Biomarkers in acute coronary syndromes and their role in diabetic patients

Diabetic patients with acute coronary syndromes are at high risk for cardiovascular complications but risk stratification in these patients remains challenging. Regularly, diabetic patients have a less typical clinical presentation, which could lead to delayed diagnosis and subsequent delayed initiation of treatment. Since diabetic patients derive particular benefit from aggressive anti-platelet therapy, early diagnostic and therapeutic risk stratification of these patients is of critical importance to improve their adverse outcome. Although the electrocardiogram remains a pivotal diagnostic tool in the evaluation of patients suspected of having an acute coronary syndrome, only significant STsegment changes provide reasonable prognostic information. Therefore, repeated assessment of circulating protein biomarkers represents a valuable diagnostic tool for improving efficacy and safety of decision-making in these patients. The combined use of biomarkers reflecting distinct pathophysiological aspects, such as myocardial necrosis, vascular inflammation, oxidative stress and neurohumoral activation, may significantly improve triage of patients with chest pain. These tools may identify those patients that are at particularly high risk for short-term and/or long-term cardiovascular events. Eventually, tailored medical and interventional treatment of diabetic patients should help to prevent these cardiac events in a cost-effective manner

Investigating five key predictive text entry with combined distance and keystroke modelling

This paper investigates text entry on mobile devices using only five-keys. Primarily to support text entry on smaller devices than mobile phones, this method can also be used to maximise screen space on mobile phones. Reported combined Fitt's law and keystroke modelling predicts similar performance with bigram prediction using a five-key keypad as is currently achieved on standard mobile phones using unigram prediction. User studies reported here show similar user performance on five-key pads as found elsewhere for novice nine-key pad users

100 years post-insulin: immunotherapy as the next frontier in type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease characterised by T cell-mediated destruction of the insulin-producing β cells in the pancreas. Similar to other autoimmune diseases, the incidence of T1D is increasing globally. The discovery of insulin 100 years ago dramatically changed the outlook for people with T1D, preventing this from being a fatal condition. As we celebrate the centenary of this milestone, therapeutic options for T1D are once more at a turning point. Years of effort directed at developing immunotherapies are finally starting to pay off, with signs of progress in new onset and even preventative settings. Here, we review a selection of immunotherapies that have shown promise in preserving β cell function and highlight future considerations for immunotherapy in the T1D setting

100 years post-insulin: immunotherapy as the next frontier in type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease characterised by T cell-mediated destruction of the insulin-producing β cells in the pancreas. Similar to other autoimmune diseases, the incidence of T1D is increasing globally. The discovery of insulin 100 years ago dramatically changed the outlook for people with T1D, preventing this from being a fatal condition. As we celebrate the centenary of this milestone, therapeutic options for T1D are once more at a turning point. Years of effort directed at developing immunotherapies are finally starting to pay off, with signs of progress in new onset and even preventative settings. Here, we review a selection of immunotherapies that have shown promise in preserving β cell function and highlight future considerations for immunotherapy in the T1D setting

Evaluation of the taste-masking effects of (2-hydroxypropyl)-β-cyclodextrin on ranitidine hydrochloride; a combined biosensor, spectroscopic and molecular modelling assessment

Taste assessment in an increasingly important aspect of formulation development, particularly for paediatric medications. Electronic taste sensing systems have the potential to offer a rapid, objective and safe method of taste assessment prior to the use of more costly human panels or animal models. In this study, the ability of the TS-5000Z taste sensing system to assess the taste masking efficiency of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) complexes with ranitidine hydrochloride was evaluated in order to explore the potential of the biosensor approach as a means of assessing taste masking by inclusion complexation. Nuclear magnetic resonance (NMR) spectroscopy and molecular docking studies were employed to identify and examine the interaction between ranitidine hydrochloride and HP-β-CyD. Taste-masking efficiencies were determined by the Euclidean distance between taste-masked formulations and the pure drug substance on a PCA score plot. The results showed that with increasing molarity of HP-β-CyD in the formulation, the distance from ranitidine hydrochloride increased, thus indicating a significant difference between the taste of the formulation and that of the pure drug. NMR studies also provided strong supporting evidence for the complexation between HP-β-CyD and ranitidine hydrochloride, with the H3′ region of the former identified as the most likely binding site for the drug. Molecular docking studies suggested that the dimethylamino and diamine groups of the drug form direct hydrogen bonds with the hydroxyl oxygen atoms of HP-β-CyD, while the furan ring docks in close proximity to H3′. This study has demonstrated that the biosensor system may provide quantitative data to assess bitterness of inclusion complexes with HP-β-CyD, while spectroscopic and modelling studies may provide a mechanistic explanation for the taste masking process. This in turn suggests that there is a role for biosensor approaches in providing early screening for taste masking using inclusion complexation and that the combination with mechanistic studies may provide insights into the molecular basis of taste and taste masking

Improving Developers\u27 Understanding of Regex Denial of Service Tools through Anti-Patterns and Fix Strategies

Regular expressions are used for diverse purposes, including input validation and firewalls. Unfortunately, they can also lead to a security vulnerability called ReDoS (Regular Expression Denial of Service), caused by a super-linear worst-case execution time during regex matching. Due to the severity and prevalence of ReDoS, past work proposed automatic tools to detect and fix regexes. Although these tools were evaluated in automatic experiments, their usability has not yet been studied; usability has not been a focus of prior work. Our insight is that the usability of existing tools to detect and fix regexes will improve if we complement them with anti-patterns and fix strategies of vulnerable regexes. We developed novel anti-patterns for vulnerable regexes, and a collection of fix strategies to fix them. We derived our anti-patterns and fix strategies from a novel theory of regex infinite ambiguity—a necessary condition for regexes vulnerable to ReDoS. We proved the soundness and completeness of our theory. We evaluated the effectiveness of our anti-patterns, both in an automatic experiment and when applied manually. Then, we evaluated how much our anti-patterns and fix strategies improve developers’ understanding of the outcome of detection and fixing tools. Our evaluation found that our anti-patterns were effective over a large dataset of regexes (N=209,188): 100% precision and 99% recall, improving the state of the art 50% precision and 87% recall. Our anti-patterns were also more effective than the state of the art when applied manually (N=20): 100% developers applied them effectively vs. 50% for the state of the art. Finally, our anti-patterns and fix strategies increased developers’ understanding using automatic tools (N=9): from median “Very weakly” to median “Strongly” when detecting vulnerabilities, and from median “Very weakly” to median “Very strongly” when fixing them

Behavioural trait assortment in a social network: Patterns and implications

This a post-print, author-produced version of an article accepted for publication in Behavioral Ecology and Sociobiology. Copyright © 2009 Springer Verlag. The definitive version is available at http://link.springer.com/article/10.1007%2Fs00265-009-0802-x#The social fine structure of a population plays a central role in ecological and evolutionary processes. Whilst many studies have investigated how morphological traits such as size affect social structure of populations, comparatively little is known about the influence of behaviours such as boldness and shyness. Using information on social interactions in a wild population of Trinidadian guppies (Poecilia reticulata), we construct a social network. For each individual in the network, we quantify its behavioural phenotype using two measures of boldness, predator inspection tendency, a repeatable and reliably measured behaviour well studied in the context of co-operation, and shoaling tendency. We observe striking heterogeneity in contact patterns, with strong ties being positively assorted and weak ties negatively assorted by our measured behavioural traits. Moreover, shy fish had more network connections than bold fish and these were on average stronger. In other words, social fine structure is strongly influenced by behavioural trait. We assert that such structure will have implications for the outcome of selection on behavioural traits and we speculate that the observed positive assortment may act as an amplifier of selection contributing to the maintenance of co-operation during predator inspection

High index contrast photonic platforms for on-chip Raman spectroscopy

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively

Rapid detection of BRCA1/2 recurrent mutations in Chinese breast and ovarian cancer patients with multiplex SNaPshot genotyping panels.

BRCA1/2 mutations are significant risk factors for hereditary breast and ovarian cancer (HBOC), its mutation frequency in HBOC of Chinese ethnicity is around 9%, in which nearly half are recurrent mutations. In Hong Kong and China, genetic testing and counseling are not as common as in the West. To reduce the barrier of testing, a multiplex SNaPshot genotyping panel that targeted 25 Chinese BRCA1/2 mutation hotspots was developed, and its feasibility was evaluated in a local cohort of 441 breast and 155 ovarian cancer patients. For those who tested negative, they were then subjected to full-gene testing with next-generation sequencing (NGS). BRCA mutation prevalence in this cohort was 8.05% and the yield of the recurrent panel was 3.52%, identifying over 40% of the mutation carriers. Moreover, from 79 Chinese breast cancer cases recruited overseas, 2 recurrent mutations and one novel BRCA2 mutation were detected by the panel and NGS respectively. The developed genotyping panel showed to be an easy-to-perform and more affordable testing tool that can provide important contributions to improve the healthcare of Chinese women with cancer as well as family members that harbor high risk mutations for HBOC

Collaborative Gaze Channelling for Improved Cooperation During Robotic Assisted Surgery

The use of multiple robots for performing complex tasks is becoming a common practice for many robot applications. When different operators are involved, effective cooperation with anticipated manoeuvres is important for seamless, synergistic control of all the end-effectors. In this paper, the concept of Collaborative Gaze Channelling (CGC) is presented for improved control of surgical robots for a shared task. Through eye tracking, the fixations of each operator are monitored and presented in a shared surgical workspace. CGC permits remote or physically separated collaborators to share their intention by visualising the eye gaze of their counterparts, and thus recovers, to a certain extent, the information of mutual intent that we rely upon in a vis-à-vis working setting. In this study, the efficiency of surgical manipulation with and without CGC for controlling a pair of bimanual surgical robots is evaluated by analysing the level of coordination of two independent operators. Fitts' law is used to compare the quality of movement with or without CGC. A total of 40 subjects have been recruited for this study and the results show that the proposed CGC framework exhibits significant improvement (p<0.05) on all the motion indices used for quality assessment. This study demonstrates that visual guidance is an implicit yet effective way of communication during collaborative tasks for robotic surgery. Detailed experimental validation results demonstrate the potential clinical value of the proposed CGC framework. © 2012 Biomedical Engineering Society.link_to_subscribed_fulltex