828 research outputs found

    Development of a meteoroid penetration distributed transducer Third quarterly report

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    Impact calibration tests in development of meteoroid penetration distributed transduce

    Past and future interannual variability in Arctic sea ice in coupled climate models

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    The diminishing Arctic sea ice pack has been widely studied, but previous research has mostly focused on time-mean changes in sea ice rather than on short-term variations that also have important physical and societal consequences. In this study we test the hypothesis that future interannual Arctic sea ice area variability will increase by utilizing 40 independent simulations from the Community Earth System Model's Large Ensemble (CESM-LE) for the 1920–2100 period and augment this with simulations from 12 models participating in the Coupled Model Intercomparison Project Phase 5 (CMIP5). Both CESM-LE and CMIP5 models project that ice area variability will indeed grow substantially but not monotonically in every month. There is also a strong seasonal dependence in the magnitude and timing of future variability increases that is robust among CESM ensemble members. The variability generally correlates with the average ice retreat rate, before there is an eventual disappearance in both terms as the ice pack becomes seasonal in summer and autumn by late century. The peak in variability correlates best with the total area of ice between 0.2 and 0.6&thinsp;m monthly thickness, indicating that substantial future thinning of the ice pack is required before variability maximizes. Within this range, the most favorable thickness for high areal variability depends on the season, especially whether ice growth or ice retreat processes dominate. Our findings suggest that thermodynamic melting (top, bottom, lateral) and growth (frazil, congelation) processes are more important than dynamical mechanisms, namely ice export and ridging, in controlling ice area variability.</p

    Importance of exposure route for behavioural responses in Lumbriculus variegatus Müller (Oligochaeta: Lumbriculida) in short-term exposures to Pb

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    Abstract Goal, Scope and Background Lumbriculus variegatus Müller (Oligochaeta), a common freshwater sediment-dweller, has frequently been used in toxicokinetic studies, although has been less used in ecotoxicity tests. Methods For the first time the Multispecies Freshwater Biomonitor® (MFB) was applied in a short-term whole-sediment toxicity test. The MFB automatically and quantitatively recorded the spontaneous locomotory behaviour of Lumbriculus variegatus in exposures with two compartments, water and sediment. The study questioned, whether the animals altered their locomotion depending on the compartment which was spiked with lead (Pb). Results and Discussion As in the exposures to Pb-contaminated water/clean sediment, the animals exposed to Pb-contaminated sediment/clean water showed higher activities in intermediate Pb-concentrations. This indicates, that spontaneous locomotory activity is affected by Pb-concentrations at sublethal levels regardless of whether the Pb-concentration is found in the water or in the sediment, because these animals use both environmental compartments simultaneously. However, within the same Pb-levels, the animals showed higher locomotory activity in contaminated water compared with contaminated sediment. This indicates a possible tendency to withdraw from (‘avoidance’) contaminated water into the clean sediment compartment, whereas there was no withdrawal from contaminated sediment into clean water. The latter might be explained by the fact that withdrawal from sediment to water might increase the risk of predation and drift in nature, whereas retracting to sediment might provide shelter. Conclusions The study showed that spontaneous locomotory responses of L. variegatus to Pb depend on whether the water or sediment is contaminated. The study also concluded that the Multispecies Freshwater Biomonitor® can be applied effectively in sediment toxicity testing. Recommendations and Perspectives More emphasis should be given to the interactions of water/sediment in sediment ecotoxicity tests to better simulate field conditions and increase ecological realism in risk assessment, especially as quantitative recording methods exisit

    Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin–paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial

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    Background: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin–paclitaxel compared with placebo plus carboplatin–paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. Patients and methods: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1: 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin–paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. Results: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin–paclitaxel versus carboplatin–paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin–paclitaxel was consistent with the first interim analysis. Conclusions: Dostarlimab in combination with carboplatin–paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.</p

    Scanning Electrochemical Microscopy. Theory of the Feedback Mode

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    The steady-state current that flows between the scanning tlp (a disk ultramicroelectrode imbedded in an Insulating sheath) and a planar sample substrate in a scannlng electrochemical microscope (SECM) operating in the feedback mode is calculated by the finite element method with an exponentlaily expandlng grld, for both conductlve and Insulating samples. For conductlve substrates the tip current, representing, for example, the oxidatkn reactlon of R to 0, is enhanced by flow of R generated at the substrate to the tlp and is a functlon of tiphubstrate distance, d , but not the radius of the lnsuiatlng sheath. For insulating substrates, the tlp current Is decreased by blockage of the diffusion of R to the tip by the substrate and depends upon d and the Insulating sheath radius. The theoretical results are compared to experimental studies

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease:A randomized controlled trial

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    Objective: The aim of the study is to determine the effect of lutein combined with vitamin and mineral supplementation on contrast sensitivity in people with age-related macular disease (ARMD). Design: A prospective, 9-month, double-masked randomized controlled trial. Setting: Aston University, Birmingham, UK and a UK optometric clinical practice. Subjects: Age-related maculopathy (ARM) and atrophic age-related macular degeneration (AMD) participants were randomized (using a random number generator) to either placebo (n = 10) or active (n=15) groups. Three of the placebo group and two of the active group dropped out. Interventions: The active group supplemented daily with 6 mg lutein combined with vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured using the Pelli-Robson chart, for which the study had 80% power at the 5% significance level to detect a change of 0.3log units. Results: The CS score increased by 0.07 ± 0.07 and decreased by 0.02 ± 0.18 log units for the placebo and active groups, respectively. The difference between these values is not statistically significant (z = 0.903, P = 0.376). Conclusion: The results suggest that 6 mg of lutein supplementation in combination with other antioxidants is not beneficial for this group. Further work is required to establish optimum dosage levels

    Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study

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    Background: New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Methods: Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Results: Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. Conclusion: If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen

    Polychlorinated Biphenyl Sorption and Availability in Field-Contaminated Sediments†

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    Traditional and new relationships of polychlorinated biphenyl (PCB) distribution among the solid phases, the free aqueous phase, and biolipids are comprehensively reviewed using seven well-characterized freshwater and marine sediments polluted with PCBs. The traditional relationship relating free aqueous concentration and biolipid concentration to sediment total organic carbon, compound octanol−water partitioning coefficient, and solid-phase contaminant concentration overestimates measured free aqueous concentrations and biolipid concentrations by mean factors of 8 and 33, respectively. By contrast, relationships based on measured free aqueous phase concentrations or the PCB mass fraction desorbed from sediment provide reasonable predictions of biolipid concentrations. Solid-phase concentration-based predictions perform better when sorption to amorphous organic matter and black carbon (BC) is distinguished. Contrary to previously published relationships, BC sorption appears to be linear for free aqueous PCB-congener concentrations in the picogram to microgram per liter range
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