Recent Decisions

Comments on recent decisions by Joseph P. Summers, William J. Luff, Jr., Thomas Kavadas, Jr., Joseph A. Marino, James J. Harrington, Cornelius J. Collins, George P. McAndrews, Richard M. Bies, George A. Pelletier, Jr., Thomas M. Clusserath, and Rocco L. Puntureri

Recent Decisions

Comments on recent decisions by John C. Hirschfeld, Thomas Kavadas, Jr., Thomas A. McNish, Joseph A. Marino, Rocco L. Puntureri, Edward M. O\u27Toole, Paul B. Coffey, J. Michael Guenther, and Gerald M. Gallivan

Recent Decisions

Comments on recent decisions by Paul B. Coffey, Joseph A. Marino, Thomas Kavadas, Jr., John C. Hirschfeld, Thomas L. Shaffer, W. R. Kennedy, John R. Martzell, and John F. Beggan

Type and Timing of Rehabilitation Following Acute and Subacute Spinal Cord Injury: A Systematic Review

Objectives: The objective of this study was to conduct a systematic review of the literature to address the following clinical questions: In adult patients with acute and subacute complete or incomplete traumatic SCI, (1) does the time interval between injury and commencing rehabilitation affect outcome?; (2) what is the comparative effectiveness of different rehabilitation strategies, including different intensities and durations of treatment?; (3) are there patient or injury characteristics that affect the efficacy of rehabilitation?; and (4) what is the cost-effectiveness of various rehabilitation strategies? Methods: A systematic search was conducted for literature published through March 31, 2015 that evaluated rehabilitation strategies in adults with acute or subacute traumatic SCI at any level. Studies were critically appraised individually and the overall strength of evidence was evaluated using methods proposed by the GRADE (Grades of Recommendation Assessment, Development and Evaluation) working group. Results: The search strategy yielded 384 articles, 19 of which met our inclusion criteria. Based on our results, there was no difference between body weight–supported treadmill training and conventional rehabilitation with respect to improvements in Functional Independence Measure (FIM) Locomotor score, Lower Extremity Motor Scores, the distance walked in 6 minutes or gait velocity over 15.2 m. Functional electrical therapy resulted in slightly better FIM Motor, FIM Self-Care, and Spinal Cord Independence Measure Self-Care subscores compared with conventional occupational therapy. Comparisons using the Toronto Rehabilitation Institute Hand Function Test demonstrated no differences between groups in 7 of 9 domains. There were no clinically important differences in Maximal Lean Test, Maximal Sidewards Reach Test, T-shirt Test, or the Canadian Occupational Performance Measure between unsupported sitting training and standard in-patient rehabilitation. Conclusion: The current evidence base for rehabilitation following acute and subacute spinal cord injury is limited. Methodological challenges have contributed to this and further research is still needed. © 2017, © The Author(s) 2017

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Chronic neurohormonal and mechanical stresses are central fea-tures of heart disease. Increasing evidence supports a role forthe transient receptor potential canonical channels TRPC3 andTRPC6 in this pathophysiology. Channel expression for both is nor-mally very low but is increased by cardiac disease, and geneticgain- or loss-of-function studies support contributions to hypertro-phy and dysfunction. Selective small-molecule inhibitors remainscarce, and none target both channels, which may be useful giventhe high homology among them and evidence of redundant sig-naling. Here we tested selective TRPC3/6 antagonists (GSK2332255Band GSK2833503A; IC50,3–21 nM against TRPC3 and TRPC6) andfound dose-dependent blockade of cell hypertrophy signaling trig-gered by angiotensin II or endothelin-1 in HEK293T cells as well as inneonatal and adult cardiac myocytes. In vivo efficacy in mice andrats was greatly limited by rapid metabolism and high protein bind-ing, although antifibrotic effects with pressure overload were ob-served. Intriguingly, although gene deletion of TRPC3 or TRPC6alone did not protect against hypertrophy or dysfunction frompressure overload, combined deletion was protective, support-ing the value of dual inhibition. Further development of thispharmaceutical class may yield a useful therapeutic agent forheart disease management.Fil: Seo, Kinya. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Rainer, Peter P.. Johns Hopkins Medical Institutions. Department of Medicine; Estados Unidos. Medical University of Graz. Department of Medicine; AustriaFil: Shalkey Hahn, Virginia. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Lee, Dong-ik. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Jo, Su-Hyun. Kangwon National University School of Medicine; Corea del Sur. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Andersen, Asger. Aarhus University Hospital. Department of Cardiology; DinamarcaFil: Liu, Ting. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Xu, Xiaoping. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Willette, Robert N.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Lepore, John J.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Marino, Joseph P.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Birnbaumer, Lutz. ational Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Schnackenberg, Christine G.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Kass, David A.. Johns Hopkins Medical Institutions. Department of Medicine; Estados Unido

Ubiquitous giant Ly α\alpha nebulae around the brightest quasars at z∼3.5z\sim3.5 revealed with MUSE

Direct Ly $\alpha$ imaging of intergalactic gas at $z\sim2$ has recently revealed giant cosmological structures around quasars, e.g. the Slug Nebula (Cantalupo et al. 2014). Despite their high luminosity, the detection rate of such systems in narrow-band and spectroscopic surveys is less than 10%, possibly encoding crucial information on the distribution of gas around quasars and the quasar emission properties. In this study, we use the MUSE integral-field instrument to perform a blind survey for giant Ly $\alpha$ nebulae around 17 bright radio-quiet quasars at $3<z<4$ that does not suffer from most of the limitations of previous surveys. After data reduction and analysis performed with specifically developed tools, we found that each quasar is surrounded by giant Ly $\alpha$ nebulae with projected sizes larger than 100 physical kpc and, in some cases, extending up to 320 kpc. The circularly averaged surface brightness profiles of the nebulae appear very similar to each other despite their different morphologies and are consistent with power laws with slopes $\approx-1.8$. The similarity between the properties of all these nebulae and the Slug Nebula suggests a similar origin for all systems and that a large fraction of gas around bright quasars could be in a relatively "cold" (T$\sim$10$^4$K) and dense phase. In addition, our results imply that such gas is ubiquitous within at least 50 kpc from bright quasars at $3<z<4$ independently of the quasar emission opening angle, or extending up to 200 kpc for quasar isotropic emission.Comment: 19 pages, 9 figures, 3 Tables, accepted to Ap

The MUSE Hubble Ultra Deep Field Survey X. Lyα\alpha Equivalent Widths at 2.9<z<6.62.9 < z < 6.6

We present rest-frame Ly$\alpha$ equivalent widths (EW) of 417 Ly$\alpha$ emitters (LAEs) detected with Multi Unit Spectroscopic Explorer (MUSE) on the Very Large Telescope (VLT) at $2.9 < z < 6.6$ in the Hubble Ultra Deep Field. Based on the deep MUSE spectroscopy and ancillary Hubble Space Telescope (HST) photometry data, we carefully measured EW values taking into account extended Ly$\alpha$ emission and UV continuum slopes ($\beta$). Our LAEs reach unprecedented depths, both in Ly$\alpha$ luminosities and UV absolute magnitudes, from log($L_{\rm Ly\alpha}$/erg s$^{-1}$) $\sim$41.0 to 43.0 and from Muv $\sim$ -16 to -21 (0.01-1.0 $L^{*}_{\rm z=3}$). The EW values span the range of $\sim$ 5 to 240 \AA\ or larger, and their distribution can be well fitted by an exponential law $N = N_{\rm 0}$ exp($-$EW/$w_{\rm 0}$). Owing to the high dynamic range in Muv, we find that the scale factor, $w_{\rm 0}$, depends on Muv in the sense that including fainter Muv objects increases $w_{\rm 0}$, i.e., the Ando effect. The results indicate that selection functions affect the EW scale factor. Taking these effects into account, we find that our $w_{\rm 0}$ values are consistent with those in the literature within $1\sigma$ uncertainties at $2.9 < z < 6.6$ at a given threshold of Muv and $L_{\rm Ly\alpha}$. Interestingly, we find 12 objects with EW $>200$ \AA\ above $1\sigma$ uncertainties. Two of these 12 LAEs show signatures of merger or AGN activity: the weak CIV $\lambda 1549$ emission line. For the remaining 10 very large EW LAEs, we find that the EW values can be reproduced by young stellar ages ($< 100$ Myr) and low metallicities ($\lesssim 0.02$ $Z_{\rm \odot}$). Otherwise, at least part of the Ly$\alpha$ emission in these LAEs needs to arise from anisotropic radiative transfer effects, fluorescence by hidden AGN or quasi-stellar object activity, or gravitational cooling.Comment: 22 pages, 12 figures, 9 tables, accepted for publication in A&A (MUSE UDF Series Paper X