Noncompaction Cardiomyopathy, Sick Sinus Disease, and Aortic Dilatation: Too Much for a Single Diagnosis?

HCN4 mutations have been reported in association with sick sinus syndrome. A more complex phenotype, including noncompaction cardiomyopathy and aortic dilatation, has recently emerged. We report 3 family members with the pathogenic p.Gly482Arg variant, emphasizing the importance of considering HCN4 mutations when this combination of features is encountered in clinical practice. (Level of Difficulty: Advanced.

Clinical significance of inferolateral early repolarisation and late potentials in children with Brugada Syndrome.

INTRODUCTION: The clinical utility of inferolateral early repolarisation (ER) and late potentials (LP) in children with Brugada Syndrome (BrS) has not been previously evaluated. The aim of this study was to determine the prevalence of electrocardiographic (ECG) abnormalities in children with BrS, and to investigate their relationship with clinical outcomes. METHODS: 43 patients with BrS and 47 controls aged ≤18 undergoing systematic clinical and ECG evaluation, including signal-averaged ECG (SAECG) and pharmacological provocation testing, between 2003 and 2019 were included. RESULTS: Four patients with BrS (9%) presented with a spontaneous type 1 Brugada pattern; the remaining 39 (91%) were diagnosed following ajmaline provocation testing. Twelve BrS patients (28%) had late potentials (LP) on SAECG compared to 1 (2%) in controls (p = 0.001). LP were more common in 5 patients with a high-risk phenotype (60% vs 24%) but this was not statistically significant. Twelve patients with BrS (28%) had inferolateral early repolarisation (ER) and 2 (5%) had fractionated QRS (f-QRS), but there were no statistically-significant differences with controls in these parameters. A significant arrhythmia (non-sustained ventricular tachycardia or atrial fibrillation) was seen in 4 patients (9%). CONCLUSIONS: This study shows a high prevalence of SAECG abnormalities in children with BrS compared with controls, but this was not significantly associated with a high-risk phenotype

Chronic heart block in dogs; a method for producing experimental heart failure

A method is described for the production of chronic atrioventricular block in dogs, by incision of the region of the bundle of His through the open right atrium during temporary caval occlusion. Exercise tolerances, chest x-ray films, electrocardiograms, phonocardiograms, cardiac outputs, intracardiac pressures, femoral pressures, and left ventricular coronary flows were obtained preoperatively and from 1 to 10 months postoperatively. The majority of the animals developed clinical, laboratory, and pathological evidence of congestive heart failure. All animals had generalized myocardial hypertrophy

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.<p></p> Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.<p></p> Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.<p></p> Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Gamma-Ray Burst Afterglows as Probes of Environment and Blastwave Physics

We use a new approach to obtain limits on the absorbing columns towards an initial sample of 10 long Gamma-Ray Bursts observed with BeppoSAX and selected on the basis of their good optical and nIR coverage, from simultaneous fits to nIR, optical and X-ray afterglow data, in count space and including the effects of metallicity. In no cases is a MIV-like ext,inction preferred, when testing MW, LMC and SMC extinction laws. The 2175A bump would in principle be detectable in all these afterglows, but is not present in the data. An SMC-like gas-to-dust ratio or lower value can be ruled out for 4 of the hosts analysed here (assuming Sh4C metallicity and extinction law) whilst the remainder of the sample have too large an error to discriminate. We provide a more accurate estimate of the line-of-sight extinction and improve upon the uncertainties for the majority of the extinction measurements made in previous studies of this sample. We discuss this method to determine extinction values in comparison with the most commonly employed existing methods

Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

Detection of Wolf-Rayet stars in host galaxies of Gamma-Ray Bursts (GRBs): are GRBs produced by runaway massive stars ejected from high stellar density regions ?

We have obtained deep spectroscopic observations of several nearby gamma-ray burst (GRB) host galaxies revealing for the first time the presence of Wolf-Rayet (WR) stars and numerous O stars located in rich and compact clusters or star forming regions. Surprisingly, high spatial resolution imaging shows that the GRBs and the associated supernovae did not occur in these regions, but several hundreds of parsec away. Considering various scenarios for GRB progenitors, we do not find any simple explanation of why they should be preferentially born in regions with low stellar densities. All the examined GRBs and associated SNe have occurred 400 to 800 pc from very high density stellar environments including large numbers of WR stars. Such distances can be travelled through at velocities of 100 km/s or larger, assuming the travel time to be the typical life time of WR stars. It leads us to suggest that GRB progenitors may be runaway massive stars ejected from compact massive star clusters. The ejection from such super star clusters may lead to a spin-up of these stars, producing the loss of the hydrogen and/or helium envelopes leading to the origin of the type Ibc supernovae associated with GRBs. If this scenario applies tocd text/Sc all GRBs, it provides a natural explanation of the very small fraction of massive stars that emit a GRB at the end of their life. An alternative to this scenario could be a binary origin for GRBs, but this still requires an explanation of why it would preferentially occur in low stellar density regions.Comment: (1) GEPI, Observatoire de Paris-Meudon, France, (2) Observatoire de Geneve, Switzerland, (3) Laboratoire d'Astrophysique Toulouse-Tarbes, France,(4) Steward Observatory, University of Arizona, US

GRB 021004: Tomography of a gamma-ray burst progenitor and its host galaxy

We analyse the distribution of matter around the progenitor star of gamma-ray burst GRB 021004 as well as the properties of its host galaxy with high-resolution echelle as well as near-infrared spectroscopy. Observations were taken by the 8.2m Very Large Telescope with the Ultraviolet and Visual Echelle spectrograph (UVES) and the Infrared Spectrometer And Array Camera (ISAAC) between 10 and 14 hours after the onset of the event. We report the first detection of emission lines from a GRB host galaxy in the near-infrared, detecting H-alpha and the [O III] doublet. These allow an independent measurement of the systemic redshift (z = 2.3304 +/- 0.0005) which is not contaminated by absorption as the Ly-alpha line is, and the deduction of properties of the host galaxy. From the visual echelle spectroscopy, we find several absorption line groups spanning a range of about 3,000 km/s in velocity relative to the redshift of the host galaxy. The absorption profiles are very complex with both velocity-broadened components extending over several 100 km/s and narrow lines with velocity widths of only 20 km/s. By analogy with QSO absorption line studies, the relative velocities,widths, and degrees of ionization of the lines ("line-locking", "ionization--velocity correlation") show that the progenitor had both an extremely strong radiation field and several distinct mass loss phases (winds). These results are consistent with GRB progenitors being massive stars, such as Luminous Blue Variables (LBVs) or Wolf--Rayet stars, providing a detailed picture of the spatial and velocity structure of the GRB progenitor star at the time of explosion. The host galaxy is a prolific star-forming galaxy with a SFR of about 40 solar masses per year.Comment: 11 pages, 5 figures. Accepted for publication in Astronomy and Astrophysics

An optical supernova associated with the X-ray flash XRF 060218

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes - analogues of GRBs, but with lower luminosities and fewer gamma-rays - can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.Comment: Final published versio