Capsule-based ultrasound-mediated targeted gastrointestinal drug delivery

Diseases which are prevalent in the gastrointestinal (GI) tract, such as Crohn's disease, are a topic of increasing concern because diagnosis and specific treatment are difficult and may be ineffective. New techniques are therefore sought after and this paper describes a proof-of-concept tethered capsule for targeted drug delivery (TDD) in the GI tract. The capsule consists of a camera, illumination, a drug delivery channel and an ultrasound (US) transducer. The transducer is described in detail, including a comparison of different piezoceramic materials that has been carried out. It was found that PZ54 (Ferroperm Piezoceramics, Kvistgaard, Denmark) was the most suitable material for our application. When driven at 4 Vpp, the outer diameter 5 mm PZ54 transducer operates at a frequency f = 4.05 MHz providing an acoustic pressure, Pac = 125 kPa, with a beam diameter, BD = 0.75 mm at the focus. Pressures in the range 50 - 300 kPa have been previously reported as suitable for sonoporation, a process vital in many TDD applications, so this is a promising result. Basic functional testing of the capsule was performed by supplying glass microbubbles (MBs) through the drug delivery channel into the US focus, monitored via the onboard camera. It was found that the acoustic radiation forces have a clear influence on the MBs, significantly changing their direction at the US focus. This suggests that drugs may be targeted to specific tissue in the GI tract by the new capsule. The results translate into a capsule configuration with the potential to be clinically and biologically useful

A prototype therapeutic capsule endoscope for ultrasound-mediated targeted drug delivery

The prevalence of gastrointestinal (GI) diseases such as Crohn’s disease, which is chronic and incurable, are increasing worldwide. Treatment often involves potent drugs with unwanted side effects. The technological–pharmacological combination of capsule endoscopy with ultrasound-mediated targeted drug delivery (UmTDD) described in this paper carries new potential for treatment of these diseases throughout the GI tract. We describe a proof-of-concept UmTDD capsule and present preliminary results to demonstrate its promise as an autonomous tool to treat GI diseases

A hydraulically driven colonoscope

BACKGROUND: Conventional colonoscopy requires a high degree of operator skill and is often painful for the patient. We present a preliminary feasibility study of an alternative approach where a self-propelled colonoscope is hydraulically driven through the colon. METHODS: A hydraulic colonoscope which could be controlled manually or automatically was developed and assessed in a test bed modelled on the anatomy of the human colon. A conventional colonoscope was used by an experienced colonoscopist in the same test bed for comparison. Pressures and forces on the colon were measured during the test. RESULTS: The hydraulic colonoscope was able to successfully advance through the test bed in a comparable time to the conventional colonoscope. The hydraulic colonoscope reduces measured loads on artificial mesenteries, but increases intraluminal pressure compared to the colonoscope. Both manual and automatically controlled modes were able to successfully advance the hydraulic colonoscope through the colon. However, the automatic controller mode required lower pressures than manual control, but took longer to reach the caecum. CONCLUSIONS: The hydraulic colonoscope appears to be a viable device for further development as forces and pressures observed during use are comparable to those used in current clinical practice

Working memory, reading ability and the effects of distance and typicality on anaphor resolution in children

We investigated the time course of anaphor resolution in children and whether this is modulated by individual differences in working memory and reading skill. The eye movements of 30 children (10?11 years) were monitored as they read short paragraphs in which (1) the semantic typicality of an antecedent and (2) its distance in relation to an anaphor were orthogonally manipulated. Children showed effects of distance and typicality on the anaphor itself and also on the word to the right of the anaphor, suggesting that anaphoric processing begins immediately but continues after the eyes have left the anaphor. Furthermore, children showed no evidence of resolving anaphors in the most difficult condition (distant atypical antecedent), suggesting that anaphoric processing that is demanding may not occur online in children of this age. Finally, working memory capacity and reading comprehension skill affect the magnitude and time course of typicality and distance effects during anaphoric processing

HelexKids:a word frequency database for Greek and Cypriot primary school children

In this article, we introduce HelexKids, an online written-word database for Greek-speaking children in primary education (Grades 1 to 6). The database is organized on a grade-by-grade basis, and on a cumulative basis by combining Grade 1 with Grades 2 to 6. It provides values for Zipf, frequency per million, dispersion, estimated word frequency per million, standard word frequency, contextual diversity, orthographic Levenshtein distance, and lemma frequency. These values are derived from 116 textbooks used in primary education in Greece and Cyprus, producing a total of 68,692 different word types. HelexKids was developed to assist researchers in studying language development, educators in selecting age-appropriate items for teaching, as well as writers and authors of educational books for Greek/Cypriot children. The database is open access and can be searched online at www.helexkids.org