Evolution of Neutron-Star, Carbon-Oxygen White-Dwarf Binaries

At least one, but more likely two or more, eccentric neutron-star, carbon-oxygen white-dwarf binaries with an unrecycled pulsar have been observed. According to the standard scenario for evolving neutron stars which are recycled in common envelope evolution we expect to observe \gsim 50 such circular neutron star-carbon oxygen white dwarf binaries, since their formation rate is roughly equal to that of the eccentric binaries and the time over which they can be observed is two orders of magnitude longer, as we shall outline. We observe at most one or two such circular binaries and from that we conclude that the standard scenario must be revised. Introducing hypercritical accretion into common envelope evolution removes the discrepancy by converting the neutron star into a black hole which does not emit radio waves, and therefore would not be observed.Comment: 25 pages, 1 figure, accepted in Ap

Transcatheter edge-to-edge repair of tricuspid regurgitation in the Netherlands:state of the art and future perspectives

Despite the high prevalence and adverse clinical outcomes of severe tricuspid regurgitation (TR), conventional treatment options, surgical or pharmacological, are limited. Surgery is associated with a high peri-operative risk and medical treatment has not clearly resulted in clinical improvements. Therefore, there is a high unmet need to reduce morbidity and mortality in patients with severe TR. During recent years, several transcatheter solutions have been studied. This review focuses on the transcatheter edge-to-edge repair of TR (TTVR) with respect to patient selection, the procedure, pre- and peri-procedural echocardiographic assessments and clinical outcomes. Furthermore, we highlight the current status of TTVR in the Netherlands and provide data from our initial experience at the University Medical Centre Groningen

Different Aspects of Classical Pathway Overactivation in Patients With C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis

The rare and heterogeneous kidney disorder C3 glomerulopathy (C3G) is characterized by dysregulation of the alternative pathway (AP) of the complement system. C3G is often associated with autoantibodies stabilizing the AP C3 convertase named C3 nephritic factors (C3NeF). The role of classical pathway (CP) convertase stabilization in C3G and related diseases such as immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) remains largely unknown. Here, we investigated the CP convertase activity in patients with C3G and IC-MPGN. Using a refined two-step hemolytic assay, we measured the stability of CP convertases directly in the serum of 52 patients and 17 healthy controls. In four patients, CP convertase activity was prolonged compared to healthy controls, i.e. the enzymatic complex was stabilized. In three patients (2 C3G, 1 IC-MPGN) the convertase stabilization was caused by immunoglobulins, indicating the presence of autoantibodies named C4 nephritic factors (C4NeFs). Importantly, the assay also enabled detection of non-immunoglobulin-mediated stabilization of the CP convertase in one patient with C3G. Prolonged CP convertase activity coincided with C3NeF activity in all patients and for up to 70 months of observation. Crucially, experiments with C3-depleted serum showed that C4NeFs stabilized the CP C3 convertase (C4bC2a), that does not contain C3NeF epitopes. All patients with prolonged CP convertase activity showed clear signs of complement activation, i.e. lowered C3 and C5 levels and elevated levels of C3d, C3bc, C3bBbP, and C5b-9. In conclusion, this work provides new insights into the diverse aspects and (non-)immunoglobulin nature of factors causing CP convertase overactivity in C3G/IC-MPGN.</p

Mining treatment patterns of glucose-lowering medications for type 2 diabetes in the Netherlands

Rationale and objectives Different classes of glucose-lowering medications are used for patients with type 2 diabetes mellitus (T2DM) management. It is unclear how often these medications are prescribed in clinical practice. In this study, we aimed to describe treatment patterns of glucose-lowering medications in patients with T2DM in the Netherlands. Methods We studied a cohort of 73 819 patients with T2DM, aged ≥45 years with a first prescription for oral glucose-lowering medication between 2011 and 2017. We used the NControl database with dispensing data from 800 pharmacies in the Netherlands. Prevalence of each glucose-lowering medication class during 6 years after the index date was calculated. Using SQL Server, we identified stepwise patterns of medication prescription in this population. Findings During the study period, prevalence of biguanides (BIGU) decreased from 95.6% to 80.8% and use of sulfonylureas (SU) increased from 27.3% to 42.3%. 55.2% of all patient

The Temperature and Cooling Age of the White-Dwarf Companion to the Millisecond Pulsar PSR B1855+09

We report on Keck and {\em Hubble Space Telescope} observations of the binary millisecond pulsar PSR B1855+09. We detect its white-dwarf companion and measure \mv=25.90\pm0.12 and \mi=24.19\pm0.11 (Vega system). From the reddening-corrected color, (\mv-\mi)_0=1.06\pm0.21, we infer a temperature \Teff=4800\pm800 K. The white-dwarf mass is known accurately from measurements of the Shapiro delay of the pulsar signal, \Mcomp=0.258^{+0.028}_{-0.016} \Msun. Hence, given a cooling model, one can use the measured temperature to determine the cooling age. The main uncertainty in the cooling models for such low-mass white dwarfs is the amount of residual nuclear burning, which is set by the thickness of the hydrogen layer surrounding the helium core. From the properties of similar systems, it has been inferred that helium white dwarfs form with thick hydrogen layers, with mass \simgt3\times10^{-3} \Msun, which leads to significant additional heating. This is consistent with expectations from simple evolutionary models of the preceding binary evolution. For PSR B1855+09, though, such models lead to a cooling age of $\sim10$Gyr, which is twice the spin-down age of the pulsar. It could be that the spin-down age were incorrect, which would call the standard vacuum dipole braking model into question. For two other pulsar companions, however, ages well over 10 Gyr are inferred, indicating that the problem may lie with the cooling models. There is no age discrepancy for models in which the white dwarfs are formed with thinner hydrogen layers (\simlt3\times10^{-4} \Msun).Comment: 7 pages, 1 figure, aas4pp2.sty. Accepted for publication in ApJ

The Role of Helium Stars in the Formation of Double Neutron Stars

We have calculated the evolution of 60 model binary systems consisting of helium stars in the mass range of M_He= 2.5-6Msun with a 1.4Msun neutron star companion to investigate the formation of double neutron star systems.Orbital periods ranging from 0.09 to 2 days are considered, corresponding to Roche lobe overflow starting from the helium main sequence to after the ignition of carbon burning in the core. We have also examined the evolution into a common envelope phase via secular instability, delayed dynamical instability, and the consequence of matter filling the neutron star's Roche lobe. The survival of some close He-star neutron-star binaries through the last mass transfer episode (either dynamically stable or unstable mass transfer phase) leads to the formation of extremely short-period double neutron star systems (with P<~0.1days). In addition, we find that systems throughout the entire calculated mass range can evolve into a common envelope phase, depending on the orbital period at the onset of mass transfer. The critical orbital period below which common envelope evolution occurs generally increases with M_He. In addition, a common envelope phase may occur during a short time for systems characterized by orbital periods of 0.1-0.5 days at low He-star masses (~ 2.6-3.3Msun). The existence of a short-period population of double neutron stars increases the predicted detection rate of inspiral events by ground-based gravitational-wave detectors and impacts their merger location in host galaxies and their possible role as gamma-ray burst progenitors. We use a set of population synthesis calculations and investigate the implications of the mass-transfer results for the orbital properties of DNS populations.Comment: 30 pages, Latex (AASTeX), 1 table, 8 figures. To appear in ApJ, v592 n1 July 20, 200

Comparing modeling strategies combining changes in multiple serum tumor biomarkers for early prediction of immunotherapy non-response in non-small cell lung cancer

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICI) are at risk of adverse events (AEs) even though not all patients will benefit. Serum tumor markers (STMs) are known to reflect tumor activity and might therefore be useful to predict response, guide treatment decisions and thereby prevent AEs.OBJECTIVE: This study aims to compare a range of prediction methods to predict non-response using multiple sequentially measured STMs.METHODS: Nine prediction models were compared to predict treatment non-response at 6-months (n = 412) using bi-weekly CYFRA, CEA, CA-125, NSE, and SCC measurements determined in the first 6-weeks of therapy. All methods were applied to six different biomarker combinations including two to five STMs. Model performance was assessed based on sensitivity, while model training aimed at 95% specificity to ensure a low false-positive rate.RESULTS: In the validation cohort, boosting provided the highest sensitivity at a fixed specificity across most STM combinations (12.9% -59.4%). Boosting applied to CYFRA and CEA achieved the highest sensitivity on the validation data while maintaining a specificity &gt;95%.CONCLUSIONS: Non-response in NSCLC patients treated with ICIs can be predicted with a specificity &gt;95% by combining multiple sequentially measured STMs in a prediction model. Clinical use is subject to further external validation.</p

The Classification of Obsessive–Compulsive and Related Disorders in the ICD-11

Background To present the rationale for the new Obsessive–Compulsive and Related Disorders (OCRD) grouping in the Mental and Behavioural Disorders chapter of the Eleventh Revision of the World Health Organization’s International Classification of Diseases and Related Health Problems (ICD-11), including the conceptualization and essential features of disorders in this grouping. Methods Review of the recommendations of the ICD-11 Working Group on the Classification for OCRD. These sought to maximize clinical utility, global applicability, and scientific validity. Results The rationale for the grouping is based on common clinical features of included disorders including repetitive unwanted thoughts and associated behaviours, and is supported by emerging evidence from imaging, neurochemical, and genetic studies. The proposed grouping includes obsessive–compulsive disorder, body dysmorphic disorder, hypochondriasis, olfactory reference disorder, and hoarding disorder. Body-focused repetitive behaviour disorders, including trichotillomania and excoriation disorder are also included. Tourette disorder, a neurological disorder in ICD-11, and personality disorder with anankastic features, a personality disorder in ICD-11, are recommended for cross-referencing. Limitations Alternative nosological conceptualizations have been described in the literature and have some merit and empirical basis. Further work is needed to determine whether the proposed ICD-11 OCRD grouping and diagnostic guidelines are mostly likely to achieve the goals of maximizing clinical utility and global applicability. Conclusion It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders

Discovery of Five Binary Radio Pulsars

We report on five binary pulsars discovered in the Parkes multibeam Galactic plane survey. All of the pulsars are old, with characteristic ages 1-11 Gyr, and have relatively small inferred magnetic fields, 5-90e8 G. The orbital periods range from 1.3 to 15 days. As a group these objects differ from the usual low-mass binary pulsars (LMBPs): their spin periods of 9-88 ms are relatively long; their companion masses, 0.2-1.1 Msun, are, in at least some cases, suggestive of CO or more massive white dwarfs; and some of the orbital eccentricities, 1e-5 < e < 0.002, are unexpectedly large. We argue that these observed characteristics reflect binary evolution that is significantly different from that of LMBPs. We also note that intermediate-mass binary pulsars apparently have a smaller scale-height than LMBPs.Comment: 5 pages, 4 embedded EPS figs, accepted for publication by ApJ Letter

Strange stars in low-mass binary pulsar systems

Based on observational facts and a variety of theoretical arguments we discuss in this work the possibility that pulsars in Low-Mass Binary Pulsar systems could be strange stars rather than neutron stars. It is shown that, although subject to reasonable uncertainties, the consideration of the physics of the SQM core and thin normal crusts leads to the prediction of several observed features of the magnetic field history of these systems whitin this working hypothesis.Comment: 6 pages, no figures, PlainTex file submitted to IJMP