Antitachycardia Pacemakers in Congenital Heart Disease

BackgroundMany patients with congenital heart disease (CHD) acquire rhythm abnormalities related to their repair, most commonly intraatrial reentrant tachycardia (IART). Treatment of IART in CHD is often multifaceted, and may include medication, ablation, and pacing. Evidence regarding the use of antitachycardia pacing therapies is limited.ObjectiveThe aim of the study is to define the use and efficacy of antitachycardia pacing in patients with CHD at a single center.ResultsEighty implants were performed on 72 patients between 2000 and 2010. Follow‐up data of more than 3 months were available for 56 patients; median follow‐up time was 2.8 years. Twenty (36%) patients received successful antitachycardia pacing at a median 1.3 years postimplant. For those patients with IART after implant, antitachycardia pacing was successful in 57%. Patients with two‐ventricle repairs were more likely to have successful antitachycardia pacing than those with one‐ventricle palliation (45% vs. 17%, P = .04). Patients with documented IART had more successful antitachycardia pacing than those with no documented atrial tachycardia prior to implant (46% vs. 7%, P = .006). Early complications of antitachycardia pacemaker implant occurred in six patients (11%); late complications after implant occurred in three patients (5.6%). Of the initial 72 patients implanted, there were six deaths (8%).ConclusionsAntitachycardia pacing therapies were successful in the majority of CHD patients who had IART after implant. Patients without documented atrial tachycardia prior to implant were unlikely to require or receive successful therapy from antitachycardia pacemaker. Those patients postatrial switch procedure who had documented IART prior to implant had the highest incidence of successful antitachycardia pacing therapies. Antitachycardia pacemaker implantation is an adjunct to the management of IART in CHD patients, but may not benefit patients who have not yet demonstrated IART.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111221/1/chd12230.pd

Radio continuum observations of Class I protostellar disks in Taurus: constraining the greybody tail at centimetre wavelengths

We present deep 1.8 cm (16 GHz) radio continuum imaging of seven young stellar objects in the Taurus molecular cloud. These objects have previously been extensively studied in the sub-mm to NIR range and their SEDs modelled to provide reliable physical and geometrical parametres.We use this new data to constrain the properties of the long-wavelength tail of the greybody spectrum, which is expected to be dominated by emission from large dust grains in the protostellar disk. We find spectra consistent with the opacity indices expected for such a population, with an average opacity index of beta = 0.26+/-0.22 indicating grain growth within the disks. We use spectra fitted jointly to radio and sub-mm data to separate the contributions from thermal dust and radio emission at 1.8 cm and derive disk masses directly from the cm-wave dust contribution. We find that disk masses derived from these flux densities under assumptions consistent with the literature are systematically higher than those calculated from sub-mm data, and meet the criteria for giant planet formation in a number of cases.Comment: submitted MNRA

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit/hyperactivity disorder: study protocol for a randomized controlled trial

Background: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day– night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD. Methods: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 – < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-β = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up. This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted.The trial is funded by the EU Framework Programme for Research and Innovation, Horizon 2020 (Project no. 667302). Funding period: January 2016–December 2020. This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. Some local funds additionally contributed to carry out this study, especially for the preparation of the interventions: FBO research activity is by the Spanish Ministry of Economy and Competitiveness – MINECO (RYC-2011-09011) and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Unit of Excellence on Exercise and Health (UCEES)

The Ocean Sampling Day Consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation