Prospects of observing continuous gravitational waves from known pulsars

Several past searches for gravitational waves from a selection of known pulsars have been performed with data from the science runs of the Laser Inferometer Gravitational-wave Observatory (LIGO) gravitational wave detectors. So far these have lead to no detection, but upper limits on the gravitational wave amplitudes have been set. Here we study our intrinsic ability to detect, and estimate the gravitational wave amplitude for non-accreting pulsars. Using spin-down limits on emission as a guide we examine amplitudes that would be required to observe known pulsars with future detectors (Advanced LIGO, Advanced Virgo and the Einstein Telescope), assuming that they are triaxial stars emitting at precisely twice the known rotation frequency. Maximum allowed amplitudes depend on the stars' equation of state (e.g. a normal neutron star, a quark star, a hybrid star) and the theoretical mass quadrupoles that they can sustain. We study what range of quadrupoles, and therefore equations of state, would be consistent with being able to detect these sources. For globular cluster pulsars, with spin-downs masked by accelerations within the cluster, we examine what spin-down values gravitational wave observations would be able to set. For all pulsars we also alternatively examine what internal magnetic fields they would need to sustain observable ellipticities.Comment: version to be published in Monthly Notices of the Royal Astronomical Societ

Topology of non-linear structure in the 2dF Galaxy Redshift Survey

We study the evolution of non-linear structure as a function of scale in samples from the 2dF Galaxy Redshift Survey, constituting over 221 000 galaxies at a median redshift of z=0.11. The two flux-limited galaxy samples, located near the southern galactic pole and the galactic equator, are smoothed with Gaussian filters of width ranging from 5 to 8 Mpc/h to produce a continuous galaxy density field. The topological genus statistic is used to measure the relative abundance of overdense clusters to void regions at each scale; these results are compared to the predictions of analytic theory, in the form of the genus statistic for i) the linear regime case of a Gaussian random field; and ii) a first-order perturbative expansion of the weakly non-linear evolved field. The measurements demonstrate a statistically significant detection of an asymmetry in the genus statistic between regions corresponding to low- and high-density volumes of the universe. We attribute the asymmetry to the non-linear effects of gravitational evolution and biased galaxy formation, and demonstrate that these effects evolve as a function of scale. We find that neither analytic prescription satisfactorily reproduces the measurements, though the weakly non-linear theory yields substantially better results in some cases, and we discuss the potential explanations for this result.Comment: 13 pages, matching proof to be published in MNRAS; new version adds reference and corrects figure

Census 2020: The effect of a census undercount in Pierce County

CAUR is partnering with GTCF to provide data for a Census 2020 campaign in Pierce County. The purpose of this campaign is to provide materials and information about the importance of a complete and accurate census count. The research materials provided by CAUR will be used to provide information for a public education video and materials to be distributed to community leaders as they encourage constituents to actively participate in the upcoming 2020 Census. Census data has a wide variety of applications, both public/government and in private industry. CAUR worked closely with GTCF to identify four different use cases for census data that help convey the importance of having a complete and accurate count. These use cases represent aspects of day-to-day life for Pierce County residents that might be changed if the census count is inaccurate. For example, we present details on how bus routes might be altered if are using inaccurate census data, due to significant undercounts, potentially missing entire neighborhoods where bus service would be needed. We also evaluate the difference in federal funding to Pierce County if 10% of residents do not complete their census forms. The examples we use here provide insight into the issues that arise from both inaccurate and incomplete census data. In some of our use cases, we simulate an inaccurate census count in key areas. For example, we simulate the differences of siting a new health clinic if some houses incorrectly report the number of children in their homes. In other cases we examine the repercussions of failing to complete the census entirely. Federal grants are sometimes based on the number of residents in an area, and if the census count does not include all residents, then there is a proportional drop in grant funding. It is important to relay the message that the census is important, and that it should be completed honestly and accurately

A bicarbonate-rich liquid condensed phase in non-saturated solutions in the absence of divalent cations.

Bicarbonate (HCO3 -) and sodium (Na+)-containing solutions contain droplets of a separate, bicarbonate-rich liquid condensed phase (LCP) that have higher concentrations of HCO3 - relative to the bulk solution in which they reside. The existence and composition of the LCP droplets has been investigated by nanoparticle tracking analysis, nuclear magnetic resonance spectroscopy, refractive index measurements and X-ray pair distribution function analysis. The bicarbonate-rich LCP species is a previously unaccounted-for, ionic phenomenon which occurs even in solutions with solely monovalent cations. Its existence requires re-evaluation of models used to describe and model aqueous solution physicochemistry, especially those used to describe and model carbonate mineral formation

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology

Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2

Background Entrectinib is a potent inhibitor of ROS1 (in addition to TRKA/B/C), designed to effectively penetrate the central nervous system (CNS); brain metastases are common in patients with advanced ROS1 fusion-positive NSCLC. Entrectinib achieves therapeutic levels in the CNS with antitumor activity in multiple intracranial tumor models. We present an updated integrated safety and efficacy analysis from three Phase I/II studies of entrectinib (ALKA-372-001 [EudraCT 2012-000148-88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]) in patients with locally advanced or metastatic ROS1 fusion-positive NSCLCs. Methods The analysis included patients with ROS1 inhibitor-naive NSCLC harboring a ROS1 fusion identified via nucleic acid-based diagnostic platforms. The ROS1 safety-evaluable population included patients with ROS1 fusion-positive NSCLC who received ≥1 dose of entrectinib; the integrated efficacy analysis included patients with at least 6 months of follow-up. Tumor assessments were done at week 4 and every 8 weeks thereafter. Blinded independent central review (BICR), RECIST v1.1 was performed. Primary endpoints by BICR: overall response rate (ORR) and duration of response (DOR). Key secondary endpoints: progression-free survival (PFS), safety. Additional endpoints: intracranial ORR (complete/partial responses), DOR in patients with an intracranial response, PFS in patients with baseline CNS disease. Results In the ROS1 safety-evaluable population (n=134), at least one treatment-related AE (TRAE) of any grade was seen in 93% of patients. Patients with at least one TRAE by highest grade were: grade 1/2, 59%; grade 3, 31%; grade 4, 4%. There were no grade 5 TRAEs. TRAEs led to dose reduction or discontinuation in 34% and 5% of patients, respectively. In the efficacy-evaluable population (n=53 patients with treatment-naive, ROS1 fusion-positive NSCLC; median age 53 years, 64% female, 59% never smokers), BICR-assessed ORR was 77% (95% CI 64-88), complete responses n=3 (6%). Median BICR-assessed DOR: 25 mo (95% CI 11-35). Median BICR-assessed PFS: 26 mo (95% CI 16-37) and 14 mo (95% CI 5-NR) for patients without (n=30) and with CNS disease (n=23) at baseline, respectively. In patients with baseline CNS disease (per BICR assessment, n=20), intracranial ORR was 55% (95% CI 32-77) and median intracranial DOR in patients with an intracranial response (n=11) was 13 mo (95% CI 6-not reached). Conclusion Entrectinib is highly active in patients with ROS1 fusion-positive NSCLC, including those with CNS disease. Entrectinib is well tolerated and has a manageable safety profile. Citation Format: Alexander Drilon, Fabrice Barlesi, Filippo De Braud, Byoung Chul Cho, Myung-Ju Ahn, Salvatore Siena, Matthew G. Krebs, Chia-Chi Lin, Tom John, Daniel SW Tan, Takashi Seto, Rafal Dziadziuszko, Hendrick-Tobias Arkenau, Christian Rolfo, Jurgen Wolf, Chenglin Ye, Todd Riehl, Susan Eng, Robert C. Doebele. Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT192