Ischemic Stroke as the Initial Manifestation of Neurosyphilis in a Young Adult Patient Positive for Human Immunodeficiency Virus

A 31-year-old man with pontine infarction was referred to our hospital for further evaluation and treatment. At admission, his neurological examination was unremarkable. No lymphadenopathy or skin lesions were found. The Treponema pallidum haemagglutination test, rapid plasma regain test and fluorescent treponemal antibody absorption test of immunoglobulin G were positive in both serum and cerebrospinal fluid (CSF). CSF analysis showed lymphocytic pleocytosis. The patient had male-to-male sexual contact and was found to be HIV positive. Physicians should be aware that acute ischaemic stroke may be the first manifestation of neurosyphilis in a young adult, especially with HIV infection.

Neural representations of social and non-social uncertainty in human decision making

The social landscape is filled with an intricate web of species-specific desired objects and course of actions. Humans are highly social animals and, as they navigate this landscape, they need to produce adapted decision-making behaviour. Traditionally social and non-social neural mechanisms affecting choice have been investigated using different approaches. Recently, in an effort to unite these findings, two main theories have been proposed to explain how the brain might encode social and non-social motivational decision-making: the extended common currency and the social valuation specific schema (Ruff & Fehr 2014). One way to test these theories is to directly compare neural activity related to social and non-social decision outcomes within the same experimental setting. Here we address this issue by focusing on the neural substrates of social and non-social forms of uncertainty. Using functional magnetic resonance imaging (fMRI) we directly compared the neural representations of reward and risk prediction and errors (RePE and RiPE) in social and non- social situations using gambling games. We used a trust betting game to vary uncertainty along a social dimension (trustworthiness), and a card game (Preuschoff et al. 2006) to vary uncertainty along a non-social dimension (pure risk). The trust game was designed to maintain the same structure of the card game. In a first study, we exposed a divide between subcortical and cortical regions when comparing the way these regions process social and non-social forms of uncertainty during outcome anticipation. Activity in subcortical regions reflected social and non-social RePE, while activity in cortical regions correlated with social RePE and non-social RiPE. The second study focused on outcome delivery and integrated the concept of RiPE in non-social settings with that of fairness and monetary utility maximisation in social settings. In particular these results corroborate recent models of anterior insula function (Singer et al. 2009; Seth 2013), and expose a possible neural mechanism that weights fairness and uncertainty but not monetary utility. The third study focused on functionally defined regions of the early visual cortex (V1) showing how activity in these areas, traditionally considered only visual, might reflect motivational prediction errors in addition to known perceptual prediction mechanisms (den Ouden et al 2012). On the whole, while our results do not support unilaterally one or the other theory modeling the underlying neural dynamics of social and non-social forms of decision making, they provide a working framework where both general mechanisms might coexist.

'Explicit Learning: an Effort towards Human Scheduling Algorithms'

Abstract Scheduling problems are generally NP-hard combinatorial problems, and a lot of research has been done to solve these problems heuristically. However, most of the previous approaches are problem-specific and research into the development of a general scheduling algorithm is still in its infancy. Mimicking the natural evolutionary process of the survival of the fittest, Genetic Algorithms (GAs) have attracted much attention in solving difficult scheduling problems in recent years. Some obstacles exist when using GAs: there is no canonical mechanism to deal with constraints, which are commonly met in most real-world scheduling problems, and small changes to a solution are difficult. To overcome both difficulties, indirect approaches have been presented (in [1] and [2]) for nurse scheduling and driver scheduling, where GAs are used by mapping the solution space, and separate decoding routines then build solutions to the original problem. In our previous indirect GAs, learning is implicit and is restricted to the efficient adjustment of weights for a set of rules that are used to construct schedules. The major limitation of those approaches is that they learn in a non-human way: like most existing construction algorithms, once the best weight combination is found, the rules used in the construction process are fixed at each iteration. However, normally a long sequence of moves is needed to construct a schedule and using fixed rules at each move is thus unreasonable and not coherent with human learning processes. When a human scheduler is working, he normally builds a schedule step by step following a set of rules. After much practice, the scheduler gradually masters the knowledge of which solution parts go well with others. He can identify good parts and is aware of the solution quality even if the scheduling process is not completed yet, thus having the ability to finish a schedule by using flexible, rather than fixed, rules. In this research we intend to design more human-like scheduling algorithms, by using ideas derived from Bayesian Optimization Algorithms (BOA) and Learning Classifier Systems (LCS) to implement explicit learning from past solutions. BOA can be applied to learn to identify good partial solutions and to complete them by building a Bayesian network of the joint distribution of solutions [3]. A Bayesian network is a directed acyclic graph with each node corresponding to one variable, and each variable corresponding to individual rule by which a schedule will be constructed step by step. The conditional probabilities are computed according to an initial set of promising solutions. Subsequently, each new instance for each node is generated by using the corresponding conditional probabilities, until values for all nodes have been generated. Another set of rule strings will be generated in this way, some of which will replace previous strings based on fitness selection. If stopping conditions are not met, the Bayesian network is updated again using the current set of good rule strings. The algorithm thereby tries to explicitly identify and mix promising building blocks. It should be noted that for most scheduling problems the structure of the network model is known and all the variables are fully observed. In this case, the goal of learning is to find the rule values that maximize the likelihood of the training data. Thus learning can amount to 'counting' in the case of multinomial distributions. In the LCS approach, each rule has its strength showing its current usefulness in the system, and this strength is constantly assessed [4]. To implement sophisticated learning based on previous solutions, an improved LCS-based algorithm is designed, which consists of the following three steps. The initialization step is to assign each rule at each stage a constant initial strength. Then rules are selected by using the Roulette Wheel strategy. The next step is to reinforce the strengths of the rules used in the previous solution, keeping the strength of unused rules unchanged. The selection step is to select fitter rules for the next generation. It is envisaged that the LCS part of the algorithm will be used as a hill climber to the BOA algorithm. This is exciting and ambitious research, which might provide the stepping-stone for a new class of scheduling algorithms. Data sets from nurse scheduling and mall problems will be used as test-beds. It is envisaged that once the concept has been proven successful, it will be implemented into general scheduling algorithms. It is also hoped that this research will give some preliminary answers about how to include human-like learning into scheduling algorithms and may therefore be of interest to researchers and practitioners in areas of scheduling and evolutionary computation. References 1. Aickelin, U. and Dowsland, K. (2003) 'Indirect Genetic Algorithm for a Nurse Scheduling Problem', Computer & Operational Research (in print). 2. Li, J. and Kwan, R.S.K. (2003), 'Fuzzy Genetic Algorithm for Driver Scheduling', European Journal of Operational Research 147(2): 334-344. 3. Pelikan, M., Goldberg, D. and Cantu-Paz, E. (1999) 'BOA: The Bayesian Optimization Algorithm', IlliGAL Report No 99003, University of Illinois. 4. Wilson, S. (1994) 'ZCS: A Zeroth-level Classifier System', Evolutionary Computation 2(1), pp 1-18.

MRI indices of functional recovery following intracerebral implantation of a human neural stem cell line in a pre-clinical model of ischaemic stroke

Stem cell therapy for ischaemic stroke is an emerging field in light of an increasing number of patients surviving with permanent disability. Several allogenic and autologous cells types are now in clinical trials with preliminary evidence of safety. Some clinical studies have reported functional improvements in some patients. After initial safety evaluation in a Phase 1 study, the conditionally immortalised human neural stem cell line CTX0E03 is currently in a Phase 2 clinical trial (PISCES-II). Previous pre-clinical studies conducted by ReNeuron Ltd, showed evidence of functional recovery in the Bilateral Asymmetry test up to 6 weeks following transplantation into rodent brain, 4 weeks after middle cerebral artery occlusion. Resting-state fMRI is increasingly used to investigate brain function in health and disease, and may also act as a predictor of recovery due to known network changes in the post-stroke recovery period. Resting-state methods have also been applied to non-human primates and rodents which have been found to have analogous resting-state networks to humans. The sensorimotor resting-state network of rodents is impaired following experimental focal ischaemia of the middle cerebral artery territory. However, the effects of stem cell implantation on brain functional networks has not previously been investigated. Prior studies assessed sensorimotor function following sub-cortical implantation of CTX0E03 cells in the rodent post-stroke brain but with no MRI assessments of functional improvements. This thesis presents research on the effect of sub-cortical implantation of CTX0E03 cells on the resting- state sensorimotor network and sensorimotor deficits in the rat following experimental stroke, using protocols based on previous work with this cell line. The work in this thesis identified functional tests of appropriate sensitivity for long-term dysfunction suitable for this laboratory, and investigated non-invasive monitoring of physiological variables required to optimize BOLD signal stability within a high-field MRI scanner. Following experimental stroke, rats demonstrated expected sensorimotor dysfunction and changes in the resting-state sensorimotor network. CTX0E03 cells did not improve post-stroke functional outcome (compared to previous studies) and with no changes in resting-state sensorimotor network activity. However, in control animals, we observed changes in functional networks due to the stereotaxic procedure. This illustrates the sensitivity of resting-state fMRI to stereotaxic procedures. We hypothesise that the damage caused by cell or vehicle implantation may have prevented functional and network recovery which has not been previously identified due to the application of different functional tests. The findings in this thesis represent one of few pre-clinical studies in resting-state fMRI network changes post-stroke and the only to date applying this technique to evaluate functional outcomes following a clinically applicable human neural stem cell treatment for ischaemic stroke. It was found that injury caused by stereotaxic injection should be taken into account when assessing the effectiveness of treatment.

Comparative assessment of seller’s staining test (SST) and direct fluorescent antibody test for rapid and accurate laboratory diagnosis of rabies.

Background: Rabies causes 55, 000 annual human deaths globally and about 10,000 people are exposed annually in Nigeria. Diagnosis of animal rabies in most African countries has been by direct microscopic examination. In Nigeria, the Seller’s stain test (SST) was employed until 2009. Before then, both SST and dFAT were used concurrently until the dFAT became the only standard method. Objective: This study was designed to assess the sensitivity and specificity of the SST in relation to the ‘gold standard’ dFAT in diagnosis of rabies in Nigeria. Methods: A total of 88 animal specimens submitted to the Rabies National Reference Laboratory, Nigeria were routinely tested for rabies by SST and dFAT. Results: Overall, 65.9% of the specimens were positive for rabies by SST, while 81.8% were positive by dFAT. The sensitivity of SST in relation to the gold standard dFAT was 81.0% (95% CIs; 69.7% - 88.6%), while the specificity was 100% (95% CIs; 76% - 100%). Conclusion: The relatively low sensitivity of the SST observed in this study calls for its replacement with the dFAT for accurate diagnosis of rabies and timely decisions on administration of PEP to prevent untimely deaths of exposed humans.

Evaluation of an in-house molecular HIV-1 test to assess mother-to-child HIV-1 transmission in Angola (the APEHC cohort)

Poster presented at the 17th Annual International Meeting of the Institute of Human Virology. Baltimore, 27-30 September 2015

Effect on the disability index of adult patients with benign paroxysmal positional vertigo using vestibular rehabilitation and human movement

Objective: determine the effect on the disability index of adult patients with benign paroxysmal positional vertigo (BPPV) using vestibular rehabilitation therapy (VRT) and human movement. Subjects: six subjects with an average age of 49.5 ± 14.22 years who have been diagnosed with benign paroxysmal positional vertigo by an otolaryngologist. Instruments: the Dizziness Handicap Inventory and a questionnaire to determine impact on the quality of life of patients with this pathology (Ceballos and Vargas, 2004). Procedure: subjects underwent vestibular therapy for four weeks together with habituation and balance exercises in a semi-supervised manner. Two measurements were performed, one before and one after the vestibular therapy and researchers determined if there was any improvement in the physical, functional, and emotional dimensions. Statistical analysis: descriptive statistics and Student’s t-test of repeated measures were applied to analyze results obtained. Results: significant statistical differences were found in the physical dimension between the pre-test (19.33 ± 4.67 points) and post-test (13 ± 7.24 points) (t = 2.65; p < 0.05).  In contrast, no significant statistical differences were found in the functional (t = 2.44; p>0.05), emotional (t = 2.37; p>0.05) or general dimensions (t = 2.55; p>0.05). Conclusion: vestibular therapy with a semi-supervised human movement program improved the index of disability due to vertigo (physical dimension) in BPPV subjects.

UNDERSTANDING ESSAY RATING AS A SOCIALLY MEDIATED ACTIVITY: THE CASE OF A HIGH-STAKES ENGLISH TEST IN CHINA

Thesis (Ph.D, Education) -- Queen's University, 2016-09-22 22:05:24.246

Trace elements and electrolytes in human resting mixed saliva after exercise

Objectives—Exercise is known to cause changes in the concentration of salivary components such as amylase, Na, and Cl. The aim of this investigation was to evaluate the eVect of physical exercise on the levels of trace elements and electrolytes in whole (mixed) saliva. Methods—Forty subjects performed a maximal exercise test on a cycle ergometer. Samples of saliva were obtained before and immediately after the exercise test. Sample concentrations of Fe, Mg, Sc, Cr, Mn, Co, Cu, Zn, Se, Sr, Ag, Sb, Cs, and Hg were determined by inductively coupled plasma mass spectrometry and concentrations of Ca and Na by atomic absorption spectrometry. Results—After exercise, Mg and Na levels showed a significant increase (p<0.05) while Mn levels fell (p<0.05). Zn/Cu molar ratios were unaVected by exercise. Conclusions—Intense physical exercise induced changes in the concentrations of only three (Na, Mg, and Mn) of the 16 elements analysed in the saliva samples. Further research is needed to assess the clinical implications of these findings.

Review of Program Integrity Operations At Six Managed Care Organizations Delivering Medicaid Services under a Contract with the South Carolina Department of Health & Human Services

The State contracted with six managed care organizations to deliver Medicaid managed care at an annual cost of $2.7 billion, representing 10% of the State’s annual budget, to 750,000 Medicaid beneficiaries in South Carolina. This review’s scope and objectives were: Test the six MCOs’ compliance and effective execution of the SCDHHS’s managed care contract “Section 11 - Program Integrity” focusing on the operational components of pre-payment review and post-payment review. Identify opportunities to improve SCDHHS’s biennial managed care contract, contract monitoring, and MCO compliance and effective execution of the contract.

Role of the human chymase (CMA1) in the conversion of big-endothelin-1 to endothelin-1 (1-31)

Abstract : The chymase-dependant pathway responsible for converting Big ET-1 to ET-1 was established in vitro. It has only been recently, in 2009, that our group demonstrated that the conversion of Big ET-1 to ET-1 (1-31) can occur in vivo in mice (Simard et al., 2009), knowing that ET-1 (1-31) is converted to ET-1 via NEP in vivo (Fecteau et al., 2005). In addition, our laboratory demonstrated in 2013 that mMCP-4, the murine analogue of human chymase, produces ET-1 (1-31) from the Big ET-1 precursor (Houde et al. 2013). Thus far, in the literature, there are no specific characterizations of recombinant chymases (human or murine). In fact, the group of Murakami published in 1995 a study characterizing the CMA1 (human chymase) in a chymostatin-dependent fashion, using Angiotensin I as a substrate (Murakami et al., 1995). However, chymostatin is a non-specific inhibitor of chymase. It has been shown that chymostatin can inhibit elastase, an enzyme that can convert Angiotensin I to Angiotensin II (Becari et al., 2005). Based on these observations, the proposed hypothesis in the present study suggests that recombinant as well as extracted CMA1 from LUVA (human mast cell line), in addition to soluble fractions of human aortas, convert Big ET-1 into ET-1 (1-31 ) in a TY-51469 (a chymase-specific inhibitor) sensitive manner. In a second component, we studied the enzyme kinetics of CMA1 with regard to the Big ET-1 and Ang I substrate. The affinity of CMA1 against Big ET-1 was greater compared to Ang I (KM Big ET- 1: 12.55 μM and Ang I: 37.53 μM). However, CMA1 was more effective in cleaving Ang I compared to Big ET-1 (Kcat / KM Big ET-1: 6.57 x 10-5 μM-1.s-1 and Ang I: 1.8 x 10-4 ΜM-1.s- 1). In a third component involving in vivo experiments, the pressor effects of Big ET-1, ET-1 and Ang I were tested in conscious mMCP-4 KO mice compared to wild-type mice. The increase in mean arterial pressure after administration of Big ET-1 was greater in wild-type mice compared to mMCP- 4 KO mice. This effect was not observed after administration of ET-1 and / or Ang I.

Normative reference values for the 20-meter shuttlerun test in a population-based sample of schoolchildren in Bogota, Colombia: The FUPRECOL Study

Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio-metabolic risk.

Functional and neural mechanisms of human fear conditioning: studies in healthy and brain-damaged individuals

Fear conditioning represents the learning process by which a stimulus, after repeated pairing with an aversive event, comes to evoke fear and becomes intrinsically aversive. This learning is essential to organisms throughout the animal kingdom and represents one the most successful laboratory paradigm to reveal the psychological processes that govern the expression of emotional memory and explore its neurobiological underpinnings. Although a large amount of research has been conducted on the behavioural or neural correlates of fear conditioning, some key questions remain unanswered. Accordingly, this thesis aims to respond to some unsolved theoretic and methodological issues, thus furthering our understanding of the neurofunctional basis of human fear conditioning both in healthy and brain-damaged individuals. Specifically, in this thesis, behavioural, psychophysiological, lesion and non-invasive brain stimulation studies were reported. Study 1 examined the influence of normal aging on context-dependent recall of extinction of fear conditioned stimulus. Study 2 aimed to determine the causal role of the ventromedial PFC (vmPFC) in the acquisition of fear conditioning by systematically test the effect of bilateral vmPFC brain-lesion. Study 3 aimed to interfere with the reconsolidation process of fear memory by the means of non-invasive brain stimulation (i.e. TMS) disrupting PFC neural activity. Finally, Study 4 aimed to investigate whether the parasympathetic – vagal – modulation of heart rate might reflect the anticipation of fearful, as compared to neutral, events during classical fear conditioning paradigm. Evidence reported in this PhD thesis might therefore provide key insights and deeper understanding of critical issues concerning the neurofunctional mechanisms underlying the acquisition, the extinction and the reconsolidation of fear memories in humans.

Safe and Collaborative Navigation & Interaction With Mobile Manipulators in Domestic Appliance Test Labs

Safe collaboration between a robot and human operator forms a critical requirement for deploying a robotic system into a manufacturing and testing environment. In this dissertation, the safety requirement for is developed and implemented for the navigation system of the mobile manipulators. A methodology for human-robot co-existence through a 3d scene analysis is also investigated. The proposed approach exploits the advance in computing capability by relying on graphic processing units (GPU’s) for volumetric predictive human-robot contact checking. Apart from guaranteeing safety of operators, human-robot collaboration is also fundamental when cooperative activities are required, as in appliance test automation floor. To achieve this, a generalized hierarchical task controller scheme for collision avoidance is developed. This allows the robotic arm to safely approach and inspect the interior of the appliance without collision during the testing procedure. The unpredictable presence of the operators also forms dynamic obstacle that changes very fast, thereby requiring a quick reaction from the robot side. In this aspect, a GPU-accelarated distance field is computed to speed up reaction time to avoid collision between human operator and the robot. An automated appliance testing also involves robotized laundry loading and unloading during life cycle testing. This task involves Laundry detection, grasp pose estimation and manipulation in a container, inside the drum and during recovery grasping. A wrinkle and blob detection algorithms for grasp pose estimation are developed and grasp poses are calculated along the wrinkle and blobs to efficiently perform grasping task. By ranking the estimated laundry grasp poses according to a predefined cost function, the robotic arm attempt to grasp poses that are more comfortable from the robot kinematic side as well as collision free on the appliance side. This is achieved through appliance detection and full-model registration and collision free trajectory execution using online collision avoidance.

In vitro characterization of the three-dimensional strain pattern in human vertebrae affected by metastases

La colonna vertebrale è la principale sede di metastasi, le quali possono alterare la normale distribuzione dei tessuti ossei e ridurre la capacità della vertebra di sostenere carichi. L’instabilità spinale causata dalle metastasi, tuttavia, è di difficile determinazione. La caratterizzazione meccanica delle vertebre metastatiche permetterebbe di identificare e, di conseguenza trattare, quelle ad alto rischio di frattura. In questo studio, ho valutato il comportamento meccanico a rottura di vertebre umane affette da metastasi misurando in vitro il campo di deformazione. Undici provini, costituiti da due vertebre centrali, una metastatica e una sana, sono stati preparati e scansionati applicando carichi graduali di compressione in una micro-tomografia computerizzata (μCT). Le deformazioni principali sono state misurate attraverso un algoritmo globale di Digital Volume Correlation (DVC) e successivamente sono state analizzate. Lo studio ha rivelato che le vertebre con metastasi litiche raggiungono deformazioni maggiori delle vertebre sane. Invece, le metastasi miste non assicurano un comportamento univoco in quanto combinano gli effetti antagonisti delle lesioni litiche e blastiche. Dunque la valutazione è stata estesa a possibili correlazioni tra il campo di deformazione e la microstruttura della vertebra. L'analisi ha identificato le regioni in cui parte la frattura (a più alta deformazione), senza identificare, in termini microstrutturali, una zona preferenziale di rottura a priori. Infatti, alcune zone con un pattern trabecolare denso, presunte più rigide, hanno mostrato deformazioni maggiori di quelle dei tessuti sani, sottolineando l’importanza della valutazione della qualità del tessuto osseo. Questi risultati, generalizzati su un campione più ampio, potrebbero essere utilizzati per implementare nuovi criteri negli attuali sistemi di valutazione dell'instabilità spinale.