DEVELOPMENT OF A HUMANOID ROBOT ARM FOR USE IN URBAN ENVIRONMENTS

The Bucknell Humanoid Robot Arm project was developed in order toprovide a lightweight robotic arm for the IHMC / Bucknell University bipedal robot that will provide a means of manipulation and facilitate operations in urban environments. The resulting fabricated arm described in this thesis weighs only 13 pounds, and is capable of holding 11 pounds fully outstretched, lifting objects such as tools, and it can open doors. It is also capable of being easily integrated with the IHMC / Bucknell University biped. This thesis provides an introduction to robots themselves, discusses the goals of the Bucknell Humanoid Robot Arm project, provides a background on some of the existing robots, and shows how the Bucknell Humanoid Robot Arm fits in with the studies that have been completed. After reading these studies, important items such as design trees and operational scenarios were completed. The completion of these items led to measurable specifications and later the design requirements and specifications. A significant contribution of this thesis to the robotics discipline involves the design of the actuator itself. The arm uses of individual, lightweight, compactly designed actuators to achieve desired capabilities and performance requirements. Many iterations were completed to get to the final design of each actuator. After completing the actuators, the design of the intermediate links and brackets was finalized. Completion of the design led to the development of a complex controls system which used a combination of Clanguage and Java.

Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes

During sepsis, liver dysfunction is common, and failure of mitochondria to effectively couple oxygen consumption with energy production has been described. In addition to sepsis, pharmacological agents used to treat septic patients may contribute to mitochondrial dysfunction. This study addressed the hypothesis that remifentanil interacts with hepatic mitochondrial oxygen consumption. The human hepatoma cell line HepG2 and their isolated mitochondria were exposed to remifentanil, with or without further exposure to tumor necrosis factor-α (TNF-α). Mitochondrial oxygen consumption was measured by high-resolution respirometry, Caspase-3 protein levels by Western blotting, and cytokine levels by ELISA. Inhibitory κBα (IκBα) phosphorylation, measurement of the cellular ATP content and mitochondrial membrane potential in intact cells were analysed using commercial ELISA kits. Maximal cellular respiration increased after one hour of incubation with remifentanil, and phosphorylation of IκBα occurred, denoting stimulation of nuclear factor κB (NF-κB). The effect on cellular respiration was not present at 2, 4, 8 or 16 hours of incubation. Remifentanil increased the isolated mitochondrial respiratory control ratio of complex-I-dependent respiration without interfering with maximal respiration. Preincubation with the opioid receptor antagonist naloxone prevented a remifentanil-induced increase in cellular respiration. Remifentanil at 10× higher concentrations than therapeutic reduced mitochondrial membrane potential and ATP content without uncoupling oxygen consumption and basal respiration levels. TNF-α exposure reduced respiration of complex-I, -II and -IV, an effect which was prevented by prior remifentanil incubation. Furthermore, prior remifentanil incubation prevented TNF-α-induced IL-6 release of HepG2 cells, and attenuated fragmentation of pro-caspase-3 into cleaved active caspase 3 (an early marker of apoptosis). Our data suggest that remifentanil increases cellular respiration of human hepatocytes and prevents TNF-α-induced mitochondrial dysfunction. The results were not explained by uncoupling of mitochondrial respiration.

Improved effectiveness of partner notification for patients with sexually transmitted infections: systematic review

OBJECTIVE: To examine the effectiveness of methods to improve partner notification by patient referral (index patient has responsibility for informing sex partners of their exposure to a sexually transmitted infection). DESIGN: Systematic review of randomised trials of any intervention to supplement simple patient referral. DATA SOURCES: Seven electronic databases searched (January 1990 to December 2005) without language restriction, and reference lists of retrieved articles. REVIEW METHODS: Selection of trials, data extraction, and quality assessment were done by two independent reviewers. The primary outcome was a reduction of incidence or prevalence of sexually transmitted infections in index patients. If this was not reported data were extracted according to a hierarchy of secondary outcomes: number of partners treated; number of partners tested or testing positive; and number of partners notified, located, or elicited. Random effects meta-analysis was carried out when appropriate. RESULTS: 14 trials were included with 12 389 women and men diagnosed as having gonorrhoea, chlamydia, non-gonococcal urethritis, trichomoniasis, or a sexually transmitted infection syndrome. All studies had methodological weaknesses that could have biased their results. Three strategies were used. Six trials examined patient delivered partner therapy. Meta-analysis of five of these showed a reduced risk of persistent or recurrent infection in patients with chlamydia or gonorrhoea (summary risk ratio 0.73, 95% confidence interval 0.57 to 0.93). Supplementing patient referral with information for partners was as effective as patient delivered partner therapy. Neither strategy was effective in women with trichomoniasis. Two trials found that providing index patients with chlamydia with sampling kits for their partners increased the number of partners who got treated. CONCLUSIONS: Involving index patients in shared responsibility for the management of sexual partners improves outcomes. Health professionals should consider the following strategies for the management of individual patients: patient delivered partner therapy, home sampling for partners, and providing additional information for partners.

Comparison of amplification methods for transcriptomic analyses of low abundance prokaryotic RNA sources

Microarrays have established as instrumental for bacterial detection, identification, and genotyping as well as for transcriptomic studies. For gene expression analyses using limited numbers of bacteria (derived from in vivo or ex vivo origin, for example), RNA amplification is often required prior to labeling and hybridization onto microarrays. Evaluation of the fidelity of the amplification methods is crucial for the robustness and reproducibility of microarray results. We report here the first utilization of random primers and the highly processive Phi29 phage polymerase to amplify material for transcription profiling analyses. We compared two commercial amplification methods (GenomiPhi and MessageAmp kits) with direct reverse-transcription as the reference method, focusing on the robustness of mRNA quantification using either microarrays or quantitative RT-PCR. Both amplification methods using either poly-A tailing followed by in vitro transcription, or direct strand displacement polymerase, showed appreciable linearity. Strand displacement technique was particularly affordable compared to in vitro transcription-based (IVT) amplification methods and consisted in a single tube reaction leading to high amplification yields. Real-time measurements using low-, medium-, and highly expressed genes revealed that this simple method provided linear amplification with equivalent results in terms of relative messenger abundance as those obtained by conventional direct reverse-transcription.

Calibration of a surgical microscope with automated zoom lenses using an active optical tracker

BACKGROUND: In this paper, we present a new method for the calibration of a microscope and its registration using an active optical tracker. METHODS: Practically, both operations are done simultaneously by moving an active optical marker within the field of view of the two devices. The IR LEDs composing the marker are first segmented from the microscope images. By knowing their corresponding three-dimensional (3D) position in the optical tracker reference system, it is possible to find the transformation matrix between the referential of the two devices. Registration and calibration parameters can be extracted directly from that transformation. In addition, since the zoom and focus can be modified by the surgeon during the operation, we propose a spline based method to update the camera model to the new setup. RESULTS: The proposed technique is currently being used in an augmented reality system for image-guided surgery in the fields of ear, nose and throat (ENT) and craniomaxillofacial surgeries. CONCLUSIONS: The results have proved to be accurate and the technique is a fast, dynamic and reliable way to calibrate and register the two devices in an OR environment.

GENERATING PLANS IN CONCURRENT, PROBABILISTIC, OVER-SUBSCRIBED DOMAINS

Planning in realistic domains typically involves reasoning under uncertainty, operating under time and resource constraints, and finding the optimal subset of goals to work on. Creating optimal plans that consider all of these features is a computationally complex, challenging problem. This dissertation develops an AO* search based planner named CPOAO* (Concurrent, Probabilistic, Over-subscription AO*) which incorporates durative actions, time and resource constraints, concurrent execution, over-subscribed goals, and probabilistic actions. To handle concurrent actions, action combinations rather than individual actions are taken as plan steps. Plan optimization is explored by adding two novel aspects to plans. First, parallel steps that serve the same goal are used to increase the plan’s probability of success. Traditionally, only parallel steps that serve different goals are used to reduce plan execution time. Second, actions that are executing but are no longer useful can be terminated to save resources and time. Conventional planners assume that all actions that were started will be carried out to completion. To reduce the size of the search space, several domain independent heuristic functions and pruning techniques were developed. The key ideas are to exploit dominance relations for candidate action sets and to develop relaxed planning graphs to estimate the expected rewards of states. This thesis contributes (1) an AO* based planner to generate parallel plans, (2) domain independent heuristics to increase planner efficiency, and (3) the ability to execute redundant actions and to terminate useless actions to increase plan efficiency.

Drug-specific in vitro release of IL-2, IL-5, IL-13 and IFN-gamma in patients with delayed-type drug hypersensitivity

BACKGROUND: The most prevalent drug hypersensitivity reactions are T-cell mediated. The only established in vitro test for detecting T-cell sensitization to drugs is the lymphocyte transformation test, which is of limited practicability. To find an alternative in vitro method to detect drug-sensitized T cells, we screened the in vitro secretion of 17 cytokines/chemokines by peripheral blood mononuclear cells (PBMC) of patients with well-documented drug allergies, in order to identify the most promising cytokines/chemokines for detection of T-cell sensitization to drugs. METHODS: Peripheral blood mononuclear cell of 10 patients, five allergic to beta-lactams and five to sulfanilamides, and of five healthy controls were incubated for 3 days with the drug antigen. Cytokine concentrations were measured in the supernatants using commercially available 17-plex bead-based immunoassay kits. RESULTS: Among the 17 cytokines/chemokines analysed, interleukin-2 (IL-2), IL-5, IL-13 and interferon-gamma (IFN-gamma) secretion in response to the drugs were significantly increased in patients when compared with healthy controls. No difference in cytokine secretion patterns between sulfonamide- and beta-lactam-reactive PBMC could be observed. The secretion of other cytokines/chemokines showed a high variability among patients. CONCLUSION: The measurement of IL-2, IL-5, IL-13 or IFN-gamma or a combination thereof might be a useful in vitro tool for detection of T-cell sensitization to drugs. Secretion of these cytokines seems independent of the type of drug antigen and the phenotype of the drug reaction. A study including a higher number of patients and controls will be needed to determine the exact sensitivity and specificity of this test.

Landmark-based augmented reality system for paranasal and transnasal endoscopic surgeries

BACKGROUND: In this paper we present a landmark-based augmented reality (AR) endoscope system for endoscopic paranasal and transnasal surgeries along with fast and automatic calibration and registration procedures for the endoscope. METHODS: Preoperatively the surgeon selects natural landmarks or can define new landmarks in CT volume. These landmarks are overlaid, after proper registration of preoperative CT to the patient, on the endoscopic video stream. The specified name of the landmark, along with selected colour and its distance from the endoscope tip, is also augmented. The endoscope optics are calibrated and registered by fast and automatic methods. Accuracy of the system is evaluated in a metallic grid and cadaver set-up. RESULTS: Root mean square (RMS) error of the system is 0.8 mm in a controlled laboratory set-up (metallic grid) and was 2.25 mm during cadaver studies. CONCLUSIONS: A novel landmark-based AR endoscope system is implemented and its accuracy is evaluated. Augmented landmarks will help the surgeon to orientate and navigate the surgical field. Studies prove the capability of the system for the proposed application. Further clinical studies are planned in near future.

Methods for identification of Staphylococcus aureus isolates in cases of bovine mastitis

A total of 272 staphylococcal isolates from cases of bovine mastitis (159 Staphylococcus aureus) belonging to 12 different species were identified with ID32 STAPH galleries, and 51 of them were confirmed by 16S rRNA gene (rrs) sequencing. The same isolates were examined for their hemolytic activity on sheep blood agar, DNase activity, and coagulase activity and with two rapid identification kits (Slidex Staph Plus kit and RAPIDEC Staph from Bio-Merieux). The results of this study confirm those obtained by other groups with hemolysis, DNase, and coagulase. Only 50% of S. aureus isolates from mastitis cases show coagulase activity after 4 h of incubation, and a 24-h incubation is necessary for the full sensitivity of this test. In contrast to results from other studies with human isolates, the Slidex Staph Plus kit was not sensitive enough for the identification of S. aureus from bovine mastitis samples. The aurease test of the RAPIDEC Staph kit showed 100% sensitivity and 100% specificity. Used in conjunction with hemolysis patterns, the RAPIDEC Staph kit is therefore very well adapted to rapid, efficient, and cost-effective identification of S. aureus in cultures from bovine mastitis samples. Sequencing of rrs genes also proved very efficient in identifying the Staphylococcus species encountered in these samples and confirming phenotypical identification results with unsatisfactory scores. With continuously improving technologies and decreasing costs, genetic identification methods like rrs gene sequencing will soon find a place in routine veterinary diagnostics.

Strategies for partner notification for sexually transmitted infections, including HIV

BACKGROUND Partner notification (PN) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection (STI) and the need to obtain treatment. For the person (index patient) with a curable STI, PN aims to eradicate infection and prevent re-infection. For sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of sexual networks and populations, the aim of PN is to interrupt chains of STI transmission. For people with viral STI, PN aims to identify undiagnosed infections, which can facilitate access for their sexual partners to treatment and help prevent transmission. OBJECTIVES To assess the effects of different PN strategies in people with STI, including human immunodeficiency virus (HIV) infection. SEARCH METHODS We searched electronic databases (the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language restrictions. We scanned reference lists of potential studies and previous reviews and contacted experts in the field. We searched three trial registries. We conducted the most recent search on 31 August 2012. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) or quasi-RCTs comparing two or more PN strategies. Four main PN strategies were included: patient referral, expedited partner therapy, provider referral and contract referral. Patient referral means that the patient notifies their sexual partners, either with (enhanced patient referral) or without (simple patient referral) additional verbal or written support. In expedited partner therapy, the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. In provider referral, health service personnel notify the partners. In contract referral, the index patient is encouraged to notify partner, with the understanding that the partners will be contacted if they do not visit the health service by a certain date. DATA COLLECTION AND ANALYSIS We analysed data according to paired partner referral strategies. We organised the comparisons first according to four main PN strategies (1. enhanced patient referral, 2. expedited partner therapy, 3. contract referral, 4. provider referral). We compared each main strategy with simple patient referral and then with each other, if trials were available. For continuous outcome measures, we calculated the mean difference (MD) with 95% confidence intervals (CI). For dichotomous variables, we calculated the risk ratio (RR) with 95% CI. We performed meta-analyses where appropriate. We performed a sensitivity analysis for the primary outcome re-infection rate of the index patient by excluding studies with attrition of greater than 20%. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. MAIN RESULTS We included 26 trials (17,578 participants, 9015 women and 8563 men). Five trials were conducted in developing countries. Only two trials were conducted among HIV-positive patients. There was potential for selection bias, owing to the methods of allocation used and of performance bias, owing to the lack of blinding in most included studies. Seven trials had attrition of greater than 20%, increasing the risk of bias.The review found moderate-quality evidence that expedited partner therapy is better than simple patient referral for preventing re-infection of index patients when combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71, 95% CI 0.56 to 0.89, I(2) = 39%). When studies with attrition greater than 20% were excluded, the effect of expedited partner therapy was attenuated (2 trials; RR 0.8, 95% CI 0.62 to 1.04, I(2) = 0%). In trials restricted to index patients with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to 1.35, I(2) = 22%). Expedited partner therapy also increased the number of partners treated per index patient (three trials) when compared with simple patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to 0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not superior to enhanced patient referral in preventing re-infection (3 trials; RR 0.96, 95% CI 0.60 to 1.53, I(2) = 33%, low-quality evidence). Home sampling kits for partners (four trials) did not result in lower rates of re-infection in the index case (measured in one trial), or higher numbers of partners elicited (three trials), notified (two trials) or treated (one trial) when compared with simple patient referral. There was no consistent evidence for the relative effects of provider, contract or other patient referral methods. In one trial among men with non-gonococcal urethritis, more partners were treated with provider referral than with simple patient referral (MD 0.5, 95% CI 0.37 to 0.63). In one study among people with syphilis, contract referral elicited treatment of more partners than provider referral (MD 2.2, 95% CI 1.95 to 2.45), but the number of partners receiving treatment was the same in both groups. Where measured, there was no statistical evidence of differences in the incidence of adverse effects between PN strategies. AUTHORS' CONCLUSIONS The evidence assessed in this review does not identify a single optimal strategy for PN for any particular STI. When combining trials of STI causing urethritis or cervicitis, expedited partner therapy was more successful than simple patient referral for preventing re-infection of the index patient but was not superior to enhanced patient referral. Expedited partner therapy interventions should include all components that were part of the trial intervention package. There was insufficient evidence to determine the most effective components of an enhanced patient referral strategy. There are too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. More high-quality RCTs of PN strategies for HIV and syphilis, using biological outcomes, are needed.

Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases

Growing evidence suggests a prominent role of the complement system in the pathogenesis of cardio- and cerebrovascular diseases (CVD). Mannan-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-2 of the complement lectin pathway contribute to clot formation and may represent an important link between inflammation and thrombosis. MBL-associated protein MAp44 has shown cardioprotective effects in murine models. However, MAp44 has never been measured in patients with CVD and data on MASP levels in CVD are scarce. Our aim was to investigate for the first time plasma levels of MAp44 and MASP-1, -2, -3 concomitantly in patients with CVD. We performed a pilot study in 50 healthy volunteers, in stable coronary artery disease (CAD) patients with one-vessel (n = 51) or three-vessel disease (n = 53) and age-matched controls with normal coronary arteries (n = 53), 49 patients after myocardial infarction (MI) and 66 patients with acute ischaemic stroke. We measured MAp44 and MASP-1 levels by in-house time-resolved immunofluorometric assays. MASP-2 and MASP-3 levels were measured using commercial enzyme-linked immunosorbent assay kits. MASP-1 levels were highest in subacute MI patients and lowest in acute stroke patients. MASP-2 levels were lower in MI and stroke patients compared with controls and CAD patients. MASP-3 and MAp44 levels did not differ between groups. MASP or MAp44 levels were not associated with severity of disease. MASP and MAp44 levels were associated with cardiovascular risk factors including dyslipidaemia, obesity and hypertension. Our results suggest that MASP levels may be altered in vascular diseases. Larger studies are needed to confirm our results and elucidate the underlying mechanisms.

Expression, purification, and projection structure by single particle electron microscopy of functional human TRPM4 heterologously expressed in Xenopus laevis oocytes

Despite efforts implicating the cationic channel transient receptor potential melastatin member 4 (TRPM4) to cardiac, nervous, and immunological pathologies, little is known about its structure and function. In this study, we optimized the requirements for purification and extraction of functional human TRPM4 protein and investigated its supra-molecular assembly. We selected the Xenopus laevis oocyte expression system because it lacks endogenous TRPM4 expression, it is known to overexpress functional human membrane channels, can be used for structure-function analysis within the same system, and is easily scaled to improve yield and develop moderate throughput capabilities through the use of robotics. Negative-stain electron microscopy (EM) revealed various sized low-resolution particles. Single particle analysis identified the majority of the projections represented the monomeric form with additional oligomeric structures potentially characterized as tetramers. Two-electrode voltage clamp electrophysiology demonstrated that human TRPM4 is functionally expressed at the oocyte plasma membrane. This study opens the door for medium-throughput screening and structure-function determination of this important therapeutically relevant target.

Comparison of freehand-navigated and aiming device-navigated targeting of liver lesions

BACKGROUND Accurate needle placement is crucial for the success of percutaneous radiological needle interventions. We compared three guiding methods using an optical-based navigation system: freehand, using a stereotactic aiming device and active depth control, and using a stereotactic aiming device and passive depth control. METHODS For each method, 25 punctures were performed on a non-rigid phantom. Five 1 mm metal screws were used as targets. Time requirements were recorded, and target positioning errors (TPE) were measured on control scans as the distance between needle tip and target. RESULTS Time requirements were reduced using the aiming device and passive depth control. The Euclidian TPE was similar for each method (4.6 ± 1.2-4.9 ± 1.7 mm). However, the lateral component was significantly lower when an aiming device was used (2.3 ± 1.3-2.8 ± 1.6 mm with an aiming device vs 4.2 ± 2.0 mm without). DISCUSSION Using an aiming device may increase the lateral accuracy of navigated needle insertion.

ARMin III – arm therapy exoskeleton with an ergonomic shoulder actuation

Rehabilitation robots have become important tools in stroke rehabilitation. Compared to manual arm training, robot-supported training can be more intensive, of longer duration and more repetitive. Therefore, robots have the potential to improve the rehabilitation process in stroke patients. Whereas a majority of previous work in upper limb rehabilitation robotics has focused on end-effector-based robots, a shift towards exoskeleton robots is taking place because they offer a better guidance of the human arm, especially for movements with a large range of motion. However, the implementation of an exoskeleton device introduces the challenge of reproducing the motion of the human shoulder, which is one of the most complex joints of the body. Thus, this paper starts with describing a simplified model of the human shoulder. On the basis of that model, a new ergonomic shoulder actuation principle that provides motion of the humerus head is proposed, and its implementation in the ARMin III arm therapy robot is described. The focus lies on the mechanics and actuation principle. The ARMin III robot provides three actuated degrees of freedom for the shoulder and one for the elbow joint. An additional module provides actuated lower arm pro/supination and wrist flexion/extension. Five ARMin III devices have been manufactured and they are currently undergoing clinical evaluation in hospitals in Switzerland and in the United States.