Impact pressures of turbulent high-velocity jets plunging in pools with flat bottom

Dynamic pressures created by the impact of high-velocity turbulent jets plunging in a water pool with flat bottom were investigated. Pressure fluctuations were sampled at 1kHz at the jet outlet and at the pool bottom using piezo-resistive pressure transducers, jet velocities of up to 30m/s and pool depth to jet diameter ratios from 2.8 to 11.4. The high-velocity jets entrain air in the pool in conditions similar to prototype applications at water release structures of dams. The intermittent character of plunge pool flows was investigated for shallow and deep pools, based on high order moments and time correlations. Maximum intermittency was observed for pool depths at 5.6 jet diameters, which approximate the core development length. Wall pressure skewness was shown to allow identifying the zone of influence of downward and upward moving current

Scour potential at Laouzas Dam

Laouzas Dam, owned and operated by Electricité de France (EDF), is a 52 m high double-curvature arch dam in a large valley located on the Vèbre River in the Languedoc-Roussillon Midi Pyrénées region of France. The dam is founded on heavily fractured granite and migmatite rock. It houses a surface spillway equipped with 3 radial gates. The radial gates are positioned such that their gate lip is systematically located about 1m upstream of the spillway crest itself. This particular design generates aerated jets that do not behave like normal falling jets. Despite the absence of severe spillages since dam construction in 1961-1965, the ones observed in the past have allowed creating locally a 5 m deep scour hole along the right hand side of the rock mass. The granite and migmatite have significant unconfined compressive strength. The rock mass fracturing is composed of 3-4 joint sets and shows desquamation joints affecting both abutments. EDF has commissioned a numerical study to assess scour potential downstream of the dam as well as the positive influence of rock anchors, by using the Comprehensive Scour Model (CSM)

Rock scour in Australia: some latest Queensland experiences

From 2010, a succession of floods in eastern Australia, and particularly in Queensland, brought about spillway operation at high head dams with return periods in the region of Annual Exceedance Probabilities (AEP) of up to 1 in 2,000 years. As such, a number of spillways experienced extensive scour of rock downstream – including Boondooma Dam and Paradise Dam – the subject of the present paper. For both dams, part of the scour assessment process has been to utilise a large-scale physical model to obtain transient data which, together with the detailed geologic assessment, have been incorporated into the numerical scour modelling procedures developed by Dr Erik Bollaert. This paper will first of all describe the features of the 2011 and 2013 flood events at both dams, as well as the resulting rock scour and damage on both spillways and the geology of the rock area below. The paper will then go on to describe the computational scour modelling procedures of calibration and application, used in conjunction with a large-scale physical model of both dam and spillway, demonstrating a “system” approach to spillway scour analysis for plunge pools and similar situations with energy dissipation on natural materials

Exceptional river gorge formation from unexceptional floods

An understanding of rates and mechanisms of incision and knickpoint retreat in bedrock rivers is fundamental to perceptions of landscape response to external drivers, yet only sparse field data are available. Here we present eye witness accounts and quantitative surveys of rapid, amphitheatre-headed gorge formation in unweathered granite from the overtopping of a rock-cut dam spillway by small-moderate floods (~100–1,500 m3 s−1). The amount of erosion demonstrates no relationship with flood magnitude or bedload availability. Instead, structural pattern of the bedrock through faults and joints appears to be the primary control on landscape change. These discontinuities facilitate rapid erosion (>270 m headward retreat; ~100 m incision; and ~160 m widening over 6 years) principally through fluvial plucking and block topple. The example demonstrates the potential for extremely rapid transient bedrock erosion even when rocks are mechanically strong and flood discharges are moderate. These observations are relevant to perceived models of gorge formation and knickpoint retreat

miR-15a-5p and miR-21-5p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2

Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance. This study aimed to identify miRNAs involved in chemoresistance in AML patients and to define their target genes. We focused on cytogenetically normal AML patients with wild-type NPM1 without FLT3-ITD as the treatment of this subset of patients with intermediate-risk cytogenetics is not well established. We analysed baseline AML samples by small RNA sequencing and compared the profile of chemoresistant to chemosensitive AML patients. Among the miRNAs significantly overexpressed in chemoresistant patients, we revealed miR-15a-5p and miR-21-5p as miRNAs with a major role in chemoresistance in AML. We showed that miR-15a-5p and miR-21-5p overexpression decreased apoptosis induced by cytarabine and/or daunorubicin. PDCD4, ARL2 and BTG2 genes were found to be targeted by miR-15a-5p, as well as PDCD4 and BTG2 by miR-21-5p. Inhibition experiments of the three target genes reproduced the functional effect of both miRNAs on chemosensitivity. Our study demonstrates that miR-15a-5p and miR-21-5p are overexpressed in a subgroup of chemoresistant AML patients. Both miRNAs induce chemoresistance by targeting three pro-apoptotic genes PDCD4, ARL2 and BTG2

Why Are Clinicians Not Embracing the Results from Pivotal Clinical Trials in Severe Sepsis? A Bayesian Analysis

BACKGROUND: Five pivotal clinical trials (Intensive Insulin Therapy; Recombinant Human Activated Protein C [rhAPC]; Low-Tidal Volume; Low-Dose Steroid; Early Goal-Directed Therapy [EGDT]) demonstrated mortality reduction in patients with severe sepsis and expert guidelines have recommended them to clinical practice. Yet, the adoption of these therapies remains low among clinicians. OBJECTIVES: We selected these five trials and asked: Question 1--What is the current probability that the new therapy is not better than the standard of care in my patient with severe sepsis? Question 2--What is the current probability of reducing the relative risk of death (RRR) of my patient with severe sepsis by meaningful clinical thresholds (RRR >15%; >20%; >25%)? METHODS: Bayesian methodologies were applied to this study. Odds ratio (OR) was considered for Question 1, and RRR was used for Question 2. We constructed prior distributions (enthusiastic; mild, moderate, and severe skeptic) based on various effective sample sizes of other relevant clinical trials (unfavorable evidence). Posterior distributions were calculated by combining the prior distributions and the data from pivotal trials (favorable evidence). MAIN FINDINGS: Answer 1--The analysis based on mild skeptic prior shows beneficial results with the Intensive Insulin, rhAPC, and Low-Tidal Volume trials, but not with the Low-Dose Steroid and EGDT trials. All trials' results become unacceptable by the analyses using moderate or severe skeptic priors. Answer 2--If we aim for a RRR>15%, the mild skeptic analysis shows that the current probability of reducing death by this clinical threshold is 88% for the Intensive Insulin, 62-65% for the Low-Tidal Volume, rhAPC, EGDT trials, and 17% for the Low-Dose Steroid trial. The moderate and severe skeptic analyses show no clinically meaningful reduction in the risk of death for all trials. If we aim for a RRR >20% or >25%, all probabilities of benefits become lower independent of the degree of skepticism. CONCLUSIONS: Our clinical threshold analysis offers a new bedside tool to be directly applied to the care of patients with severe sepsis. Our results demonstrate that the strength of evidence (statistical and clinical) is weak for all trials, particularly for the Low-Dose Steroid and EGDT trials. It is essential to replicate the results of each of these five clinical trials in confirmatory studies if we want to provide patient care based on scientifically sound evidence

Effects of resuscitation with crystalloid fluids on cardiac function in patients with severe sepsis

<p>Abstract</p> <p>Background</p> <p>The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension.</p> <p>Methods</p> <p>Ninety-four severe sepsis patients with hypotension were randomly assigned to three groups. The patients received the following injections within 15 min at initial treatment: Ns group (n = 32), 5 ml/kg normal saline; Hs group (n = 30), with 5 ml/kg 3.5% sodium chloride; and Sb group (n = 32), 5 ml/kg 5% sodium bicarbonate. Cardiac output (CO), systolic blood pressure, mean arterial pressure (MAP), body temperature, heart rate, respiratory rate and blood gases were measured.</p> <p>Results</p> <p>There were no differences among the three groups in CO, MAP, heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up, and no significant differences in observed mortality rate after 28 days. However, improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups. Sodium bicarbonate increased the base excess but did not alter blood pH, lactic acid or [HCO₃]^-values; and neither 3.5% hypertonic saline nor 5% sodium bicarbonate altered the Na⁺, K⁺, Ca²⁺or Cl^-levels.</p> <p>Conclusion</p> <p>All three crystalloid solutions may be used for initial volume loading in severe sepsis, and sodium bicarbonate confers a limited benefit on humans with severe sepsis.</p> <p>Trial registration</p> <p>ISRCTN36748319.</p