Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

INTRODUCTION: Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD. METHODS: Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 10(6) cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 10(6) cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 10(6) aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction. RESULTS: Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3. CONCLUSIONS: Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters

The Variable Stars and Blue Horizontal Branch of the Metal-Rich Globular Cluster NGC 6441

We present time-series VI photometry of the metal-rich ([Fe/H] = -0.53) globular cluster NGC 6441. Our color-magnitude diagram shows that the extended blue horizontal branch seen in Hubble Space Telescope data exists in the outermost reaches of the cluster. The red clump slopes nearly parallel to the reddening vector. A component of this slope is due to differential reddening, but part is intrinsic. The blue horizontal branch stars are more centrally concentrated than the red clump stars. We have discovered about 50 new variable stars near NGC 6441, among them eight or more RR Lyrae stars which are very probably cluster members. Comprehensive period searches over the range 0.2-1.0 days yielded unusually long periods (0.5-0.9 days) for the fundamental pulsators compared with field RR Lyrae of the same metallicity. Three similar long-period RR Lyrae are known in other metal-rich globulars. With over ten examples in hand, it seems that a distinct sub-class of RR Lyrae is emerging. The observed properties of the horizontal branch stars are in reasonable agreement with recent models which invoke deep mixing to enhance the atmospheric helium abundance, while they conflict with models which assume high initial helium abundance. The light curves of the c-type RR Lyrae seem to have unusually long rise times and sharp minima. Reproducing these light curves in stellar pulsation models may provide another means of constraining the physical variables responsible for the anomalous blue horizontal branch extension and sloped red clump observed in NGC 6441.Comment: 30 pages plus 6 EPS and 6 JPEG figures; uses AAS TeX. Accepted by the Astronomical Journal. Minor changes include computing He abundance, modifications to Figs 1 and 8, and expansion on idea that blue HB stars may be produced in binarie

The Phase Space and Stellar Populations of Cluster Galaxies at z ~ 1: Simultaneous Constraints on the Location and Timescale of Satellite Quenching

We investigate the velocity vs. position phase space of z ~ 1 cluster galaxies using a set of 424 spectroscopic redshifts in 9 clusters drawn from the GCLASS survey. Dividing the galaxy population into three categories: quiescent, star-forming, and poststarburst, we find that these populations have distinct distributions in phase space. Most striking are the poststarburst galaxies, which are commonly found at small clustercentric radii with high clustercentric velocities, and appear to trace a coherent ``ring" in phase space. Using several zoom simulations of clusters we show that the coherent distribution of the poststarbursts can be reasonably well-reproduced using a simple quenching scenario. Specifically, the phase space is best reproduced if satellite quenching occurs on a rapid timescale (0.1 < tau_{Q} < 0.5 Gyr) after galaxies make their first passage of R ~ 0.5R_{200}, a process that takes a total time of ~ 1 Gyr after first infall. We compare this quenching timescale to the timescale implied by the stellar populations of the poststarburst galaxies and find that the poststarburst spectra are well-fit by a rapid quenching (tau_{Q} = 0.4^{+0.3}_{-0.4} Gyr) of a typical star-forming galaxy. The similarity between the quenching timescales derived from these independent indicators is a strong consistency check of the quenching model. Given that the model implies satellite quenching is rapid, and occurs well within R_{200}, this would suggest that ram-pressure stripping of either the hot or cold gas component of galaxies are the most plausible candidates for the physical mechanism. The high cold gas consumption rates at z ~ 1 make it difficult to determine if hot or cold gas stripping is dominant; however, measurements of the redshift evolution of the satellite quenching timescale and location may be capable of distinguishing between the two.Comment: 10 pages, 4 figures, submitted to the Ap

Cell Therapy in Veterinary Medicine as a Proof-of-Concept for Human Therapies: Perspectives From the North American Veterinary Regenerative Medicine Association

In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach

The Canada-UK Deep Submillimetre Survey: The Survey of the 14-hour field

We have used SCUBA to survey an area of 50 square arcmin, detecting 19 sources down to a 3sigma sensitivity limit of 3.5 mJy at 850 microns. We have used Monte-Carlo simulations to assess the effect of source confusion and noise on the SCUBA fluxes and positions, finding that the fluxes of sources in the SCUBA surveys are significantly biased upwards and that the fraction of the 850 micron background that has been resolved by SCUBA has been overestimated. The radio/submillmetre flux ratios imply that the dust in these galaxies is being heated by young stars rather than AGN. We have used simple evolution models based on our parallel SCUBA survey of the local universe to address the major questions about the SCUBA sources: (1) what fraction of the star formation at high redshift is hidden by dust? (2) Does the submillimetre luminosity density reach a maximum at some redshift? (3) If the SCUBA sources are proto-ellipticals, when exactly did ellipticals form? However, we show that the observations are not yet good enough for definitive answers to these questions. There are, for example, acceptable models in which 10 times as much high-redshift star formation is hidden by dust as is seen at optical wavelengths, but also acceptable ones in which the amount of hidden star formation is less than that seen optically. There are acceptable models in which very little star formation occurred before a redshift of three (as might be expected in models of hierarchical galaxy formation), but also ones in which 30% of the stars have formed by this redshift. The key to answering these questions are measurements of the dust temperatures and redshifts of the SCUBA sources.Comment: 41 pages (latex), 17 postscript figures, to appear in the November issue of the Astronomical Journa

A theory-based online health behaviour intervention for new university students (U@Uni): results from a randomised controlled trial

BACKGROUND Too few young people engage in behaviours that reduce the risk of morbidity and premature mortality, such as eating healthily, being physically active, drinking sensibly and not smoking. This study sought to assess the efficacy and cost-effectiveness of a theory-based online health behaviour intervention (based on self-affirmation theory, the Theory of Planned Behaviour and implementation intentions) targeting these behaviours in new university students, in comparison to a measurement-only control. METHODS Two-weeks before starting university all incoming undergraduates at the University of Sheffield were invited to take part in a study of new students' health behaviour. A randomised controlled design, with a baseline questionnaire, and two follow-ups (1 and 6 months after starting university), was used to evaluate the intervention. Primary outcomes were measures of the four health behaviours targeted by the intervention at 6-month follow-up, i.e., portions of fruit and vegetables, metabolic equivalent of tasks (physical activity), units of alcohol, and smoking status. RESULTS The study recruited 1,445 students (intervention n = 736, control n = 709, 58% female, Mean age = 18.9 years), of whom 1,107 completed at least one follow-up (23% attrition). The intervention had a statistically significant effect on one primary outcome, smoking status at 6-month follow-up, with fewer smokers in the intervention arm (8.7%) than in the control arm (13.0%; Odds ratio = 1.92, p = .010). There were no significant intervention effects on the other primary outcomes (physical activity, alcohol or fruit and vegetable consumption) at 6-month follow-up. CONCLUSIONS The results of the RCT indicate that the online health behaviour intervention reduced smoking rates, but it had little effect on fruit and vegetable intake, physical activity or alcohol consumption, during the first six months at university. However, engagement with the intervention was low. Further research is needed before strong conclusions can be made regarding the likely effectiveness of the intervention to promote health lifestyle habits in new university students. TRIAL REGISTRATION Current Controlled Trials, ISRCTN67684181

Understanding Face and Shame: A Servant-Leadership and Face Management Model

Clergy can have a negative impact on churches and other individuals when they knowingly or unknowingly attempt to save face, that is, try to protect their standing or reputation. The desire to gain face and the fear of losing face and feeling ashamed will likely permeate clergy’s decision-making processes without even being noticed. This study explores the essence of face and face management and the relationship between face management and two characteristics of servant-leadership—awareness and healing—in both Chinese and American churches through the methodology of hermeneutic phenomenology. Prior to this study, to my knowledge, no hermeneutic phenomenological research of face management has been conducted in a church setting. Through a review of the literature, four areas are explored: face and shame, face management, servant-leadership, and face, shame, and face management within the church. This study obtained approval from the Institutional Review Board and informed consent from the participants. Three Chinese and three American Christian ministers were chosen to complete a question sheet and participate in two semi-structured interview sessions. A first cycle of open coding and second cycle of pattern coding were used during data analysis. Face experiences are discussed in light of eight major themes: body, triggers, becoming, face concepts, strategies, emotions, servant-leadership, and the church. Findings from the study help build a servant-leadership and face management model, which can offer an anchored approach for clergy and pastoral counselors to address face and shame and to develop therapeutic interventions

High-spectral-resolution Observations of the Optical Filamentary Nebula Surrounding NGC 1275

We present new high-spectral-resolution observations (R = λ/Δλ = 7000) of the filamentary nebula surrounding NGC 1275, the central galaxy of the Perseus cluster. These observations have been obtained with SITELLE, an imaging Fourier transform spectrometer installed on the Canada–France–Hawai Telescope with a field of view of 11′×11′ , encapsulating the entire filamentary structure of ionized gas despite its large size of 80 kpc × 50 kpc. Here, we present renewed fluxes, velocities, and velocity dispersion maps that show in great detail the kinematics of the optical nebula at [S ii] λ6716, [S ii] λ6731, [N ii] λ6584, Hα (6563 Å), and [N ii] λ6548. These maps reveal the existence of a bright flattened disk-shaped structure in the core extending to r ∼10 kpc and dominated by a chaotic velocity field. This structure is located in the wake of X-ray cavities and characterized by a high mean velocity dispersion of 134 km s−1. The disk-shaped structure is surrounded by an extended array of filaments spread out to r ∼ 50 kpc that are 10 times fainter in flux, remarkably quiescent, and have a uniform mean velocity dispersion of 44 km s−1. This stability is puzzling given that the cluster core exhibits several energetic phenomena. Based on these results, we argue that there are two mechanisms that form multiphase gas in clusters of galaxies: a first triggered in the wake of X-ray cavities leading to more turbulent multiphase gas and a second, distinct mechanism, that is gentle and leads to large-scale multiphase gas spreading throughout the core