Building nonparametric nn-body force fields using Gaussian process regression

Constructing a classical potential suited to simulate a given atomic system is a remarkably difficult task. This chapter presents a framework under which this problem can be tackled, based on the Bayesian construction of nonparametric force fields of a given order using Gaussian process (GP) priors. The formalism of GP regression is first reviewed, particularly in relation to its application in learning local atomic energies and forces. For accurate regression it is fundamental to incorporate prior knowledge into the GP kernel function. To this end, this chapter details how properties of smoothness, invariance and interaction order of a force field can be encoded into corresponding kernel properties. A range of kernels is then proposed, possessing all the required properties and an adjustable parameter $n$ governing the interaction order modelled. The order $n$ best suited to describe a given system can be found automatically within the Bayesian framework by maximisation of the marginal likelihood. The procedure is first tested on a toy model of known interaction and later applied to two real materials described at the DFT level of accuracy. The models automatically selected for the two materials were found to be in agreement with physical intuition. More in general, it was found that lower order (simpler) models should be chosen when the data are not sufficient to resolve more complex interactions. Low $n$ GPs can be further sped up by orders of magnitude by constructing the corresponding tabulated force field, here named "MFF".Comment: 31 pages, 11 figures, book chapte

Evaluation of multi-exponential curve fitting analysis of oxygen-quenched phosphorescence decay traces for recovering microvascular oxygen tension histograms

Although it is generally accepted that oxygen-quenched phosphorescence decay traces can be analyzed using the exponential series method (ESM), its application until now has been limited to a few (patho)physiological studies, probably because the reliability of the recovered oxygen tension (pO2) histograms has never been extensively evaluated and lacks documentation. The aim of this study was, therefore, to evaluate the use of the ESM to adequately determine pO2 histograms from phosphorescence decay traces. For this purpose we simulated decay traces corresponding to uni- and bimodal pO2 distributions and recovered the pO2 histograms at different signal-to-noise ratios (SNRs). Ultimately, we recovered microvascular pO2 histograms measured in the rat kidney in a model of endotoxemic shock and fluid resuscitation and showed that the mean microvascular oxygen tension, 〈pO2〉, decreased after induction of endotoxemia and that after 2 h of fluid resuscitation, 〈pO2〉 remained low, but the hypoxic peak that had arisen during endotoxemia was reduced. This finding illustrates the importance of recovering pO2 histograms under (patho)physiological conditions. In conclusion, this study has characterized how noise affects the recovery of pO2 histograms using the ESM and documented the reliability of the ESM for recovering both low- and high-pO2 distributions for SNRs typically found in experiments. This study might therefore serve as a frame of reference for investigations focused on oxygen (re)distribution during health and disease and encourage researchers to (re-)analyze data obtained in (earlier) studies possibly revealing new insights into complex disease states and treatment strategies

Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Quantitative assessment of renal perfusion and oxygenation by invasive probes: basic concepts

Renal tissue hypoperfusion and hypoxia are early key elements in the pathophysiology of acute kidney injury of various origins, and may also promote progression from acute injury to chronic kidney disease. Here we describe basic principles of methodology to quantify renal hemodynamics and tissue oxygenation by means of invasive probes in experimental animals. Advantages and disadvantages of the various methods are discussed in the context of the heterogeneity of renal tissue perfusion and oxygenation.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by a separate chapter describing the experimental procedure and data analysis

EYE DISEASE IN NEWLY-DIAGNOSED LEPROSY PATIENTS IN EASTERN NEPAL

To determine the magnitude of eye lesions in newly diagnosed leprosy patients we examined their eyes. The Eastern Leprosy Control Project was supported by The Netherlands Leprosy Relief Association; we used the regional clinic in Biratnagar and 5 mobile clinics in surrounding districts as our survey area. All patients who presented at the clinics over 10 weeks, diagnosed as having untreated leprosy were included. Of the 260 examined patients 97 (37.3%, 95% confidence interval 28.3-40.3%) had an eye lesion; 12/260 patients (4.6%, 95% confidence interval 2.0-7.2%) had sight-threatening lesions (lagophthalmos, iris involvement, corneal anaesthesia), directly related to leprosy; 46 (17.7%) patients were diagnosed as having some degree of cataract; 2 patients were aphakic; 3 patients (1.2%) were blind according to the WHO definition. In this series of new and untreated leprosy patients many eye lesions found are not relevant or leprosy related. There were 9 new patients with lagophthalmos, some too longstanding to treat with steroids. We found 3 patients with iris involvement. The figures we found for eye lesions, sight-threatening lesions and blindness are low when compared to other studies. The number of patients with any grade of cataract is high. The average total of leprosy patients who were blind can be compared with the average total who are blind in the general population

DISABILITIES OF HANDS, FEET AND EYES IN NEWLY-DIAGNOSED LEPROSY PATIENTS IN EASTERN NEPAL

The objective of the study was to determine the magnitude of hand/feet/eye disabilities in newly diagnosed leprosy patients by examining all newly diagnosed leprosy patients who presented at the Eastern Leprosy Control Project (supported by The Netherlands Leprosy Relief Association), made up of a regional clinic in Biratnagar and 5 mobile clinics in surrounding districts. The study comprised of all new and previously untreated patients who presented at the clinics over a 10-week period who were diagnosed as leprosy sufferers. Of the 260 leprosy patients examined 12 (4.6%) had sight-threatening lesions (lagophthalmos, iris involvement, corneal anaesthesia); 3 patients were blind due to cataract; 96/260 patients (37.0%, 95% confidence interval 35.0-43.0%) had 1 or more disabilities of their hands and/or feet. The most frequently found disabilities were sensory loss of the hands and feet, claw hand and plantar ulcers. According to the WHO disability grading 60% had no disabilities, 19% had grade 1 and 21% had grade 2 disability. Disability assessment is very important not only to evaluate the effectiveness of the control programme but also for the patient, whose most important worry is the stigmatizing deformities leprosy patients suffer. The earlier detection of sensory loss might reduce these secondary deformities