1,521 research outputs found

    External validation of serum hCG cutoff levels for prediction of resistance to single-agent chemotherapy in patients with persistent trophoblastic disease

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    Van Trommel et al have previously shown that serum human chorionic gonadotropin (hCG) cutoff levels can provide early prediction of resistance to first-line methotrexate (MTX) in patients with persistent trophoblastic disease (PTD). In this study, we validate this approach of prediction of resistance to single-agent chemotherapy in an independent and larger cohort of PTD patients using a different hCG assay. Receiver operating characteristics (ROC) curves were constructed to determine hCG cutoff levels and sensitivity between patients cured on single-agent chemotherapy (control group) and patients requiring change to combination chemotherapy (study group). Receiver operating characteristics analysis identified an hCG cutoff value of 737 IU l−1 that enabled us to predict the subsequent development of single-agent chemotherapy resistance in 52% of patients before their fourth MTX course at 97.5% specificity. This would have enabled an earlier switch to combination chemotherapy reducing the MTX exposure by an average of 2.5 courses. The present findings confirm that serum hCG cutoff levels predict resistance to single-agent therapy earlier than traditional methods. Change to combination chemotherapy should be considered for patients whose serum hCG levels exceed these hCG cutoff values. For patients not exceeding the hCG cutoff levels, static or rising hCG levels should still be included in the criteria for change of chemotherapy

    Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

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    <p><b>Background:</b> Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.</p> <p><b>Methods and Findings:</b> Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.</p> <p><b>Conclusions:</b> Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.</p&gt

    Satisfaction and compliance in hormonal contraception: the result of a multicentre clinical study on women's experience with the ethinylestradiol/norelgestromin contraceptive patch in Italy

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    <p>Abstract</p> <p>Background</p> <p>For many women finding the right contraceptive method can be challenging and consistent and correct use over a lifetime is difficult. Even remembering to take a birth control pill every day can be a challenge. The primary objective of this study was to evaluate women's experience with a weekly ethinylestradiol/norelgestromin contraceptive patch (EE/NGMN patch), given new technologies recently developed in hormonal contraception to increase women's options in avoiding daily dosing.</p> <p>Methods</p> <p>In 24 Italian sites, 207 women received the EE/NGMN patch for up to 6 cycles. At study end, overall satisfaction and preference, as well as compliance, efficacy and safety, were evaluated.</p> <p>Results</p> <p>175 women (84.5%) completed the study. The overall satisfaction rate was 88%; convenience and once-a-week frequency of the patch were especially appreciated. At baseline, 82 women (39.4%) were using a contraceptive method, mainly oral contraceptives and barrier methods, but only 45.1% were very satisfied/satisfied; after 6 months with the patch, 86.3% of this subset was very satisfied/satisfied. Considering the method used in the 3 months before the study entry, 78.1% strongly preferred/preferred the patch, for convenience (53.9%), ease of use/simplicity (28.9%), fewer (9.2%) and less severe (2.6%) side effects. Compliance was very high: 1034/1110 cycles (93.2%) were completed with perfect compliance and the mean subject's compliance score was 90%. One on-therapy pregnancy occurred. The patch was safe and well tolerated: adverse events frequency was low, with predominantly single reports of each event. Most of them started and subsided during cycle 1.</p> <p>Conclusion</p> <p>This study demonstrated that the EE/NGMN patch is associated with high satisfaction levels and excellent compliance. At study end, the majority of women indicated that they would continue using the patch.</p

    Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE(TM) study in patients with previously treated CLL/SLL.

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    In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs. ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared to patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs. later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations

    The Hubble Constant

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    I review the current state of determinations of the Hubble constant, which gives the length scale of the Universe by relating the expansion velocity of objects to their distance. There are two broad categories of measurements. The first uses individual astrophysical objects which have some property that allows their intrinsic luminosity or size to be determined, or allows the determination of their distance by geometric means. The second category comprises the use of all-sky cosmic microwave background, or correlations between large samples of galaxies, to determine information about the geometry of the Universe and hence the Hubble constant, typically in a combination with other cosmological parameters. Many, but not all, object-based measurements give H0H_0 values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc. This is in mild discrepancy with CMB-based measurements, in particular those from the Planck satellite, which give values of 67-68km/s/Mpc and typical errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that accuracy rather than precision is the remaining problem in a good determination of the Hubble constant. Whether a discrepancy exists, and whether new physics is needed to resolve it, depends on details of the systematics of the object-based methods, and also on the assumptions about other cosmological parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200

    Suspected Motor Problems and Low Preference for Active Play in Childhood Are Associated with Physical Inactivity and Low Fitness in Adolescence

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    Background - This prospective longitudinal study investigates whether suspected motor problems and low preference for active play in childhood are associated with physical inactivity and low cardiorespiratory fitness in adolescence. Methodology/Principal Findings - The study sample consisted of the Northern Finland Birth Cohort 1986 (NFBC 1986) composed of 5,767 children whose parents responded to a postal inquiry concerning their children's motor skills at age 8 years and who themselves reported their physical activity at age 16 years. Cardiorespiratory fitness was measured with a cycle ergometer test at age 16 years. Odds ratios (OR) and their 95% confidence intervals (95% CI) for the level of physical activity and fitness were obtained from multinomial logistic regression and adjusted for socio-economic position and body mass index. Low preference for active play in childhood was associated with physical inactivity (boys: OR 3.31, 95% CI 2.42–4.53; girls: OR 1.79, 95% CI 1.36–2.36) and low cardiorespiratory fitness (boys: OR 1.87, 95% CI 1.27–2.74; girls: OR 1.52, 95% CI 1.09–2.11) in adolescence. Suspected gross (OR 2.16, 95% CI 1.33–3.49) and fine (OR 1.88, 95% CI 1.35–2.60) motor problems were associated with physical inactivity among boys. Children with suspected motor problems and low preference for active play tended to have an even higher risk of physical inactivity in adolescence. Conclusions/Significance - Low preference for active play in childhood was associated with physical inactivity and low cardiorespiratory fitness in adolescence. Furthermore, children with suspected motor problems and low preference for active play tended to have an even higher risk of physical inactivity in adolescence. Identification of children who do not prefer active play and who have motor problems may allow targeted interventions to support their motor learning and participation in active play and thereby promote their physical activity and fitness in later life.peerReviewe

    Declining extra-pair paternity with laying order associated with initial incubation behavior, but independent of final clutch size in the blue tit

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    Although functional explanations for female engagement in extra-pair copulation have been studied extensively in birds, little is known about how extra-pair paternity is linked to other fundamental aspects of avian reproduction. However, recent studies indicate that the occurrence of extra-pair offspring may generally decline with laying order, possibly because stimulation by eggs induces incubation, which may suppress female motivation to acquire extra-pair paternity. Here we tested whether experimental inhibition of incubation during the laying phase, induced by the temporary removal of eggs, resulted in increased extra-pair paternity, in concert with a later cessation of laying, in blue tits (Cyanistes caeruleus). As expected, experimental females showed a more gradual increase in nocturnal incubation duration over the laying phase and produced larger clutches than controls. Moreover, incubation duration on the night after the first egg was laid predicted how extra-pair paternity declined with laying order, with less incubation being associated with more extra-pair offspring among the earliest eggs in the clutch. However, incubation duration on this first night was unrelated to our experimental treatment and independent of final clutch size. Consequently, the observed decline in extra-pair paternity with laying order was unaffected by our manipulation and larger clutches included proportionally fewer extra-pair offspring. We suggest that female physiological state prior to laying, associated with incubation at the onset of laying, determines motivation to acquire extra-pair paternity independent of final clutch size. This decline in proportion of extra-pair offspring with clutch size may be a general pattern within bird species

    Selective patterning of ZnO nanorods on silicon substrates using nanoimprint lithography

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    In this research, nanoimprint lithography (NIL) was used for patterning crystalline zinc oxide (ZnO) nanorods on the silicon substrate. To fabricate nano-patterned ZnO nanorods, patterning of an n-octadecyltrichlorosilane (OTS) self-assembled monolayers (SAMs) on SiO2 substrate was prepared by the polymer mask using NI. The ZnO seed layer was selectively coated only on the hydrophilic SiO2 surface, not on the hydrophobic OTS SAMs surface. The substrate patterned with the ZnO seed layer was treated with the oxygen plasma to oxidize the silicon surface. It was found that the nucleation and initial growth of the crystalline ZnO were proceeded only on the ZnO seed layer, not on the silicon oxide surface. ZnO photoluminescence spectra showed that ZnO nanorods grown from the seed layer treated with plasma showed lower intensity than those untreated with plasma at 378 nm, but higher intensity at 605 nm. It is indicated that the seed layer treated with plasma produced ZnO nanorods that had a more oxygen vacancy than those grown from seed layer untreated with plasma. Since the oxygen vacancies on ZnO nanorods serve as strong binding sites for absorption of various organic and inorganic molecules. Consequently, a nano-patterning of the crystalline ZnO nanorods grown from the seed layer treated with plasma may give the versatile applications for the electronics devices
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