Background
Acute illness, existing co‐morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The ...aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery.
Methods
This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2‐week blocks over a continuous 3‐month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation.
Results
A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30‐day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30‐day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin‐converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c‐statistic 0·65).
Discussion
Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability.
AKI following major gastrointestinal surgery is common, occurring in 1 in 7 patients, and is strongly associated with increased risk of peri‐operative death. A pre‐operative prognostic model has been developed to identify patients at high risk of post‐operative AKI.
Needs external validation
At least 28 randomised, controlled trials have compared outcomes of surgery for rectal cancer combined with preoperative or postoperative radiotherapy with those of surgery alone. We have done a ...collaborative meta-analysis of these results to give a more balanced view of the total evidence and to increase statistical precision.
We centrally checked and analysed individual patient data from 22 randomised comparisons between preoperative (6350 patients in 14 trials) or postoperative (2157 in eight trials) radiotherapy and no radiotherapy for rectal cancer.
Overall survival was only marginally better in patients who were allocated to radiotherapy than in those allocated to surgery alone (62%
vs 63% died; p=0·06). Rates of apparently curative resection were not improved by preoperative radiotherapy (85% radiotherapy
vs 86% control). Yearly risk of local recurrence was 46% (SE 6) lower in those who had preoperative radiotherapy than in those who had surgery alone (p=0·00001), and 37% (10) lower in those who had postoperative treatment than those who had surgery alone (p=0·002). Fewer patients who had preoperative radiotherapy died from rectal cancer than did those who had surgery alone (45%
vs 50%, respectively, p=0·0003), but early (≤1 year after treatment) deaths from other causes increased (8%
vs 4% died, p<0·0001).
Preoperative radiotherapy (at biologically effective doses ≥30 Gy) reduces risk of local recurrence and death from rectal cancer. If safety can be improved without compromising effectiveness, then overall survival would be moderately improved by use of preoperative radiotherapy, especially for young, high risk patients. Postoperative radiotherapy also reduces local recurrence, but short preoperative radiation schedules seem to be at least as effective as longer schedules.
We report measurements of the electron transport through atomic-scale constrictions and tunnel junctions between ferromagnetic electrodes. Structures are fabricated using a combination of e-beam ...lithography and controlled electromigration. Sample geometries are chosen to allow independent control of electrode bulk magnetizations. As junction size is decreased to the single channel limit, conventional anisotropic magnetoresistance (AMR) increases in magnitude, approaching the size expected for tunneling magnetoresistance (TMR) upon tunnel junction formation. Significant mesoscopic variations are seen in the magnitude and sign of the magnetoresistance, and no evidence is found of large ballistic magnetoresistance effects.
Phys. Rev. Lett. 93, 266802 (2004) In single-molecule transistors, we observe inelastic cotunneling features
that correspond energetically to vibrational excitations of the molecule, as
determined by ...Raman and infrared spectroscopy. This is a form of inelastic
electron tunneling spectroscopy of single molecules, with the transistor
geometry allowing in-situ tuning of the electronic states via a gate electrode.
The vibrational features shift and change shape as the electronic levels are
tuned near resonance, indicating significant modification of the vibrational
states. When the molecule contains an unpaired electron, we also observe
vibrational satellite features around the Kondo resonance.
Aims
Given the selectivity of clinical trial patients and meager representation of elderly in the major implantable cardioverter defibrillator (ICD) randomized trials (<25%), whether such data apply ...to elderly patients overall is unclear. The purpose of our study is to understand the influence of age on mortality after ICD implantation.
Methods and results
We performed a retrospective cohort study of 502 consecutive patients receiving ICDs from 1993 to 2003 at a single university hospital. The primary predictor was patient age, categorized as <65, 65-75, and >75 years at ICD implantation. The primary outcome was time to death. Mean follow-up was 4 years. Median survival after ICD implantation was 5.3 years among subjects >75 years, less than half that of the youngest group. After adjusting for potential confounders, compared with subjects <65 years of age, patients >75 years hazard ratio (HR), 4.7; 95% confidence interval (CI), 2.8-7.9; P < 0.001 and those 65-75 years (HR, 2.8; 95% CI, 1.7-4.8; P < 0.001) were at greater risk of death. Increased age was associated with higher total, cardiac, and non-cardiac mortality (all P ≤ 0.001).
Conclusion
Age at ICD implantation is strongly and independently associated with mortality. Age should be considered among potential co-morbidities in anticipating survival of the elderly patient prior to ICD implantation.
Development of successful neutralizing antibodies is dependent upon broad epitope coverage to increase the likelihood of achieving therapeutic function. Recent advances in synthetic biology have ...allowed us to conduct an epitope binning study on a large panel of antibodies identified to bind to Ebola virus glycoprotein with only published sequences.
A rapid, first-pass epitope binning experiment revealed seven distinct epitope families that overlapped with known structural epitopes from the literature. A focused set of antibodies was selected from representative clones per bin to guide a second-pass binning that revealed previously unassigned epitopes, confirmed epitopes known to be associated with neutralizing antibodies, and demonstrated asymmetric blocking of EBOV GP from allosteric effectors reported from literature.
Critically, this workflow allows us to probe the epitope landscape of EBOV GP without any prior structural knowledge of the antigen or structural benchmark clones. Incorporating epitope binning on hundreds of antibodies during early stage antibody characterization ensures access to a library's full epitope coverage, aids in the identification of high quality reagents within the library that recapitulate this diversity for use in other studies, and ultimately enables the rational development of therapeutic cocktails that take advantage of multiple mechanisms of action such as cooperative synergistic effects to enhance neutralization function and minimize the risk of mutagenic escape. The use of high-throughput epitope binning during new outbreaks such as the current COVID-19 pandemic is particularly useful in accelerating timelines due to the large amount of information gained in a single experiment.
We report electronic transport measurements of single-molecule transistor devices incorporating bipyridyl-dinitro oligophenylene-ethynylene dithiol (BPDN-DT), a molecule known to exhibit conductance ...switching in other measurement configurations. We observe hysteretic conductance switching in 8% of devices with measurable currents, and find that dependence of the switching properties on gate voltage is rare when compared to other single-molecule transistor devices. This suggests that polaron formation is unlikely to be responsible for switching in these devices. We discuss this and alternative switching mechanisms.
Phys. Rev. Lett. 95, 256803 (2005) We report Kondo resonances in the conduction of single-molecule transistors
based on transition metal coordination complexes. We find Kondo temperatures in
excess ...of 50 K, comparable to those in purely metallic systems. The observed
gate dependence of the Kondo temperature is inconsistent with observations in
semiconductor quantum dots and a simple single-dot-level model. We discuss
possible explanations of this effect, in light of electronic structure
calculations.
In single-molecule transistors, we observe inelastic cotunneling features that correspond energetically to vibrational excitations of the molecule, as determined by Raman and infrared spectroscopy. ...This is a form of inelastic electron tunneling spectroscopy of single molecules, with the transistor geometry allowing in-situ tuning of the electronic states via a gate electrode. The vibrational features shift and change shape as the electronic levels are tuned near resonance, indicating significant modification of the vibrational states. When the molecule contains an unpaired electron, we also observe vibrational satellite features around the Kondo resonance.
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