haemodynamic severity (+141±133 AU/year in mild AS, +279±189 AU/year in moderate AS and +361±293 AU/year in severe AS, p<0.0001), and both baseline MPG and baseline AVC were independent determinants of AVC progression (p<0.0001). AS progressed faster with increasing haemodynamic or anatomic severity. Our results suggest that a medical strategy aimed at preventing AVC progression may be useful in all subsets of patients with AS including those with severe AS and support the recommended closer follow-up of patients with AS as AS severity increases. COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

SU-E-J-262: Variability in Texture Analysis of Gynecological Tumors in the Context of An 18F-FDG PET Adaptive Protocol

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

Nawrocki, J; Chino, J; Das, S

Purpose: This study examines the effect on texture analysis due to variable reconstruction of PET images in the context of an adaptive FDG PET protocol for node positive gynecologic cancer patients. By measuring variability in texture features from baseline and intra-treatment PET-CT, we can isolate unreliable texture features due to large variation. Methods: A subset of seven patients with node positive gynecological cancers visible on PET was selected for this study. Prescribed dose varied between 45–50.4Gy, with a 55–70Gy boost to the PET positive nodes. A baseline and intratreatment (between 30–36Gy) PET-CT were obtained on a Siemens Biograph mCT. Eachmore » clinical PET image set was reconstructed 6 times using a TrueX+TOF algorithm with varying iterations and Gaussian filter. Baseline and intra-treatment primary GTVs were segmented using PET Edge (MIM Software Inc., Cleveland, OH), a semi-automatic gradient-based algorithm, on the clinical PET and transferred to the other reconstructed sets. Using an in-house MATLAB program, four 3D texture matrices describing relationships between voxel intensities in the GTV were generated: co-occurrence, run length, size zone, and neighborhood difference. From these, 39 textural features characterizing texture were calculated in addition to SUV histogram features. The percent variability among parameters was first calculated. Each reconstructed texture feature from baseline and intra-treatment per patient was normalized to the clinical baseline scan and compared using the Wilcoxon signed-rank test in order to isolate variations due to reconstruction parameters. Results: For the baseline scans, 13 texture features showed a mean range greater than 10%. For the intra scans, 28 texture features showed a mean range greater than 10%. Comparing baseline to intra scans, 25 texture features showed p <0.05. Conclusion: Variability due to different reconstruction parameters increased with treatment, however, the majority of texture features showed significant changes during treatment independent of reconstruction effects.« less

Psychological effects of custody disputes on children.

PubMed

Wolman, R; Taylor, K

1991-01-01

This two-group, repeated measures examination of the psychological impact of child custody contests on children reports a subset of data from an ongoing longitudinal study of 95 children and their parents from 43 divorcing families. The authors report clinical observations concerning children's experience of custody litigation, as well as comparisons of baseline and post-test responses of contested and uncontested groups on measures of locus of control, separation anxiety and family concept. Contested children exhibited significantly greater internality of control orientation than the normative sample. Contested children's test scores also suggested significantly less separation anxiety and significantly more positive family concept than the uncontested group at post-test. The implications of these unanticipated findings are discussed.

Risk and protective factors for structural brain ageing in the eighth decade of life.

PubMed

Ritchie, Stuart J; Tucker-Drob, Elliot M; Cox, Simon R; Dickie, David Alexander; Del C Valdés Hernández, Maria; Corley, Janie; Royle, Natalie A; Redmond, Paul; Muñoz Maniega, Susana; Pattie, Alison; Aribisala, Benjamin S; Taylor, Adele M; Clarke, Toni-Kim; Gow, Alan J; Starr, John M; Bastin, Mark E; Wardlaw, Joanna M; Deary, Ian J

2017-11-01

Individuals differ markedly in brain structure, and in how this structure degenerates during ageing. In a large sample of human participants (baseline n = 731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the magnitude of mean change and variability in changes in MRI measures of brain macrostructure (grey matter, white matter, and white matter hyperintensity volumes) and microstructure (fractional anisotropy and mean diffusivity from diffusion tensor MRI). All indices showed significant average change with age, with considerable heterogeneity in those changes. We then tested eleven socioeconomic, physical, health, cognitive, allostatic (inflammatory and metabolic), and genetic variables for their value in predicting these differences in changes. Many of these variables were significantly correlated with baseline brain structure, but few could account for significant portions of the heterogeneity in subsequent brain change. Physical fitness was an exception, being correlated both with brain level and changes. The results suggest that only a subset of correlates of brain structure are also predictive of differences in brain ageing.

Cocaine Dependence Treatment Data: Methods for Measurement Error Problems With Predictors Derived From Stationary Stochastic Processes

PubMed Central

Guan, Yongtao; Li, Yehua; Sinha, Rajita

2011-01-01

In a cocaine dependence treatment study, we use linear and nonlinear regression models to model posttreatment cocaine craving scores and first cocaine relapse time. A subset of the covariates are summary statistics derived from baseline daily cocaine use trajectories, such as baseline cocaine use frequency and average daily use amount. These summary statistics are subject to estimation error and can therefore cause biased estimators for the regression coefficients. Unlike classical measurement error problems, the error we encounter here is heteroscedastic with an unknown distribution, and there are no replicates for the error-prone variables or instrumental variables. We propose two robust methods to correct for the bias: a computationally efficient method-of-moments-based method for linear regression models and a subsampling extrapolation method that is generally applicable to both linear and nonlinear regression models. Simulations and an application to the cocaine dependence treatment data are used to illustrate the efficacy of the proposed methods. Asymptotic theory and variance estimation for the proposed subsampling extrapolation method and some additional simulation results are described in the online supplementary material. PMID:21984854

N+3 Small Commercial Efficient and Quiet Transportation for Year 2030-2035

NASA Technical Reports Server (NTRS)

DAngelo, Martin M.; Gallman, John; Johnson, Vicki; Garcia, Elena; Tai, Jimmy; Young, Russell

2010-01-01

This study develops a future scenario that enables convenient point-to-point commercial air travel via a large network of community airports and a new class of small airliners. A network demand and capacity study identifies current and future air travel demands and the capacity of this new network to satisfy these demands. A current technology small commercial airliner is defined to meet the needs of the new network, as a baseline for evaluating the improvement brought about by advanced technologies. Impact of this new mode of travel on the infrastructure and surrounding communities of the small airports in this new N+3 network are also evaluated. Year 2030-2035 small commercial airliner technologies are identified and a trade study conducted to evaluate and select those with the greatest potential for enhancing future air travel and the study metrics. The selected advanced air vehicle concept is assessed against the baseline aircraft, and an advanced, but conventional aircraft, and the study metrics. The key technologies of the selected advanced air vehicle are identified, their impact quantified, and risk assessments and roadmaps defined.

Evaluating Three Insar Time-Series Methods to Assess Creep Motion, Case Study: Masouleh Landslide in North Iran

NASA Astrophysics Data System (ADS)

Mirzaee, S.; Motagh, M.; Akbari, B.; Wetzel, H. U.; Roessner, S.

2017-05-01

Masouleh is one of the ancient cities located in a high mountainous area in Gilan province of northern Iran. The region is threatened by a hazardous landslide, which was last activated in 1998, causing 32 dead and 45 injured. Significant temporal decorrelation caused by dense vegetation coverage within the landslide area makes the use of Synthetic Aperture Radar Interferometry (InSAR) for monitoring landslide movement very challenging. In this paper, we investigate the capability of three InSAR time-series techniques for evaluating creep motion on Masouleh landslide. The techniques are Persistent Scatterer Interferometry (PSI), Small BAseline Subset (SBAS) and SqueeSAR. The analysis is done using a dataset of 33 TerraSAR-X images in SpotLight (SL) mode covering a period of 15 months between June 2015 and September 2016. Results show the distinguished capability of SqueeSAR method in comparison to 2 other techniques for assessing landslide movement. The final number of scatterers in the landslide body detected by PSI and SBAS are about 70 and 120 respectively while this increases to about 345 in SqueeSAR. The coherence of interferograms improved by about 37% for SqueeSAR as compared to SBAS. The same rate of displacement was observed in those regions where all the methods were able to detect scatterers. Maximum rates of displacement detected by SqueeSAR technique in the northern edge, older and younger part of the landslide body are about -39, -65 and -22 mm/y, respectively.

Spatial and temporal variations in creep rate along the El Pilar fault at the Caribbean-South American plate boundary (Venezuela), from InSAR

NASA Astrophysics Data System (ADS)

Pousse Beltran, Léa.; Pathier, Erwan; Jouanne, François; Vassallo, Riccardo; Reinoza, Carlos; Audemard, Franck; Doin, Marie Pierre; Volat, Matthieu

2016-11-01

In eastern Venezuela, the Caribbean-South American plate boundary follows the El Pilar fault system. Previous studies based on three GPS campaigns (2003-2005-2013) demonstrated that the El Pilar fault accommodates the whole relative displacement between the two tectonic plates (20 mm/yr) and proposed that 50-60% of the slip is aseismic. In order to quantify the possible variations of the aseismic creep in time and space, we conducted an interferometric synthetic aperture radar (InSAR) time series analysis, using the (NSBAS) New Small BAseline Subset method, on 18 images from the Advanced Land Observing Satellite (ALOS-1) satellite spanning the 2007-2011 period. During this 3.5 year period, InSAR observations show that aseismic slip decreases eastward along the fault: the creep rate of the western segment reaches 25.3 ± 9.4 mm/yr on average, compared to 13.4 ± 6.9 mm/yr on average for the eastern segment. This is interpreted, through slip distribution models, as being related to coupled and uncoupled areas between the surface and 20 km in depth. InSAR observations also show significant temporal creep rate variations (accelerations) during the considered time span along the western segment. The transient behavior of the creep is not consistent with typical postseismic afterslip following the 1997 Ms 6.8 earthquake. The creep is thus interpreted as persistent aseismic slip during an interseismic period, which has a pulse- or transient-like behavior.

Atmospheric corrections in interferometric synthetic aperture radar surface deformation - a case study of the city of Mendoza, Argentina

NASA Astrophysics Data System (ADS)

Balbarani, S.; Euillades, P. A.; Euillades, L. D.; Casu, F.; Riveros, N. C.

2013-09-01

Differential interferometry is a remote sensing technique that allows studying crustal deformation produced by several phenomena like earthquakes, landslides, land subsidence and volcanic eruptions. Advanced techniques, like small baseline subsets (SBAS), exploit series of images acquired by synthetic aperture radar (SAR) sensors during a given time span. Phase propagation delay in the atmosphere is the main systematic error of interferometric SAR measurements. It affects differently images acquired at different days or even at different hours of the same day. So, datasets acquired during the same time span from different sensors (or sensor configuration) often give diverging results. Here we processed two datasets acquired from June 2010 to December 2011 by COSMO-SkyMed satellites. One of them is HH-polarized, and the other one is VV-polarized and acquired on different days. As expected, time series computed from these datasets show differences. We attributed them to non-compensated atmospheric artifacts and tried to correct them by using ERA-Interim global atmospheric model (GAM) data. With this method, we were able to correct less than 50% of the scenes, considering an area where no phase unwrapping errors were detected. We conclude that GAM-based corrections are not enough for explaining differences in computed time series, at least in the processed area of interest. We remark that no direct meteorological data for the GAM-based corrections were employed. Further research is needed in order to understand under what conditions this kind of data can be used.

Quantification of intra-tumour cell proliferation heterogeneity using imaging descriptors of 18F fluorothymidine-positron emission tomography

NASA Astrophysics Data System (ADS)

Willaime, J. M. Y.; Turkheimer, F. E.; Kenny, L. M.; Aboagye, E. O.

2013-01-01

Intra-tumour heterogeneity is a characteristic shared by all cancers. We explored the use of texture variables derived from images of [18F]fluorothymidine-positron emission tomography (FLT-PET), thus notionally assessing the heterogeneity of proliferation in individual tumours. Our aims were to study the range of textural feature values across tissue types, verify the repeatability of these image descriptors and further, to explore associations with clinical response to chemotherapy in breast cancer patients. The repeatability of 28 textural descriptors was assessed in patients who had two FLT-PET scans prior to therapy using relative differences and the intra-class correlation coefficient (ICC). We tested associations between features at baseline and clinical response measured in 11 patients after three cycles of chemotherapy, and explored changes in FLT-PET at one week after the start of therapy. A subset of eight features was characterized by low variations at baseline (<±30%) and high repeatability (0.7 ≤ ICC ≤ 1). The intensity distribution profile suggested fewer highly proliferating cells in lesions of non-responders compared to responders at baseline. A true increase in CV and homogeneity was measured in four out of six responders one week after the start of therapy. A number of textural features derived from FLT-PET are altered following chemotherapy in breast cancer, and should be evaluated in larger clinical trials for clinical relevance.

Preliminary differences in resting state MEG functional connectivity pre- and post-ketamine in major depressive disorder.

PubMed

Nugent, Allison C; Robinson, Stephen E; Coppola, Richard; Zarate, Carlos A

2016-08-30

Functional neuroimaging techniques including magnetoencephalography (MEG) have demonstrated that the brain is organized into networks displaying correlated activity. Group connectivity differences between healthy controls and participants with major depressive disorder (MDD) can be detected using temporal independent components analysis (ICA) on beta-bandpass filtered Hilbert envelope MEG data. However, the response of these networks to treatment is unknown. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects. We obtained MEG recordings before and after open-label infusion of 0.5mg/kg ketamine in MDD subjects (N=13) and examined networks previously shown to differ between healthy individuals and those with MDD. Connectivity between the amygdala and an insulo-temporal component decreased post-ketamine in MDD subjects towards that observed in control subjects at baseline. Decreased baseline connectivity of the subgenual anterior cingulate cortex (sgACC) with a bilateral precentral network had previously been observed in MDD compared to healthy controls, and the change in connectivity post-ketamine was proportional to the change in sgACC glucose metabolism in a subset (N=8) of subjects receiving [11F]FDG-PET imaging. Ketamine appeared to reduce connectivity, regardless of whether connectivity was abnormally high or low compared to controls at baseline. These preliminary findings suggest that sgACC connectivity may be directly related to glutamate levels. Published by Elsevier Ireland Ltd.

Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin.

PubMed

Overman, Michael J; Morris, Van; Moinova, Helen; Manyam, Ganiraju; Ensor, Joe; Lee, Michael S; Eng, Cathy; Kee, Bryan; Fogelman, David; Shroff, Rachna T; LaFramboise, Thomas; Mazard, Thibault; Feng, Tian; Hamilton, Stanley; Broom, Bradley; Lutterbaugh, James; Issa, Jean-Pierre; Markowitz, Sanford D; Kopetz, Scott

2016-10-11

Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high. This phase I/II study in CRC (phase II portion restricted to CIMP-high CRC), treated fluoropyrimidine/oxaliplatin refractory patients with azacitidine (75 mg/m2/day subcutaneously D1-5) and CAPOX (capecitibine and oxaliplatin) every three weeks. Twenty-six patients (pts) were enrolled in this study: 15 pts (12 treated at MTD) in phase I and 11 pts in phase II. No dose limiting toxicities were observed. A total of 14 pts were CIMP-high. No responses were seen. CIMP-high status did not correlate with efficacy endpoints [stable disease (SD) or progression-free survival (PFS)] or baseline vimentin methylation level. Changes in vimentin methylation over time did not correlate with efficacy outcomes. Baseline methylated vimentin correlated with tumor volume (P<0.001) and higher levels of baseline methylation correlated with the obtainment of stable disease (P=0.04). Azacitidine and CAPOX were well tolerated with high rates of stable disease in CIMP-high pts, but no objective responses. Serum methylated vimentin may be associated with benefit from a regimen including a hypomethylation agent, although this study is not able to separate a potential prognostic or predictive role for the biomarker.

Detecting and Measuring Land Subsidence in Houston-Galveston, Texas using Interferometric Synthetic Aperture Radar (InSAR) and Global Positioning System Data, 2012-2016

NASA Astrophysics Data System (ADS)

Reed, A.; Baker, S.

2016-12-01

Several cities in the Houston-Galveston (HG) region in Texas have subsided up to 13 feet over several decades due to natural and anthropogenic processes [Yu et al. 2014]. Land subsidence, a gradual sinking of the Earth's surface, is an often human-induced hazard and a major environmental problem expedited by activities such as mining, oil and gas extraction, urbanization and excessive groundwater pumping. We are able to detect and measure subsidence in HG using interferometric synthetic aperture radar (InSAR) and global positioning systems (GPS). Qu et al. [2015] used ERS, Envisat, and ALOS-1 to characterize subsidence in HG from 1995 to 2011, but a five-year gap in InSAR measurements exists due to a lack of freely available SAR data. We build upon the previous study by comparing subsidence patterns detected by Sentinel-1 data starting in July 2015. We used GMT5SAR to generate a stack of interferograms with perpendicular baselines less than 100 meters and temporal baselines less than 100 days to minimize temporal and spatial decorrelation. We applied the short baseline subset (SBAS) time series processing using GIAnT and compared our results with GPS measurements. The implications of this work will strengthen land subsidence monitoring systems in HG and broadly aid in the development of effective water resource management policies and strategies.

Changes in body composition over 8 years in a randomized trial of a lifestyle intervention: the look AHEAD study.

PubMed

Pownall, Henry J; Bray, George A; Wagenknecht, Lynne E; Walkup, Michael P; Heshka, Stanley; Hubbard, Van S; Hill, James; Kahn, Steven E; Nathan, David M; Schwartz, Anne V; Johnson, Karen C

2015-03-01

To determine the effects of an intensive lifestyle intervention versus a comparison group on body composition in obese or overweight persons with type 2 diabetes at baseline and at 1, 4, and 8 years. Body composition was measured by dual-energy X-ray absorptiometry in a subset of 1019 Look AHEAD study volunteers randomized to intervention or comparison groups. The intervention was designed to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. The comparison group received social support and diabetes education. At 1 year, the intervention group lost fat (5.6 ± 0.2 kg) and lean mass (2.3 ± 0.1 kg) but regained fat (∼100%) and lost lean mass between years 1 and 8. Between baseline and year 8, weight loss was greater in intervention versus comparison groups (4.0 ± 0.4 vs. 2.3 ± 0.4 kg); comparison group weight loss was mostly lean mass (2.1 ± 0.17 kg). Fat mass in the intervention group was lower than that of the comparison group at all post-baseline time points. Reduced fat mass may place the intervention group at a lower risk of obesity-linked sequelae, a hypothesis that can be tested by future studies of this cohort. © 2015 The Obesity Society.

Periodontal therapy alters gene expression of peripheral blood monocytes

PubMed Central

Papapanou, Panos N.; Sedaghatfar, Michael H.; Demmer, Ryan T.; Wolf, Dana L.; Yang, Jun; Roth, Georg A.; Celenti, Romanita; Belusko, Paul B.; Lalla, Evanthia; Pavlidis, Paul

2009-01-01

Aims We investigated the effects of periodontal therapy on gene expression of peripheral blood monocytes. Methods Fifteen patients with periodontitis gave blood samples at four time points: 1 week before periodontal treatment (#1), at treatment initiation (baseline, #2), 6-week (#3) and 10-week post-baseline (#4). At baseline and 10 weeks, periodontal status was recorded and subgingival plaque samples were obtained. Periodontal therapy (periodontal surgery and extractions without adjunctive antibiotics) was completed within 6 weeks. At each time point, serum concentrations of 19 biomarkers were determined. Peripheral blood monocytes were purified, RNA was extracted, reverse-transcribed, labelled and hybridized with AffymetrixU133Plus2.0 chips. Expression profiles were analysed using linear random-effects models. Further analysis of gene ontology terms summarized the expression patterns into biologically relevant categories. Differential expression of selected genes was confirmed by real-time reverse transcriptase-polymerase chain reaction in a subset of patients. Results Treatment resulted in a substantial improvement in clinical periodontal status and reduction in the levels of several periodontal pathogens. Expression profiling over time revealed more than 11,000 probe sets differentially expressed at a false discovery rate of <0.05. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis and cell signalling. Conclusions The data suggest that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect. PMID:17716309

The Queensland study of Melanoma: Environmental and Genetic Associations (Q-MEGA). Study design, baseline characteristics, and repeatability of phenotype and sun exposure measures

PubMed Central

Baxter, Amanda J.; Hughes, Maria Celia; Kvaskoff, Marina; Siskind, Victor; Shekar, Sri; Aitken, Joanne F.; Green, Adele C.; Duffy, David L.; Hayward, Nicholas K.; Martin, Nicholas G.; Whiteman, David C.

2013-01-01

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia which has the world’s highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland study of Melanoma: Environmental and Genetic Associations, which followed-up four population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. 3,471 participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002–2005. Updated data on environmental and phenotypic risk factors, and 2,777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from six to 17 years later, are also described. PMID:18361720

Incidence, Progression, and Associated Risk Factors of Posterior Vitreous Detachment in Type 2 Diabetes Mellitus: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS II, Report No. 7).

PubMed

Gella, Laxmi; Raman, Rajiv; Pal, Swakshyar Saumya; Ganesan, Suganeswari; Sharma, Tarun

2017-01-01

To report the incidence and progression of posterior vitreous detachment (PVD) and factors influencing the same in a cohort of patients with type 2 diabetes in a South Indian population. A subset of 615 subjects from Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study II were included in this study. All of the subjects underwent detailed ophthalmic evaluation including stereo fundus photography. The status of PVD was assessed using B-scan ultrasonography. A p value of <0.05 was considered statistically significant. The incidence of either incomplete PVD (IPVD) or complete PVD (CPVD) from no PVD at baseline visit was 80.8%. Of them, 32.63% converted to CPVD from IPVD at baseline. High prevalence of emmetropia was observed in subjects with stable No PVD. Risk factors associated with the conversion of CPVD from no PVD and IPVD at baseline were age (OR: 1.04, p = 0.002), myopia (OR: 2.14, p = 0.009), and increase in axial length (OR: 1.35, p = 0.004). Subjects undergoing cataract surgery were at 2.32 times higher risk of converting to CPVD (p = 0.038). Independent risk factors for the progression of PVD were increase in age, myopia, increased axial length, and cataract surgery.

Characteristics of High-Cost Patients Diagnosed with Opioid Abuse.

PubMed

Shei, Amie; Rice, J Bradford; Kirson, Noam Y; Bodnar, Katharine; Enloe, Caroline J; Birnbaum, Howard G; Holly, Pamela; Ben-Joseph, Rami

2015-10-01

Prescription opioid abuse is associated with substantial economic burden, with estimates of incremental annual per-patient health care costs of diagnosed opioid abuse exceeding $10,000 in prior literature. A subset of patients diagnosed with opioid abuse has disproportionately high health care costs, but little is known about the characteristics of these patients.  To describe the characteristics of a subset of patients diagnosed with opioid abuse with disproportionately high health care costs to assist physicians and managed care organizations in targeting interventions at the costliest patients. This retrospective claims data analysis identified patients aged 12 to 64 years diagnosed with opioid abuse/dependence in the OptumHealth Reporting and Insights medical and pharmacy claims database, Quarter 1 (Q1) 1999-Q1 2012. Inclusion criteria required that patients had a diagnosis of opioid abuse during or after Q1 2006, no prior diagnoses of opioid abuse, and continuous non-HMO coverage over an 18-month study period. The study period comprised a 12-month observation period centered on the date of the first opioid abuse diagnosis (index date) and a 6-month baseline period immediately preceding the observation period. Patients in the top 20% of total health care costs in the observation period were classified as "high-cost patients," and the remaining patients were classified as "lower-cost patients." Patient characteristics, comorbidities, health care resource use, and health care costs were compared between high-cost patients and lower-cost patients using chi-square tests for dichotomous variables and Wilcoxon rank-sum tests for continuous variables. In addition, multivariate regression was used to assess the relationship between patient characteristics in the baseline period and total health care costs in the observation period among all patients diagnosed with opioid abuse.  9,291 patients diagnosed with opioid abuse met the inclusion criteria. The 20% of patients classified as high-cost patients accounted for approximately two thirds of the total health care costs of patients diagnosed with opioid abuse. Compared with lower-cost patients, high-cost patients were older (42.5 vs. 36.1; P  less than  0.001) and more likely to be female (55.9% vs. 42.9%; P  less than  0.001). They had a higher comorbidity burden at baseline, as reflected in the Charlson Comorbidity Index (0.8 vs. 0.2; P  less than  0.001), and rates of conditions such as chronic pulmonary disease (12.9% vs. 5.6%; P  less than  0.001) and mild/moderate diabetes (8.4% vs. 3.4%; P  less than  0.001). High-cost patients also had higher rates of nonopioid substance abuse diagnoses (12.4% vs. 8.9%; P  less than  0.001) and psychotic disorders (26.5% vs. 13.6%; P  less than  0.001). In the observation period, high-cost patients continued to have higher rates of nonopioid substance abuse diagnoses (53.0% vs. 47.2%; P  less than  0.001) and psychotic disorders (67.1% vs. 47.5%; P  less than  0.001). In addition, they had greater medical resource use across all places of service (i.e., inpatient, emergency department, outpatient, drug/alcohol rehabilitation facility, and other) compared with lower-cost patients. The mean observation period health care costs of high-cost patients was $89,177 compared with $11,653 for lower-cost patients (P  less than  0.001). High-cost patients had higher medical costs linked to claims with an opioid abuse diagnosis in absolute terms, but the share of total medical costs attributed to such claims was lower among high-cost patients than among lower-cost patients. While many baseline characteristics were found to have a statistically significant (P  less than  0.05) association with observation period health care costs, only 27.3% of the variation in observation period health care costs was explained by patient characteristics in the baseline period. This study found that the costliest patients diagnosed with opioid abuse had high rates of preexisting and concurrent chronic comorbidities and mental health conditions, suggesting potential indicators for targeted intervention and a need for greater awareness and screening of comorbid conditions. Opioid abuse may exacerbate existing conditions and make it difficult for patients to adhere to treatment plans for those underlying conditions. Baseline patient characteristics explained only a small share of the variation in observation period health care costs, however. Future research should explore the degree to which other factors not captured in administrative claims data (e.g., severity of abuse) can explain the wide variation in health care costs among opioid abusers.

40 CFR 63.1281 - Control equipment requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... requirements for sources except small glycol dehydration units. Owners and operators of small glycol dehydration units shall comply with the control requirements in paragraph (f) of this section. (1) The control... or operator shall determine glycol dehydration unit baseline operations (as defined in § 63.1271...

40 CFR 63.1281 - Control equipment requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... requirements for sources except small glycol dehydration units. Owners and operators of small glycol dehydration units shall comply with the control requirements in paragraph (f) of this section. (1) The control... or operator shall determine glycol dehydration unit baseline operations (as defined in § 63.1271...

The relationship of renal function to outcome: A post hoc analysis from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study.

PubMed

Lip, Gregory Y H; Al-Saady, Naab; Ezekowitz, Michael D; Banach, Maciej; Goette, Andreas

2017-11-01

The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion. Efficacy and safety outcomes and time in therapeutic range in the warfarin arm were analyzed in relation to CrCl in prespecified ranges ≥15 and ≤30, >30 and ≤50, >50 and <80, and ≥80 mL/min, and an exploratory ≥95-mL/min analysis. A total of 1,095 subjects were randomized to edoxaban and 1,104 to enoxaparin-warfarin. Mean age was 64.3±10 and 64.2±11 years. Mean time in therapeutic range was progressively lower with reducing CrCl strata, being 66.8% in those with CrCl >30 to ≤50 compared with 71.8% in those with CrCl ≥80. The odds ratios for the primary efficacy and safety end points were comparable for the different predefined renal function strata; given the small numbers, the 95% CI included 1.0. In the subset of those with CrCl ≥95, the odds ratios showed consistency with the other CrCl strata. When CrCl was assessed as a continuous variable, there was a nonsignificant trend toward higher major or clinically relevant nonmajor bleeding with reducing CrCl levels, with no significant differences between the 2 treatment arms. When we assessed CrCl at baseline compared with end of treatment, there were no significant differences in CrCl change between the edoxaban and enoxaparin-warfarin arms. The proportions with worsening of renal function (defined as a decrease of >20% from baseline) were similar in the 2 treatment arms. Given the small number of events in ENSURE-AF, no effect of renal (dys)function was demonstrated in comparing edoxaban to enoxaparin-warfarin for cardioversion; efficacy and safety of edoxaban remained consistent even in patients with normal or supranormal renal function. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydrothermal fluid flow models of Campi Flegrei caldera, Italy constrained by InSAR surface deformation time series observations

NASA Astrophysics Data System (ADS)

Lundgren, P.; Lanari, R.; Manzo, M.; Sansosti, E.; Tizzani, P.; Hutnak, M.; Hurwitz, S.

2008-12-01

Campi Flegrei caldera, Italy, located along the Bay of Naples, has a long history of significant vertical deformation, with the most recent large uplift (>1.5m) occurring in 1983-1984. Each episode of uplift has been followed by a period of subsidence that decreases in rate with time and may be punctuated by brief episodes of lesser uplift. The large amplitude of the major uplifts that occur without volcanic activity, and the subsequent subsidence has been argued as evidence for hydrothermal amplification of any magmatic source. The later subsidence and its temporal decay have been argued as due to diffusion of the pressurized caldera fill material into the less porous surrounding country rock. We present satellite synthetic aperture radar (SAR) interferometry (InSAR) time series analysis of ERS and Envisat data from the European Space Agency, based on exploiting the Small Baseline Subset (SBAS) approach [Berardino et al., 2002]; this allows us to generate maps of relative surface deformation though time, beginning in 1992 through 2007, that are relevant to both ascending and descending satellite orbits. The general temporal behavior is one of subsidence punctuated by several lesser uplift episodes. The spatial pattern of deformation can be modeled through simple inflation/deflation sources in an elastic halfspace. Given the evidence to suggest that fluids may play a significant role in the temporal deformation of Campi Flegrei, rather than a purely magmatic or magma chamber-based interpretation, we model the temporal and spatial evolution of surface deformation as a hydrothermal fluid flow process. We use the TOUGH2-BIOT2 set of numerical codes [Preuss et al., 1999; Hsieh, 1996], which couple multi-phase (liquid-gas) and multi-component (H2O-CO2) fluid flow in a porous or fractured media with plane strain deformation and fluid flow in a linearly elastic porous medium. We explore parameters related to the depth and temporal history of fluid injection, fluid composition, circulation geometries, and the physical properties of the media, to explain the InSAR time series. References: Berardino, P., R. Lanari, E. Sansosti (2002), A new Algorithm for surface deformation monitoring based on small baseline differential SAR interferograms, IEEE Transactions on Geoscience and Remote Sensing, 40, 11, 2375-2383. Pruess, L., C. Oldenburg, and G. Moridis (1999), TOUGH2 user's guide, version 2.0, Paper LBNL-43134, Lawrence Berkeley Natl. Lab., Berkeley, Calif. Hsieh, P. A. (1996), Deformation-induced changes in hydraulic head during ground-water withdrawal, Ground Water, 34, 1082-1089.

Biology and clinical relevance of noncoding sno/scaRNAs.

PubMed

Cao, Thuy; Rajasingh, Sheeja; Samanta, Saheli; Dawn, Buddhadeb; Bittel, Douglas C; Rajasingh, Johnson

2018-02-01

Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that perform various biological functions, including biochemical modifications of other RNAs, precursors of miRNA, splicing, and telomerase activity. The small Cajal body-associated RNAs (scaRNAs) are a subset of the snoRNA family and collect in the Cajal body where they perform their canonical function to biochemically modify spliceosomal RNAs prior to maturation. Failure of sno/scaRNAs have been implicated in pathology such as congenital heart anomalies, neuromuscular disorders, and various malignancies. Thus, understanding of sno/scaRNAs demonstrates the clinical value. Copyright © 2018 Elsevier Inc. All rights reserved.

Prospective Associations Between the Cortisol Awakening Response and First Onsets of Anxiety Disorders Over a Six-Year Follow-up – 2013 Curt Richter Award Winner

PubMed Central

Adam, Emma K.; Vrshek-Schallhorn, Suzanne; Kendall, Ashley D.; Mineka, Susan; Zinbarg, Richard E.; Craske, Michelle G.

2014-01-01

Cross-sectional associations have been found between anxiety disorders (ADs) and hypothalamic-pituitary-adrenal (HPA) axis functioning, as measured by levels of salivary cortisol, but prospective data are lacking, as are studies examining specific ADs. We have previously shown that one aspect of the diurnal rhythm of cortisol, the cortisol awakening response (CAR), prospectively predicts both new onsets and recurrences of major depressive disorder (MDD). Here we sought to examine whether it also predicts ADs. Participants (N=232) were drawn from the larger Northwestern-UCLA Youth Emotion Project, a two-site, longitudinal study of older adolescents, which aims to identify common and specific risk factors for mood and anxiety disorders. After baseline interviews for mental health diagnoses, a subset of adolescents completed a three-day cortisol sampling protocol measuring the CAR and other diurnal rhythm indices. Participants with past or current anxiety disorders at the time of cortisol measurement were excluded and Cox regression (survival analysis) was used to predict first onsets of ADs over the subsequent six years. AD onsets (N=25), the largest subset of which were social anxiety disorder (SAD) onsets (N=11), were observed over six annual follow up diagnostic interviews. Even when statistically adjusting for past and prospective MDD onsets and other covariates, a higher CAR significantly predicted increased first onsets of ADs (HR = 2.20, p < .05). A higher CAR was also a strong and significant predictor of the subset of SAD onsets (HR = 5.37, p < .005). Implications for the etiology of ADs, with a focus on SAD, are discussed. PMID:24767619

Bone marrow chimeric mice reveal a role for CX₃CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium.

PubMed

Vukovic, Jana; Blomster, Linda V; Chinnery, Holly R; Weninger, Wolfgang; Jung, Steffen; McMenamin, Paul G; Ruitenberg, Marc J

2010-10-01

Macrophages in the olfactory neuroepithelium are thought to play major roles in tissue homeostasis and repair. However, little information is available at present about possible heterogeneity of these monocyte-derived cells, their turnover rates, and the role of chemokine receptors in this process. To start addressing these issues, this study used Cx₃cr1(gfp) mice, in which the gene sequence for eGFP was knocked into the CX₃CR1 gene locus in the mutant allele. Using neuroepithelial whole-mounts from Cx₃cr1(gfp/+) mice, we show that eGFP(+) cells of monocytic origin are distributed in a loose network throughout this tissue and can be subdivided further into two immunophenotypically distinct subsets based on MHC-II glycoprotein expression. BM chimeric mice were created using Cx₃cr1(gfp/+) donors to investigate turnover of macrophages (and other monocyte-derived cells) in the olfactory neuroepithelium. Our data indicate that the monocyte-derived cell population in the olfactory neuroepithelium is actively replenished by circulating monocytes and under the experimental conditions, completely turned over within 6 months. Transplantation of Cx₃cr1(gfp/gfp) (i.e., CX₃CR1-deficient) BM partially impaired the replenishment process and resulted in an overall decline of the total monocyte-derived cell number in the olfactory epithelium. Interestingly, replenishment of the CD68(low)MHC-II(+) subset appeared minimally affected by CX₃CR1 deficiency. Taken together, the established baseline data about heterogeneity of monocyte-derived cells, their replenishment rates, and the role of CX₃CR1 provide a solid basis to further examine the importance of different monocyte subsets for neuroregeneration at this unique frontier with the external environment.

Memory, Mood, and Vitamin D in Persons with Parkinson’s Disease

PubMed Central

Peterson, Amie L.; Murchison, Charles; Zabetian, Cyrus; Leverenz, James B.; Watson, G. Stennis; Montine, Thomas; Carney, Natasha; Bowman, Gene L.; Edwards, Karen; Quinn, Joseph F.

2014-01-01

Background Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation. Objective To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson’s disease (PD). Methods This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson’s Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitamin D concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets. Results Using a multivariate model, higher vitamin concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t =−3.08, p = 0.0083) in the non-demented subset. Conclusions Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study. PMID:24081441

Physical function metric over measure: An illustration with the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Functional Assessment of Cancer Therapy (FACT).

PubMed

Kaat, Aaron J; Schalet, Benjamin D; Rutsohn, Joshua; Jensen, Roxanne E; Cella, David

2018-01-01

Measuring patient-reported outcomes (PROs) is becoming an integral component of quality improvement initiatives, clinical care, and research studies in cancer, including comparative effectiveness research. However, the number of PROs limits comparability across studies. Herein, the authors attempted to link the Functional Assessment of Cancer Therapy-General Physical Well-Being (FACT-G PWB) subscale with the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) calibrated item bank. The also sought to augment a subset of the conceptually most similar FACT-G PWB items with PROMIS PF items to improve the linking. Baseline data from 5506 participants in the Measuring Your Health (MY-Health) study were used to identify the optimal items for linking FACT-G PWB with PROMIS PF. A mixed methods approach identified the optimal items for creating the 5-item FACT/PROMIS-PF5 scale. Both the linked and augmented relationships were cross-validated using the follow-up MY-Health data. A 5-item FACT-G PWB item subset was found to be optimal for linking with PROMIS PF. In addition, a 2-item subset, including only items that were conceptually very similar to the PROMIS item bank content, were augmented with 3 PROMIS PF items. This new FACT/PROMIS-PF5 provided superior score recovery. The PROMIS PF metric allows for the evaluation of the extent to which similar questionnaires can be linked and therefore expressed on the same metric. These results allow for the aggregation of existing data and provide an optimal measure for future studies wishing to use the FACT yet also report on the PROMIS PF metric. Cancer 2018;124:153-60. © 2017 American Cancer Society. © 2017 American Cancer Society.

Prospective associations between the cortisol awakening response and first onsets of anxiety disorders over a six-year follow-up--2013 Curt Richter Award Winner.

PubMed

Adam, Emma K; Vrshek-Schallhorn, Suzanne; Kendall, Ashley D; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G

2014-06-01

Cross-sectional associations have been found between anxiety disorders (ADs) and hypothalamic-pituitary-adrenal (HPA) axis functioning, as measured by levels of salivary cortisol, but prospective data are lacking, as are studies examining specific ADs. We have previously shown that one aspect of the diurnal rhythm of cortisol, the cortisol awakening response (CAR), prospectively predicts both new onsets and recurrences of major depressive disorder (MDD). Here we sought to examine whether it also predicts ADs. Participants (N=232) were drawn from the larger Northwestern-UCLA Youth Emotion Project, a two-site, longitudinal study of older adolescents, which aims to identify common and specific risk factors for mood and anxiety disorders. After baseline interviews for mental health diagnoses, a subset of adolescents completed a three-day cortisol sampling protocol measuring the CAR and other diurnal rhythm indices. Participants with past or current anxiety disorders at the time of cortisol measurement were excluded and Cox regression (survival analysis) was used to predict first onsets of ADs over the subsequent six years. AD onsets (N=25), the largest subset of which were social anxiety disorder (SAD) onsets (N=11), were observed over six annual follow up diagnostic interviews. Even when statistically adjusting for past and prospective MDD onsets and other covariates, a higher CAR significantly predicted increased first onsets of ADs (HR=2.20, p<.05). A higher CAR was also a strong and significant predictor of the subset of SAD onsets (HR=5.37, p<.005). Implications for the etiology of ADs, with a focus on SAD, are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single-cell systems level analysis of human Toll-Like-Receptor activation defines a chemokine signature in Systemic Lupus Erythematosus

PubMed Central

O'Gorman, William E.; Hsieh, Elena W.Y.; Savig, Erica S.; Gherardini, Pier Federico; Hernandez, Joseph D.; Hansmann, Leo; Balboni, Imelda M.; Utz, Paul J.; Bendall, Sean C.; Fantl, Wendy J.; Lewis, David B.; Nolan, Garry P.; Davis, Mark M.

2015-01-01

Background Activation of Toll-Like Receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in Systemic Lupus Erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has previously not been described. Objective To characterize TLR activation across multiple immune cell subsets and individuals, with the goal of establishing a reference framework against which to compare pathological processes. Methods Peripheral whole blood samples were stimulated with TLR ligands, and analyzed by mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied seventeen healthy volunteer donors and eight newly diagnosed untreated SLE patients. Results Our data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of NK and T cells selectively induced NF-κB in response to TLR2 ligands. CD14hi monocytes exhibited the most polyfunctional cytokine expression patterns, with over 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared amongst a group of healthy donors, with minimal intra- and inter- individual variability. Furthermore, autoimmune disease altered baseline cytokine production, as newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity. Conclusion Mass cytometry analysis defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in inflammatory disease, such as SLE. PMID:26037552

Distributed Turboelectric Propulsion for Hybrid Wing Body Aircraft

NASA Technical Reports Server (NTRS)

Kim, Hyun Dae; Brown, Gerald V.; Felder, James L.

2008-01-01

Meeting future goals for aircraft and air traffic system performance will require new airframes with more highly integrated propulsion. Previous studies have evaluated hybrid wing body (HWB) configurations with various numbers of engines and with increasing degrees of propulsion-airframe integration. A recently published configuration with 12 small engines partially embedded in a HWB aircraft, reviewed herein, serves as the airframe baseline for the new concept aircraft that is the subject of this paper. To achieve high cruise efficiency, a high lift-to-drag ratio HWB was adopted as the baseline airframe along with boundary layer ingestion inlets and distributed thrust nozzles to fill in the wakes generated by the vehicle. The distributed powered-lift propulsion concept for the baseline vehicle used a simple, high-lift-capable internally blown flap or jet flap system with a number of small high bypass ratio turbofan engines in the airframe. In that concept, the engine flow path from the inlet to the nozzle is direct and does not involve complicated internal ducts through the airframe to redistribute the engine flow. In addition, partially embedded engines, distributed along the upper surface of the HWB airframe, provide noise reduction through airframe shielding and promote jet flow mixing with the ambient airflow. To improve performance and to reduce noise and environmental impact even further, a drastic change in the propulsion system is proposed in this paper. The new concept adopts the previous baseline cruise-efficient short take-off and landing (CESTOL) airframe but employs a number of superconducting motors to drive the distributed fans rather than using many small conventional engines. The power to drive these electric fans is generated by two remotely located gas-turbine-driven superconducting generators. This arrangement allows many small partially embedded fans while retaining the superior efficiency of large core engines, which are physically separated but connected through electric power lines to the fans. This paper presents a brief description of the earlier CESTOL vehicle concept and the newly proposed electrically driven fan concept vehicle, using the previous CESTOL vehicle as a baseline.

Secure Overlay Services (SOS)

DTIC Science & Technology

2004-08-01

special node in the SOS architecture that is easily reached, called the beacon. 3. The beacon forwards the packet to a “secret” node, called the secret servlet...whose identity is known to only a small subset of participants in the SOS architecture. 6 4. The secret servlet forwards the packet to...address is the secret servlet. In the following discussion, we motivate why the SOS architecture requires the series of steps described above

Preventative Therapeutics for Heterotopic Ossification

DTIC Science & Technology

2016-12-01

lamellar bone within soft tissue after severe traumatic in- jury [10]. It is known to develop in the majority of combat- related amputations, and early...in- jury pattern alone and in various combinations. Lastly, we evaluated the time course of gene expression for a small subset of genes at given...demonstrated in a murine Achilles tenotomy plus partial-thickness dorsum burn in- jury model that injured mice develop endochondral ectopic bone and

A Novel Inhibitor Of Topoisomerase I is Selectively Toxic For A Subset of Non-Small Cell Lung Cancer Cell Lines | Office of Cancer Genomics

Cancer.gov

SW044248, identified through a screen for chemicals that are selectively toxic for NSCLC cell lines, was found to rapidly inhibit macromolecular synthesis in sensitive, but not in insensitive cells. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was non-toxic to immortalized human bronchial cell lines.

Gender and Ethnicity Classification from Small Subsets of Human Body Measurements

DTIC Science & Technology

2014-03-01

SIGNATURE PAGE Using Government drawings, specifications, or other data included in this document for any purpose other than Government procurement...does not in any way obligate the U.S. Government. The fact that the Government formulated or supplied the drawings, specifications, or other data does...collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources

Genome-wide analyses of four major histone modifications in Arabidopsis hybrids at the germinating seed stage.

PubMed

Zhu, Anyu; Greaves, Ian K; Dennis, Elizabeth S; Peacock, W James

2017-02-07

Hybrid vigour (heterosis) has been used for decades in cropping agriculture, especially in the production of maize and rice, because hybrid varieties exceed their parents in plant biomass and seed yield. The molecular basis of hybrid vigour is not fully understood. Previous studies have suggested that epigenetic systems could play a role in heterosis. In this project, we investigated genome-wide patterns of four histone modifications in Arabidopsis hybrids in germinating seeds. We found that although hybrids have similar histone modification patterns to the parents in most regions of the genome, they have altered patterns at specific loci. A small subset of genes show changes in histone modifications in the hybrids that correlate with changes in gene expression. Our results also show that genome-wide patterns of histone modifications in geminating seeds parallel those at later developmental stages of seedlings. Ler/C24 hybrids showed similar genome-wide patterns of histone modifications as the parents at an early germination stage. However, a small subset of genes, such as FLC, showed correlated changes in histone modification and in gene expression in the hybrids. The altered patterns of histone modifications for those genes in hybrids could be related to some heterotic traits in Arabidopsis, such as flowering time, and could play a role in hybrid vigour establishment.

Genetic Contribution to Non-Squamous, Non-Small Cell Lung Cancer in Non-Smokers.

PubMed

Carr, Shamus R; Akerley, Wallace; Cannon-Albright, Lisa

2018-04-04

Lung carcinogenesis is strongly influenced by environmental and heritable factors. The genetic contribution to the different histologies is unknown. A population-based computerized genealogy resource linked to a statewide cancer registry of lung cancer cases (n=5408) was analyzed to evaluate the heritable contribution to lung cancer histology in smoking (n=1751) and non-smoking cases (n=818). Statistical methods were used to test for significant excess relatedness of lung cancer cases. Significant excess distant relatedness was observed for all lung cancer histology subgroups analyzed except the small cell lung cancer subset (p=0.213). When smoking and non-smoking histologic subsets of lung cancer were considered, excess relatedness was observed only in non-smoking NSCLC (n=653; p=0.026) and, particularly, in those non-smokers with non-squamous histology (n=561; p=0.036). Sixty one pedigrees were identified which demonstrated a significant excess risk of non-smoking, non-squamous lung cancer cases; and an excess of female cases was observed among the cases in these high-risk pedigrees. This analysis supports a genetic predisposition to lung cancer carcinogenesis in non-smoking, non-squamous NSCLC cases. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Herd behaviour experimental testing in laboratory artificial stock market settings. Behavioural foundations of stylised facts of financial returns

NASA Astrophysics Data System (ADS)

Manahov, Viktor; Hudson, Robert

2013-10-01

Many scholars express concerns that herding behaviour causes excess volatility, destabilises financial markets, and increases the likelihood of systemic risk. We use a special form of the Strongly Typed Genetic Programming (STGP) technique to evolve a stock market divided into two groups-a small subset of artificial agents called ‘Best Agents’ and a main cohort of agents named ‘All Agents’. The ‘Best Agents’ perform best in term of the trailing return of a wealth moving average. We then investigate whether herding behaviour can arise when agents trade Dow Jones, General Electric, and IBM financial instruments in four different artificial stock markets. This paper uses real historical quotes of the three financial instruments to analyse the behavioural foundations of stylised facts such as leptokurtosis, non-IIDness, and volatility clustering. We found evidence of more herding in a group of stocks than in individual stocks, but the magnitude of herding does not contribute to the mispricing of assets in the long run. Our findings suggest that the price formation process caused by the collective behaviour of the entire market exhibit less herding and is more efficient than the segmented market populated by a small subset of agents. Hence, greater genetic diversity leads to greater consistency with fundamental values and market efficiency.

The p14 fusion-associated small transmembrane (FAST) protein effects membrane fusion from a subset of membrane microdomains.

PubMed

Corcoran, Jennifer A; Salsman, Jayme; de Antueno, Roberto; Touhami, Ahmed; Jericho, Manfred H; Clancy, Eileen K; Duncan, Roy

2006-10-20

The reovirus fusion-associated small transmembrane (FAST) proteins are a unique family of viral membrane fusion proteins. These nonstructural viral proteins induce efficient cell-cell rather than virus-cell membrane fusion. We analyzed the lipid environment in which the reptilian reovirus p14 FAST protein resides to determine the influence of the cell membrane on the fusion activity of the FAST proteins. Topographical mapping of the surface of fusogenic p14-containing liposomes by atomic force microscopy under aqueous conditions revealed that p14 resides almost exclusively in thickened membrane microdomains. In transfected cells, p14 was found in both Lubrol WX- and Triton X-100-resistant membrane complexes. Cholesterol depletion of donor cell membranes led to preferential disruption of p14 association with Lubrol WX (but not Triton X-100)-resistant membranes and decreased cell-cell fusion activity, both of which were reversed upon subsequent cholesterol repletion. Furthermore, co-patching analysis by fluorescence microscopy indicated that p14 did not co-localize with classical lipid-anchored raft markers. These data suggest that the p14 FAST protein associates with heterogeneous membrane microdomains, a distinct subset of which is defined by cholesterol-dependent Lubrol WX resistance and which may be more relevant to the membrane fusion process.

Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

PubMed

Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

2012-10-01

Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

CHIPMUNK: A Virtual Synthesizable Small-Molecule Library for Medicinal Chemistry, Exploitable for Protein-Protein Interaction Modulators.

PubMed

Humbeck, Lina; Weigang, Sebastian; Schäfer, Till; Mutzel, Petra; Koch, Oliver

2018-03-20

A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a novel virtual library of small molecules which are synthesizable from purchasable educts, called CHIPMUNK (CHemically feasible In silico Public Molecular UNiverse Knowledge base). Altogether, CHIPMUNK covers over 95 million compounds and encompasses regions of the chemical space that are not covered by existing databases. The coverage of CHIPMUNK exceeds the chemical space spanned by the Lipinski rule of five to foster the exploration of novel and difficult target classes. The analysis of the generated property space reveals that CHIPMUNK is well suited for the design of protein-protein interaction inhibitors (PPIIs). Furthermore, a recently developed structural clustering algorithm (StruClus) for big data was used to partition the sub-libraries into meaningful subsets and assist scientists to process the large amount of data. These clustered subsets also contain the target space based on ChEMBL data which was included during clustering. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.

PubMed

Gaillard, Carlo A; Bock, Andreas H; Carrera, Fernando; Eckardt, Kai-Uwe; Van Wyck, David B; Bansal, Sukhvinder S; Cronin, Maureen; Meier, Yvonne; Larroque, Sylvain; Roger, Simon D; Macdougall, Iain C

2016-01-01

Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600μg/L) or lower (100-200μg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.

G-STRATEGY: Optimal Selection of Individuals for Sequencing in Genetic Association Studies

PubMed Central

Wang, Miaoyan; Jakobsdottir, Johanna; Smith, Albert V.; McPeek, Mary Sara

2017-01-01

In a large-scale genetic association study, the number of phenotyped individuals available for sequencing may, in some cases, be greater than the study’s sequencing budget will allow. In that case, it can be important to prioritize individuals for sequencing in a way that optimizes power for association with the trait. Suppose a cohort of phenotyped individuals is available, with some subset of them possibly already sequenced, and one wants to choose an additional fixed-size subset of individuals to sequence in such a way that the power to detect association is maximized. When the phenotyped sample includes related individuals, power for association can be gained by including partial information, such as phenotype data of ungenotyped relatives, in the analysis, and this should be taken into account when assessing whom to sequence. We propose G-STRATEGY, which uses simulated annealing to choose a subset of individuals for sequencing that maximizes the expected power for association. In simulations, G-STRATEGY performs extremely well for a range of complex disease models and outperforms other strategies with, in many cases, relative power increases of 20–40% over the next best strategy, while maintaining correct type 1 error. G-STRATEGY is computationally feasible even for large datasets and complex pedigrees. We apply G-STRATEGY to data on HDL and LDL from the AGES-Reykjavik and REFINE-Reykjavik studies, in which G-STRATEGY is able to closely-approximate the power of sequencing the full sample by selecting for sequencing a only small subset of the individuals. PMID:27256766

Iterative Stable Alignment and Clustering of 2D Transmission Electron Microscope Images

PubMed Central

Yang, Zhengfan; Fang, Jia; Chittuluru, Johnathan; Asturias, Francisco J.; Penczek, Pawel A.

2012-01-01

SUMMARY Identification of homogeneous subsets of images in a macromolecular electron microscopy (EM) image data set is a critical step in single-particle analysis. The task is handled by iterative algorithms, whose performance is compromised by the compounded limitations of image alignment and K-means clustering. Here we describe an approach, iterative stable alignment and clustering (ISAC) that, relying on a new clustering method and on the concepts of stability and reproducibility, can extract validated, homogeneous subsets of images. ISAC requires only a small number of simple parameters and, with minimal human intervention, can eliminate bias from two-dimensional image clustering and maximize the quality of group averages that can be used for ab initio three-dimensional structural determination and analysis of macromolecular conformational variability. Repeated testing of the stability and reproducibility of a solution within ISAC eliminates heterogeneous or incorrect classes and introduces critical validation to the process of EM image clustering. PMID:22325773

Iterative CT reconstruction using coordinate descent with ordered subsets of data

NASA Astrophysics Data System (ADS)

Noo, F.; Hahn, K.; Schöndube, H.; Stierstorfer, K.

2016-04-01

Image reconstruction based on iterative minimization of a penalized weighted least-square criteria has become an important topic of research in X-ray computed tomography. This topic is motivated by increasing evidence that such a formalism may enable a significant reduction in dose imparted to the patient while maintaining or improving image quality. One important issue associated with this iterative image reconstruction concept is slow convergence and the associated computational effort. For this reason, there is interest in finding methods that produce approximate versions of the targeted image with a small number of iterations and an acceptable level of discrepancy. We introduce here a novel method to produce such approximations: ordered subsets in combination with iterative coordinate descent. Preliminary results demonstrate that this method can produce, within 10 iterations and using only a constant image as initial condition, satisfactory reconstructions that retain the noise properties of the targeted image.

Isolation and Flow Cytometry Analysis of Innate Lymphoid Cells from the Intestinal Lamina Propria.

PubMed

Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

2017-01-01

The intestinal mucosa constitutes the biggest surface area of the body. It is constantly challenged by bacteria, commensal and pathogenic, protozoa, and food-derived irritants. In order to maintain homeostasis, a complex network of signaling circuits has evolved that includes contributions of immune cells. In recent years a subset of lymphocytes, which belong to the innate immune system, has caught particular attention. These so-called innate lymphoid cells (ILC) reside within the lamina propria of the small and large intestines and rapidly respond to environmental challenges. They provide immunity to various types of infections but may also contribute to organ homeostasis as they produce factors acting on epithelial cells thereby enhancing barrier integrity. Here, we describe how these cells can be isolated from their environment and provide an in-depth protocol how to visualize the various ILC subsets by flow cytometry.

On a phase diagram for random neural networks with embedded spike timing dependent plasticity.

PubMed

Turova, Tatyana S; Villa, Alessandro E P

2007-01-01

This paper presents an original mathematical framework based on graph theory which is a first attempt to investigate the dynamics of a model of neural networks with embedded spike timing dependent plasticity. The neurons correspond to integrate-and-fire units located at the vertices of a finite subset of 2D lattice. There are two types of vertices, corresponding to the inhibitory and the excitatory neurons. The edges are directed and labelled by the discrete values of the synaptic strength. We assume that there is an initial firing pattern corresponding to a subset of units that generate a spike. The number of activated externally vertices is a small fraction of the entire network. The model presented here describes how such pattern propagates throughout the network as a random walk on graph. Several results are compared with computational simulations and new data are presented for identifying critical parameters of the model.

Estimation of the lower and upper bounds on the probability of failure using subset simulation and random set theory

NASA Astrophysics Data System (ADS)

Alvarez, Diego A.; Uribe, Felipe; Hurtado, Jorge E.

2018-02-01

Random set theory is a general framework which comprises uncertainty in the form of probability boxes, possibility distributions, cumulative distribution functions, Dempster-Shafer structures or intervals; in addition, the dependence between the input variables can be expressed using copulas. In this paper, the lower and upper bounds on the probability of failure are calculated by means of random set theory. In order to accelerate the calculation, a well-known and efficient probability-based reliability method known as subset simulation is employed. This method is especially useful for finding small failure probabilities in both low- and high-dimensional spaces, disjoint failure domains and nonlinear limit state functions. The proposed methodology represents a drastic reduction of the computational labor implied by plain Monte Carlo simulation for problems defined with a mixture of representations for the input variables, while delivering similar results. Numerical examples illustrate the efficiency of the proposed approach.

High-dimensional cluster analysis with the Masked EM Algorithm

PubMed Central

Kadir, Shabnam N.; Goodman, Dan F. M.; Harris, Kenneth D.

2014-01-01

Cluster analysis faces two problems in high dimensions: first, the “curse of dimensionality” that can lead to overfitting and poor generalization performance; and second, the sheer time taken for conventional algorithms to process large amounts of high-dimensional data. We describe a solution to these problems, designed for the application of “spike sorting” for next-generation high channel-count neural probes. In this problem, only a small subset of features provide information about the cluster member-ship of any one data vector, but this informative feature subset is not the same for all data points, rendering classical feature selection ineffective. We introduce a “Masked EM” algorithm that allows accurate and time-efficient clustering of up to millions of points in thousands of dimensions. We demonstrate its applicability to synthetic data, and to real-world high-channel-count spike sorting data. PMID:25149694

Optimisation algorithms for ECG data compression.

PubMed

Haugland, D; Heber, J G; Husøy, J H

1997-07-01

The use of exact optimisation algorithms for compressing digital electrocardiograms (ECGs) is demonstrated. As opposed to traditional time-domain methods, which use heuristics to select a small subset of representative signal samples, the problem of selecting the subset is formulated in rigorous mathematical terms. This approach makes it possible to derive algorithms guaranteeing the smallest possible reconstruction error when a bounded selection of signal samples is interpolated. The proposed model resembles well-known network models and is solved by a cubic dynamic programming algorithm. When applied to standard test problems, the algorithm produces a compressed representation for which the distortion is about one-half of that obtained by traditional time-domain compression techniques at reasonable compression ratios. This illustrates that, in terms of the accuracy of decoded signals, existing time-domain heuristics for ECG compression may be far from what is theoretically achievable. The paper is an attempt to bridge this gap.

Rationale and design of the PREFERS (Preserved and Reduced Ejection Fraction Epidemiological Regional Study) Stockholm heart failure study: an epidemiological regional study in Stockholm county of 2.1 million inhabitants.

PubMed

Linde, Cecilia; Eriksson, Maria J; Hage, Camilla; Wallén, Håkan; Persson, Bengt; Corbascio, Matthias; Lundeberg, Joakim; Maret, Eva; Ugander, Martin; Persson, Hans

2016-10-01

Heart failure (HF) with preserved (HFpEF) or reduced (HFrEF) ejection fraction is associated with poor prognosis and quality of life. While the incidence of HFrEF is declining and HF treatment is effective, HFpEF is increasing, with no established therapy. PREFERS Stockholm is an epidemiological study with the aim of improving clinical care and research in HF and to find new targets for drug treatment in HFpEF (https://internwebben.ki.se/sites/default/files/20150605_4d_research_appendix_final.pdf). Patients with new-onset HF (n = 2000) will be characterized at baseline and after 1-year follow-up by standardized protocols for clinical evaluation, echocardiography, and ECG. In one subset undergoing elective coronary bypass surgery (n = 100) and classified according to LV function, myocardial biopsies will be collected during surgery, and cardiac magnetic resonance (CMR) imaging will be performed at baseline and after 1 year. Blood and tissue samples will be stored in a biobank. We will characterize and compare new-onset HFpEF and HFrEF patients regarding clinical findings and cardiac imaging, genomics, proteomics, and transcriptomics from blood and cardiac biopsies, and by established biomarkers of fibrosis, inflammation, haemodynamics, haemostasis, and thrombosis. The data will be explored by state-of-the-art bioinformatics methods to investigate gene expression patterns, sequence variation, DNA methylation, and post-translational modifications, and using systems biology approaches including pathway and network analysis. In this epidemiological HF study with biopsy studies in a subset of patients, we aim to identify new biomarkers of disease progression and to find pathophysiological mechanisms to support explorations of new treatment regimens for HFpEF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Automatic ICD-10 multi-class classification of cause of death from plaintext autopsy reports through expert-driven feature selection.

PubMed

Mujtaba, Ghulam; Shuib, Liyana; Raj, Ram Gopal; Rajandram, Retnagowri; Shaikh, Khairunisa; Al-Garadi, Mohammed Ali

2017-01-01

Widespread implementation of electronic databases has improved the accessibility of plaintext clinical information for supplementary use. Numerous machine learning techniques, such as supervised machine learning approaches or ontology-based approaches, have been employed to obtain useful information from plaintext clinical data. This study proposes an automatic multi-class classification system to predict accident-related causes of death from plaintext autopsy reports through expert-driven feature selection with supervised automatic text classification decision models. Accident-related autopsy reports were obtained from one of the largest hospital in Kuala Lumpur. These reports belong to nine different accident-related causes of death. Master feature vector was prepared by extracting features from the collected autopsy reports by using unigram with lexical categorization. This master feature vector was used to detect cause of death [according to internal classification of disease version 10 (ICD-10) classification system] through five automated feature selection schemes, proposed expert-driven approach, five subset sizes of features, and five machine learning classifiers. Model performance was evaluated using precisionM, recallM, F-measureM, accuracy, and area under ROC curve. Four baselines were used to compare the results with the proposed system. Random forest and J48 decision models parameterized using expert-driven feature selection yielded the highest evaluation measure approaching (85% to 90%) for most metrics by using a feature subset size of 30. The proposed system also showed approximately 14% to 16% improvement in the overall accuracy compared with the existing techniques and four baselines. The proposed system is feasible and practical to use for automatic classification of ICD-10-related cause of death from autopsy reports. The proposed system assists pathologists to accurately and rapidly determine underlying cause of death based on autopsy findings. Furthermore, the proposed expert-driven feature selection approach and the findings are generally applicable to other kinds of plaintext clinical reports.

Automatic ICD-10 multi-class classification of cause of death from plaintext autopsy reports through expert-driven feature selection

PubMed Central

Mujtaba, Ghulam; Shuib, Liyana; Raj, Ram Gopal; Rajandram, Retnagowri; Shaikh, Khairunisa; Al-Garadi, Mohammed Ali

2017-01-01

Objectives Widespread implementation of electronic databases has improved the accessibility of plaintext clinical information for supplementary use. Numerous machine learning techniques, such as supervised machine learning approaches or ontology-based approaches, have been employed to obtain useful information from plaintext clinical data. This study proposes an automatic multi-class classification system to predict accident-related causes of death from plaintext autopsy reports through expert-driven feature selection with supervised automatic text classification decision models. Methods Accident-related autopsy reports were obtained from one of the largest hospital in Kuala Lumpur. These reports belong to nine different accident-related causes of death. Master feature vector was prepared by extracting features from the collected autopsy reports by using unigram with lexical categorization. This master feature vector was used to detect cause of death [according to internal classification of disease version 10 (ICD-10) classification system] through five automated feature selection schemes, proposed expert-driven approach, five subset sizes of features, and five machine learning classifiers. Model performance was evaluated using precisionM, recallM, F-measureM, accuracy, and area under ROC curve. Four baselines were used to compare the results with the proposed system. Results Random forest and J48 decision models parameterized using expert-driven feature selection yielded the highest evaluation measure approaching (85% to 90%) for most metrics by using a feature subset size of 30. The proposed system also showed approximately 14% to 16% improvement in the overall accuracy compared with the existing techniques and four baselines. Conclusion The proposed system is feasible and practical to use for automatic classification of ICD-10-related cause of death from autopsy reports. The proposed system assists pathologists to accurately and rapidly determine underlying cause of death based on autopsy findings. Furthermore, the proposed expert-driven feature selection approach and the findings are generally applicable to other kinds of plaintext clinical reports. PMID:28166263

Bone formation is suppressed with multi-stressor military training.

PubMed

Hughes, Julie M; Smith, Martha A; Henning, Paul C; Scofield, Dennis E; Spiering, Barry A; Staab, Jeffery S; Hydren, Jay R; Nindl, Bradley C; Matheny, Ronald W

2014-11-01

To determine the effects of US Army Ranger Training, an 8-week, physically demanding program (energy expenditure of 2,500-4,500 kcal/day) with energy restriction (deficit of 1,000-4,000 kcal/day) and sleep deprivation (<4 h sleep/night) on bone metabolism. Blood was collected from 22 men (age 24 ± 4 years) before and after training. Follow-up measurements were made in a subset of 8 subjects between 2 and 6 weeks after training. Serum was analyzed for bone formation biomarkers [bone alkaline phosphatase (BAP) and osteocalcin (OCN)], bone resorption biomarkers [C-telopeptide cross-links of type I collagen (CTX) and tartrate-resistant acid phosphatase (TRAP5b)], calcium, parathyroid hormone (PTH), and vitamin D 25(OH)D increased significantly by 37.3 ± 45.2 % with training [corrected]. A repeated-measures ANOVA with time as the only factor was used to analyze data on the subset of 8 subjects who completed follow-up data collection. BAP and OCN significantly decreased by 22.8 ± 15.5% (pre 41.9 ± 10.1; post 31.7 ± 7.8 ng/ml) and 21.0 ± 23.3% (pre 15.0 ± 3.5; post 11.3 ± 2.1 ng/ml), respectively, with training, suggesting suppressed bone formation. OCN returned to baseline, while BAP remained suppressed 2-6 weeks post-training. TRAP5b significantly increased by 57.5 ± 51.6% (pre 3.0 ± 0.9; post 4.6 ± 1.4 ng/ml) from pre- to post-training, suggesting increased bone resorption, and returned to baseline 2-6 weeks post-training. PTH Increased significantly by 37.3 ± 45.2% with training. No changes in CTX, calcium, or PTH were detected. These data indicate that multi-stressor military training results in increased bone resorption and suppressed bone formation, with recovery of bone metabolism 2-6 weeks after completion of training.

Switched Memory B Cells Are Increased in Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis and Their Change Over Time Is Related to Response to Tumor Necrosis Factor Inhibitors.

PubMed

Marasco, Emiliano; Aquilani, Angela; Cascioli, Simona; Moneta, Gian Marco; Caiello, Ivan; Farroni, Chiara; Giorda, Ezio; D'Oria, Valentina; Marafon, Denise Pires; Magni-Manzoni, Silvia; Carsetti, Rita; De Benedetti, Fabrizio

2018-04-01

To investigate whether abnormalities in B cell subsets in patients with juvenile idiopathic arthritis (JIA) correlate with clinical features and response to treatment. A total of 109 patients diagnosed as having oligoarticular JIA or polyarticular JIA were enrolled in the study. B cell subsets in peripheral blood and synovial fluid were analyzed by flow cytometry. Switched memory B cells were significantly increased in patients compared to age-matched healthy controls (P < 0.0001). When patients were divided according to age at onset of JIA, in patients with early-onset disease (presenting before age 6 years) the expansion in switched memory B cells was more pronounced than that in patients with late-onset disease and persisted throughout the disease course. In longitudinal studies, during methotrexate (MTX) treatment, regardless of the presence or absence of active disease, the number of switched memory B cells increased significantly (median change from baseline 36% [interquartile range {IQR} 15, 66]). During treatment with MTX plus tumor necrosis factor inhibitors (TNFi), in patients maintaining disease remission, the increase in switched memory B cells was significantly lower than that in patients who experienced active disease (median change from baseline 4% [IQR -6, 32] versus 41% [IQR 11, 73]; P = 0.004). The yearly rate of increases in switched memory B cells was 1.5% in healthy controls, 1.2% in patients who maintained remission during treatment with MTX plus TNFi, 4.7% in patients who experienced active disease during treatment with MTX plus TNFi, and ~4% in patients treated with MTX alone. Switched memory B cells expand during the disease course at a faster rate in JIA patients than in healthy children. This increase is more evident in patients with early-onset JIA. TNFi treatment inhibits this increase in patients who achieve and maintain remission, but not in those with active disease. © 2018, American College of Rheumatology.

EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period.

PubMed

Masic, U; Harrold, J A; Christiansen, P; Cuthbertson, D J; Hardman, C A; Robinson, E; Halford, J C G

2017-02-01

Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n=116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n=50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. Clinical Trials: NCT02591134; registered: 23.10.2015. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present▿

PubMed Central

Tenney, Daniel J.; Rose, Ronald E.; Baldick, Carl J.; Levine, Steven M.; Pokornowski, Kevin A.; Walsh, Ann W.; Fang, Jie; Yu, Cheng-Fang; Zhang, Sharon; Mazzucco, Charles E.; Eggers, Betsy; Hsu, Mayla; Plym, Mary Jane; Poundstone, Patricia; Yang, Joanna; Colonno, Richard J.

2007-01-01

Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase substitutions M204V and L180M plus additional changes at T184, S202, or M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound. PMID:17178796

Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present.

PubMed

Tenney, Daniel J; Rose, Ronald E; Baldick, Carl J; Levine, Steven M; Pokornowski, Kevin A; Walsh, Ann W; Fang, Jie; Yu, Cheng-Fang; Zhang, Sharon; Mazzucco, Charles E; Eggers, Betsy; Hsu, Mayla; Plym, Mary Jane; Poundstone, Patricia; Yang, Joanna; Colonno, Richard J

2007-03-01

Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase substitutions M204V and L180M plus additional changes at T184, S202, or M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound.

Temporal and spatial distributions of sediment mercury at salt pond wetland restoration sites, San Francisco Bay, CA, USA

USGS Publications Warehouse

Miles, A.K.; Ricca, M.A.

2010-01-01

Decommissioned agricultural salt ponds within south San Francisco Bay, California, are in the process of being converted to habitat for the benefit of wildlife as well as water management needs and recreation. Little is known of baseline levels of contaminants in these ponds, particularly mercury (Hg), which has a well established legacy in the Bay. In this study we described spatial and short-term temporal variations in sediment Hg species concentrations within and among the Alviso and Eden Landing salt ponds in the southern region of San Francisco Bay. We determined total Hg (Hgt) and methylmercury (MeHg) in the top 5 cm of sediment of most ponds in order to establish baseline conditions prior to restoration, sediment Hgt concentrations in a subset of these ponds after commencement of restoration, and variation in MeHg concentrations relative to sediment Hgt, pH, and total Fe concentrations and water depth and salinity in the subset of Alviso ponds. Inter-pond differences were greatest within the Alviso pond complex, where sediment Hgt concentrations averaged (arithmetic mean) 0.74 ??g/g pre and 1.03 ??g/g post-restoration activity compared to 0.11 ??g/g pre and post at Eden Landing ponds. Sediment Hgt levels at Alviso were fairly stable temporally and spatially, whereas MeHg levels were variable relative to restoration activities across time and space. Mean (arithmetic) sediment MeHg concentrations increased (2.58 to 3.03 ng/g) in Alviso and decreased (2.20 to 1.03 ng/g) in Eden Landing restoration ponds during the study. Differences in MeHg levels were related to water depth and pH, but these relationships were not consistent between years or among ponds and were viewed with caution. Factors affecting MeHg levels in these ponds (and in general) are highly complex and require in-depth study to understand.

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury

PubMed Central

Liu, Wei; Soderlund, Karl; Senseney, Justin S.; Joy, David; Yeh, Ping-Hong; Ollinger, John; Sham, Elyssa B.; Liu, Tian; Wang, Yi; Oakes, Terrence R.; Riedy, Gerard

2017-01-01

Purpose To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. Materials and Methods The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multi-echo gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. Results Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping–derived quantitative measures of microhemorrhages also decreased over time: −0.85 mm3 per day ± 1.59 for total volume (P = .039) and −0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016). Conclusion The number of microhemorrhages and quantitative susceptibility mapping–derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage. PMID:26371749

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury.

PubMed

Liu, Wei; Soderlund, Karl; Senseney, Justin S; Joy, David; Yeh, Ping-Hong; Ollinger, John; Sham, Elyssa B; Liu, Tian; Wang, Yi; Oakes, Terrence R; Riedy, Gerard

2016-02-01

To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multiecho gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping-derived quantitative measures of microhemorrhages also decreased over time: -0.85 mm(3) per day ± 1.59 for total volume (P = .039) and -0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016). The number of microhemorrhages and quantitative susceptibility mapping-derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage. © RSNA, 2015.

Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER.

PubMed

Yamaguchi, Junichi; Kawada-Watanabe, Erisa; Koyanagi, Ryo; Arashi, Hiroyuki; Sekiguchi, Haruki; Nakao, Koichi; Tobaru, Tetsuya; Tanaka, Hiroyuki; Oka, Toshiaki; Endo, Yasuhiro; Saito, Katsumi; Uchida, Tatsuro; Matsui, Kunihiko; Ogawa, Hiroshi; Hagiwara, Nobuhisa

2018-05-05

We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia. This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach. Copyright © 2018 Elsevier B.V. All rights reserved.

The Subsidence Signature Due To Groundwater Extraction as Inferred from Remote Sensing Data in Mexico City

NASA Astrophysics Data System (ADS)

Patel, V.; Chen, J.

2015-12-01

Mexico City is facing a severe water shortage; current drought conditions in the city have led to an increase in the demand for groundwater, the pumping of which can cause significant land subsidence. In this study we explored what new information interferometric synthetic aperture radar (InSAR) data collected by the TerraSAR-X satellite could bring to water resource managers in the city so that they can efficiently and sustainably allocate water resources. Previous work done over Mexico City indicates that InSAR can be used to detect deformation due to groundwater pumping. Cabral-Cano et al. (2008) processed InSAR data acquired from ERS between 1996-2000 and from ENVISAT between 2003-2005. They compared the deformation map to geology maps of the region with information obtained by seismic methods. They found that a spatial correlation between the land deformation and the presence of young lacustrine clay beds, which indicate that the subsidence was caused by fluid pressure loss in the aquitard. They also concluded that the subsidence, for the most part, had no seasonal variation and continues to occur at near-constant, high rates. TerraSAR-­X satellite data is known to be more sensitive to small deformations than the data from satellites used in previous studies in the region because of its frequent revisit cycle, short wavelength, and accurate orbital information. For this project, we derived long sequences of crustal deformation time series from TerraSAR-­X data between May 2011 and December 2012 using the Small Baseline Subset (SBAS) method. The resulting time series was then compared to GPS data for calibration and validation. We observed a long-term deformation that was similar to those found in previous studies. The next step in our work is to determine whether the increased sensitivity of the TerraSAR-­X data allows us to detect a seasonal deformation pattern over the study area.

Deformation signals from InSAR time series analysis related to the 2007 and 2011 east rift zone intrusions at Kilauea Volcano, Hawaii

NASA Astrophysics Data System (ADS)

Baker, S.; Amelung, F.

2011-12-01

Located on the Big Island of Hawaii, Kilauea volcano is one of the most active volcanoes on Earth with continuous eruptive activity since 1983. The eruptive activity is predominately from the Pu'u O'o vent within the east rift zone, but periodic intrusions occur in the upper east rift zone between the summit and Pu'u O'o. These intrusions occur as dikes typically accompanied by fissure openings and eruptions of small volumes of lava. Interferometric synthetic aperture radar (InSAR) provides surface displacement measurements showing how the ground moves before, during, and after these intrusions. Given the recent increase in the number of active or planned SAR satellites and the more frequent repeat-pass times, InSAR is proving to be a valuable monitoring tool for volcanic hazards. Using data from Radarsat-1, Envisat, ALOS, and TerraSAR-X satellites, we generate line-of-sight InSAR time series using the small baseline subset (SBAS) which provides dense spatial and temporal coverage at Kilauea covering the 17 June 2007 and 5 March 2011 intrusions. For these two events, the summit caldera area switches from deflation to inflation months to years before both intrusions, and just prior to the intrusions we observe increased rates of inflation accompanied by elevated seismic activity in the upper east rift zone. Observations of the intrusion relate surface displacement and the response of the summit caldera area provide insight into the shallow magmatic system and the connectivity of the system. By combining InSAR time series with other geophysical data sets (such as seismic or GPS), we obtain more details about the associated hazard and a better understanding of the time-dependent relationship between what we are measuring and the controlling processes at the volcano.

Denaturant-Dependent Conformational Changes in a [beta]-Trefoil Protein: Global and Residue-Specific Aspects of an Equilibrium Denaturation Process

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

Latypov, Ramil F.; Liu, Dingjiang; Jacob, Jaby

2010-01-12

Conformational properties of the folded and unfolded ensembles of human interleukin-1 receptor antagonist (IL-1ra) are strongly denaturant-dependent as evidenced by high-resolution two-dimensional nuclear magnetic resonance (NMR), limited proteolysis, and small-angle X-ray scattering (SAXS). The folded ensemble was characterized in detail in the presence of different urea concentrations by 1H-15N HSQC NMR. The {beta}-trefoil fold characteristic of native IL-1ra was preserved until the unfolding transition region beginning at 4 M urea. At the same time, a subset of native resonances disappeared gradually starting at low denaturant concentrations, indicating noncooperative changes in the folded state. Additional evidence of structural perturbations came frommore » the chemical shift analysis, nonuniform and bell-shaped peak intensity profiles, and limited proteolysis. In particular, the following nearby regions of the tertiary structure became progressively destabilized with increasing urea concentrations: the {beta}-hairpin interface of trefoils 1 and 2 and the H2a-H2 helical region. These regions underwent small-scale perturbations within the native baseline region in the absence of populated molten globule-like states. Similar regions were affected by elevated temperatures known to induce irreversible aggregation of IL-1ra. Further evidence of structural transitions invoking near-native conformations came from an optical spectroscopy analysis of its single-tryptophan variant W17A. The increase in the radius of gyration was associated with a single equilibrium unfolding transition in the case of two different denaturants, urea and guanidine hydrochloride (GuHCl). However, the compactness of urea- and GuHCl-unfolded molecules was comparable only at high denaturant concentrations and deviated under less denaturing conditions. Our results identified the role of conformational flexibility in IL-1ra aggregation and shed light on the nature of structural transitions within the folded ensembles of other {beta}-trefoil proteins, such as IL-1{beta} and hFGF-1.« less

Comparative Analysis of Argonaute-dependent Small RNA Pathways in Drosophila

PubMed Central

Zhou, Rui; Hotta, Ikuko; Denli, Ahmet M.; Hong, Pengyu; Perrimon, Norbert; Hannon, Gregory J.

2008-01-01

Summary The specificity of RNAi pathways is determined by several classes of small RNAs, which include siRNAs, piRNAs, endo-siRNAs, and microRNAs (miRNAs). These small RNAs are invariably incorporated into large Argonaute (Ago)-containing effector complexes known as RNA-induced silencing complexes (RISCs), which they guide to silencing targets. Both genetic and biochemical strategies have yielded conserved molecular components of small RNA biogenesis and effector machineries. However, given the complexity of these pathways, there are likely to be additional components and regulators that remain to be uncovered. We have undertaken a comparative and comprehensive RNAi screen to identify genes that impact three major Ago-dependent small RNA pathways that operate in Drosophila S2 cells. We identify subsets of candidates that act positively or negatively in siRNA, endo-siRNA and miRNA pathways. Our studies indicate that many components are shared among all three Argonaute-dependent silencing pathways, though each is also impacted by discrete sets of genes. PMID:19026789

An ensemble method for extracting adverse drug events from social media.

PubMed

Liu, Jing; Zhao, Songzheng; Zhang, Xiaodi

2016-06-01

Because adverse drug events (ADEs) are a serious health problem and a leading cause of death, it is of vital importance to identify them correctly and in a timely manner. With the development of Web 2.0, social media has become a large data source for information on ADEs. The objective of this study is to develop a relation extraction system that uses natural language processing techniques to effectively distinguish between ADEs and non-ADEs in informal text on social media. We develop a feature-based approach that utilizes various lexical, syntactic, and semantic features. Information-gain-based feature selection is performed to address high-dimensional features. Then, we evaluate the effectiveness of four well-known kernel-based approaches (i.e., subset tree kernel, tree kernel, shortest dependency path kernel, and all-paths graph kernel) and several ensembles that are generated by adopting different combination methods (i.e., majority voting, weighted averaging, and stacked generalization). All of the approaches are tested using three data sets: two health-related discussion forums and one general social networking site (i.e., Twitter). When investigating the contribution of each feature subset, the feature-based approach attains the best area under the receiver operating characteristics curve (AUC) values, which are 78.6%, 72.2%, and 79.2% on the three data sets. When individual methods are used, we attain the best AUC values of 82.1%, 73.2%, and 77.0% using the subset tree kernel, shortest dependency path kernel, and feature-based approach on the three data sets, respectively. When using classifier ensembles, we achieve the best AUC values of 84.5%, 77.3%, and 84.5% on the three data sets, outperforming the baselines. Our experimental results indicate that ADE extraction from social media can benefit from feature selection. With respect to the effectiveness of different feature subsets, lexical features and semantic features can enhance the ADE extraction capability. Kernel-based approaches, which can stay away from the feature sparsity issue, are qualified to address the ADE extraction problem. Combining different individual classifiers using suitable combination methods can further enhance the ADE extraction effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

Uses of NHANES biomarker data for chemical risk ...

EPA Pesticide Factsheets

Background. Each year, the US NHANES measures hundreds of chemical biomarkers in samples from thousands of study participants. These biomarker measurements are meant to track trends and identify subsets of the US population with elevated exposures. There is now interest in further utilizing the NHANES data to inform chemical risk assessments. Objectives. This article highlights: 1) the extent to which NHANES chemical biomarker data have been evaluated, 2) groups of chemicals that have been studied, 3) data analysis approaches, and 4) opportunities for using these data to inform chemical risk assessments.Methods. A literature search (1999-2013) was performed to identify publications in which NHANES data were reported. Manual curation identified only the subset of publications that clearly utilized chemical biomarker data. This subset was evaluated for chemical groupings, data analysis approaches, and overall trends.Results. A small percentage of yearly NHANES-related publications reported on chemical biomarkers (8% yearly average). Of eleven chemical groups, metals/metalloids were most frequently evaluated (49%), followed by pesticides (9%) and environmental phenols (7%). Studies of multiple chemical groups were also common (8%). Publications linking chemical biomarkers to health metrics have increased dramatically in recent years. New studies are addressing challenges related to NHANES data interpretation in health risk contexts.Conclusions. This articl

Density-Dependent Quantized Least Squares Support Vector Machine for Large Data Sets.

PubMed

Nan, Shengyu; Sun, Lei; Chen, Badong; Lin, Zhiping; Toh, Kar-Ann

2017-01-01

Based on the knowledge that input data distribution is important for learning, a data density-dependent quantization scheme (DQS) is proposed for sparse input data representation. The usefulness of the representation scheme is demonstrated by using it as a data preprocessing unit attached to the well-known least squares support vector machine (LS-SVM) for application on big data sets. Essentially, the proposed DQS adopts a single shrinkage threshold to obtain a simple quantization scheme, which adapts its outputs to input data density. With this quantization scheme, a large data set is quantized to a small subset where considerable sample size reduction is generally obtained. In particular, the sample size reduction can save significant computational cost when using the quantized subset for feature approximation via the Nyström method. Based on the quantized subset, the approximated features are incorporated into LS-SVM to develop a data density-dependent quantized LS-SVM (DQLS-SVM), where an analytic solution is obtained in the primal solution space. The developed DQLS-SVM is evaluated on synthetic and benchmark data with particular emphasis on large data sets. Extensive experimental results show that the learning machine incorporating DQS attains not only high computational efficiency but also good generalization performance.

Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin.

PubMed

Kollef, Marin H; Rello, Jordi; Cammarata, Sue K; Croos-Dabrera, Rodney V; Wunderink, Richard G

2004-03-01

To assess the effect of baseline variables, including treatment, on clinical cure and survival rates in patients with Gram-positive, ventilator-associated pneumonia (VAP). Retrospective analysis of two randomized, double-blind studies. Multinational study with 134 sites. 544 patients with suspected Gram-positive VAP, including 264 with documented Gram-positive VAP and 91 with methicillin-resistant S. aureus (MRSA) VAP. Linezolid 600 mg or vancomycin 1 g every 12 h for 7-21 days, each with aztreonam. Clinical cure rates assessed 12-28 days after the end of therapy and excluding indeterminate or missing outcomes significantly favored linezolid in the Gram-positive and MRSA subsets. Logistic regression showed that linezolid was an independent predictor of clinical cure with odds ratios of 1.8 for all patients, 2.4 for Gram-positive VAP, and 20.0 for MRSA VAP. Kaplan-Meier survival rates favored linezolid in the MRSA subset. Logistic regression showed that linezolid was an independent predictor of survival with odds ratios of 1.6 for all patients, 2.6 for Gram-positive VAP, and 4.6 for MRSA VAP. Initial linezolid therapy was associated with significantly better clinical cure and survival rates than was initial vancomycin therapy in patients with MRSA VAP.

A modified fetal heart rate tracing interpretation system for prediction of cesarean section

PubMed Central

Schnettler, William T.; Rogers, Jennifer; Barber, Rachel E.; Hacker, Michele R.

2013-01-01

Objective To investigate whether a modified version of the 2008 National Institute of Child Health and Human Development (NICHD) interpretation system upon admission decreases cesarean delivery risk. Methods This retrospective cohort study ascribed a modified category to the first 30 min of fetal heart rate (FHR) tracings in labor. Category I was divided into two subsets (Ia and Ib) by the presence of accelerations. Category II was divided into four subsets (IIa–IId) based on baseline FHR, variability, response to stimulation and decelerations. Log-binomial regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). Results A category was ascribed to 910 women. Most FHR tracings were Category Ia (65.8%), Ib (7.7%), IIb (11.8%) and IId (14.0%). Category Ib tracings (fewer than two accelerations) were 2.26 (95% CI: 1.13–4.52) times more likely to result in cesarean delivery for abnormal FHR tracing than Category Ia tracings. A similar increase in risk was seen when comparing Category IIb and Category IId with Category Ia. Conclusion Application of a modified version of the 2008 NICHD FHR interpretation system to the initial 30 min of labor can identify women at increased risk of cesarean delivery for abnormal FHR tracing. PMID:21942513

Internet Pornography Use, Perceived Addiction, and Religious/Spiritual Struggles.

PubMed

Grubbs, Joshua B; Exline, Julie J; Pargament, Kenneth I; Volk, Fred; Lindberg, Matthew J

2017-08-01

Prior work has demonstrated that religious beliefs and moral attitudes are often related to sexual functioning. The present work sought to examine another possibility: Do sexual attitudes and behaviors have a relationship with religious and spiritual functioning? More specifically, do pornography use and perceived addiction to Internet pornography predict the experience of religious and spiritual struggle? It was expected that feelings of perceived addiction to Internet pornography would indeed predict such struggles, both cross-sectionally and over time, but that actual pornography use would not. To test these ideas, two studies were conducted using a sample of undergraduate students (N = 1519) and a sample of adult Internet users in the U.S. (N = 713). Cross-sectional analyses in both samples found that elements of perceived addiction were related to the experience of religious and spiritual struggle. Additionally, longitudinal analyses over a 1-year time span with a subset of undergraduates (N = 156) and a subset of adult web users (N = 366) revealed that perceived addiction to Internet pornography predicted unique variance in struggle over time, even when baseline levels of struggle and other related variables were held constant. Collectively, these findings identify perceived addiction to Internet pornography as a reliable predictor of religious and spiritual struggle.

Analysis of a novel protocol of combined induction chemotherapy and concurrent chemoradiation in unresected non-small-cell lung cancer: a ten-year experience with vinblastine, Cisplatin, and radiation therapy.

PubMed

Waters, Eugenie; Dingle, Brian; Rodrigues, George; Vincent, Mark; Ash, Robert; Dar, Rashid; Inculet, Richard; Kocha, Walter; Malthaner, Richard; Sanatani, Michael; Stitt, Larry; Yaremko, Brian; Younus, Jawaid; Yu, Edward

2010-07-01

The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Astronomical observatories on the Moon

NASA Astrophysics Data System (ADS)

Swanson, Paul N.; Cutts, James A.

1994-06-01

The Space Exploration Initiative presents an opportunity to construct astronomical telescopes on the Moon using the infrastructure provided by the lunar outpost. Small automatically deployed telescopes can be carried on the survey missions, be deployed on the lunar surface and be operated remotely from the Earth. Possibilities for early, small optical telescopes are a zenith pointed transit telescope, a student telescope, and a 0.5 to 1 meter automatic, fully steerable telescope. After the lunar outpost is established the lunar interferometers will be constructed in an evolutionary fashion. There are three lunar interferometers which have been studied. The most ambitious is the optical interferometer with a 1 to 2 -km baseline and seven 1.5 aperture elements arranged in a 'Y' configuration with a central beam combiner. The Submillimeter interferometer would use seven, 5-m reflectors in a 'Y' or circular configuration with a 1-km baseline. The Very Low Frequency (VLF) array would operate below 30 mHz with as many as 100 elements and a 200-km baseline.

Next-generation Event Horizon Telescope developments: new stations for enhanced imaging

NASA Astrophysics Data System (ADS)

Palumbo, Daniel; Johnson, Michael; Doeleman, Sheperd; Chael, Andrew; Bouman, Katherine

2018-01-01

The Event Horizon Telescope (EHT) is a multinational Very Long Baseline Interferometry (VLBI) network of dishes joined to resolve general relativistic behavior near a supermassive black hole. The imaging quality of the EHT is largely dependent upon the sensitivity and spatial frequency coverage of the many baselines between its constituent telescopes. The EHT already contains many highly sensitive dishes, including the crucial Atacama Large Millimeter/Submillimeter Array (ALMA), making it viable to add smaller, cheaper telescopes to the array, greatly improving future capabilities of the EHT. We develop tools for optimizing the positions of new dishes in planned arrays. We also explore the feasibility of adding small orbiting dishes to the EHT, and develop orbital optimization tools for space-based VLBI imaging. Unlike the Millimetron mission planned to be at L2, we specifically treat near-earth orbiters, and find rapid filling of spatial frequency coverage across a large range of baseline lengths. Finally, we demonstrate significant improvement in image quality when adding small dishes to planned arrays in simulated observations.

Effect of Long-Term Hormonal Therapy (vs Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate-Risk Prostate Cancer Patients Treated on NRG Oncology RTOG 9202

PubMed Central

Mirhadi, Amin J.; Zhang, Qiang; Hanks, Gerald E.; Lepor, Herbert; Grignon, David J.; Peters, Christopher A.; Rosenthal, Seth A.; Zeitzer, Kenneth; Radwan, John S.; Lawton, Colleen; Parliament, Matthew B.; Reznik, Robert S.; Sandler, Howard M.

2017-01-01

Purpose NRG Oncology RTOG 9202 was a randomized trial testing long-term adjuvant androgen deprivation (LTAD) versus initial androgen deprivation only (STAD) with external beam radiation therapy (RT) in mostly high-risk and some intermediate-risk prostate cancer patients. RTOG 9408 found an overall survival (OS) advantage in patients with cT1b-T2b disease and prostate-specific antigen (PSA) <20 ng/mL, with benefit observed mostly among intermediate-risk patients. It was still unknown whether intermediate-risk patients would experience an additional survival benefit with LTAD; thus, we performed a secondary analysis to explore whether LTAD had any incremental benefit beyond STAD among the intermediate-risk subset of RTOG 9202. The study endpoints were OS, disease-specific survival (DSS), and PSA failure (PSAF). Methods and Materials An analysis was performed for all patients enrolled in RTOG 9202 defined as intermediate-risk (cT2 disease, PSA<10 ng/mL, and Gleason score = 7 or cT2 disease, PSA 10-20 ng/mL, and Gleason score <7). This review yielded 133 patients: 74 (STAD) and 59 (LTAD). The Kaplan-Meier method was used to estimate OS; the cumulative incidence approach was used to estimate DSS and PSAF. A 2-sided test was used, with significance level defined to be .05. Results With over 11 years of median follow-up, 39 STAD patients were alive and 33 LTAD patients were alive. There was no difference in OS (10-year estimates, 61% STAD vs 65% LTAD; P=.53), DSS (10-year DSS, 96% vs 97%; P=.72), or PSAF (10-year PSAF, 53% vs 55%; P=.99) between groups. Conclusion LTAD did not confer a benefit in terms of OS, DSS, or PSAF rates in the intermediate-risk subset in this study. Whereas the subset was relatively small, treatment assignment was randomly applied, and a trend in favor of LTAD would have been of interest. Given the small number of disease-specific deaths observed and lack of benefit with respect to our endpoints, this secondary analysis does not suggest that exploration of longer hormonal therapy is worth testing in the intermediate-risk prostate cancer subset. PMID:28126300