A hybrid Constraint Programming/Mixed Integer Programming framework for the preventive signaling maintenance crew scheduling problem

This research has been carried out as part of the PhD research project funded by Technical University of Denmark and Banedanmark company which is responsible for the operation and maintenance of the Danish railway network. This work has been partially funded by the DAASE project, EPSRC programme grant EP/J017515/1

Serum-neuroproteins, near-infrared spectroscopy, and cognitive outcome after beach-chair shoulder surgery: observational cohort study analyses

BACKGROUND: Cerebral hypoxia may occur during surgery but currently used cerebral oxygenation saturation (rSO2) monitors remain controversial with respect to improving clinical outcome. Novel neuroprotein biomarkers are potentially released into systemic circulation and combined with near-infrared spectroscopy (NIRS) could clarify the presence of per-operative cerebral hypoxia. We investigated changes to serum-neuroprotein concentrations postsurgically, paired with NIRS and cognitive outcome, in patients operated in the beach chair position (BCP). METHODS: A prospective cohort in 28 shoulder surgery patients placed in the BCP. Blood samples were collected before induction of anaesthesia, and 2 hours and 3-5 days postoperatively. We analysed blood-levels of biomarkers including tau and neurofilament light (NFL). We post hoc assessed the cross-wise relationship between biomarker levels and postsurgical changes in cognitive function and intraoperatively monitored rSO2 from NIRS. RESULTS: Serum-NFL decreased from 24.2 pg/mL to 21.5 (P=0.02) 2 hours postoperatively, then increased to 27.7 pg/mL on day 3-5 (P=0.03). Conversely, s-tau increased from 0.77 pg/mL to 0.98 (2 h), then decreased to 0.81 on day 3-5 (P=0.08). In 14/28 patients, episodic rSO2 below 55% occurred, and the duration <55% was correlated to change in s-tau (P<0.05). The cognitive function z-score at 1 week and 3 mo. correlated to the change in tau (P=0.01), but not to NFL. CONCLUSION: Some biomarkers were significantly changed with surgery in the beach chair position. The change was at some points associated to postoperative cognitive decline, and to intraoperative low rSO2. (237)

Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery

OBJECTIVES: To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery. DESIGN: Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial. SETTING: Single-center study from a primary heart center in Denmark. PARTICIPANTS: Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement. INTERVENTIONS: Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD. MEASUREMENTS AND MAIN RESULTS: A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability. CONCLUSIONS: Postoperative serum levels of tau and GFAP were elevated significantly in patients with POCD who underwent cardiac surgery at discharge; however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge

System Theoretic Process Analysis: a literature survey on the approaches used for improving the safety in complex systems

Computer systems are becoming increasingly complex, specially interactive software systems, namely software user interfaces. The scientic community relies on dierent methods to assess their safety. This article provides an updated literature survey on hazard analysis approaches used to improve the safety of complex systems. To support the survey, we conceptualise complex systems, highlighting the challenge in terms of assessing their safety. We provide a brief overview on the approaches historically available to tackle issues in those systems, along with their most common methods. Finally, the article focuses in one method of a non-traditional approach, which is described in more details, along with some of its extensions, which seeks to improve the hazard analysis in complex systems

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

Nitrogen transfer from forage legumes to nine neighbouring plants in a multi-species grassland

Legumes play a crucial role in nitrogen supply to grass-legume mixtures for ruminant fodder. To quantify N transfer from legumes to neighbouring plants in multi-species grasslands we established a grass-legume-herb mixture on a loamy-sandy site in Denmark. White clover (Trifolium repens L.), red clover (Trifolium pratense L.) and lucerne (Medicago sativa L.) were leaf-labelled with 15N enriched urea during one growing season. N transfer to grasses (Lolium perenne L. and xfestulolium), white clover, red clover, lucerne, birdsfoot trefoil (Lotus corniculatus L.), chicory (Cichorium intybus L.), plantain (Plantago lanceolata L.), salad burnet (Sanguisorba minor L.)and caraway (Carum carvi L.) was assessed. Neighbouring plants contained greater amounts of N derived from white clover (4.8 gm-2) compared with red clover (2.2 gm-2) and lucerne (1.1 gm-2). Grasses having fibrous roots received greater amounts of N from legumes than dicotyledonous plants which generally have taproots. Slurry application mainly increased N transfer from legumes to grasses. During the growing season the three legumes transferred approximately 40 kg N ha-1 to neighbouring plants. Below-ground N transfer from legumes to neighbouring plants differed among nitrogen donors and nitrogen receivers and may depend on root characteristics and regrowth strategies of plant species in the multi-species grassland

Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery

BACKGROUND: Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function. METHODS: In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1–2 weeks before surgery, at discharge from the hospital (2–5 days after surgery), and at 3 months after surgery. RESULTS: CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42. CONCLUSIONS: The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction

ABCD Neurocognitive Prediction Challenge 2019: Predicting individual fluid intelligence scores from structural MRI using probabilistic segmentation and kernel ridge regression

We applied several regression and deep learning methods to predict fluid intelligence scores from T1-weighted MRI scans as part of the ABCD Neurocognitive Prediction Challenge (ABCD-NP-Challenge) 2019. We used voxel intensities and probabilistic tissue-type labels derived from these as features to train the models. The best predictive performance (lowest mean-squared error) came from Kernel Ridge Regression (KRR; $\lambda=10$), which produced a mean-squared error of 69.7204 on the validation set and 92.1298 on the test set. This placed our group in the fifth position on the validation leader board and first place on the final (test) leader board.Comment: Winning entry in the ABCD Neurocognitive Prediction Challenge at MICCAI 2019. 7 pages plus references, 3 figures, 1 tabl