Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?

Background Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P. Methods The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300–799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n = 184) or a cinacalcet-based regimen (n = 368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (≤4.5 and ≤5.5 mg/dL) in relation to achievement of iPTH ≤300 pg/mL during the efficacy assessment phase (EAP; weeks 17–23). Results Patients who achieved iPTH ≤ 300 pg/mL (or a reduction of ≥30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ≤ 300 pg/mL, 43% achieved P ≤4.5 mg/dL and 70% achieved P ≤5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ≤ 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ≤300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ≤4.5 mg/dL during EAP in patients above this threshold at baseline. Conclusions This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received

The properties, origin and evolution of stellar clusters in galaxy simulations and observations

We investigate the properties and evolution of star particles in two simulations of isolated spiral galaxies, and two galaxies from cosmological simulations. Unlike previous numerical work, where typically each star particle represents one ‘cluster’, for the isolated galaxies we are able to model features we term ‘clusters’ with groups of particles. We compute the spatial distribution of stars with different ages, and cluster mass distributions, comparing our findings with observations including the recent LEGUS survey. We find that spiral structure tends to be present in older (100s Myrs) stars and clusters in the simulations compared to the observations. This likely reflects differences in the numbers of stars or clusters, the strength of spiral arms, and whether the clusters are allowed to evolve. Where we model clusters with multiple particles, we are able to study their evolution. The evolution of simulated clusters tends to follow that of their natal gas clouds. Massive, dense, long-lived clouds host massive clusters, whilst short-lived clouds host smaller clusters which readily disperse. Most clusters appear to disperse fairly quickly, in basic agreement with observational findings. We note that embedded clusters may be less inclined to disperse in simulations in a galactic environment with continuous accretion of gas onto the clouds than isolated clouds and correspondingly, massive young clusters which are no longer associated with gas tend not to occur in the simulations. Caveats of our models include that the cluster densities are lower than realistic clusters, and the simplistic implementation of stellar feedback

The impact of a high-fat diet in mice is dependent on duration and age, and differs between muscles.

Prolonged high-fat diets (HFD) can cause intramyocellular lipids (IMCL) accumulation that may negatively affect muscle function. We investigated the duration of a HFD required to instigate these changes, and whether effects are muscle-specific and aggravated in older age. Muscle morphology was determined in the soleus, extensor digitorum longus (EDL) and diaphragm muscles from female CD-1 mice divided into 5 groups: young fed a HFD for 8 weeks (YS-HFD, n=16), young fed a HFD for 16 weeks (YL-HFD, n=28) and young control (Y-CON, n=28). The young animals were 20 weeks old at the end of the experiment. Sixty 70-week-old female CD-1 mice received either a normal diet (O-CON, n=30) or a HFD for 9 weeks (OS-HFD, n=30). Body mass, body mass index and IMCL content increased in old OS-HFD (p≤0.003). In the young mice, this increase was seen in YL-HFD and not YS-HFD (p≤0.006). The soleus and diaphragm fibre cross-sectional area (FCSA) in YL-HFD was larger compared to Y-CON (p≤0.004) while old mice had a larger soleus FCSA compared to CON after only 9 weeks on a HFD (p<0.001). The FCSA of the EDL muscle did not differ significantly between groups. Oxidative capacity of fibres increased in young only, irrespective of HFD duration (p<0.001). High-fat diet-induced morphological changes occur earlier in the old animals when compared to young, and adaptations to HFD are muscle-specific with the EDL being least responsive

A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells

Mutations in the inositol 5-phosphatase OCRL cause Lowe syndrome and Dent's disease. Although OCRL, a direct clathrin interactor, is recruited to late-stage clathrin-coated pits, clinical manifestations have been primarily attributed to intracellular sorting defects. Here we show that OCRL loss in Lowe syndrome patient fibroblasts impacts clathrin-mediated endocytosis and results in an endocytic defect. These cells exhibit an accumulation of clathrin-coated vesicles and an increase in U-shaped clathrin-coated pits, which may result from sequestration of coat components on uncoated vesicles. Endocytic vesicles that fail to lose their coat nucleate the majority of the numerous actin comets present in patient cells. SNX9, an adaptor that couples late-stage endocytic coated pits to actin polymerization and which we found to bind OCRL directly, remains associated with such vesicles. These results indicate that OCRL acts as an uncoating factor and that defects in clathrin-mediated endocytosis likely contribute to pathology in patients with OCRL mutations

Candidate LBV stars in galaxy NGC 7793 found via HST photometry + MUSE spectroscopy

Only about 19 Galactic and 25 extragalactic bonafide luminous blue variables (LBVs) are known to date. This incomplete census prevents our understanding of this crucial phase of massive star evolution which leads to the formation of heavy binary black holes via the classical channel. With large samples of LBVs one could better determine the duration and maximum stellar luminosity which characterize this phase. We search for candidate LBVs (cLBVs) in a new galaxy, NGC 7793. For this purpose, we combine high spatial resolution images from two Hubble Space Telescope (HST) programs with optical spectroscopy from the Multi Unit Spectroscopic Explorer (MUSE). By combining PSF-fitting photometry measured on F547M, F657N, and F814W images, with restrictions on point-like appearance (at HST resolution) and H α luminosity, we find 100 potential cLBVs, 36 of which fall in the MUSE fields. Five of the latter 36 sources are promising cLBVs which have MV ≤ −7 and a combination of: H α with a P-Cygni profile; no [O I]λ6300 emission; weak or no [O III]λ5007 emission; large [N II]/H α relative to H II regions; and [S II]λ6716/[S II]λ6731∼1⁠. It is not clear if these five cLBVs are isolated from O-type stars, which would favour the binary formation scenario of LBVs. Our study, which approximately covers one fourth of the optical disc of NGC 7793, demonstrates how by combining the above HST surveys with multi-object spectroscopy from 8-m class telescopes, one can efficiently find large samples of cLBVs in nearby galaxies

Star cluster formation in the most extreme environments: Insights from the HiPEEC survey

We present the Hubble imaging Probe of Extreme Environments and Clusters (HiPEEC) survey. We fit HST NUV to NIR broadband and H$\alpha$ fluxes, to derive star cluster ages, masses, extinctions and determine the star formation rate (SFR) of 6 merging galaxies. These systems are excellent laboratories to trace cluster formation under extreme gas physical conditions, rare in the local universe, but typical for star-forming galaxies at cosmic noon. We detect clusters with ages of 1-500 Myr and masses that exceed $10^7$ M$_\odot$. The recent cluster formation history and their distribution within the host galaxies suggest that systems like NGC34, NGC1614, NGC4194 are close to their final coalescing phase, while NGC3256, NGC3690, NGC6052 are at an earlier/intermediate stage. A Bayesian analysis of the cluster mass function in the age interval 1-100 Myr provides strong evidence in 4 of the 6 galaxies that an exponentially truncated power law better describes the observed mass distributions. For two galaxies, the fits are inconclusive due to low number statistics. We determine power-law slopes $\beta \sim-1.5$ to $-2.0$, and truncation masses, M$_c$, between $10^6$ and a few times $10^7$ M$_\odot$, among the highest values reported in the literature. Advanced mergers have higher M$_c$ than early/intermediate merger stage galaxies, suggesting rapid changes in the dense gas conditions during the merger. We compare the total stellar mass in clusters to the SFR of the galaxy, finding that these systems are among the most efficient environments to form star clusters in the local universe.Comment: Accepted for publication in MNRAS; data and catalogues will be released at this URL http://dx.doi.org/10.17909/t9-cn0b-ht8

A combined CFD-experimental method for abrasive erosion testing of concrete

Serious damage may occur to concrete hydraulic structures, such as water galleries, spillways, and stilling basins, due to the abrasive erosion caused by the presence of solid particles in the flow. This underlines the importance of being capable in providing characterization of the concrete from the point of view of its vulnerability to abrasive erosion, in order to improve the design of the structure and the material selection. Nevertheless, the existing apparatus for concrete abrasive erosion testing are either far from allowing realistic simulation of the actual environment in which this phenomenon occurs, or show a large degree of complexity and cost. An alternative method has been developed with the aid of Computational Fluid Dynamics (CFD). CFD was first employed to verify the effectiveness of a new laboratory equipment. Afterwards, a parameter has been introduced which, by successful comparison against preliminary experiments, proved suitable to quantify the effect of the fluid dynamic conditions on the concrete abrasive erosion, thereby opening the way to CFD-based customization of the apparatus. In the future, the synergy of numerical and physical modelling will allow developing predictive models for concrete erosion, making it possible to reliably simulate real structures