1,643 research outputs found
Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours
Can the fluctuations of the quantum vacuum solve the cosmological constant problem?
The cosmological constant problem arises because the magnitude of vacuum
energy density predicted by quantum mechanics is about 120 orders of magnitude
larger than the value implied by cosmological observations of accelerating
cosmic expansion. Recently, some of the current authors proposed that the
stochastic nature of the quantum vacuum can resolve this tension [Q, Wang, Z.
Zhu, and W. G. Unruh, Phys. Rev. D 95, 103504, 2017]. By treating the
fluctuations in the vacuum seriously and allowing fluctuations up to some
high-energy cutoff at which Quantum Field Theory is believed to break down, a
parametric resonance effect arises that leads to a slow expansion and
acceleration. In this work, we thoroughly examine the implications of this
proposal by investigating the resulting dynamics. First, we improve upon
numerical calculations in the original work and show that convergence issues
had overshadowed some important effects. Correct calculations reverse some of
the conclusions in [Q. Wang, Z. Zhu, and W. G. Unruh, Phys. Rev. D 95, 103504,
2017], however the premise that parametric resonance can explain a very slowly
accelerating expansion appears to remain sound. After improving the resolution
and efficiency of the numerical tests, we explore a wider range of cutoff
energies, and examine the effects of multiple particle fields. We introduce a
simple model using the Mathieu equation (a prototypical example of parametric
resonance), and find that it closely matches numerical results in regimes where
its assumptions are valid. Using this model, we extrapolate to find that in a
universe with 28 bosonic fields and a high-energy cutoff 40 times higher than
the Planck energy, the acceleration would be comparable to what is observed.Comment: 19 pages, 12 figure
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Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis.
Variation in major histocompatibility complex genes on chromosome 6p21.3, specifically the human leukocyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for multiple sclerosis (MS). Previous studies of DRB1 variation and both MS susceptibility and phenotypic expression have lacked statistical power to detect modest genotypic influences, and have demonstrated conflicting results. Results derived from analyses of 1339 MS families indicate DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was strongly associated in families (P=7.8x10(-31)), and a dominant DRB1*15 dose effect was confirmed (OR=7.5, 95% CI=4.4-13.0, P<0.0001). A modest dose effect was also detected for DRB1*03; however, in contrast to DRB1*15, this risk was recessive (OR=1.8, 95% CI=1.1-2.9, P=0.03). Strong evidence for under-transmission of DRB1*14 (P=5.7x10(-6)) even after accounting for DRB1*15 (P=0.03) was present, confirming a protective effect. In addition, a high risk DRB1*15 genotype bearing DRB1*08 was identified (OR=7.7, 95% CI=4.1-14.4, P<0.0001), providing additional evidence for trans DRB1 allelic interactions in MS. Further, a significant DRB1*15 association observed in primary progressive MS families (P=0.0004), similar to relapsing-remitting MS families, suggests that DRB1-related mechanisms are contributing to both phenotypes. In contrast, results obtained from 2201 MS cases argue convincingly that DRB1*15 genotypes do not modulate age of onset, or significantly influence disease severity measured using expanded disease disability score and disease duration. These results contribute substantially to our understanding of the DRB1 locus and MS, and underscore the importance of using large sample sizes to detect modest genetic effects, particularly in studies of genotype-phenotype relationships
Feature integration in natural language concepts
Two experiments measured the joint influence of three key sets of semantic features on the frequency with which artifacts (Experiment 1) or plants and creatures (Experiment 2) were categorized in familiar categories. For artifacts, current function outweighed both originally intended function and current appearance. For biological kinds, appearance and behavior, an inner biological function, and appearance and behavior of offspring all had similarly strong effects on categorization. The data were analyzed to determine whether an independent cue model or an interactive model best accounted for how the effects of the three feature sets combined. Feature integration was found to be additive for artifacts but interactive for biological kinds. In keeping with this, membership in contrasting artifact categories tended to be superadditive, indicating overlapping categories, whereas for biological kinds, it was subadditive, indicating conceptual gaps between categories. It is argued that the results underline a key domain difference between artifact and biological concepts
Placebo-controlled study in neuromyelitis optica : ethical and design considerations
BACKGROUND: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. OBJECTIVE: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity. METHODS: We assessed the "standard of care" for NMO to establish the ethical framework for a placebo-controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. RESULTS: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. CONCLUSION: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path
A randomized, placebo-controlled phase 2 trial of laquinimod in primary progressive multiple sclerosis
OBJECTIVE: To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS). METHODS: In the randomized, double-blind, placebo-controlled, phase 2 study ARPEGGIO (A Randomized Placebo-controlled trial Evaluating laquinimod in PPMS, Gauging Gradations In MRI and clinical Outcomes), eligible PPMS patients were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.5 mg or matching placebo. Percentage brain volume change (PBVC; primary endpoint) from baseline to week 48 was assessed by MRI. Secondary and exploratory endpoints included clinical and MRI measures. Efficacy endpoints were evaluated using a predefined, hierarchical statistical testing procedure. Safety was monitored throughout the study. The laquinimod 1.5 mg dose arm was discontinued on January 1, 2016 due to findings of cardiovascular events. RESULTS: 374 patients were randomized to laquinimod 0.6 mg (n = 139) or 1.5 mg (n = 95) or placebo (n = 140). ARPEGGIO did not meet the primary endpoint of significant treatment effect with laquinimod 0.6 mg versus placebo on PBVC from baseline to week 48 (adjusted mean difference = 0.016%, p = 0.903). Laquinimod 0.6 mg reduced the number of new T2 brain lesions at week 48 (risk ratio = 0.4; 95% confidence interval, 0.26-0.69; p = 0.001). Incidence of adverse events was higher among patients treated with laquinimod 0.6 mg (83%) versus laquinimod 1.5 mg (66%) and placebo (78%). CONCLUSIONS: Laquinimod 0.6 mg did not demonstrate a statistically significant effect on brain volume loss in PPMS at week 48
Search for nucleon decays with EXO-200
A search for instability of nucleons bound in Xe nuclei is reported
with 223 kgyr exposure of Xe in the EXO-200 experiment. Lifetime
limits of 3.3 and 1.9 yrs are established for
nucleon decay to Sb and Te, respectively. These are the most
stringent to date, exceeding the prior decay limits by a factor of 9 and 7,
respectively
Deep Neural Networks for Energy and Position Reconstruction in EXO-200
We apply deep neural networks (DNN) to data from the EXO-200 experiment. In
the studied cases, the DNN is able to reconstruct the relevant parameters -
total energy and position - directly from raw digitized waveforms, with minimal
exceptions. For the first time, the developed algorithms are evaluated on real
detector calibration data. The accuracy of reconstruction either reaches or
exceeds what was achieved by the conventional approaches developed by EXO-200
over the course of the experiment. Most existing DNN approaches to event
reconstruction and classification in particle physics are trained on Monte
Carlo simulated events. Such algorithms are inherently limited by the accuracy
of the simulation. We describe a unique approach that, in an experiment such as
EXO-200, allows to successfully perform certain reconstruction and analysis
tasks by training the network on waveforms from experimental data, either
reducing or eliminating the reliance on the Monte Carlo.Comment: Accepted version. 33 pages, 28 figure
Problem gambling: a suitable case for social work?
Problem gambling attracts little attention from health and social care agencies
in the UK. Prevalence surveys suggest that 0.6% of the population are
problem gamblers and it is suggested that for each of these individuals,
10–17 other people, including children and other family members, are
affected. Problem gambling is linked to many individual and social problems
including: depression, suicide, significant debt, bankruptcy, family conflict,
domestic violence, neglect and maltreatment of children and offending.
This makes the issue central to social work territory. Yet, the training of
social workers in the UK has consistently neglected issues of addictive
behaviour. Whilst some attention has been paid in recent years to substance
abuse issues, there has remained a silence in relation to gambling
problems. Social workers provide more help for problems relating to addictions
than other helping professions. There is good evidence that treatment,
and early intervention for gambling problems, including psycho-social and
public health approaches, can be very effective. This paper argues that
problem gambling should be moved onto the radar of the social work profession,
via inclusion on qualifying and post-qualifying training programmes
and via research and dissemination of good practice via institutions such as
the Social Care Institute for Excellence (SCIE).
Keywords: problem gambling; addictive behaviour; socia
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