Photoacoustic‐Guided Surgery with Indocyanine Green‐Coated Superparamagnetic Iron Oxide Nanoparticle Clusters

A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real‐time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles—with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20–30% of the total weight (ICG + SPIO). The ICG–SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG–SPIO clusters, animals undergoing PA‐guided surgery demonstrate increased progression‐free survival compared to animals undergoing microscopic surgery.     

A Data‐driven Segmentation for the Shoulder Complex

The human shoulder complex is perhaps the most complicated joint in the human body being comprised of a set of three bones, muscles, tendons, and ligaments. Despite this anatomical complexity, computer graphics models for motion capture most often represent this joint as a simple ball and socket. In this paper, we present a method to determine a shoulder skeletal model that, when combined with standard skinning algorithms, generates a more visually pleasing animation that is a closer approximation to the actual skin deformations of the human body. We use a data‐driven approach and collect ground truth skin deformation data with an optical motion capture system with a large number of markers (200 markers on the shoulder complex alone). We cluster these markers during movement sequences and discover that adding one extra joint around the shoulder improves the resulting animation qualitatively and quantitatively yielding a marker set of approximately 70 markers for the complete skeleton. We demonstrate the effectiveness of our skeletal model by comparing it with ground truth data as well as with recorded video. We show its practicality by integrating it with the conventional rendering/animation pipeline.     

Cognitive-bias toward gaming-related words and disinhibition in World of Warcraft gamers

This study investigated cognitive biases toward gaming-related words and differences in cognitive performance among twelve World of Warcraft players (WWP) and thirty non-players (NP). We measured response to valenced common English and WoW jargon words using a computer-based go/no-go task. Sometimes positive valence words were the targets for the ‘go’ response, with negative-valence words as the distracters, sometimes the reverse. Target discrimination (d′) and response disinhibition (C) were calculated using a signal detection analysis. Based on questionnaire responses, there were no differences between groups in depression, anxiety, smoking or drinking, but WWP reported significantly more screen and gaming time (17.31 h/week versus 4.12 among NP). WWP had faster reaction time (RT) and better discrimination of targets from distracters (high d′) but also showed higher disinhibition (low C). WWP also showed cognitive-bias toward game-related words in the form of higher d′ for WoW jargon than common English and more disinhibition to positive-valence WoW jargon. Similar to past studies which have found alcoholics to have cognitive biases toward alcohol-related words, WWP who play frequently showed cognitive biases toward words related to the World of Warcraft game.     

Exploring alternatives for transition verification

When an implementation under test (IUT) is state-based, and its expected abstract behavior is given in terms of a finite state machine (FSM), a checking sequence generated from a specification FSM and applied to an IUT for testing can provide us with high-level confidence in the correct functional behavior of our implementation. One of the issues here is to generate efficient checking sequences in terms of their lengths. As a major characteristics, a checking sequence must contain all β-sequences for transition verification. In this paper, we discuss the possibility of reducing the lengths of checking sequences by making use of the invertible transitions in the specification FSM to increase the choice of β-sequences to be considered for checking sequence generation. We present a sufficient condition for adopting alternative β-sequences and illustrate typical ways of incorporating these alternative β-sequences into existing methods for checking sequence generation to reduce the lengths. Compared to the direct use of three existing methods, our experiments show that most of the time the saving gained by adopting alternative β-sequences falls in the range of 10–40%.     

Benchmarking stereo-derived DSMs to lidar by land cover and slope for resource development in northern Ontario,Canada

Topographic and elevation data are essential in the development of supporting infrastructure around mining sites. The de facto standard for acquiring elevation data is through light detection and ranging (lidar). The high labour and monetary cost of acquiring lidar has fostered more cost-effective approaches for creating elevation models that use stereo photogrammetry. To assess the accuracy of stereo-photogrammetry-derived elevation models and their potential application, we benchmark satellite (Worldview-2) and aircraft (South Central Ontario Orthoimagery Project; SCOOP) stereo-derived digital surface models (DSMs) against a lidar-derived DSM. Our results show that both stereo-derived DSMs have strong monotonic correlations with lidar across a range of land-cover types and slopes. The overall vertical accuracy of Worldview-2 and SCOOP DSMs are similar and do not meet the United States National Digital Elevation Program (NDEP) standards. However, accuracy assessment across land-cover types and slope categories show that specific land cover types (i.e. grass, row crops/pasture, sparse vegetation and marsh) on gently sloping terrain compare well to lidar data and meet NDEP accuracy standards. We situate the presented research in the context of northern resource development and discuss opportunities to improve the vertical accuracy of stereo-derived DSMs, for example, through unmanned aerial systems.     

Modeling the glucose regulatory system in extreme preterm infants

Background

Premature infants represent a significant proportion of the neonatal intensive care population. Blood glucose homeostasis in this group is often disturbed by immaturity of endogenous regulatory systems and the stress of their condition. Hypo- and hyperglycemia are frequently reported in very low birth weight infants, and more mature infants often experience low levels of glycemia. A model capturing the unique fundamental dynamics of the neonatal glucose regulatory system could be used to develop better blood glucose control methods.

Methods

A metabolic system model is adapted from adult critical care to the unique physiological case of the neonate. Integral-based fitting methods were used to identify time-varying insulin sensitivity and non-insulin mediated glucose uptake profiles. The clinically important predictive ability of the model was assessed by assuming insulin sensitivity was constant over prediction intervals of 1, 2 and 4 h forward and comparing model-simulated versus actual clinical glucose values for all recorded interventions. The clinical data included 1091 glucose measurements over 3567 total patient hours, along with all associated insulin and nutritional infusion data, for N = 25 total cases. Ethics approval was obtained from the Upper South A Regional Ethics Committee for this study.

Results

The identified model had a median absolute percentage error of 2.4% [IQR: 0.9-4.8%] between model-fitted and clinical glucose values. Median absolute prediction errors at 1-, 2- and 4-h intervals were 5.2% [IQR: 2.5-10.3%], 9.4% [IQR: 4.5-18.4%] and 13.6% [IQR: 6.3-27.6%] respectively.

Conclusions

The model accurately captures and predicts the fundamental dynamic behaviors of the neonatal metabolism well enough for effective clinical decision support in glycemic control. The adaptation from adult to a neonatal case is based on the data from the literature. Low prediction errors and very low fitting errors indicate that the fundamental dynamics of glucose metabolism in both premature neonates and critical care adults can be described by similar mathematical models.     

The impact of cultural differences in offshore outsourcing—Case study results from German–Indian application development projects

Offshore outsourcing to vendors in foreign countries causes unique challenges which need to be understood and managed effectively. This paper explores cultural differences in IS offshoring arrangements involving German client organizations that outsource application development activities to Indian vendors. For this purpose, a research framework is developed based on both theoretical considerations and specific empirical observations from multiple case studies. The goal is to (1) explore the nature of cultural differences in offshore outsourcing arrangements in depth and to (2) analyze the relationship between those cultural differences and offshore outsourcing success. Based on the case findings, implications and practices for the management of offshore development projects are outlined. The results indicate that cultural differences in terms of power distance, IS designer values, and an active versus passive working attitude critically affect several dimensions of relationship quality, thereby influencing offshore outsourcing success. A clear definition of roles and mechanisms, strong leadership, and an active management of culture by adapting to either the client’s or the vendor’s national culture appeared to be effective ways to manage cultural differences.

Integral-based filtering of continuous glucose sensor measurements for glycaemic control in critical care

Hyperglycaemia is prevalent in critical illness and increases the risk of further complications and mortality, while tight control can reduce mortality up to 43%. Adaptive control methods are capable of highly accurate, targeted blood glucose regulation using limited numbers of manual measurements due to patient discomfort and labour intensity. Therefore, the option to obtain greater data density using emerging continuous glucose sensing devices is attractive. However, the few such systems currently available can have errors in excess of 20-30%. In contrast, typical bedside testing kits have errors of approximately 7-10%. Despite greater measurement frequency larger errors significantly impact the resulting glucose and patient specific parameter estimates, and thus the control actions determined creating an important safety and performance issue. This paper models the impact of the continuous glucose monitoring system (CGMS, Medtronic, Northridge, CA) on model-based parameter identification and glucose prediction. An integral-based fitting and filtering method is developed to reduce the effect of these errors. A noise model is developed based on CGMS data reported in the literature, and is slightly conservative with a mean Clarke Error Grid (CEG) correlation of R=0.81 (range: 0.68-0.88) as compared to a reported value of R=0.82 in a critical care study. Using 17 virtual patient profiles developed from retrospective clinical data, this noise model was used to test the methods developed. Monte-Carlo simulation for each patient resulted in an average absolute 1-h glucose prediction error of 6.20% (range: 4.97-8.06%) with an average standard deviation per patient of 5.22% (range: 3.26-8.55%). Note that all the methods and results are generalizable to similar applications outside of critical care, such as less acute wards and eventually ambulatory individuals. Clinically, the results show one possible computational method for managing the larger errors encountered in emerging continuous blood glucose sensors, thus enabling their more effective use in clinical glucose regulation studies.     

Sterol and steryl ester regulation of phospholipase A2 from the mosquito parasiteLagenidium giganteum

Lagenidium giganteum, a facultative parasite of mosquito larvae, cannot synthesize sterols, and requires an exogenous source of these lipids in order to enter its reproductive cycle. This parasite grows vegetatively in the absence of sterols, but requires cholesterol or structurally related compounds to produce motile zoospores, which are the only stage capable of infecting mosquitoes. Sterols structurally related to cholesterol and some steryl esters inhibited the activity ofL. giganteum phospholipase A₂ (PLA₂), an enzyme that hydrolyzes fatty acids from thesn-2 position of glycerophospholipids. Sterols that induce reproduction inhibitedL. giganteum PLA₂ activity, while sterols and steroids that do not support sporulation had minimal effect. Most steryl esters had no effect on enzyme activity, but cholesteryl arachidonate (CA) was a potent inhibitor of parasite PLA₂. Not all enzymes partly purified using a DEAE-Sephacel column were affected by these lipids, demonstrating selective inhibition of specific enzymes. Potency was enhanced by up to several orders of magnitude if epoxy fatty acids were esterified to the cholesterol nucleus. The steryl ester pool was dynamic during morphogenesis, and the fatty acid composition of the steryl esters did not mimic total cell or membrane (glycerophospholipid) fatty acid composition asL. giganteum proceeded through its growth cycle. Synthesis of CA and monoepoxy CA by the parasite was confirmed using electrospray mass spectrometry and collision-induced dissociation. Steryl derivatives selectively inhibited PLA₂ enzymes from bovine pancreas, snake venom, and human cytoplasmic 85-kDa PLA₂.