Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

An evaluation of a self-calibrating infrared radiometer for measuring sea-surface temperature

An inversion method is presented that determines mesoscale sea surface currents using satellite altimeter data. The method directly uses geostrophic cross-track velocity components, expands the unknown velocity components with spline functions, and includes weighted constraints for divergence and kinetic energy. The success of this method is measured by the misfit between input and output velocities and depends on the weights of the constraints, the irregular space-time data distribution of the altimeter data, and the nonstationary character of mesoscale oceanic features. Negative effects of the irregular spatial distribution of the altimeter data are overcome by partitioning the larger regions of interest into smaller subareas to make independent inversions. The relatively weak effects of subtrack temporal separations in the presence of slowing evolving fields are addressed by temporal interpolations, which provide the more important benefit of filling in missing data.\ud \ud The procedure is evaluated for the Geosat, Topex-Poseidon, and ERS-1 altimeter sampling geometries determining their “oceanic” resolutions by using simulated stationary and nonstationary velocity fields. As expected for stationary fields the best spatial resolutions correspond to altimeters with the densest data distributions, that is, the longest repeat periods. The smallest scale resolved is approximately 100 km for Geosat (17-day repeat) and ERS-1 (35-day repeat) and is approximately 150 km for Topex-Poseidon (10-day repeat). Tests with simulated nonstationary “eddies” show that the propagation at typical Rossby wave phase speeds (<0.04 m s⁻¹) degrades the solutions only slightly if scales are greater than approximately 200 km for Topex-Poseidon and 150 km for Geosat and ERS-1 17-day periods, even without temporal interpolation. Combination of Topex-Poseidon and ERS-1 data over 17 days provides the best resolution, allowing eddy spatial scales of 100 km to be resolved at the same propagation speeds.\ud \ud Applications of the inverse method to data from the Geosat and Topex-Poseidon missions indicate that application of the method results in spatial resolution similar to the synthetic experiments. Qualitative comparisons to acoustic Doppler current profilers, satellite surface temperature, and dynamic height fields show that application of the method to Geosat data resolves the larger mesoscale structures of a meandering jet in the California Current. Use of temporal interpolation provides little benefit, due to the slow propagation times of the 100–200-km scale features resolved by the method, but it does help fill in missing data for Geosat. Application of the method to Topex-Poseidon data is not as successful but still resolves the largest-scale structure. The results of application to the synthetic data suggest that it is possible to achieve greater resolution by combining two or more satellite altimeter datasets such as Topex-Poseidon and ERS-1