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

Supporting the development of climate-resilient water safety plans through a risk-screening framework for drinking water source protection

Climate change-induced impacts on water-quality challenge risk management of drinking water. Uncertainty around future changes and limited resources require approaches that enable prioritisation at regional or national scale for planning and adaptive intervention. This paper presents a framework for risk screening drinking water supplies, providing a staged approach to building the capacity for integrating climate change into risk management. The framework is applied to drinking water sources of the Scottish national drinking water provider, developing raw water trajectories for indicative water-quality parameters (water colour and Escherichia coli). It establishes baseline understanding of water-quality controls through multivariate statistical analysis. It incorporates climate and land-use change into the model using climate (UKCP18) and land-use projections. The results suggest potential higher organic carbon production in soils from increased production with higher temperature, combined with reduced dilution and drought effects from reductions in summer rainfall. For E. coli, risks arise through land-use change leading to potential agricultural intensification. The framework supports the targeted development of climate-resilient Water Safety Plans, prioritising systems most at risk of raw water-quality deteriorations. It emphasises source protection to maintain or improve regulatory compliance, minimise socioeconomic and environmental harms, and generate additional benefits

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

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

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

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

Information Asymmetries and the Value-Relevance of Cash Flow and Accounting Figures – Empirical Analysis and Implications for Managerial Accounting

While some of the modern performance measures used in managerial accounting rely on cash flow based figures others try to take advantage of the information content of accounting figures. However, whether the additional information content in the accrual components of earnings improves the internal performance measurement is an open empirical question. To shed light on this question, I examine the correlation between operating cash flows and earnings with firm's total shareholder returns. Using fixed firm effects regression methods for a large sample of German listed firms covering some 5,000 firm years, the analysis shows that generally operating cash flow and earnings are both positively correlated with total shareholder return. However, with increasing information asymmetry earnings become less correlated with the firm's stock market performance and operating cash flows dominate earnings in explaining total shareholder return (and vice versa). These results suggest that, the information content of accounting figures is only relevant in settings characterized by low information asymmetries and, thus, there is no one-size-fits-all performance measure for managerial accounting purposes