Development, Validation, and Modelling of Image Guidance Systems for Surgery

Image guidance systems for surgery enable the surgeon to make use of information from various sources during surgery. Such systems have the potential to improve outcomes for patients by allowing the surgeon to easily assimilate prior knowledge from pre-operative clinical scans as well as novel intra-operative imaging techniques. A key challenge is how to filter and process this information to allow it to be presented in an accurate, timely, and intuitive manner. Badly designed or poorly understood image guidance systems risk distracting the surgeon with irrelevant or incorrect information, leading to patient harm. The aim of my research is to develop tools to better quantify the performance of surgical image guidance systems, and measure how the system performance affects patient outcomes. I will present the results of my work developing the “SmartLiver”[1] image guidance system for minimally invasive liver surgery. I will follow this with a proposal for a generalised model of image guidance systems as multi input control systems

ZOOM or Non-ZOOM? Assessing spinal cord diffusion tensor imaging protocols for multi-centre studies

The purpose of this study was to develop and evaluate two spinal cord (SC) diffusion tensor imaging (DTI) protocols, implemented at multiple sites (using scanners from two different manufacturers), one available on any clinical scanner, and one using more advanced options currently available in the research setting, and to use an automated processing method for unbiased quantification. DTI parameters are sensitive to changes in the diseased SC. However, imaging the cord can be technically challenging due to various factors including its small size, patient-related and physiological motion, and field inhomogeneities. Rapid acquisition sequences such as Echo Planar Imaging (EPI) are desirable but may suffer from image distortions. We present a multi-centre comparison of two acquisition protocols implemented on scanners from two different vendors (Siemens and Philips), one using a reduced field-of-view (rFOV) EPI sequence, and one only using options available on standard clinical scanners such as outer volume suppression (OVS). Automatic analysis was performed with the Spinal Cord Toolbox for unbiased and reproducible quantification of DTI metrics in the white matter. Images acquired using the rFOV sequence appear less distorted than those acquired using OVS alone. SC DTI parameter values obtained using both sequences at all sites were consistent with previous measurements made at 3T. For the same scanner manufacturer, DTI parameter inter-site SDs were smaller for the rFOV sequence compared to the OVS sequence. The higher inter-site reproducibility (for the same manufacturer and acquisition details, i.e. ZOOM data acquired at the two Philips sites) of rFOV compared to the OVS sequence supports the idea that making research options such as rFOV more widely available would improve accuracy of measurements obtained in multi-centre clinical trials. Future multi-centre studies should also aim to match the rFOV technique and signal-to-noise ratios in all sequences from different manufacturers/sites in order to avoid any bias in measured DTI parameters and ensure similar sensitivity to pathological changes

A Practical Voter-Verifiable Election Scheme

We present an election scheme designed to allow voters to verify that their vote is accurately included in the count. The scheme provides a high degree of transparency whilst ensuring the secrecy of votes. Assurance is derived from close auditing of all the steps of the vote recording and counting process with minimal dependence on the system components. Thus, assurance arises from verification of the election rather than having to place trust in the correct behaviour of components of the voting system. The scheme also seeks to make the voter interface as familiar as possible

Resident Perception of Academic Skills Training and Impact on Academic Career Choice

Objectives: 1) To evaluate residents' perceptions of the quality of training in basic academic skills and the availability and quality of research resources during residency; 2) to evaluate the association between these attitudes and choice of an academic career; and 3) to assess residents' attitudes toward the importance of postgraduate fellowship training for success in an academic career. Methods: A 15-item survey was administered to all U.S. emergency medicine (EM) residents in conjunction with the February 1997 American Board of Emergency Medicine (ABEM) In-service Examination. The survey assessed resident interest in a career in academic EM, and resident perception of the general quality of training in academic (research and teaching) skills. Residents were also asked to rate the quality of their training in the following specific academic skills: medical and grant writing, bedside teaching, lecturing, the use of computers, study design, statistics, and the use of audiovisual aids. Resident perceptions of the availability of the following resources were also assessed: teaching and research role models, data collection and analysis support, laboratory facilities, financial support of research, research fundamentals lectures, and computers. Results: The response rate was 93%. Forty-four percent of the respondents were interested in academic EM, 36.6% were undecided, and 19.6% were not interested in an academic career. On a scale of 1 (unprepared) to 5 (well prepared), the residents rated their overall preparedness for an academic career fairly high (3.97 [0.86]). In contrast, they perceived the quality of their training in the specific academic skill areas assessed and research resource availability to be only fair. Despite resident perception of relatively inadequate training in basic academic skills, only 24% of the respondents indicated that they believed fellowship training was important for success in an academic career. Logistic regression analyses demonstrated that participation in a research project in medical school, the length of the training program (4- vs 3-year), being a first-year resident, and a better perception of one's overall academic skill preparation were factors independently associated with having a greater interest in an academic career. Conclusions: A relatively high percentage of residents initially express an interest in an academic career, but this interest wanes as residency progresses. A minority of residents believe that their training provides them with the specific skills needed to succeed in academics, or with adequate exposure to research resources or mentors. Emergency medicine may be able to increase the number of qualified academic faculty by recruiting medical students with prior research experience, and providing residents with better research training and role models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72196/1/j.1553-2712.2000.tb00499.x.pd

Huntington's disease phenocopies are clinically and genetically heterogeneous

Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD-like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD-like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral-pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty-five patients with syndromes consistent with HD, who were HD expansion-negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. (c) 2008 Movement Disorder Society

Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens

Charge 4e4e superconductivity from pair density wave order in certain high temperature superconductors

A number of spectacular experimental anomalies\cite{li-2007,fujita-2005} have recently been discovered in certain cuprates, notably {\LBCO} and {\LNSCO}, which exhibit unidirectional spin and charge order (known as ``stripe order''). We have recently proposed to interpret these observations as evidence for a novel ``striped superconducting'' state, in which the superconducting order parameter is modulated in space, such that its average is precisely zero. Here, we show that thermal melting of the striped superconducting state can lead to a number of unusual phases, of which the most novel is a charge $4e$ superconducting state, with a corresponding fractional flux quantum $hc/4e$. These are never-before observed states of matter, and ones, moreover, that cannot arise from the conventional Bardeen-Cooper-Schrieffer (BCS) mechanism. Thus, direct confirmation of their existence, even in a small subset of the cuprates, could have much broader implications for our understanding of high temperature superconductivity. We propose experiments to observe fractional flux quantization, which thereby could confirm the existence of these states.Comment: 5 pages, 2 figures; new version in Nature Physics format with a discussion of the effective Josephson coupling J2 and minor changes. Mildly edited abstract. v3: corrected versio

Formal security analysis of NFC M-coupon protocols using Casper/FDR

Near field communication (NFC) is a standard-based, radio frequency (RF), wireless communication technology that allows data to be exchanged between devices that are less than 20 cm apart. NFC security protocols require formal security analysis before massive adoptions, in order to check whether these protocols meet its requirements and goals. In this paper we formally analyse NFC-based mobile coupon protocols using formal methods (Casper/FDR). We find an attack against the advanced protocol, and then we provide a solution that addresses the vulnerability formally

Oculogyric crises: Etiology, pathophysiology and therapeutic approaches

Oculogyric crisis (OGC) describes the clinical phenomenon of sustained dystonic, conjugate and typically upward deviation of the eyes lasting from seconds to hours. It was initially observed in patients with postencephalitic parkinsonism, but since then a number of conditions have been associated with OGC. These include drug-induced reactions, hereditary and sporadic movement disorders, and focal brain lesions. Here, we systematically review the literature and discuss the spectrum of disorders associated with OGC in order to aid clinicians place this rare but distinctive clinical sign into the appropriate diagnostic context. We also provide a brief synthesis of putative pathophysiological mechanisms, as well as therapeutic recommendations based on the literature and our own experience

Palliative care in urgent need of recognition and development in general practice: the example of Germany

Background: Specialist palliative care is being increasingly recognised and developed to improve end-of-life care in many developed countries. However, only a small proportion of the total number of patients with incurable, progressive diseases actually has direct contact with specialist palliative care practitioners. Using the German situation as an example, the main purpose of this paper is to argue that the emphasis on specialist palliative care services without a similar encouragement of primary palliative care will deliver a constrained service