Prostate Biopsy Assistance System with Gland Deformation Estimation for Enhanced Precision

Computer-assisted prostate biopsies became a very active research area during the last years. Prostate tracking makes it possi- ble to overcome several drawbacks of the current standard transrectal ultrasound (TRUS) biopsy procedure, namely the insufficient targeting accuracy which may lead to a biopsy distribution of poor quality, the very approximate knowledge about the actual location of the sampled tissues which makes it difficult to implement focal therapy strategies based on biopsy results, and finally the difficulty to precisely reach non-ultrasound (US) targets stemming from different modalities, statistical atlases or previous biopsy series. The prostate tracking systems presented so far are limited to rigid transformation tracking. However, the gland can get considerably deformed during the intervention because of US probe pres- sure and patient movements. We propose to use 3D US combined with image-based elastic registration to estimate these deformations. A fast elastic registration algorithm that copes with the frequently occurring US shadows is presented. A patient cohort study was performed, which yielded a statistically significant in-vivo accuracy of 0.83+-0.54mm.Comment: This version of the paper integrates a correction concerning the local similarity measure w.r.t. the proceedings (this typing error could not be corrected before editing the proceedings

New Mechatronic Systems for the Diagnosis and Treatment of Cancer

Both two dimensional (2D) and three dimensional (3D) imaging modalities are useful tools for viewing the internal anatomy. Three dimensional imaging techniques are required for accurate targeting of needles. This improves the efficiency and control over the intervention as the high temporal resolution of medical images can be used to validate the location of needle and target in real time. Relying on imaging alone, however, means the intervention is still operator dependent because of the difficulty of controlling the location of the needle within the image. The objective of this thesis is to improve the accuracy and repeatability of needle-based interventions over conventional techniques: both manual and automated techniques. This includes increasing the accuracy and repeatability of these procedures in order to minimize the invasiveness of the procedure. In this thesis, I propose that by combining the remote center of motion concept using spherical linkage components into a passive or semi-automated device, the physician will have a useful tracking and guidance system at their disposal in a package, which is less threatening than a robot to both the patient and physician. This design concept offers both the manipulative transparency of a freehand system, and tremor reduction through scaling currently offered in automated systems. In addressing each objective of this thesis, a number of novel mechanical designs incorporating an remote center of motion architecture with varying degrees of freedom have been presented. Each of these designs can be deployed in a variety of imaging modalities and clinical applications, ranging from preclinical to human interventions, with an accuracy of control in the millimeter to sub-millimeter range

The different dimensions of livelihood impacts of Payments for Environmentals Services (PES) schemes: A systematic review

Through a systematic review of peer-reviewed and grey literature, this paper analyzes evidence of the livelihood impacts of Payments for Environmental Services (PES). Forty-six studies assessed PES livelihood impacts. The assessments presented more positive livelihood impacts than negative ones, focusing on financial benefits. Non-monetary and non-material impacts of PES were largely understudied. Most reviews focused on ES providers, hindering the understanding of broader societal impacts. The review yielded examples where participants lost from their participation or where improvements in one livelihood dimension paralleled deterioration in another. Consequently, we identified key research gaps in: i) understanding the social and cultural impacts of PES, ii) evaluating environmental and economic additionality from improving other ES at the expense of cultural ones, iii) and assessing PES impacts in terms of trade-offs between multiple livelihood dimensions. Moreover, increased knowledge is needed on the impact of PES on changes in household expenditure and choice, and on trade-offs between household income and inequality in ES provider communities. Finally, if PES schemes are implemented to sustainably improve livelihoods, targeting disaggregated populations, understanding equity and social power relations within and between ES providers and users, and better monitoring and evaluation systems that consider locally relevant livelihood dimensions are needed

Quantification of Plasma and Urine Thymidine and 2'-Deoxyuridine by LC-MS/MS for the Pharmacodynamic Evaluation of Erythrocyte Encapsulated Thymidine Phosphorylase in Patients with Mitochondrial Neurogastrointestinal Encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disorder caused by mutations in TYMP, leading to a deficiency in thymidine phosphorylase and a subsequent systemic accumulation of thymidine and 2'-deoxyuridine. Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is under clinical development as an enzyme replacement therapy for MNGIE. Bioanalytical methods were developed according to regulatory guidelines for the quantification of thymidine and 2'-deoxyuridine in plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for supporting the pharmacodynamic evaluation of EE-TP. Samples were deproteinized with 5% perchloric acid (v/v) and the supernatants analyzed using a Hypercarb column (30 × 2.1 mm, 3 µm), with mobile phases of 0.1% formic acid in methanol and 0.1% formic acid in deionized water. Detection was conducted using an ion-spray interface running in positive mode. Isotopically labelled thymidine and 2'-deoxyuridine were used as internal standards. Calibration curves for both metabolites showed linearity (r > 0.99) in the concentration ranges of 10-10,000 ng/mL for plasma, and 1-50 µg/mL for urine, with method analytical performances within the acceptable criteria for quality control samples. The plasma method was successfully applied to the diagnosis of two patients with MNGIE and the quantification of plasma metabolites in three patients treated with EE-TP

Collagen-Fibrinogen Lyophilised Scaffolds for Soft Tissue Regeneration

A significant body of research has considered collagen as a scaffold material for soft tissue regeneration. The main structural component of extra-cellular matrix (ECM), collagen’s advantages over synthetic polymers are numerous. However, for applications where higher stiffness and stability are required, significant cross-linking may affect bioactivity. A carbodiimide (EDC) cross-linking route consumes carboxylate groups that are key to collagen’s essential cell recognition motifs (GxOGER). Fibrinogen was considered as a promising additive as it plays a key role in the process of wound repair and contains RGD integrin binding sites which bind to a variety of cells, growth factors and cytokines. Fibrinogen’s binding sites however, also contain the same carboxylate groups as collagen. We have successfully produced highly interconnected, porous collagen-fibrinogen scaffolds using a lyophilisation technique and micro-computed tomography demonstrated minimal influence of either fibrinogen content or cross-linking concentration on the scaffold structure. The specific biological effect of fibrinogen additions into cross-linked collagen are considered by using films as a model for the struts of bulk scaffolds. By considering various additions of fibrinogen to the collagen film with increasing degrees of cross-linking, this study demonstrates a significant biological advantage with fibrinogen addition across the cross-linking concentrations typically applied to collagen-based scaffolds.The authors wish to acknowledge the support of the European Research Council for the Advanced Grant 320598 awarded to REC and the EPSRC for the Established Career Fellowship EP/N019938/1 awarded to REC and SMB. They also wish to acknowledge funding for DB from the Peoples Programme of the EU 7th Framework Programme (RAE no: PHF-GA-2013-624904)

The use of ICT in the assessment of modern languages: the English context and European viewpoints

The ever increasing explosion of highly attractive multimedia resources on offer has boosted the use of information and communication technology (ICT) in the teaching and learning of modern languages. The use of ICT to assess languages is less frequent, however, although online testing is starting to develop. This paper examines the national context for the assessment of modern foreign language proficiency in England, outlines the kinds of assessment currently available and the development of electronic forms of assessment and compares the above with the survey results of a European Union (EU) funded project on current good practice in online assessment of languages in other European countries. The findings indicate that speaking is inadequately served by online testing as tests currently focus primarily on receptive language skills. The implications for future successful online testing include the incorporation of interactive skills and effective formative feedback

The problem of authority in revelation

From Preface: The problem of authority in religion can be stated as follows: what is the finally authoritative source and judge of religious truth? This was the fundamental question which Jesus Himself raised when He came to the Jews. It was the fundamental problem of the Reformation. It is also the fundamental problem that confronts the Church in our time. But it has never ceased to be the perennial question underlying all religious and philosophical thought

Conformational flexibility within the small domain of human serine racemase

Serine racemase (SR) is a pyridoxal 5′-phosphate (PLP)-containing enzyme that converts L-serine to D-serine, an endogenous co-agonist for the N-methyl-D-aspartate receptor (NMDAR) subtype of glutamate ion channels. SR regulates D-serine levels by the reversible racemization of L-serine to D-serine, as well as the catabolism of serine by α,β-elimination to produce pyruvate. The modulation of SR activity is therefore an attractive therapeutic approach to disorders associated with abnormal glutamatergic signalling since it allows an indirect modulation of NMDAR function. In the present study, a 1.89 Å resolution crystal structure of the human SR holoenzyme (including the PLP cofactor) with four subunits in the asymmetric unit is described. Comparison of this new structure with the crystal structure of human SR with malonate (PDB entry 3l6b) shows an interdomain cleft that is open in the holo structure but which disappears when the inhibitor malonate binds and is enclosed. This is owing to a shift of the small domain (residues 78–155) in human SR similar to that previously described for the rat enzyme. This domain movement is accompanied by changes within the twist of the central four-stranded β-sheet of the small domain, including changes in the φ–ψ angles of all three residues in the C-terminal β-strand (residues 149–151). In the malonate-bound structure, Ser84 (a catalytic residue) points its side chain at the malonate and is preceded by a six-residue β-strand (residues 78–83), but in the holoenzyme the β-strand is only four residues (78–81) and His82 has φ–ψ values in the α-helical region of the Ramachandran plot. These data therefore represent a crystallographic platform that enables the structure-guided design of small-molecule modulators for this important but to date undrugged target

From beliefs to success: Utilizing an expanded TAM to predict web page development success

The technology acceptance model (TAM) is a popular model for the prediction of information systems acceptance behaviors, defining a causal linkage between beliefs, attitudes, intentions, and the usage of information technologies. Since its inception, numerous studies have utilized the TAM, providing empirical support for the model in both traditional and Internet-based computing settings. This article describes a research study that utilizes an adaptation of the TAM to predict successful Web page development, as an introduction of the TAM to a new domain, and the testing of a new dependent variable within the model. The study found some evidence to support the use of the TAM as a starting point for the prediction of Web development success, finding causal linkages between the belief constructs and the attitude constructs, and the intent construct and the successful development of Web pages. However, additional research is required to further study the expanded model introduced within this article. Keywords: computer attitudes; internet attitudes; system development success; technology acceptance model (TAM

Families with infants: a general approach to solve hard partition problems

We introduce a general approach for solving partition problems where the goal is to represent a given set as a union (either disjoint or not) of subsets satisfying certain properties. Many NP-hard problems can be naturally stated as such partition problems. We show that if one can find a large enough system of so-called families with infants for a given problem, then this problem can be solved faster than by a straightforward algorithm. We use this approach to improve known bounds for several NP-hard problems as well as to simplify the proofs of several known results. For the chromatic number problem we present an algorithm with $O^*((2-\varepsilon(d))^n)$ time and exponential space for graphs of average degree $d$. This improves the algorithm by Bj\"{o}rklund et al. [Theory Comput. Syst. 2010] that works for graphs of bounded maximum (as opposed to average) degree and closes an open problem stated by Cygan and Pilipczuk [ICALP 2013]. For the traveling salesman problem we give an algorithm working in $O^*((2-\varepsilon(d))^n)$ time and polynomial space for graphs of average degree $d$. The previously known results of this kind is a polyspace algorithm by Bj\"{o}rklund et al. [ICALP 2008] for graphs of bounded maximum degree and an exponential space algorithm for bounded average degree by Cygan and Pilipczuk [ICALP 2013]. For counting perfect matching in graphs of average degree~$d$ we present an algorithm with running time $O^*((2-\varepsilon(d))^{n/2})$ and polynomial space. Recent algorithms of this kind due to Cygan, Pilipczuk [ICALP 2013] and Izumi, Wadayama [FOCS 2012] (for bipartite graphs only) use exponential space.Comment: 18 pages, a revised version of this paper is available at http://arxiv.org/abs/1410.220