Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not ...established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference - 69%, 95% CI - 127% to - 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment.Trial registration: ACTRN12617000545369, registered 18th April 2017.
The specification of the hepatic identity during human liver development is strictly controlled by extrinsic signals, yet it is still not clear how cells respond to these exogenous signals by ...activating secretory cascades, which are extremely relevant, especially in 3D self-organizing systems. Here, we investigate how the proteins secreted by human pluripotent stem cells (hPSCs) in response to developmental exogenous signals affect the progression from endoderm to the hepatic lineage, including their competence to generate nascent hepatic organoids. By using microfluidic confined environment and stable isotope labeling with amino acids in cell culture-coupled mass spectrometry (SILAC-MS) quantitative proteomic analysis, we find high abundancy of extracellular matrix (ECM)-associated proteins. Hepatic progenitor cells either derived in microfluidics or exposed to exogenous ECM stimuli show a significantly higher potential of forming hepatic organoids that can be rapidly expanded for several passages and further differentiated into functional hepatocytes. These results prove an additional control over the efficiency of hepatic organoid formation and differentiation for downstream applications.
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•Microfluidic confined environment enhances hepatic differentiation of hPSCs•SILAC-based proteomic analysis reveals high abundance of secreted ECM proteins•ECM deposition and remodeling correlate with cell-ECM receptor overexpression•Either endogenous or exogenous ECM enhances organoid formation and differentiation
Michielin et al. investigate the secretome of human pluripotent stem cells undergoing hepatic differentiation by coupling microfluidics with SILAC proteomic analysis. They reveal a role of soluble ECM protein accumulation and deposition and leverage these insights to efficiently and robustly derive hepatic organoids from hiPSCs.
The Canadian Penning Trap mass spectrometer at the Californium Rare Isotope Breeder Upgrade (CARIBU) facility was used to measure the masses of eight neutron-rich isotopes of Nd and Sm. These ...measurements are the first to push into the region of nuclear masses relevant to the formation of the rare-earth abundance peak at A∼165 by the rapid neutron-capture process. We compare our results with theoretical predictions obtained from "reverse engineering" the mass surface that best reproduces the observed solar abundances in this region through a Markov chain Monte Carlo technique. Our measured masses are consistent with the reverse-engineering predictions for a neutron star merger wind scenario.
An experiment was performed at Lawrence Berkeley National Laboratory's 88-in. Cyclotron to determine the mass number of a superheavy element. The measurement resulted in the observation of two ...α-decay chains, produced via the ^{243}Am(^{48}Ca,xn)^{291-x}Mc reaction, that were separated by mass-to-charge ratio (A/q) and identified by the combined BGS+FIONA apparatus. One event occurred at A/q=284 and was assigned to ^{284}Nh (Z=113), the α-decay daughter of ^{288}Mc (Z=115), while the second occurred at A/q=288 and was assigned to ^{288}Mc. This experiment represents the first direct measurements of the mass numbers of superheavy elements, confirming previous (indirect) mass-number assignments.
For the past two decades the Canadian Penning Trap mass spectrometer (CPT) has been utilized to study various disciplines of nuclear physics through precision mass measurements. Since moving to the ...Californium Rare Isotope Breeder Upgrade (CARIBU) facility, the CPT experimental program has focused on neutron-rich nuclei whose masses may play an important role in the astrophysical r process. Through a recent upgrade of the detector system, the phase-imaging ion-cyclotron-resonance (PI-ICR) technique has been successfully implemented. This method offers several benefits which drastically improve the experimental sensitivity of the CPT to the most neutron-rich nuclei produced at CARIBU. Here we describe the PI-ICR procedure at the CPT, give an overview of the systematic sources of uncertainty in the system, and provide new mass results for 142I, 146La, and 163Gd which were made possible through this upgrade.
In an experiment performed at Lawrence Berkeley National Laboratory's 88-inch cyclotron, the isotope 244Md was produced in the 209Bi (40Ar , 5n) reaction. Decay properties of 244Md were measured at ...the focal plane of the Berkeley Gas-filled Separator, and the mass number assignment of A = 244 was confirmed with the apparatus for the identification of nuclide A . The isotope 244Md is reported to have one, possibly two, α -decaying states with α energies of 8.66(2) and 8.31(2) MeV and half-lives of 0.4 + 0.4 − 0.1 and ∼ 6 s , respectively. Additionally, first evidence of the α decay of 236Bk was observed and is reported.
The Canadian Penning Trap mass spectrometer has made mass measurements of 33 neutron-rich nuclides provided by the new Californium Rare Isotope Breeder Upgrade facility at Argonne National ...Laboratory. The studied region includes the 132Sn double shell closure and ranges in Z from In to Cs, with Sn isotopes measured out to A=135, and the typical measurement precision is at the 100 ppb level or better. The region encompasses a possible major waiting point of the astrophysical r process, and the impact of the masses on the r process is shown through a series of simulations. These first-ever simulations with direct mass information on this waiting point show significant increases in waiting time at Sn and Sb in comparison with commonly used mass models, demonstrating the inadequacy of existing models for accurate r-process calculations.
Self-harm is one of the most common reasons for admission to an intensive care unit (ICU). While most patients with self-harm survive the ICU admission, little is known about their outcomes after ...hospital discharge. We conducted a retrospective cohort study of patients in the Barwon region in Victoria admitted to the ICU with self-harm (between 1998 and 2018) who survived to hospital discharge. The primary objective was to determine mortality after hospital discharge, and secondarily estimate relative survival, years of potential life lost, cause of death and factors associated with death. Over the 20-year study period, there were 710 patients in the cohort. The median patient age was 37 years (interquartile range (IQR) 26-48 years). A total of 406 (57%) were female, and 527 (74%) had a prior psychiatric diagnosis. The incidence of ICU admission increased over time (incidence rate ratio 1.05; 95% confidence interval (CI) 1.03-1.06 per annum). There were 105 (15%) patients who died after hospital discharge. Relative survival decreased each year after discharge, with the greatest decrement during the first 12 months. At ten years, relative survival was 0.85 (95% CI 0.81-0.88). The median years of potential life lost was 35 (IQR 22-45). Cause of death was self-harm in 27%, possible self-harm in 32% and medical disease in 41%. The only factors associated with mortality were male sex, older age and re-admission to ICU with self-harm. Further population studies are required to confirm these findings, and to understand what interventions may improve long-term survival in this relatively young group of critically ill patients.
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