Cross correlation of ambient seismic noise is known to result in time series from which station‐station travel‐time measurements can be made. Part of the reason that these cross‐correlation ...travel‐time measurements are reliable is that there exists a theoretical framework that quantifies how these travel times depend on the features of the ambient noise. However, corresponding theoretical results do not currently exist to describe how the amplitudes of the cross correlation depend on such features. For example, currently it is not possible to take a given distribution of noise sources and calculate the cross correlation amplitudes one would expect from such a distribution. Here, we provide a ray‐theoretical framework for calculating cross correlations. This framework differs from previous work in that it explicitly accounts for attenuation as well as the spatial distribution of sources and therefore can address the issue of quantifying amplitudes in noise correlation measurements. After introducing the general framework, we apply it to two specific problems. First, we show that we can quantify the amplitudes of coherency measurements, and find that the decay of coherency with station‐station spacing depends crucially on the distribution of noise sources. We suggest that researchers interested in performing attenuation measurements from noise coherency should first determine how the dominant sources of noise are distributed. Second, we show that we can quantify the signal‐to‐noise ratio of noise correlations more precisely than previous work, and that these signal‐to‐noise ratios can be estimated for given situations prior to the deployment of seismometers. It is expected that there are applications of the theoretical framework beyond the two specific cases considered, but these applications await future work.
Key Points
To construct a framework for calculating noise correlation amplitudes
To determine how correlation amplitudes depend on noise source distributions
To calculate signal‐to‐noise ratios for various source distributions
Summary Points * Despite hundreds of mHealth pilot studies, there has been insufficient programmatic evidence to inform implementation and scale-up of mHealth. * We discuss what constitutes ...appropriate research evidence to inform scale up. * Potential innovative research designs such as multi-factorial strategies, randomized controlled trials, and data farming may provide this evidence base. * We make a number of recommendations about evidence, interoperability, and the role of governments, private enterprise, and researchers in relation to the scale up of mHealth. Interventions categorized under the rubric "mobile health" or "mHealth"--broadly defined as medical and public health practice supported by mobile devices 2--span a variety of applications ranging from the use of mobile phones to improve point of service data collection 3, care delivery 4, and patient communication 5 to the use of alternative wireless devices for real-time medication monitoring and adherence support 6.
ABSTRACT Observed at z = 4.601 and with = 3.5 , W2246-0526 is the most luminous galaxy known in the universe and hosts a deeply buried active galactic nucleus (AGN)/supermassive black hole (SMBH). ...Discovered using the Wide-field Infrared Survey Explorer, W2246-0526 is classified as a hot dust-obscured galaxy, based on its luminosity and dust temperature. Here, we present spatially resolved ALMA C ii157.7 m observations of W2246-0526, providing unique insight into the kinematics of its interstellar medium (ISM). The measured C ii -to-far-infrared ratio is , implying ISM conditions that compare only with the most obscured, compact starbursts and AGNs in the local universe today. The spatially resolved C ii line is strikingly uniform and very broad, 500-600 km s−1 wide, extending throughout the entire galaxy over about 2.5 kpc, with modest shear. Such a large, homogeneous velocity dispersion indicates a highly turbulent medium. W2246-0526 is unstable in terms of the energy and momentum that are being injected into the ISM, strongly suggesting that the gas is being blown away from the system isotropically, likely reflecting a cathartic state on its road to becoming an unobscured quasar. W2246-0526 provides an extraordinary laboratory to study and model the properties and kinematics of gas in an extreme environment under strong feedback, at a time when the universe was 1/10 of its current age: a system pushing the limits that can be reached during galaxy formation.
During the early development of Xenopus laevis embryos, the first mitotic cell cycle is long (∼85 min) and the subsequent 11 cycles are short (∼30 min) and clock-like. Here we address the question of ...how the Cdk1 cell cycle oscillator changes between these two modes of operation. We found that the change can be attributed to an alteration in the balance between Wee1/Myt1 and Cdc25. The change in balance converts a circuit that acts like a positive-plus-negative feedback oscillator, with spikes of Cdk1 activation, to one that acts like a negative-feedback-only oscillator, with a shorter period and smoothly varying Cdk1 activity. Shortening the first cycle, by treating embryos with the Wee1A/Myt1 inhibitor PD0166285, resulted in a dramatic reduction in embryo viability, and restoring the length of the first cycle in inhibitor-treated embryos with low doses of cycloheximide partially rescued viability. Computations with an experimentally parameterized mathematical model show that modest changes in the Wee1/Cdc25 ratio can account for the observed qualitative changes in the cell cycle. The high ratio in the first cycle allows the period to be long and tunable, and decreasing the ratio in the subsequent cycles allows the oscillator to run at a maximal speed. Thus, the embryo rewires its feedback regulation to meet two different developmental requirements during early development.
Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of ...carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously, consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicate that TH/PINK1/Parkin pathway has a critical role in protecting hepatocytes from HBx-induced carcinogenesis. Notably, several liver-targeting therapeutic derivatives of TH facilitating prevention or therapy of steatosis have been identified. Furthermore, our proof-of-concept experiments suggest that application of T
constitutes an effective novel therapeutic or preventive option for HCC. Thus, the utilization of the agonists of TRs could be the meaningful strategy in liver relative diseases, ranging from simple hepatic steatosis to HCC.
Objective: A series of experiment were conducted to evaluate the effects of replacing a part of soybean meal (SBM) at 6% of broiler diets with fermented soybean meal (FSBM) obtained by single or ...two-stage fermentation by measuring growth performance, antioxidant activity in the jejunum and distal intestinal microflora.Methods: Soybean meal samples were prepared by single-stage fermentation using Bacillus velezensis (Bv) (FSBMB), or Lactobacillus spp. (as commercial control) (FSBML). Additional SBM sample was prepared by two-stage fermentation using Bv and subsequently using Lactobacillus brevis ATCC 367 (Lb) (FSBMB+L). Enzyme activity, chemical composition, trichloroethanoic acid-nitrogen solubility index (TCA-NSI) and antioxidant activity were measured. Then, in an in vivo study, 320 Ross308 broilers were divided into four groups with ad libitum supply of feed and water. Four groups were fed either a corn-soybean meal diet (SBM), or one of fermented SBM diets (FSBMB+L, FSBMB, and FSBML). Growth, serum characteristics, microflora, and the mRNA expression of selected genes were measured.Results: Compared to SBM, FSBMB+L contained lower galacto-oligosaccharide, allergic protein, and trypsin inhibitor, and higher TCA-NSI by about three times (p<0.05). Reducing power and 1,1-diphenyl-2-picrylhydrazyl free radical scavenging ability correlated positively with the TCA-NSI content in FSBM. Growth performances were not significantly different among four groups. In jejunum of 35-day-old broilers, partial replacement of SBM by FSBMB+L increased the activity of superoxide dismutase and catalase (CAT), and the FSBMB group had the highest catalase activity (p<0.05). Partial replacement of SBM by FSBM increased relative mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and peptide transporter 1 (PepT1) (p<0.05); however, FSBMB+L increased CAT mRNA level to 5 times of the control (p<0.05).Conclusion: Using Bv- and Lb-processed SBM through two-stage fermentation to partially replace 6% of diets will improve the gut's antioxidant activity under commercial breeding in broilers.
This study developed a survey to explore students' preferences in constructivist context‐aware ubiquitous learning environments. A constructivist context‐aware ubiquitous learning (u‐learning) ...environment survey (CULES) was developed, consisting of eight scales, including ease of use, continuity, relevance, adaptive content, multiple sources, timely guidance, student negotiation, and inquiry learning. The survey responses were gathered from 215 university students from five universities in Taiwan. The students all had actual experience of using u‐learning systems in u‐learning environments. Both exploratory and confirmatory factor analyses showed that the CULES had high reliability and validity. The structural model revealed that the provision of realistic and close‐to‐real‐life information could enhance students' preferences for timely guidance, student negotiation, and inquiry‐learning activities. In addition, the attainment of inquiry learning is quite challenging when designing u‐learning activities, as it involves the enhancement of the other CULES scales.
It has previously been shown that the Green's function between two receivers can be retrieved by cross-correlating time series of noise recorded at the two receivers. This property has been derived ...assuming that the energy in normal modes is uncorrelated and perfectly equipartitioned, or that the distribution of noise sources is uniform in space and the waves measured satisfy a high frequency approximation. Although a number of authors have successfully extracted travel-time information from seismic surface-wave noise, the reason for this success of noise tomography remains unclear since the assumptions inherent in previous derivations do not hold for dispersive surface waves on the Earth. Here, we present a simple ray-theory derivation that facilitates an understanding of how cross correlations of seismic noise can be used to make direct travel-time measurements, even if the conditions assumed by previous derivations do not hold. Our new framework allows us to verify that cross-correlation measurements of isotropic surface-wave noise give results in accord with ray-theory expectations, but that if noise sources have an anisotropic distribution or if the velocity structure is non-uniform then significant differences can sometimes exist. We quantify the degree to which the sensitivity kernel is different from the geometric ray and find, for example, that the kernel width is period-dependent and that the kernel generally has non-zero sensitivity away from the geometric ray, even within our ray theoretical framework. These differences lead to usually small (but sometimes large) biases in models of seismic-wave speed and we show how our theoretical framework can be used to calculate the appropriate corrections. Even when these corrections are small, calculating the errors within a theoretical framework would alleviate fears traditional seismologists may have regarding the robustness of seismic noise tomography.
Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients ...when salvageable tissue has been identified with imaging biomarkers.
We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale mRS) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.
Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio OR 1·49 95% CI 1·10–2·03; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 95% CI 1·05–1·80; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 1·06–2·12; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 0·52–1·11; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 1·03–4·09; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 3% vs two <1%, adjusted OR 5·58 1·22–25·50; p=0·024).
In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.
None.
Atypical antipsychotic medications are widely prescribed for the adjunctive treatment of depression, yet their total risk-benefit profile is not well understood. We thus conducted a systematic review ...of the efficacy and safety profiles of atypical antipsychotic medications used for the adjunctive treatment of depression.
We included randomized trials comparing adjunctive antipsychotic medication to placebo for treatment-resistant depression in adults. Our literature search (conducted in December 2011 and updated on December 14, 2012) identified 14 short-term trials of aripiprazole, olanzapine/fluoxetine combination (OFC), quetiapine, and risperidone. When possible, we supplemented published literature with data from manufacturers' clinical trial registries and US Food and Drug Administration New Drug Applications. Study duration ranged from 4 to 12 wk. All four drugs had statistically significant effects on remission, as follows: aripiprazole (odds ratio OR, 2.01; 95% CI, 1.48-2.73), OFC (OR, 1.42; 95% CI, 1.01-2.0), quetiapine (OR, 1.79; 95% CI, 1.33-2.42), and risperidone (OR, 2.37; 95% CI, 1.31-4.30). The number needed to treat (NNT) was 19 for OFC and nine for each other drug. All drugs with the exception of OFC also had statistically significant effects on response rates, as follows: aripiprazole (OR, 2.07; 95% CI, 1.58-2.72; NNT, 7), OFC (OR, 1.30, 95% CI, 0.87-1.93), quetiapine (OR, 1.53, 95% CI, 1.17-2.0; NNT, 10), and risperidone (OR, 1.83, 95% CI, 1.16-2.88; NNT, 8). All four drugs showed statistically significant effects on clinician-rated depression severity measures (Hedges' g ranged from 0.26 to 0.48; mean difference of 2.69 points on the Montgomery-Asberg Depression Rating Scale across drugs). On measures of functioning and quality of life, these medications produced either no benefit or a very small benefit, except for risperidone, which had a small-to-moderate effect on quality of life (g = 0.49). Treatment was linked to several adverse events, including akathisia (aripiprazole), sedation (quetiapine, OFC, and aripiprazole), abnormal metabolic laboratory results (quetiapine and OFC), and weight gain (all four drugs, especially OFC). Shortcomings in study design and data reporting, as well as use of post hoc analyses, may have inflated the apparent benefits of treatment and reduced the apparent incidence of adverse events.
Atypical antipsychotic medications for the adjunctive treatment of depression are efficacious in reducing observer-rated depressive symptoms, but clinicians should interpret these findings cautiously in light of (1) the small-to-moderate-sized benefits, (2) the lack of benefit with regards to quality of life or functional impairment, and (3) the abundant evidence of potential treatment-related harm. Please see later in the article for the Editors' Summary.
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