We report on Bayesian parameter estimation of the mass and equatorial radius of the millisecond pulsar PSR J0030+0451, conditional on pulse-profile modeling of Neutron Star Interior Composition ...Explorer X-ray spectral-timing event data. We perform relativistic ray-tracing of thermal emission from hot regions of the pulsar's surface. We assume two distinct hot regions based on two clear pulsed components in the phase-folded pulse-profile data; we explore a number of forms (morphologies and topologies) for each hot region, inferring their parameters in addition to the stellar mass and radius. For the family of models considered, the evidence (prior predictive probability of the data) strongly favors a model that permits both hot regions to be located in the same rotational hemisphere. Models wherein both hot regions are assumed to be simply connected circular single-temperature spots, in particular those where the spots are assumed to be reflection-symmetric with respect to the stellar origin, are strongly disfavored. For the inferred configuration, one hot region subtends an angular extent of only a few degrees (in spherical coordinates with origin at the stellar center) and we are insensitive to other structural details; the second hot region is far more azimuthally extended in the form of a narrow arc, thus requiring a larger number of parameters to describe. The inferred mass M and equatorial radius Req are, respectively, 1.34 − 0.16 + 0.15 M and 12.71 − 1.19 + 1.14 km , while the compactness GM R eq c 2 = 0.156 − 0.010 + 0.008 is more tightly constrained; the credible interval bounds reported here are approximately the 16% and 84% quantiles in marginal posterior mass.
Adolescent idiopathic scoliosis (AIS) disrupts spinal alignment and increases the intrinsic demand for active stabilization to maintain postural stability. Understanding the paraspinal muscle ...fatigability and its effects on spinal alignment and kinematics informs the importance of paraspinal muscle endurance for postural stability. This study aims to investigate the effects of fatigue of thoracic erector spinae on the spinal muscle activity and spinal kinematics in individuals with scoliosis. Spinal muscle activity, posture and mobility measured by electromyography and surface tomography were compared between 15 participants with scoliosis and 15 age- and gender-matched healthy controls during unilateral shoulder flexion and abduction with and without holding a 2-kg weight and performed before and after a fatigue task (prone isometric chest raise). No between-groups difference was found for the spinal extensor endurance. Erector spinae activity at the convex side of AIS group was significantly higher than that at their concave side and than that of healthy controls during shoulder elevations, regardless of the fatigue status. Significant decreases in translational and rotational mobility were found at convex side of AIS group during weighted abduction tasks after fatigue. In contrast, a significant increase in rotational mobility was demonstrated at convex side of AIS participants during weighted flexion tasks after fatigue. Our results revealed a comparable level of spinal extensor endurance between individuals with or without AIS. The increase in muscle activation post-fatigue provides no additional active postural stability but may increase the risk of back pain over the convex side in individuals with scoliosis. Findings highlight imbalances in muscles and the potential implications in optimising neuromuscular activation and endurance capacity in the rehabilitation for AIS patients. Future research is needed to investigate if endurance training of the convex-sided back extensors could optimize the impaired neuromuscular control in the AIS patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
The gut microbiome of vertebrates plays an integral role in host health by stimulating development of the immune system, aiding in nutrient acquisition and outcompeting opportunistic ...pathogens. Development of next‐generation sequencing technologies allows researchers to survey complex communities of microorganisms within the microbiome at great depth with minimal costs, resulting in a surge of studies investigating bacterial diversity of fishes. Many of these studies have focused on the microbial structure of economically significant aquaculture species with the goal of manipulating the microbes to increase feed efficiency and decrease disease susceptibility. The unravelling of intricate host–microbe symbioses and identification of core microbiome functions is essential to our ability to use the benefits of a healthy microbiome to our advantage in fish culture, as well as gain deeper understanding of bacterial roles in vertebrate health. This review aims to summarize the available knowledge on fish gastrointestinal communities obtained from metagenomics, including biases from sample processing, factors influencing assemblage structure, intestinal microbiology of important aquaculture species and description of the teleostean core microbiome.
Abstract
PSR J0740+6620 has a gravitational mass of 2.08 ± 0.07
M
⊙
, which is the highest reliably determined mass of any neutron star. As a result, a measurement of its radius will provide unique ...insight into the properties of neutron star core matter at high densities. Here we report a radius measurement based on fits of rotating hot spot patterns to Neutron Star Interior Composition Explorer (NICER) and X-ray Multi-Mirror (XMM-Newton) X-ray observations. We find that the equatorial circumferential radius of PSR J0740+6620 is
13.7
−
1.5
+
2.6
km (68%). We apply our measurement, combined with the previous NICER mass and radius measurement of PSR J0030+0451, the masses of two other ∼2
M
⊙
pulsars, and the tidal deformability constraints from two gravitational wave events, to three different frameworks for equation-of-state modeling, and find consistent results at ∼1.5–5 times nuclear saturation density. For a given framework, when all measurements are included, the radius of a 1.4
M
⊙
neutron star is known to ±4% (68% credibility) and the radius of a 2.08
M
⊙
neutron star is known to ±5%. The full radius range that spans the ±1
σ
credible intervals of all the radius estimates in the three frameworks is 12.45 ± 0.65 km for a 1.4
M
⊙
neutron star and 12.35 ± 0.75 km for a 2.08
M
⊙
neutron star.
Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP ...inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial.
To define best practice for HRD testing in HGSC the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project that incorporated a systematic review approach. The main aims were to (i) define the term ‘HRD test’; (ii) provide an overview of the biological rationale and the level of evidence supporting currently available HRD tests; (iii) provide recommendations on the clinical utility of HRD tests in clinical management of HGSC.
A broad range of repair genes, genomic scars, mutational signatures and functional assays are associated with a history of HRD. Currently, the clinical validity of HRD tests in ovarian cancer is best assessed, not in terms of biological HRD status per se, but in terms of PARPi benefit. Clinical trials evidence supports the use of BRCA mutation testing and two commercially available assays that also incorporate genomic instability for identifying subgroups of HGSCs that derive different magnitudes of benefit from PARPi therapy, albeit with some variation by clinical scenario. These tests can be used to inform treatment selection and scheduling but their use is limited by a failure to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies. Existing tests lack negative predictive value and inadequately address the complex and dynamic nature of the HRD phenotype.
Currently available HRD tests are useful for predicting likely magnitude of benefit from PARPis but better biomarkers are urgently needed to better identify current homologous recombination proficiency status and stratify HGSC management.
•Homologous recombination repair deficiency (HRD) is a common feature of high-grade serous gynaecological cancers (HGSC).•Currently, the clinical validity of HRD tests in ovarian cancer is best assessed in terms of PARPi benefit.•Germline and somatic BRCA mutation and genomic instability tests help to predict likely magnitude of benefit from a PARPi.•Existing HRD tests fail to consistently identify a subgroup of patients who derive no benefit from PARPis in most studies.•HRD is a dynamic entity and better biomarkers that capture current homologous recombination proficiency status are needed.
Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric ...carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.
AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 μg/L, or 100–299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed.
Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio RR 0·79, 95% CI 0·62–1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64–1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 14% of 558 in the ferric carboxymaltose group vs 78 14% in the placebo group; hazard ratio HR 0·96, 95% CI 0·70–1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58–0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66–0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47–0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.
In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.
Vifor Pharma.
Summary Background Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of ...lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. Methods The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. Findings Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ2 on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40–1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. Interpretation We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. Funding The Motor Neurone Disease Association of Great Britain and Northern Ireland.
Local Time Asymmetries in Jupiter's Magnetodisc Currents Lorch, C. T. S.; Ray, L. C.; Arridge, C. S. ...
Journal of geophysical research. Space physics,
February 2020, 2020-02-00, 20200201, Letnik:
125, Številka:
2
Journal Article
Recenzirano
Odprti dostop
We present an investigation into the currents within the Jovian magnetodisc using all available spacecraft magnetometer data up until 28 July 2018. Using automated data analysis processes as well as ...the most recent intrinsic field and current disk geometry models, a full local time coverage of the magnetodisc currents using 7,382 lobe traversals over 39 years is constructed. Our study demonstrates clear local time asymmetries in both the radial and azimuthal height‐integrated current densities throughout the current disk. Asymmetries persist within 30 R
J where most models assume axisymmetry. Inward radial currents are found in the previously unmapped dusk and noon sectors. Azimuthal currents are found to be weaker in the dayside magnetosphere than the nightside, in agreement with global magnetohydrodynamic simulations. The divergence of the azimuthal and radial currents indicates that downward field‐aligned currents exist within the outer dayside magnetosphere. The presence of azimuthal currents is shown to highly influence the location of the field‐aligned currents, which emphasizes the importance of the azimuthal currents in future magnetosphere‐ionosphere coupling models. Integrating the divergence of the height‐integrated current densities, we find that 1.87 MA R
J−2 of return current density required for system closure is absent.
Key Points
Radial and azimuthal current densities exhibit local time asymmetries throughout the current disk
Radial currents flow planetward in noon‐dusk sectors and azimuthal currents are weakest through noon
Downward field‐aligned currents are identified in the noon‐dusk magnetosphere
Despite recent progress in the treatment of ovarian cancer, the majority of patients eventually relapse. There is little information on the effectiveness of chemotherapy in higher treatment lines.
...Characterization of the second to sixth line therapy and its effects on survival was carried out, based on data of n = 1620 patients from three large randomized phase III trials investigating primary therapy.
Median progression-free survival (PFS) after the first, second, third, fourth and fifth relapse was 10.2 95% confidence interval (CI) 9.6–10.7, 6.4 (5.9–7.0), 5.6 (4.8–6.2), 4.4 (3.7–4.9) and 4.1 (3.0–5.1) months, respectively. Median overall survival (OS) after the first, second, third, fourth and fifth relapse was 17.6 (95% CI 16.4–18.6), 11.3 (10.4–12.9), 8.9 (7.8–9.9), 6.2 (5.1–7.7) and 5.0 (3.8–10.4) months, respectively. The most frequent second and third line chemotherapy was platinum combination (n = 313, 24.5%) and topotecan (n = 118, 23.6%), respectively. Relapse treatment improved PFS and OS at the second to fourth recurrence, although frequently not performed according to the standard of care. In multivariate analysis, platinum sensitivity and optimal primary tumor debulking were revealed as independent prognostic factors for PFS up to third relapse.
A maximum of three lines of subsequent relapse treatment seems to be beneficial for patients with recurrent ovarian cancer. Optimal primary tumor debulking and platinum sensitivity remain independent prognostic factors even after more frequent relapses.
We compare Chandra and XMM‐Newton X‐ray observations of Jupiter during 2007 with a rich multi‐instrument data set including upstream in situ solar wind measurements from the New Horizons spacecraft, ...radio emissions from the Nançay Decametric Array and Wind/Waves, and ultraviolet (UV) observations from the Hubble Space Telescope. New Horizons data revealed two corotating interaction regions (CIRs) impacted Jupiter during these observations. Non‐Io decametric bursts and UV emissions brightened together and varied in phase with the CIRs. We characterize three types of X‐ray aurorae: hard X‐ray bremsstrahlung main emission, pulsed/flared soft X‐ray emissions, and a newly identified dim flickering (varying on short time scales, but quasi‐continuously present) aurora. For most observations, the X‐ray aurorae were dominated by pulsed/flaring emissions, with ion spectral lines that were best fit by iogenic plasma. However, the brightest X‐ray aurora was coincident with a magnetosphere expansion. For this observation, the aurorae were produced by both flickering emission and erratic pulses/flares. Auroral spectral models for this observation required the addition of solar wind ions to attain good fits, suggesting solar wind entry into the outer magnetosphere or directly into the pole for this particularly bright observation. X‐ray bremsstrahlung from high energy electrons was only bright for one observation, which was during a forward shock. This bremsstrahlung was spatially coincident with bright UV main emission (power > 1 TW) and X‐ray ion spectral line dusk emission, suggesting closening of upward and downward current systems during the shock. Otherwise, the bremsstrahlung was dim, and UV main emission power was also lower (<700 GW), suggesting their power scaled together.
Key Points
We characterize three types of X‐ray aurorae (main oval, ir/regular pulses, and flickering aurorae) and compare with radio, UV, and solar wind data
Non‐Io decametric bursts occurred with UV auroral brightening, and UV and hard X‐ray main auroral emission also brightened contemporaneously
Soft X‐ray aurora was best fit by iogenic (S, O) spectral lines except during magnetospheric expansion when solar wind ion lines were needed
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