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

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 year in cardiology: imaging. The year in cardiology 2019.

No abstract available

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

Prognosis of Transient New-Onset Atrial Fibrillation During Vascular Surgery

AbstractBackgroundChronic atrial fibrillation (AF) in a non-surgical setting is associated with cardiovascular events. However, the prognosis of transient new-onset AF during vascular surgery is unknown.ObjectiveThe purpose of this study is to investigate the prognosis of new-onset AF during vascular surgery using continuous electrocardiographic monitoring (continuous-ECG).MethodsIn this study, 317 patients, all in sinus rhythm, scheduled for major vascular surgery were screened for cardiac risk factors. Continuous-ECG recordings for 72h and standard ECG on days 3, 7 and 30 were used to identify new-onset AF. Cardiac troponin T (cTnT) was measured routinely after surgery. Study endpoint was a composite of cardiac death, myocardial infarction, unstable angina and stroke (cardiovascular events) at 30 days after surgery and during late follow-up. Median follow-up was 12 (interquartile range 2–28) months.ResultsNew-onset AF was noted in 15 (4.7%) patients. All but three patients returned spontaneously to sinus rhythm. The composite endpoint of cardiovascular events within 30 days and during late follow-up occurred in 34 (11%) and 62 (20%) patients, respectively. Multivariate regression analysis showed that new-onset AF was associated with perioperative (hazard ratio (HR) 6.0; 95% CI: 2.4–15) and late cardiovascular events (HR 4.2, 95% CI: 2.1–8.8).ConclusionNew-onset AF during vascular surgery is associated with an increased incidence of 30-day and late cardiovascular events

Validation of an Immunoassay for Anti-thymidine Phosphorylase Antibodies in Patients with MNGIE Treated with Enzyme Replacement Therapy.

Erythrocyte encapsulated thymidine phosphorylase is recombinant Escherichia coli thymidine phosphorylase encapsulated within human autologous erythrocytes and is under development as an enzyme replacement therapy for the ultra-rare inherited metabolic disorder mitochondrial neurogastrointestinal encephalomyopathy. This study describes the method validation of a two-step bridging electrochemiluminescence immunoassay for the detection of anti-thymidine phosphorylase antibodies in human serum according to current industry practice and regulatory guidelines. The analytical method was assessed for screening cut point, specificity, selectivity, precision, prozone effect, drug tolerance, and stability. Key findings were a correction factor of 129 relative light units for the cut-point determination; a specificity cut point of 93% inhibition; confirmed intra-assay and inter-assay precision; assay sensitivity of 356 ng/mL; no matrix or prozone effects up to 25,900 ng/mL; a drug tolerance of 156 ng/mL; and stability at room temperature for 24 hr and up to five freeze-thaws. Immunogenicity evaluations of serum from three patients who received erythrocyte encapsulated thymidine phosphorylase under a compassionate treatment program showed specific anti-thymidine phosphorylase antibodies in one patient. To conclude, a sensitive, specific, and selective immunoassay has been validated for the measurement of anti-thymidine phosphorylase antibodies; this will be utilized in a phase II pivotal clinical trial of erythrocyte encapsulated thymidine phosphorylase

Fundamental insight into the effect of carbodiimide crosslinking on cellular recognition of collagen-based scaffolds

Research on the development of collagen constructs is extremely important in the field of tissue engineering. Collagen scaffolds for numerous tissue engineering applications are frequently crosslinked with 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide hydrochloride (EDC) in the presence of N-hydroxy-succinimide (NHS). Despite producing scaffolds with good biocompatibility and low cellular toxicity the influence of EDC/NHS crosslinking on the cell interactive properties of collagen has been overlooked. Here we have extensively studied the interaction of model cell lines with collagen I-based materials after crosslinking with different ratios of EDC in relation to the number of carboxylic acid residues on collagen. Divalent cation-dependent cell adhesion, via integrins α$_{1}$β$_{1}$, α$_{2}$β$_{1}$, α$_{10}$β$_{1}$ and α$_{11}$β$_{1}$, were sensitive to EDC crosslinking. With increasing EDC concentration, this was replaced with cation-independent adhesion. These results were replicated using purified recombinant I domains derived from integrin α$_{1}$ and α$_{2}$ subunits. Integrin α$_{2}$β$_{1}$-mediated cell spreading, apoptosis and proliferation were all heavily influenced by EDC crosslinking of collagen. Data from this rigorous study provides an exciting new insight that EDC/NHS crosslinking is utilising the same carboxylic side chain chemistry that is vital for native-like integrin-mediated cell interactions. Due to the ubiquitous usage of EDC/NHS crosslinked collagen for biomaterials fabrication this data is essential to have a full understanding in order to ensure optimized collagen-based material performance.This work was supported by the British Heart Foundation (Grant NH/11/1/28922, RG/15/4/31268, SP/15/7/31561 and RG/09/003/27122) and the ERC Advanced Grant 320598 3D-E. D. V. Bax is funded by the Peoples Programme of the EU 7th Framework Programme (RAE no: PIIF-GA-2013-624904) and was supported by an EPSRC IKC Proof of Concept Award