Atypical case of post-partum cardiomyopathy: an overlap syndrome with arrhythmogenic right ventricular cardiomyopathy?

A middle-aged female patient presented with increasing dyspnoea following delivery of her second child. Echocardiography showed left ventricular (LV) dilatation and severe global impairment of systolic function (ejection fraction < 10%) but normal right ventricular (RV) dimensions. Plasma B-type natriuretic peptide level was elevated. Post-partum cardiomyopathy (PPCM) was considered and after initiating appropriate heart failure pharmacotherapy, her symptoms improved significantly. Cardiovascular MR showed RV free wall dyskinesia and aneurysms at the LV apex, RV free wall and RV outflow tract. Genetic analysis showed a C11842T substitution in the titin gene (TTN). This is the first case to propose an overlap syndrome of PPCM and arrhythmogenic RV cardiomyopathy.published_or_final_versio

The conformal current algebra on supergroups with applications to the spectrum and integrability

We compute the algebra of left and right currents for a principal chiral model with arbitrary Wess-Zumino term on supergroups with zero Killing form. We define primary fields for the current algebra that match the affine primaries at the Wess-Zumino-Witten points. The Maurer-Cartan equation together with current conservation tightly constrain the current-current and current-primary operator product expansions. The Hilbert space of the theory is generated by acting with the currents on primary fields. We compute the conformal dimensions of a subset of these states in the large radius limit. The current algebra is shown to be consistent with the quantum integrability of these models to several orders in perturbation theory.Comment: 45 pages. Minor correction

Review of Journal of Cardiovascular Magnetic Resonance 2014

There were 102 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2014, which is a 6 % decrease on the 109 articles published in 2013. The quality of the submissions continues to increase. The 2013 JCMR Impact Factor (which is published in June 2014) fell to 4.72 from 5.11 for 2012 (as published in June 2013). The 2013 impact factor means that the JCMR papers that were published in 2011 and 2012 were cited on average 4.72 times in 2013. The impact factor undergoes natural variation according to citation rates of papers in the 2 years following publication, and is significantly influenced by highly cited papers such as official reports. However, the progress of the journal’s impact over the last 5 years has been impressive. Our acceptance rate is <25 % and has been falling because the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. For this reason, the Editors have felt that it is useful once per calendar year to summarize the papers for the readership into broad areas of interest or theme, so that areas of interest can be reviewed in a single article in relation to each other and other recent JCMR articles. The papers are presented in broad themes and set in context with related literature and previously published JCMR papers to guide continuity of thought in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality papers to JCMR for publication

First-principles derivation of the AdS/CFT Y-systems

We provide a first-principles, perturbative derivation of the AdS5/CFT4 Y-system that has been proposed to solve the spectrum problem of N=4 SYM. The proof relies on the computation of quantum effects in the fusion of some loop operators, namely the transfer matrices. More precisely we show that the leading quantum corrections in the fusion of transfer matrices induce the correct shifts of the spectral parameter in the T-system. As intermediate steps we study UV divergences in line operators up to first order and compute the fusion of line operators up to second order for the pure spinor string in AdS5xS5. We also argue that the derivation can be easily extended to other integrable models, some of which describe string theory on AdS4, AdS3 and AdS2 spacetimes.Comment: 45 pages, 5 figures; v2: minor additions, JHEP versio

A novel cardiovascular magnetic resonance risk score for predicting mortality following surgical aortic valve replacement

The increasing prevalence of patients with aortic stenosis worldwide highlights a clinical need for improved and accurate prediction of clinical outcomes following surgery. We investigated patient demographic and cardiovascular magnetic resonance (CMR) characteristics to formulate a dedicated risk score estimating long-term survival following surgery. We recruited consecutive patients undergoing CMR with gadolinium administration prior to surgical aortic valve replacement from 2003 to 2016 in two UK centres. The outcome was overall mortality. A total of 250 patients were included (68 ± 12 years, male 185 (60%), with pre-operative mean aortic valve area 0.93 ± 0.32cm2, LVEF 62 ± 17%) and followed for 6.0 ± 3.3 years. Sixty-one deaths occurred, with 10-year mortality of 23.6%. Multivariable analysis showed that increasing age (HR 1.04, P = 0.005), use of antiplatelet therapy (HR 0.54, P = 0.027), presence of infarction or midwall late gadolinium enhancement (HR 1.52 and HR 2.14 respectively, combined P = 0.12), higher indexed left ventricular stroke volume (HR 0.98, P = 0.043) and higher left atrial ejection fraction (HR 0.98, P = 0.083) associated with mortality and developed a risk score with good discrimination. This is the first dedicated risk prediction score for patients with aortic stenosis undergoing surgical aortic valve replacement providing an individualised estimate for overall mortality. This model can help clinicians individualising medical and surgical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00930735 and ClinicalTrials.gov Identifier: NCT01755936

Addressing Recruitment Challenges in the Engage-HU Trial in Young Children with Sickle Cell Disease

Background: Sickle cell disease (SCD) is a genetic disorder that causes significant medical and neurologic morbidity in children. Hydroxyurea (HU) is the primary medication used to prevent these complications. National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend offering HU to children as young as 9 months of age with SCD (HbSS or HbSB0 thalassemia) using a shared decision-making approach. Although HU has proven efficacious it remains underutilized and caregivers report that they are not always actively involved in the decision to initiate this therapy. Reasons for limited HU uptake likely include lack of clinician knowledge and training and negative caregiver perceptions. Thus, we developed the Engage-HU trial as a novel approach to address HU utilization barriers. A critical consideration for this trial was that SCD primarily affects individuals of African and Hispanic/Latino descent. In these minority populations, intervention trials are sometimes terminated early because of recruitment difficulties related to mistrust of research, caregiver burden, and transportation issues. As such, the Engage-HU trial design included best-practice strategies for recruiting people of color in research. This study describes these strategies, the initial recruitment plan, preliminary recruitment outcomes and strategies, and our procedural adaptations. Study Design and Methods: Engage-HU is a randomized control trial (NCT03442114) to assess how clinicians can engage caregivers in a shared discussion that considers their values and preferences and includes evidence that supports HU. Engage-HU compares two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD: 1) the American Society of Hematology Pocket Guide, and 2) the HU Shared-Decision Making (H-SDM) Toolkit. The study aims to recruit 174 caregivers and evaluate the effectiveness of the dissemination methods on patient-centered outcomes (caregiver confidence in decision-making and perceptions of experiencing shared decision-making) as well as HU uptake and child health outcomes. Eligible children are aged 0 to 5 years, candidates for HU, and their caregiver has not made a decision about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a stepped-wedge design. Data will be analyzed based on the intent-to-treat principle. All participants will remain in the arm of the study to which they were randomized, regardless of whether or not they receive the assigned dissemination method. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using a linear mixed effects regression model with a robust variance estimator and maximum likelihood estimation with observations clustered within site. The Engage-HU trial includes adaptations to increase recruitment such as tailored messaging, a relational recruitment approach, streamlined data collection, and a Stakeholder Advisory Committee. However, even with these adaptations, the first 6-months of the trial yielded lower than anticipated recruitment. Rather than terminate the trial or accept low enrollment, the research team implemented a series of recruitment strategies to address barriers including helping to improve research coordinator knowledge of the study purpose and adjusting no-show and follow-up procedures (e.g., calls to families after missed appointments and reminder calls before appointments). Site clinicians and clinic staff were provided with additional training so they could give more context about Engage-HU to caregivers and the study principal investigator led monthly "all coordinator" calls to provide support by sharing updates and experiences about successful recruitment. Implementation of these strategies resulted in triple the number of enrollments over the next 7-months compared to the previous 6-months (Table 1). Our goal in sharing this information is to provide lessons learned that can be implemented in future trials with the systematically underserved SCD population. It is also anticipated that methods described here may also inform clinical approaches to better engage caregivers of young children around critical clinical conversations, such as initiating medications like HU. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; RiverVest: Consultancy; Novimmune: Research Funding; Celgene: Consultancy; Tioma Therapuetics: Consultancy; Amphivena Therapeutics: Research Funding; WUGEN: Current equity holder in private company; Cell Works: Consultancy; Incyte: Consultancy. Smith-Whitley:Prime: Other: Education material; Celgene: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Neumayr:Emmaus: Consultancy; Bayer: Consultancy; CTD Holdings: Consultancy; Pfizer: Consultancy; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Micelle: Other: Site principal investigator; GBT: Other: Site principal investigator; PCORI: Other: site principal investigator; Novartis: Other: co-investigator; Bluebird Bio: Other: co-investigator; Sangamo Therapeutics: Other; Silarus: Other; Celgene: Other; La Jolla Pharmaceuticals: Other; Forma: Other; Imara: Other; National Heart, Lung, and Blood Institute: Other; Health Resources and Services Administration: Other; Centers for Disease Control and Prevention: Other; Seattle Children's Research: Other. Yates:Novartis: Research Funding. Thompson:Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; BMS: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding. </jats:sec

Fusion of line operators in conformal sigma-models on supergroups, and the Hirota equation

We study line operators in the two-dimensional sigma-model on PSl(n|n) using the current-current OPEs. We regularize and renormalize these line operators, and compute their fusion up to second order in perturbation theory. In particular we show that the transfer matrix associated to a one-parameter family of flat connections is free of divergences. Moreover this transfer matrix satisfies the Hirota equation (which can be rewritten as a Y-system, or Thermodynamic Bethe Ansatz equations) for all values of the two parameters defining the sigma-model. This provides a first-principles derivation of the Hirota equation which does not rely on the string hypothesis nor on the assumption of quantum integrability.Comment: 53 pages, 6 figures. Minor correction

Engaging Caregivers and Providers of Children With Sickle Cell Anemia in Shared Decision Making for Hydroxyurea: Protocol for a Multicenter Randomized Controlled Trial

BACKGROUND: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months. However, the uptake remains suboptimal, likely because caregivers lack information about hydroxyurea and have concerns about its safety and potential long-term side effects. Moreover, clinicians do not routinely receive training or tools, especially those that provide medical evidence and consider caregivers' preferences and values, to facilitate a shared discussion with caregivers. OBJECTIVE: The aim of this study is to understand how best to help parents of young children with sickle cell disease and their clinicians have a shared discussion about hydroxyurea (one that considers medical evidence and parent values and preferences). METHODS: We designed our study to compare the effectiveness of two methods for disseminating hydroxyurea guidelines to facilitate SDM: a clinician pocket guide (ie, usual care) and a clinician hydroxyurea SDM toolkit (H-SDM toolkit). Our primary outcomes are caregiver reports of decisional uncertainty and knowledge of hydroxyurea. The study also assesses the number of children (aged 0-5 years) who were offered and prescribed hydroxyurea and the resultant health outcomes. RESULTS: The Ethics Committee of the Cincinnati Children's Hospital Medical Center approved this study in November 2017. As of February 2021, we have enrolled 120 caregiver participants. CONCLUSIONS: The long-term objective of this study is to improve the quality of care for children with SCA. Using multicomponent dissemination methods developed in partnership with key stakeholders and designed to address barriers to high-quality care, caregivers of patients with SCA can make informed and shared decisions about their health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03442114; https://clinicaltrials.gov/ct2/show/NCT03442114. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/27650

The Crystal Structure of OprG from Pseudomonas aeruginosa, a Potential Channel for Transport of Hydrophobic Molecules across the Outer Membrane

Background: The outer membrane (OM) of Gram-negative bacteria provides a barrier to the passage of hydrophobic and hydrophilic compounds into the cell. The OM has embedded proteins that serve important functions in signal transduction and in the transport of molecules into the periplasm. The OmpW family of OM proteins, of which P. aeruginosa OprG is a member, is widespread in Gram-negative bacteria. The biological functions of OprG and other OmpW family members are still unclear. Methodology/Principal Findings: In order to obtain more information about possible functions of OmpW family members we have solved the X-ray crystal structure of P. aeruginosa OprG at 2.4 A ˚ resolution. OprG forms an eightstranded b-barrel with a hydrophobic channel that leads from the extracellular surface to a lateral opening in the barrel wall. The OprG barrel is closed off from the periplasm by interacting polar and charged residues on opposite sides of the barrel wall. Conclusions/Significance: The crystal structure, together with recent biochemical data, suggests that OprG and other OmpW family members form channels that mediate the diffusion of small hydrophobic molecules across the OM by a latera