A strongly changing accretion morphology during the outburst decay of the neutron star X-ray binary 4U 1608−52

It is commonly assumed that the properties and geometry of the accretion flow in transient low-mass X-ray binaries (LMXBs) significantly change when the X-ray luminosity decays below ∼10⁻² of the Eddington limit (L_(Edd)). However, there are few observational cases where the evolution of the accretion flow is tracked in a single X-ray binary over a wide dynamic range. In this work, we use NuSTAR and NICER observations obtained during the 2018 accretion outburst of the neutron star LMXB 4U 1608−52, to study changes in the reflection spectrum. We find that the broad Fe–Kα line and Compton hump, clearly seen during the peak of the outburst when the X-ray luminosity is ∼10³⁷ erg s⁻¹ (∼0.05 L_(Edd)), disappear during the decay of the outburst when the source luminosity drops to ∼4.5 × 10³⁵ erg s⁻¹ (∼0.002 L_(Edd)). We show that this non-detection of the reflection features cannot be explained by the lower signal-to-noise ratio at lower flux, but is instead caused by physical changes in the accretion flow. Simulating synthetic NuSTAR observations on a grid of inner disc radius, disc ionization, and reflection fraction, we find that the disappearance of the reflection features can be explained by either increased disc ionization (log ξ ≳ 4.1) or a much decreased reflection fraction. A changing disc truncation alone, however, cannot account for the lack of reprocessed Fe–Kα emission. The required increase in ionization parameter could occur if the inner accretion flow evaporates from a thin disc into a geometrically thicker flow, such as the commonly assumed formation of a radiatively inefficient accretion flow at lower mass accretion rates

Mouse Phenome Database (MPD)

The Mouse Phenome Project was launched a decade ago to complement mouse genome sequencing efforts by promoting new phenotyping initiatives under standardized conditions and collecting the data in a central public database, the Mouse Phenome Database (MPD; http://phenome.jax.org). MPD houses a wealth of strain characteristics data to facilitate the use of the laboratory mouse in translational research for human health and disease, helping alleviate problems involving experimentation in humans that cannot be done practically or ethically. Data sets are voluntarily contributed by researchers from a variety of institutions and settings, or in some cases, retrieved by MPD staff from public sources. MPD maintains a growing collection of standardized reference data that assists investigators in selecting mouse strains for research applications; houses treatment/control data for drug studies and other interventions; offers a standardized platform for discovering genotype–phenotype relationships; and provides tools for hypothesis testing. MPD improvements and updates since our last NAR report are presented, including the addition of new tools and features to facilitate navigation and data mining as well as the acquisition of new data (phenotypic, genotypic and gene expression)

Mouse Phenome Database

The Mouse Phenome Database (MPD; http://www.jax.org/phenome) is an open source, web-based repository of phenotypic and genotypic data on commonly used and genetically diverse inbred strains of mice and their derivatives. MPD is also a facility for query, analysis and in silico hypothesis testing. Currently MPD contains about 1400 phenotypic measurements contributed by research teams worldwide, including phenotypes relevant to human health such as cancer susceptibility, aging, obesity, susceptibility to infectious diseases, atherosclerosis, blood disorders and neurosensory disorders. Electronic access to centralized strain data enables investigators to select optimal strains for many systems-based research applications, including physiological studies, drug and toxicology testing, modeling disease processes and complex trait analysis. The ability to select strains for specific research applications by accessing existing phenotype data can bypass the need to (re)characterize strains, precluding major investments of time and resources. This functionality, in turn, accelerates research and leverages existing community resources. Since our last NAR reporting in 2007, MPD has added more community-contributed data covering more phenotypic domains and implemented several new tools and features, including a new interactive Tool Demo available through the MPD homepage (quick link: http://phenome.jax.org/phenome/trytools)

Dupilumab responder types and predicting factors in patients with type 2 severe asthma:A real-world cohort study

Background: Severe asthma (SA) presents a considerable healthcare challenge despite optimal standard treatment. Dupilumab, which is effective in type 2 (T2) SA patients, demonstrates variable responses, categorizing patients as non-responders, partial responders, or those achieving clinical remission. However, real-world response rates remain underexplored. Additionally, understanding the characteristics of patients achieving clinical remission is crucial for predicting favourable responses to dupilumab.Objective: To investigate responder types and identify predictors of clinical remission and non-response induced by dupilumab in a real-world cohort of SA patients.Methods: We analyzed retrospective data from SA patients undergoing dupilumab treatment in a study conducted at Franciscus Gasthuis &amp; Vlietland hospital. Data were collected at baseline and at a 12 to 24-months follow-up (T = 12). Response rates were evaluated at T = 12. Predictors of non-response and clinical remission were investigated using multivariate logistic regression analysis with a stepwise forward variable selection approach. Results: Among the 175 patients screened, 136 met the inclusion criteria. At T = 12, 31.6 % achieved clinical remission, 47.1 % were partial responders and 21.3 % were non-responders. Predictors associated with clinical remission included high baseline blood eosinophil counts (BEC) and male sex. Conversely, younger age at baseline, low baseline total immunoglobin E (IgE) and low baseline fractional exhaled nitric oxide (FeNO) levels were identified as predictors of non-response. Conclusions: Dupilumab results in clinical disease remission in one-third of the treated patients. Clinical remission is predicted by high BEC and male sex, whereas low total IgE, low FeNO and younger age indicate a lower likelihood of response.</p

Deep learning and manual assessment show that the absolute mitotic count does not contain prognostic information in triple negative breast cancer

Contains fulltext : 206059.pdf (publisher's version ) (Open Access

Intermediate Dose Low-Molecular-Weight Heparin for Thrombosis Prophylaxis:Systematic Review with Meta-Analysis and Trial Sequential Analysis

Different doses of low-molecular-weight heparin (LMWH) are registered and used for thrombosis prophylaxis. We assessed benefits and harms of thrombosis prophylaxis with a predefined intermediate-dose LMWH compared with placebo or no treatment in patients at risk of venous thromboembolism (VTE). We performed a systematic review with meta-analyses and trial sequential analyses (TSA) following The Cochrane Handbook for Systematic Reviews of Interventions . Medline, Cochrane CENTRAL, Web of Science, and Embase were searched up to December 2018. Trials were evaluated for risk of bias and quality of evidence was assessed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Seventy randomized trials with 34,046 patients were included. Eighteen (26%) had overall low risk of bias. There was a small statistically significant effect of LMWH on all-cause mortality (risk ratio [RR]: 0.96; TSA-adjusted confidence interval [TSA-adjusted CI]: 0.94-0.98) which disappeared in sensitivity analyses excluding ambulatory cancer patients (RR: 0.99; TSA-adjusted CI: 0.84-1.16). There was moderate-quality evidence for a statistically significant beneficial effect on symptomatic VTE (odds ratio [OR]: 0.59; TSA-adjusted CI: 0.53-0.67; number needed to treat [NNT]: 76; 95% CI: 60-106) and a statistically significant harmful effect on major bleeding (Peto OR: 1.66; TSA-adjusted CI: 1.31-2.10; number needed to harm [NNH]: 212; 95% CI: 142-393). There were no significant intervention effects on serious adverse events. The use of intermediate-dose LMWH for thrombosis prophylaxis compared with placebo or no treatment was associated with a small statistically significant reduction of all-cause mortality that disappeared in sensitivity analyses excluding trials that evaluated LMWH for anticancer treatment. Intermediate-dose LMWH provides benefits in terms of VTE prevention while it increases major bleeding

A NICER Discovery of a Low-Frequency Quasi-Periodic Oscillation in the Soft-Intermediate State of MAXI J1535-571

We present the discovery of a low-frequency $\approx 5.7$ Hz quasi-periodic oscillation (QPO) feature in observations of the black hole X-ray binary MAXI J1535-571 in its soft-intermediate state, obtained in September-October 2017 by the Neutron Star Interior Composition Explorer (NICER). The feature is relatively broad (compared to other low-frequency QPOs; quality factor $Q\approx 2$) and weak (1.9% rms in 3-10 keV), and is accompanied by a weak harmonic and low-amplitude broadband noise. These characteristics identify it as a weak Type A/B QPO, similar to ones previously identified in the soft-intermediate state of the transient black hole X-ray binary XTE J1550-564. The lag-energy spectrum of the QPO shows increasing soft lags towards lower energies, approaching 50 ms at 1 keV (with respect to a 3-10 keV continuum). This large phase shift has similar amplitude but opposite sign to that seen in Rossi X-ray Timing Explorer data for a Type B QPO from the transient black hole X-ray binary GX 339-4. Previous phase-resolved spectroscopy analysis of the Type B QPO in GX 339-4 pointed towards a precessing jet-like corona illuminating the accretion disk as the origin of the QPO signal. We suggest that this QPO in MAXI J1535-571 may have the same origin, with the different lag sign depending on the scale height of the emitting region and the observer inclination angle.Comment: Accepted for publication in ApJ Letter

Incidental findings during the diagnostic work-up in the head and neck cancer pathway:Effects on treatment delay and survival

Objectives: As a result of the increasing number of diagnostic scans, incidental findings (IFs) are more frequently encountered during oncological work-up in patients with head and neck squamous cell carcinomas (HNSCC). IFs are unintentional discoveries found on diagnostic imaging. Relevant IFs implicate clinical consequences, resulting in delay in oncologic treatment initiation, which is associated with unfavorable outcomes. This study is the first to investigate the incidence and nature of IFs over the years and establish the effect of relevant IFs on delay. Material and methods: This retrospective study compared two time periods (2010 & ndash;2011 and 2016 & ndash;2017), described associations between relevant IFs and delay in carepathway interval (days between first visit and treatment initiation) and assessed the effect of relevant IFs on overall two-year survival. Results: In total, 592 patients were included. At least one IF was found in 61.5% of the patients, most frequently on chest-CT. In 128 patients (21.6%) a relevant IF was identified, resulting for the majority in radiologist recommendations (e.g. additional scanning). Presence of a relevant IF was an independent significant factor associated with delay in treatment initiation. The risk of dying was higher for patients with a relevant IF, although not significant in the multivariable model (HR: 1.46, p = 0.079). Conclusion: In diagnostic work-up for HNSCC patients, relevant IFs are frequently encountered. As the frequency of additional imaging rises over the years, the number of IFs increased simultaneously. These relevant IFs yield clinical implications and this study described that relevant IFs result in significant delay in treatment initiation