Computer Simulation of Levee Erosion and Overtopping

Improved computer models of erosion have been developed, considering soil hydraulic conductivity. The models deal with erosion of levees, dams and embankments due to overtopping. The simulations trace the formation of rills and gullies, beginning with initial overtopping and continuing to final breaching. Physical models performed at 1-g and high g using a geotechnical centrifuge have been used to calibrate the models. Previous models did not consider soil hydraulic conductivity, and although results were quite good for the formation of rills and gullies and sediment quantities, breach times were underestimated. Essentially the water flow was treated as if passing over a solid surface, not entering the soil, and the total water flow was available for erosion. Thus, breach times were underestimated. Soil erodibility parameters had to be adjusted in order to achieve good agreement with breach times. The new models developed consider soil hydraulic conductivity, and produce good agreement with the performance of the physical modeling, including breach times and the use of proper soil erodibility parameters

An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology

Transmission electron microscopy (EM) is a versatile technique that can be used to image biological specimens ranging from intact eukaryotic cells to individual proteins greater than 150 kDa. There are several strategies for preparing samples for imaging by EM, including negative staining and cryogenic freezing. In the last few years, cryo-EM has undergone a 'resolution revolution', owing to both advances in imaging hardware, image processing software, and improvements in sample preparation, leading to growing number of researchers using cryo-EM as a research tool. However, cryo-EM is still a rapidly growing field, with unique challenges. Here, we summarise considerations for imaging of a range of specimens from macromolecular complexes to cells using EM

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial

Aim: To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis. Design: Multicentre three-arm randomised controlled trial. Setting: UK NHS hospitals. Target population: Hospitalised critically ill adults who have been commenced on intravenous antibiotics for sepsis. Health technology: Three protocols for guiding antibiotic discontinuation will be compared: (a) standard care; (b) standard care + daily CRP monitoring; (c) standard care + daily PCT monitoring. Standard care will be based on routine sepsis management and antibiotic stewardship. Measurement of outcomes and costs. Outcomes will be assessed to 28 days. The primary outcomes are total duration of antibiotics and safety outcome of all-cause mortality. Secondary outcomes include: escalation of care/re-admission; infection re-lapse/recurrence; antibiotic dose; length and level of critical care stay and length of hospital stay. Ninety-day all-cause mortality rates will also be collected. An assessment of cost effectiveness will be performed. Conclusion: In the setting of routine NHS care, if this trial finds that a treatment protocol based on monitoring CRP or PCT safely allows a reduction in duration of antibiotic therapy, and is cost effective, then this has the potential to change clinical practice for critically ill patients with sepsis. Moreover, if a biomarker-guided protocol is not found to be effective, then it will be important to avoid its use in sepsis and prevent ineffective technology becoming widely adopted in clinical practice

sj-docx-2-inc-10.1177_17511437231169193 – Supplemental material for biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial

Supplemental material, sj-docx-2-inc-10.1177_17511437231169193 for biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial by Paul Dark, Gavin D Perkins, Ronan McMullan, Danny McAuley, Anthony C Gordon, Jonathan Clayton, Dipesh Mistry, Keith Young, Scott Regan, Nicola McGowan, Matt Stevenson, Simon Gates, Gordon L Carlson, Tim Walsh, Nazir I Lone, Paul R Mouncey, Mervyn Singer, Peter Wilson, Tim Felton, Kay Marshall, Anower M. Hossain and Ranjit Lall in Journal of the Intensive Care Society</p

sj-docx-1-inc-10.1177_17511437231169193 – Supplemental material for biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial

Supplemental material, sj-docx-1-inc-10.1177_17511437231169193 for biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial by Paul Dark, Gavin D Perkins, Ronan McMullan, Danny McAuley, Anthony C Gordon, Jonathan Clayton, Dipesh Mistry, Keith Young, Scott Regan, Nicola McGowan, Matt Stevenson, Simon Gates, Gordon L Carlson, Tim Walsh, Nazir I Lone, Paul R Mouncey, Mervyn Singer, Peter Wilson, Tim Felton, Kay Marshall, Anower M. Hossain and Ranjit Lall in Journal of the Intensive Care Society</p

A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio Distortion on Mouse Chromosome 2

<div><p>Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 – 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, <i>R2d</i>) emerged as the strongest candidate for the causative allele. We mapped <i>R2d</i> sequences to two loci within the candidate interval. <i>R2d1</i> is located near the proximal boundary, and contains a single copy of <i>R2d</i> in all strains tested. <i>R2d2</i> maps to a 900 kb interval, and the number of <i>R2d</i> copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (<i>R2d2^WSBdel1</i>) that eliminates the majority of the <i>R2d2^WSB</i> copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for <i>R2d2^WSBdel1</i>, the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for <i>R2d2^WSBdel1</i>, thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in <i>R2d2^WSB</i> heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the <i>R2d2^WSB</i> transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system.</p></div

Transmission ratios in the progeny of <i>R2d2</i>^{<i>WSB/notWSB</i>} heterozygous F1 hybrid sires and dams.

<p>Transmission ratios in the progeny of <i>R2d2</i>^{<i>WSB/notWSB</i>} heterozygous F1 hybrid sires and dams.</p