"Kludge" gravitational waveforms for a test-body orbiting a Kerr black hole

One of the most exciting potential sources of gravitational waves for low-frequency, space-based gravitational wave (GW) detectors such as the proposed Laser Interferometer Space Antenna (LISA) is the inspiral of compact objects into massive black holes in the centers of galaxies. The detection of waves from such "extreme mass ratio inspiral" systems (EMRIs) and extraction of information from those waves require template waveforms. The systems' extreme mass ratio means that their waveforms can be determined accurately using black hole perturbation theory. Such calculations are computationally very expensive. There is a pressing need for families of approximate waveforms that may be generated cheaply and quickly but which still capture the main features of true waveforms. In this paper, we introduce a family of such "kludge" waveforms and describe ways to generate them. We assess performance of the introduced approximations by comparing "kludge" waveforms to accurate waveforms obtained by solving the Teukolsky equation in the adiabatic limit (neglecting GW backreaction). We find that the kludge waveforms do extremely well at approximating the true gravitational waveform, having overlaps with the Teukolsky waveforms of 95% or higher over most of the parameter space for which comparisons can currently be made. Indeed, we find these kludges to be of such high quality (despite their ease of calculation) that it is possible they may play some role in the final search of LISA data for EMRIs.Comment: 29 pages, 11 figures, requires subeqnarray; v2 contains minor changes for consistency with published versio

Association between fruit and vegetable intakes and mental health in the australian diabetes obesity and lifestyle cohort

Increasing prevalence of mental health disorders within the Australian population is a serious public health issue. Adequate intake of fruits and vegetables (FV), dietary fibre (DF) and resistant starch (RS) is associated with better mental and physical health. Few longitudinal studies exist exploring the temporal relationship. Using a validated food frequency questionnaire, we examined baseline FV intakes of 5845 Australian adults from the AusDiab study and estimated food group-derived DF and RS using data from the literature. Perceived mental health was assessed at baseline and 5 year follow up using SF-36 mental component summary scores (MCS). We conducted baseline cross-sectional analysis and prospective analysis of baseline dietary intake with perceived mental health at 5 years. Higher baseline FV and FV-derived DF and RS intakes were associated with better 5 year MCS (p \u3c 0.001). A higher FV intake (754 g/d vs. 251 g/d, Q4 vs. Q1) at baseline had 41% lower odds (OR = 0.59: 95% CI 0.46–0.75) of MCS below population average ( \u3c 47) at 5 year follow up. Findings were similar for FV-derived DF and RS. An inverse association was observed with discretionary food-derived DF and RS. This demonstrates the association between higher intakes of FV and FV-derived DF and RS with better 5 year mental health outcomes. Further RCTs are necessary to understand mechanisms that underlie this association including elucidation of causal effects

Observations and Theoretical Implications of the Large Separation Lensed Quasar SDSS J1004+4112

We study the recently discovered gravitational lens SDSS J1004+4112, the first quasar lensed by a cluster of galaxies. It consists of four images with a maximum separation of 14.62''. The system has been confirmed as a lensed quasar at z=1.734 on the basis of deep imaging and spectroscopic follow-up observations. We present color-magnitude relations for galaxies near the lens plus spectroscopy of three central cluster members, which unambiguously confirm that a cluster at z=0.68 is responsible for the large image separation. We find a wide range of lens models consistent with the data, but they suggest four general conclusions: (1) the brightest cluster galaxy and the center of the cluster potential well appear to be offset by several kpc; (2) the cluster mass distribution must be elongated in the North--South direction, which is consistent with the observed distribution of cluster galaxies; (3) the inference of a large tidal shear (~0.2) suggests significant substructure in the cluster; and (4) enormous uncertainty in the predicted time delays between the images means that measuring the delays would greatly improve constraints on the models. We also compute the probability of such large separation lensing in the SDSS quasar sample, on the basis of the CDM model. The lack of large separation lenses in previous surveys and the discovery of one in SDSS together imply a mass fluctuation normalization \sigma_8=1.0^{+0.4}_{-0.2} (95% CL), if cluster dark matter halos have an inner slope -1.5. Shallower profiles would require higher values of \sigma_8. Although the statistical conclusion might be somewhat dependent on the degree of the complexity of the lens potential, the discovery is consistent with the predictions of the abundance of cluster-scale halos in the CDM scenario. (Abridged)Comment: 21 pages, 24 figures, 5 tables, accepted for publication in Ap

Mapping of N−C bond formation from a series of crystalline peri‐substituted naphthalenes by charge density and solid‐state NMR methodologies

A combination of charge density studies and solid state nuclear magnetic resonance (NMR) 1JNC coupling measurements supported by periodic density functional theory (DFT) calculations is used to characterise the transition from an n–π* interaction to bond formation between a nucleophilic nitrogen atom and an electrophilic sp2 carbon atom in a series of crystalline peri‐substituted naphthalenes. As the N⋅⋅⋅C distance reduces there is a sharp decrease in the Laplacian derived from increasing charge density between the two groups at ca. N⋅⋅⋅C = 1.8 Å, with the periodic DFT calculations predicting, and heteronuclear spin‐echo NMR measurements confirming, the 1JNC couplings of ≈3–6 Hz for long C−N bonds (1.60–1.65 Å), and 1JNC couplings of 2.1 Å

Acetylcysteine has No Mechanistic Effect in Patients at Risk of Contrast-Induced Nephropathy - A Failure of Academic Clinical Science

Contrast‐induced nephropathy (CIN) is a major complication of imaging in patients with chronic kidney disease (CKD). The publication of an academic randomized controlled trial (RCT; n = 83) reporting oral (N)‐acetylcysteine (NAC) to reduce CIN led to > 70 clinical trials, 23 systematic reviews, and 2 large RCTs showing no benefit. However, no mechanistic studies were conducted to determine how NAC might work; proposed mechanisms included renal artery vasodilatation and antioxidant boosting. We evaluated the proposed mechanisms of NAC action in participants with healthy and diseased kidneys. Four substudies were performed. Two randomized, double‐blind, placebo‐controlled, three‐period crossover studies (n = 8) assessed the effect of oral and intravenous (i.v.) NAC in healthy kidneys in the presence/absence of iso‐osmolar contrast (iodixanol). A third crossover study in patients with CKD stage III (CKD3) (n = 8) assessed the effect of oral and i.v. NAC without contrast. A three‐arm randomized, double‐blind, placebo‐controlled parallel‐group study, recruiting patients with CKD3 (n = 66) undergoing coronary angiography, assessed the effect of oral and i.v. NAC in the presence of contrast. We recorded systemic (blood pressure and heart rate) and renal (renal blood flow (RBF) and glomerular filtration rate (GFR)) hemodynamics, and antioxidant status, plus biomarkers of renal injury in patients with CKD3 undergoing angiography. Primary outcome for all studies was RBF over 8 hours after the start of i.v. NAC/placebo. NAC at doses used in previous trials of renal prophylaxis was essentially undetectable in plasma after oral administration. In healthy volunteers, i.v. NAC, but not oral NAC, increased blood pressure (mean area under the curve (AUC) mean arterial pressure (MAP): mean difference 29 h⋅mmHg, P = 0.019 vs. placebo), heart rate (28 h⋅bpm, P < 0.001), and RBF (714 h⋅mL/min, 8.0% increase, P = 0.006). Renal vasodilatation also occurred in the presence of contrast (RBF 917 h⋅mL/min, 12% increase, P = 0.005). In patients with CKD3 without contrast, only a rise in heart rate (34 h⋅bpm, P = 0.010) and RBF (288 h⋅mL/min, 6.0% increase, P = 0.001) occurred with i.v. NAC, with no significant effect on blood pressure (MAP rise 26 h⋅mmHg, P = 0.156). Oral NAC showed no effect. In patients with CKD3 receiving contrast, i.v. NAC increased blood pressure (MAP rise 52 h⋅mmHg, P = 0.008) but had no effect on RBF (151 h⋅mL/min, 3.0% increase, P = 0.470), GFR (29 h⋅mL/min/1.73m², P = 0.122), or markers of renal injury. Neither i.v. nor oral NAC affected plasma antioxidant status. We found oral NAC to be poorly absorbed and have no reno‐protective effects. Intravenous, not oral, NAC caused renal artery vasodilatation in healthy volunteers but offered no protection to patients with CKD3 at risk of CIN. These findings emphasize the importance of mechanistic clinical studies before progressing to RCTs for novel interventions. Thousands were recruited to academic clinical trials without the necessary mechanistic studies being performed to confirm the approach had any chance of working

Intermediate and extreme mass-ratio inspirals — astrophysics, science applications and detection using LISA

Black hole binaries with extreme (gtrsim104:1) or intermediate (~102–104:1) mass ratios are among the most interesting gravitational wave sources that are expected to be detected by the proposed laser interferometer space antenna (LISA). These sources have the potential to tell us much about astrophysics, but are also of unique importance for testing aspects of the general theory of relativity in the strong field regime. Here we discuss these sources from the perspectives of astrophysics, data analysis and applications to testing general relativity, providing both a description of the current state of knowledge and an outline of some of the outstanding questions that still need to be addressed. This review grew out of discussions at a workshop in September 2006 hosted by the Albert Einstein Institute in Golm, Germany

Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma

Background: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease. Methods: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma). Results: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC. Conclusions: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence. Graphical Abstract

Advances in MRI Assessment of Gliomas and Response to Anti-VEGF Therapy

Bevacizumab is thought to normalize tumor vasculature and restore the blood–brain barrier, decreasing enhancement and peritumoral edema. Conventional measurements of tumor response rely upon dimensions of enhancing tumor. After bevacizumab treatment, glioblastomas are more prone to progress as nonenhancing tumor. The RANO (Response Assessment in Neuro-Oncology) criteria for glioma response use fluid-attenuated inversion recovery (FLAIR)/T2 hyperintensity as a surrogate for nonenhancing tumor; however, nonenhancing tumor can be difficult to differentiate from other causes of FLAIR/T2 hyperintensity (eg, radiation-induced gliosis). Due to these difficulties, recent efforts have been directed toward identifying new biomarkers that either predict treatment response or accurately measure response of both enhancing and nonenhancing tumor shortly after treatment initiation. This will allow for earlier treatment decisions, saving patients from the adverse effects of ineffective therapies while allowing them to try alternative therapies sooner. An active area of research is the use of physiologic imaging, which can potentially detect treatment effects before changes in tumor size are evident