Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P < .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P < .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).ConclusionNot only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed

Imaging Thermal Stratigraphy in Freshwater Lakes Using Georadar

Thermal stratification exerts significant control over biogeochemical processing in freshwater lakes. Thus, the temporal and spatial distribution of the thermal structure is an important component in understanding lake ecosystems. We present the first reported observations of lake thermal stratification from surface based georadar measurements acquired over two small freshwater lakes. This method is very useful because it can provide rapid acquisition of 2D or 3D lotic stratification

The transcriptomic evolution of mammalian pregnancy:gene expression innovations in endometrial stromal fibroblasts

The endometrial stromal fibroblast (ESF) is a cell type present in the uterine lining of therian mammals. In the stem lineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation. We call the latter cell type “neo-ESF” in contrast to “paleo-ESF” which is homologous to eutherian ESF but is not able to decidualize. In this study, we compare the transcriptomes of ESF from six therian species: Opossum (Monodelphis domestica; paleo-ESF), mink, rat, rabbit, human (all neo-ESF), and cow (secondarily nondecidualizing neo-ESF). We find evidence for strong stabilizing selection on transcriptome composition suggesting that the expression of approximately 5,600 genes is maintained by natural selection. The evolution of neo-ESF from paleo-ESF involved the following gene expression changes: Loss of expression of genes related to inflammation and immune response, lower expression of genes opposing tissue invasion, increased markers for proliferation as well as the recruitment of FOXM1, a key gene transiently expressed during decidualization. Signaling pathways also evolve rapidly and continue to evolve within eutherian lineages. In the bovine lineage, where invasiveness and decidualization were secondarily lost, we see a re-expression of genes found in opossum, most prominently WISP2, and a loss of gene expression related to angiogenesis. The data from this and previous studies support a scenario, where the proinflammatory paleo-ESF was reprogrammed to express anti-inflammatory genes in response to the inflammatory stimulus coming from the implanting conceptus and thus paving the way for extended, trans-cyclic gestation

Streambed Flux Measurement Informed by Distributed Temperature Sensing Leads to a Significantly Different Characterization of Groundwater Discharge

Groundwater discharge though streambeds is often focused toward discrete zones, indicating that preliminary reconnaissance may be useful for capturing the full spectrum of groundwater discharge rates using point-scale quantitative methods. However, many direct-contact reconnaissance techniques can be time-consuming, and remote sensing (e.g., thermal infrared) typically does not penetrate the water column to locate submerged seepages. In this study, we tested whether dozens of groundwater discharge measurements made at “uninformed” (i.e., selected without knowledge on high-resolution temperature variations at the streambed) point locations along a reach would yield significantly dierent Darcy-based groundwater discharge rates when compared with “informed” measurements, focused at streambed thermal anomalies that were identified a priori using fiber-optic distributed temperature sensing (FO-DTS). A non-parametric U-test showed a significant difference between median discharge rates for uninformed (0.05 m day 1; n = 30) and informed (0.17 m day 1; n = 20) measurement locations. Mean values followed a similar pattern (0.12 versus 0.27 m day 1), and frequency distributions for uninformed and informed measurements were also significantly different based on a Kolmogorov–Smirnov test. Results suggest that even using a quick “snapshot-in-time” field analysis of FO-DTS data can be useful in streambeds with groundwater discharge rate

Age- and sex-related ABC transporter expression in pyrethroid-susceptible and – resistant \u3ci\u3eAedes aegypti\u3c/i\u3e

Resistance mechanisms to synthetic insecticides often include point mutations and increased expression of genes encoding detoxification enzymes. Since pyrethroids are the main adulticides used against Aedes aegypti, which vectors pathogens such as Zika virus, understanding resistance to this insecticide class is of significant relevance. We focused on adenosine triphosphate (ATP)-binding cassette (ABC) transporters in the pyrethroid-resistant Puerto Rico (PR) strain of Ae. aegypti. We investigated the expression patterns of six ABC transporters previously characterized as differentially expressed in insecticide-challenged mosquitoes, or increased mRNA expression in pyrethroid-resistant Ae. aegypti, by comparing PR to the Rockefeller (Rock) susceptible strain. No constitutive differential expression between strains was detected, but expression differences for these genes was influenced by sex and age, suggesting that their role is independent from resistance in PR. Instead, ABC transporters may be induced after insecticide exposure. Challenging mosquitoes with deltamethrin, with or without ABC transporter modulators, showed that Rock and PR responded differently, but a contribution of ABC transporters to deltamethrin toxicity is suspected. Moreover, the effect of dexamethasone, which enhanced the inhibition of nerve firing by deltamethrin, was observed using a Drosophila central nervous system preparation, showing synergy of these two compounds through the potential inhibition of ABC transporters

Vitamin D Status Is Not Associated with Risk of Early Menopause

Background: Early natural menopause, the cessation of ovarian function before age 45 y, is positively associated with cardiovascular disease and other conditions. Dietary vitamin D intake has been inversely associated with early menopause; however, no previous studies have evaluated risk with regard to plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Objective: We prospectively evaluated associations of total and free 25(OH)D and vitamin D–binding protein (VDBP) concentrations and the risk of early menopause in a case-control study nested within the Nurses’ Health Study II (NHS2). We also considered associations of 25(OH)D and VDBP with anti-Müllerian hormone (AMH) concentrations. Methods: The NHS2 is a prospective study in 116,430 nurses, aged 25–42 y at baseline (1989). Premenopausal plasma blood samples were collected between 1996 and 1999, from which total 25(OH)D and VDBP concentrations were measured and free 25(OH)D concentrations were calculated. Cases experienced menopause between blood collection and age 45 y (n = 328) and were matched 1:1 by age and other factors to controls who experienced menopause after age 48 y (n = 328). Conditional logistic regression models were used to estimate ORs and 95% CIs for early menopause according to each biomarker. Generalized linear models were used to estimate AMH geometric means according to each biomarker. Results: After adjusting for smoking and other factors, total and free 25(OH)D were not associated with early menopause. Quartile 4 compared with quartile 1 ORs were 1.04 (95% CI: 0.60, 1.81) for total 25(OH)D and 0.70 (95% CI: 0.41, 1.20) for free 25(OH)D. 25(OH)D was unrelated to AMH concentrations. VDBP was positively associated with early menopause; the OR comparing the highest with the lowest quartile of VDBP was 1.80 (95% CI: 1.09, 2.98). Conclusions: Our findings suggest that total and free 25(OH)D are not importantly related to the risk of early menopause. VDBP may be associated with increased risk, but replication is warranted

Nutramara - Marine Functional Foods Research Initiative (MFFRI/07/01)

Final report of projectThe NutraMara – Marine Functional Foods Research Initiative was conceived by Sea Change - A Marine Knowledge, Research and Innovation Strategy for Ireland 2007-2013. The goal was to develop a collaborative funding mechanism that would create new research capacity and build the capabilities required to maximise the potential of Ireland’s extensive marine bioresources. By supporting a strong interdisciplinary research team, capable of exploring marine animals and plants as a sustainable source of materials for use as functional ingredients and foods, the vision for NutraMara was to position Ireland to the fore in use of marine bioresources as health beneficial ingredients. Commencing in 2008 and supported by funds of €5.2 million from the Marine Institute and the Department of Agriculture, Food and the Marine, the research programme was led by Teagasc as the head of a multi-institutional consortium. The NutraMara consortium comprises marine bioresources and bioscience expertise, with food science and technology expertise from University College Cork; University College Dublin; the National University of Ireland Galway; the University of Limerick and Ulster University. Research effort was directed towards exploring Ireland’s marine bioresources – including macro- and microalgae, finfish and shellfish from wild and cultured sources: and discards from processing fish as sources of novel ingredients with bioactive characteristics. This discovery activity involved the collection of over 600 samples from 39 species of algae and fish and the analysis of 5,800 extracts, which resulted in 3,000 positive “hits” for bioactivity. The NutraMara consortium has built a strong research capacity to identify, characterise and evaluate marine-origin bioactives for use as/in functional foods. It further built the capacity to develop model foods enhanced with these marine-origin functional ingredients; providing insights to the processing challenges associated with producing functional ingredients from marine organisms. The consortium was actively engaged in research activities designed to identify and assess bioactive compounds from available marine resources, including polyphenols, proteins/peptides, amino acids, polysaccharides, polyunsaturated fatty acids and materials with antioxidant, probiotic or prebiotic properties. A key component of NutraMara’s activities was the development of human capital. The recruitment of M.Sc. and PhD students and their integration within a dynamic research environment that has strong links to industry, provided lasting expertise and capabilities, which are relevant to the needs of Ireland’s food and marine sectors. NutraMara research led to the awarding of eighteen PhDs and recruitment of 21 post-doctoral researchers over the eight year research programme. In excess of 80 peer reviewed publications resulted from this research and more publications are planned. A further 100 posters and conference presentations were also delivered by NutraMara researchers and Principal Investigators. The development and implementation of training and exchange programmes aimed at providing early stage researchers with inter-disciplinary skills that are critical to their development as researchers, enhanced the research capacity of institutions, the industry sectors and the country as a whole. Principal Investigators involved in leading the NutraMara research programme have secured additional research grants of almost €6 million from national and international sources and are engaged in extensive research collaboration involving marine and food research expertise; an activity which did not exist prior to NutraMara. The dissemination of knowledge and transfer of research results to industry were key activities in the research programme. The research outputs and visibility of NutraMara activity nationally resulted in 10 companies engaging in research and development activity with the consortium. Regular workshops and conferences organised by NutraMara attracted close to five hundred participants from Ireland and overseas. Members of the NutraMara core PI group have contributed to the formulation of new national foods and marine research policy and national research agenda, both during the national prioritisation exercise and in sectoral research strategies. This final project report describes the process by which research targets were identified, and the results of extensive screening and evaluation of compounds extracted from marine bioresources. It also highlights the development of new protocols designed to extract compounds in ways that are food friendly. Evaluating the functional properties, bioactivity and bioavailability of high potential marine compounds involved in vitro and in vivo testing. Pilot animal and human intervention studies yielded further insight to the potential and challenges in developing marine functional ingredients. As a result of work completed within the NutraMara consortium, Ireland is well positioned to continue to contribute to the development of ingredients derived from marine organisms and in doing so support the on-going development of Ireland’s food sector.Marine Institut

Hall-conductivity sign change and fluctuations in amorphous Nbx_{x}Ge1−x_{1-x} films

The sign change in the Hall conductivity has been studied in thin amorphous Nb$_{1-x}$Ge$_x (x\approx$0.3) films. By changing the film thickness it is shown that the field at which the sign reversal occurs shifts to lower values (from above to below the mean-field transition field $H_{c2}$) with increasing film thickness. This effect can be understood in terms of a competition between a positive normal and a negative fluctuation contribution to the Hall conductivity.Comment: 5 pages, 4 figures, to appear in Phys. Rev.

Continuum Halos in Nearby Galaxies -- an EVLA Survey (CHANG-ES) -- II: First Results on NGC 4631

We present the first results from the CHANG-ES survey, a new survey of 35 edge-on galaxies to search for both in-disk as well as extra-planar radio continuum emission. The motivation and science case for the survey are presented in a companion paper (Paper I). In this paper (Paper II), we outline the observations and data reduction steps required for wide-band calibration and mapping of EVLA data, including polarization, based on C-array test observations of NGC 4631. With modest on-source observing times (30 minutes at 1.5 GHz and 75 minutes at 6 GHz for the test data) we have achieved best rms noise levels of 22 and 3.5 $\mu$Jy beam$^{-1}$ at 1.5 GHz and 6 GHz, respectively. New disk-halo features have been detected, among them two at 1.5 GHz that appear as loops in projection. We present the first 1.5 GHz spectral index map of NGC 4631 to be formed from a single wide-band observation in a single array configuration. This map represents tangent slopes to the intensities within the band centered at 1.5 GHz, rather than fits across widely separated frequencies as has been done in the past and is also the highest spatial resolution spectral index map yet presented for this galaxy. The average spectral index in the disk is $\bar\alpha_{1.5 GHz}\,=\,-0.84\,\pm\,0.05$ indicating that the emission is largely non-thermal, but a small global thermal contribution is sufficient to explain a positive curvature term in the spectral index over the band. Two specific star forming regions have spectral indices that are consistent with thermal emission. Polarization results (uncorrected for internal Faraday rotation) are consistent with previous observations and also reveal some new features. On broad scales, we find strong support for the notion that magnetic fields constrain the X-ray emitting hot gas.Comment: Accepted to the Astronomical Journal, Version 2 changes: Added acknowledgement to NRA

Aortic Annulus Diameter Determination by Multidetector Computed Tomography Reproducibility, Applicability, and Implications for Transcatheter Aortic Valve Implantation

ObjectivesThis study sought to determine the most reproducible multidetector computed tomography (MDCT) measurements of the aortic annulus and to determine methods to improve the applicability of these measurements for transcatheter aortic valve implantation.BackgroundThe reproducibility and applicability of MDCT annular measurements to guide transcatheter aortic valve implantation remain unclear.MethodsAnnular measurements were performed in 50 patients planed for transcatheter aortic valve implantation in multiple planes: basal ring (short- and long-axis, mean diameter, area-derived diameter), coronal, sagittal, and 3-chamber projections. A theoretical model was developed taking into account the differences between the most reproducible MDCT measurements and transesophageal echocardiography to guide valve size choice.ResultsThe most reproducible measurements were the area-derived diameter and basal ring average diameter (inter-reader intraclass correlation coefficient: 0.87 [95% confidence interval: 0.81 to 0.92] and 0.80 [95% confidence interval: 0.70 to 0.87]; respectively; intrareader >0.90 for all readers). These were generally larger than transesophageal echocardiography diameters (mean difference of 1.5 ± 1.6 mm and 1.1 ± 1.7 mm, respectively). When a strategy of valve-sizing is undertaken using these CT measurements using an echocardiographic sizing scale, a different THV size would be selected in 44% and 40% of cases, respectively. When adjusting the sizing cutoffs to account for the differences in observed diameters, this was reduced to 10% to 12% (p < 0.01 for both, respectively).ConclusionsThe most reproducible MDCT measurements of the annulus are the area-derived diameter and basal ring average diameter, with derived values generally larger than those obtained with echocardiography. If MDCT is used for valve sizing, a strategy incorporating these differences may be important. MDCT using these easily derived measurements may be ideally suited to sizing transcatheter aortic valves as they account for the eccentricity of the aortic annulus, are reproducible, and are noninvasive