BackgroundHuman embryonic stem cells (hESC) should enable novel insights into early human development and provide a renewable source of cells for regenerative medicine. However, because the three-dimensional hESC aggregates [embryoid bodies (hEB)] typically employed to reveal hESC developmental potential are heterogeneous and exhibit disorganized differentiation, progress in hESC technology development has been hindered.Methodology/Principal FindingsUsing a centrifugal forced-aggregation strategy in combination with a novel centrifugal-extraction approach as a foundation, we demonstrated that hESC input composition and inductive environment could be manipulated to form large numbers of well-defined aggregates exhibiting multi-lineage differentiation and substantially improved self-organization from single-cell suspensions. These aggregates exhibited coordinated bi-domain structures including contiguous regions of extraembryonic endoderm- and epiblast-like tissue. A silicon wafer-based microfabrication technology was used to generate surfaces that permit the production of hundreds to thousands of hEB per cm2.Conclusions/SignificanceThe mechanisms of early human embryogenesis are poorly understood. We report an ultra high throughput (UHTP) approach for generating spatially and temporally synchronised hEB. Aggregates generated in this manner exhibited aspects of peri-implantation tissue-level morphogenesis. These results should advance fundamental studies into early human developmental processes, enable high-throughput screening strategies to identify conditions that specify hESC-derived cells and tissues, and accelerate the pre-clinical evaluation of hESC-derived cells.

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Understanding healthcare providers' preferences, values, and beliefs around AVF eligibility is important to explain variability in practice. We conducted a survey of international surgeons, using hypothetical patient scenarios, to assess resources used, variables, perceived barriers, and absolute contraindications to access creation. A total of 134 surgeons completed the survey. Venous duplex ultrasound mapping (VDUM) was offered to all patients by 90% of US, 68% Canadian, and 63% European respondents. VDUM altered clinical decision less than 25% of the time for 33% American, 48% Canadian, and 85% European surgeons. Increased comorbidities and previous failed access were deterrents to AVF creation as was vessel size. Second choice access was the AV graft in the US and Europe and the catheter in Canada. Absolute contraindications to AVF creation included patient life expectancy <1 year, left ventricular ejection fraction (LVEF) <15%, and a history of dementia, while 42% surgeons reported no absolute contraindications. Perceived barriers included patient preferences, long wait times for surgery, and late referral to a Nephrologist. Significant variability exists in the surgical preoperative assessment of patients, and the eligibility criteria used for fistula creation. Understanding surgeons' preferences can aid in establishing standardization for VA access eligibility, including surgical assessment.

Aim Cystoscopic placement of ureteric stents during colorectal surgery (CRS) may aid in the intraoperative identification of the ureters and thus prevent ureteric injury, but may also be associated with prolonged operating time, increased cost and adverse events. No formal recommendations exist regarding the use of ureteric stents prior to CRS. Our aim was to determine the effect of prophylactic ureteric stent insertion on the risk of ureteric injury among adult patients undergoing CRS. Method A systematic search using the Ovid platform was completed. The primary outcome was risk of ureteric injury. Secondary outcomes included the risk of acute kidney injury (AKI), urinary tract infection (UTI), sepsis, length of stay (LOS) and mortality. The Paule–Mandel pooling and a random effects model was used to produce odds ratios (ORs) with 95% confidence intervals (CIs) for binary outcomes. Standardized mean differences (MD) were reported for continuous variables. Analyses were completed using R3.5. Results Nine retrospective cohort studies evaluating 98 507 patients were included. The incidence of ureteric injury was 0.6%. Overall, 5.1% of patients underwent ureteric stenting. There was no change in the odds of ureteric injury among stented patients compared with controls (OR 1.30, 95% CI 0.39‐4.29, I2 = 25%). Operating time was significantly longer (MD 49.3 min, 95% CI 35.3–63.4, I2 = 96%) in the intervention group. There was no difference in rates of AKI, UTI, sepsis, LOS or mortality between groups. Conclusion Given the retrospective nature of the identified studies, the benefit of prophylactic ureteric stenting remains uncertain. Prophylactic ureteric stenting was not associated with increased patient morbidity but did significantly increase operating time.