Identification of myocardial diffuse fibrosis by 11 heartbeat MOLLI T1 mapping: averaging to improve precision and correlation with collagen volume fraction

Objectives: Our objectives involved identifying whether repeated averaging in basal and mid left ventricular myocardial levels improves precision and correlation with collagen volume fraction for 11 heartbeat MOLLI T1 mapping versus assessment at a single ventricular level. Materials and methods: For assessment of T1 mapping precision, a cohort of 15 healthy volunteers underwent two CMR scans on separate days using an 11 heartbeat MOLLI with a 5(3)3 beat scheme to measure native T1 and a 4(1)3(1)2 beat post-contrast scheme to measure post-contrast T1, allowing calculation of partition coefficient and ECV. To assess correlation of T1 mapping with collagen volume fraction, a separate cohort of ten aortic stenosis patients scheduled to undergo surgery underwent one CMR scan with this 11 heartbeat MOLLI scheme, followed by intraoperative tru-cut myocardial biopsy. Six models of myocardial diffuse fibrosis assessment were established with incremental inclusion of imaging by averaging of the basal and mid-myocardial left ventricular levels, and each model was assessed for precision and correlation with collagen volume fraction. Results: A model using 11 heart beat MOLLI imaging of two basal and two mid ventricular level averaged T1 maps provided improved precision (Intraclass correlation 0.93 vs 0.84) and correlation with histology (R2 = 0.83 vs 0.36) for diffuse fibrosis compared to a single mid-ventricular level alone. ECV was more precise and correlated better than native T1 mapping. Conclusion: T1 mapping sequences with repeated averaging could be considered for applications of 11 heartbeat MOLLI, especially when small changes in native T1/ECV might affect clinical management

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

SummaryThe impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators

Heavy fermions: Typical phenomena and recent developments

A survey is given of typical phenomena, new materials and recent developments in heavy-fermion physics. In particular, the following topics are addressed: (i) YbNiAl, a new heavy-fermion local-moment antiferromagnet (LMM) with Neel temperature T(N) = 3 K, (ii) ''non-Fermi-liquid'' behavior at the magnetic instability in two heavy-fermion systems with intact from sublattice, i.e. orthorhombic CePt(Si1-xGex) and tetragonal U(Cu4+xAl8-x), (iii) the low-temperature properties of the anisotropic ''Kondo insulator'' CeNiSn, and (iv) some of the most unusual observations made on ''low-carrier-density'' rare-earth systems like Sm3Te4 and Sm3Se4. While the ezotic symmetry-broken (superconducting and magnetic) ground states of heavy-fermion metals are discussed in several other contributions to this volume, we focus in the remainder of this paper on the relationship between LMM ordering and heavy-fermion superconductivity: Firstly, the LMM ordered compound CeCu2Ge2 (T(N) = 4.1 K) is addressed which was recently found to become a non-magnetic heavy-fermion superconductor under high hydrostatic pressure, p greater-than-or-equal-to 70 kbar (D. Jaccard et al., Phys. Lett. A 163,475 (1992)). Point-contact spectroscopy is used to investigate in more detail the high-pressure superconducting phase of CeCU2Ge2. Secondly, we summarize high-pressure results on UPd2Al3, the first compound to show homogeneous coexistence between LMM ordering and heavy-fermion superconductivity

Assessment of pain in herpes zoster: lessons learned from antiviral trials

Pain typically accompanies acute herpes zoster and, in a proportion of patients, it persists well beyond rash healing. Pain must therefore be analyzed in trials of antiviral agents in herpes zoster, but different methods have been used to analyze pain in recent published trials. These reports are reviewed and their methodological strengths and weaknesses examined. Based on this review, recommendations for the design and analysis of future trials of antiviral agents in herpes zoster are proposed. The principal recommendation is that antiviral efficacy should be evaluated both by distinguishing post-herpetic neuralgia from acute pain and by considering pain as a continuum. The primary endpoint should address both the prevalence and duration of post-herpetic neuralgia and should be examined in those patients who have post-herpetic neuralgia. Adopting the proposed recommendations in design and analysis of future trials should facilitate comparison across trials of the efficacy of antiviral agents in the treatment of herpes zoster