Renal function, uraemia and early arteriovenous fistula failure

Background Guidance varies regarding the optimal timing of arteriovenous fistula (AVF) creation. The aim of this study was to evaluate the association between uraemia, haemodialysis and early AVF failure. Methods Immunoblotting and cell proliferation assays were performed on vascular smooth muscle cells (VSM) cells isolated from long saphenous vein samples to evaluate the cells’ ability to proliferate when stimulated with uraemic (post-dialysis) and hyperuraemic (pre-dialysis) serum. Clinical data was collected prospectively for 569 consecutive radiocephalic (RCF) and brachiocephalic (BCF) fistulae. The primary outcome was AVF failure at 6 weeks. Dialysis status (haemodialysis (HD); pre-dialysis (Pre-D)), eGFR and serum urea were evaluated to determine if they affected early AVF failure. Results Human VSM cells demonstrated increased capacity to proliferate when stimulated with hyperuraemic serum. There was no significant difference in early failure rate of either RCF or BCF depending on dialysis status (pre-D RCF 31.4% (n = 188); pre-D BCF 22.4% (n = 165); HD RCF 29.3% (n = 99); HD BCF 25.9% (n = 116); p = 0.34). There was no difference in mean eGFR between those patients with early AVF failure and those without (11.2+/-0.2 ml/min/1.73 m2 vs. 11.6+/-0.4 ml/min/1.73 m2; p = 0.47). Uraemia was associated with early AVF failure (serum urea: 35.0+/-0.7 mg/dl vs. 26.6+/-0.3 mg/dl (p &lt; 0.001)). Conclusions We present the first in vivo evidence of an association between adverse early AVF outcomes and uraemia. This is supported mechanistically by in vitro work demonstrating a pro-mitogenic effect of hyperuraemic serum. We hypothesise that uraemia-driven upregulation of VSM cell proliferation at the site of surgical insult in contributes to higher early AVF failure rates.</p

Memories of the future

The year is 2020. Sheffield University’s MSc in Electronic & Digital Library Management has been running for 10 years. What paths have its graduates’ careers taken

Predictive Efficiency Analysis : A Study of U.S. Hospitals

Workshop 2015 -Advances in DEA Theory and Applications (December 1-2, 2015)Healthcare costs are higher in the U.S. then anywhere else in the world. A significant portion of the costs are generated in hospitals. We investigate both the efficiency and the effectiveness of U.S. community hospitals using the Agency for healthcare Research and Quality’s Healthcare Cost and Utilization Project 2009-2011 Nationwide Inpatient Sample, a data set which contains all discharges from an approximate 20% sample of hospitals. Here efficiency is the productivity of the hospital measured relative to the most productive hospitals and effectiveness is how closely the hospital produced relative to the forecasted services needed. We find the effectiveness levels are slightly higher than the efficiency levels in both 2010 and 2011 indicating that hospitals are producing closer to the forecasted level than the actual service level needed. Further, both efficiency and effectiveness levels are low indicating a large variability in the level of resources hospitals use to provide the same set of services. The low effectiveness scores indicate that many hospitals have a high level of resources even relative to the forecasted demand providing some evidence for a medical arms race.The workshop is supported by JSPS (Japan Society for the Promotion of Science), Grant-in-Aid for Scientific Research (B), #25282090, titled “Studies in Theory and Applications of DEA for Forecasting Purpose.本研究はJSPS科研費 基盤研究(B) 25282090の助成を受けたものです

Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia

BACKGROUND: Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and associated biological processes regulated by FoxO during cancer cachexia are unknown. We hypothesize that FoxO is a central upstream regulator of diverse gene networks in skeletal muscle during cancer that may act coordinately to promote the wasting phenotype. METHODS: To inhibit endogenous FoxO DNA-binding, we transduced limb and diaphragm muscles of mice with AAV9 containing the cDNA for a dominant negative (d.n.) FoxO protein (or GFP control). The d.n.FoxO construct consists of only the FoxO3a DNA-binding domain that is highly homologous to that of FoxO1 and FoxO4, and which outcompetes and blocks endogenous FoxO DNA binding. Mice were subsequently inoculated with Colon-26 (C26) cells and muscles harvested 26 days later. RESULTS: Blocking FoxO prevented C26-induced muscle fiber atrophy of both locomotor muscles and the diaphragm and significantly spared force deficits. This sparing of muscle size and function was associated with the differential regulation of 543 transcripts (out of 2,093) which changed in response to C26. Bioinformatics analysis of upregulated gene transcripts that required FoxO revealed enrichment of the proteasome, AP-1 and IL-6 pathways, and included several atrophy-related transcription factors, including Stat3, Fos, and Cebpb. FoxO was also necessary for the cancer-induced downregulation of several gene transcripts that were enriched for extracellular matrix and sarcomere protein-encoding genes. We validated these findings in limb muscles and the diaphragm through qRT-PCR, and further demonstrate that FoxO1 and/or FoxO3a are sufficient to increase Stat3, Fos, Cebpb, and the C/EBPβ target gene, Ubr2. Analysis of the Cebpb proximal promoter revealed two bona fide FoxO binding elements, which we further establish are necessary for Cebpb promoter activation in response to IL-6, a predominant cytokine in the C26 cancer model. CONCLUSIONS: These findings provide new evidence that FoxO-dependent transcription is a central node controlling diverse gene networks in skeletal muscle during cancer cachexia, and identifies novel candidate genes and networks for further investigation as causative factors in cancer-induced wasting.R01 AR060217 - NIAMS NIH HHS; R01 AR060209 - NIAMS NIH HHS; T32 HD043730 - NICHD NIH HHS; R00 HL098453 - NHLBI NIH HHS; R00HL098453 - NHLBI NIH HHS; R01AR060209 - NIAMS NIH HHS; R01AR060217 - NIAMS NIH HH

Prediction of H α and [O III] emission line galaxy number counts for future galaxy redshift surveys

We perform a simulation with Galacticus, a semi-analytical galaxy formation model, to predict the number counts of H α and [O III] emitting galaxies. With a state-of-the-art N-body simulation, UNIT, we first calibrate Galacticus with the current observation of H α luminosity function. The resulting model coupled with a dust attenuation model, can reproduce the current observations, including the H α luminosity function from HiZELS and number density from WISP. We extrapolate the model prediction to higher redshift and the result is found to be consistent with previous investigations. We then use the same galaxy formation model to predict the number counts for [O III] emitting galaxies. The result provides further validation of our galaxy formation model and dust model. We present number counts of H α and [O III] emission line galaxies for three different line flux limits: 5 × 10⁻¹⁷ erg s⁻¹ cm⁻², 1 × 10⁻¹⁶ erg s⁻¹ cm⁻² (6.5σ nominal depth for WFIRST GRS), and 2 × 10⁻¹⁶ erg s⁻¹ cm⁻² (3.5σ depth of Euclid GRS). At redshift 2 < z < 3, our model predicts that WFIRST can observe hundreds of [O III] emission line galaxies per square degree with a line flux limit of 1 × 110⁻¹⁶ erg s⁻¹ cm⁻². This will provide accurate measurement of large-scale structure to probe dark energy over a huge cosmic volume to an unprecedented high redshift. Finally, we compare the flux ratio of H α/[O III] within the redshift range of 0 < z < 3. Our results show the known trend of increasing H α/[O III] flux ratio with H α flux at low redshift, which becomes a weaker trend at higher redshifts