Fabrication and testing of microfluidic devices for blood cell separation

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.Blood separation is a strategic preliminary step in preparation to on-chip biological analysis. Two microfluidic devices for on-chip blood separation are presented. Both devices will be integrated to form the separation module of a Lab on Chip for non-invasive prenatal diagnosis. In the first device, a blood plasma separator, the separation of blood cells from plasma is made possible in microchannels by bio-physical effects such as an axial migration effect and Zweifach-Fung bifurcation law. Behaviour of mussel and human blood suspensions were studied alongside the effect of different geometries. The second device aims to separate fetal nucleated red blood cells based on their magnetic susceptibility. Biocompatible materials are used in the manufacturing of both devices.The authors acknowledge the financial support of the Engineering and Physical Science Research Council (EPSRC) through the funding of the Grand Challenge Project ‘3DMintegration’, reference EP/C534212/1. This work has also been supported by the EPSRC through a Doctoral Training Account (DTA) and has been performed at the Microsystems Engineering Centre (MISEC), Heriot-Watt University, Edinburgh. We thank Tim Ryan and Phil Summersgill, Epigem Ltd. for the fabrication of the blood plasma chips. The fabrication work was carried out in the Fluence Microfluidics Application Centre supported by the DTI and the OneNE Regional Development Agency as part of the UK's MNT Network

Evaluation of Direct Rapid Immunohistochemistry Test (DRIT) for Postmortem Diagnosis of Rabies

Direct fluorescent antibody test (DFAT) is considered as the gold standard for diagnosis of rabies in infected mammals as it has high sensitivity and specificity. However, high cost and technical demand limits its utilization, particularly in developing countries including India. Therefore, in this study we evaluated recently developed direct rapid immunohistochemistry test (DRIT) for diagnosis of rabies in comparison with the DFAT. A total of 109 brain samples received during the period of 6 years from different regions of India were tested following standard protocol. The results showed 100% correlation between the two tests.

Visceral leishmaniasis cyclical trends in Bihar, India – implications for the elimination programme. [version 1; referees: 1 approved, 2 approved with reservations]

Background: Visceral leishmaniasis (VL) is a vector-borne disease of public health importance in India, with the highest burden of disease in the states of Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently targeted for elimination (annual incidence to less than one per 10,000 population) using indoor residual spraying, active case detection and treatment. Historically the disease trend in India has been regarded as cyclical with case resurgence characteristically occurring every 15 years.  Understanding this pattern is essential if the VL elimination gains are to be sustained. To better understand the cyclical trends, annual climatic indicators including rainfall, temperature and humidity over time were compared with annual VL case incidence data.  Methods: Annual climate data (rainfall, average and maximum temperature and specific humidity) from 1956-2004 were used to identify potential factors influencing VL incidence.  Months relevant to the VL life-cycle were identified and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis. The Kruskall-Wallis test was used to determine significant difference between categorical rainfall and VL incidence, whilst univariate negative binomial regression models were used to determine predictors of disease incidence. Results: The negative binomial regression model showed statistically significant associations (p 0.05).  Conclusion: The VL programme in Bihar has made significant progress in adopting best practices for improved treatment and vector control, with the aim to achieve VL elimination.  However, open access granular programme data for indoor residual spray activities and case detection is required to fully understand the role of climate in disease transmission and potential resurgence

A tablet computer-assisted motor and language skills training programme to promote communication development in children with autism: development and pilot study

Autism is a heterogenous condition, encompassing many different subtypes and presentations. Of those people with autism who lack communicative speech, some are more skilled at receptive language than their expressive difficulty might suggest. This disparity between what can be spoken and what can be understood correlates with motor and especially oral motor abilities, and thus may be a consequence of limits to oral motor skill. Point OutWords, tablet-based software targeted for this subgroup, builds on autistic perceptual and cognitive strengths to develop manual motor and oral motor skills prerequisite to communication by pointing or speaking. Although typical implementations of user-centred design rely on communicative speech, Point OutWords users were involved as co-creators both directly via their own nonverbal behavioural choices and indirectly via their communication therapists’ reports; resulting features include vectorised, high-contrast graphics, exogenous cues to help capture and maintain attention, customisable reinforcement prompts, and accommodation of open-loop visuomotor control

Adaptation of a malaria surveillance system for use in a visceral leishmaniasis elimination programme.

Background: Successful public practice relies on generation and use of high-quality data. A data surveillance system (the Disease Data Management System [DDMS]) in use for malaria was adapted for use in the Indian visceral leishmaniasis elimination programme. Methods: A situational analysis identified the data flows in current use. Taxonomic trees for the vector of visceral leishmaniasis in India, Phlebotomus argentipes, were incorporated into the DDMS to allow entry of quality assurance and insecticide susceptibility data. A new quality assurance module was created to collate the concentration of DDT that was applied to walls during the indoor residual spraying (IRS) vector control programme. Results: The DDMS was implemented in Bihar State and used to collate and manage data from sentinel sites in eight districts. Quality assurance data showed that DDT was under-applied to walls during IRS; this, combined with insecticide susceptibility data showing widespread vector resistance to DDT prompted a national policy change to using compression pumps and alpha-cypermethrin insecticide for IRS. Conclusions: The adapted DDMS centralises programmatic data and enhances evidence-based decision making and active policy change. Moving forward, further modules of the system will be implemented, allowing extended data capture and streamlined transmission of key information to decision makers

IL-33-dependent Type 2 inflammation during rhinovirus-induced asthma exacerbations in vivo

Rationale: Rhinoviruses are the major cause of asthma exacerbations; however, its underlying mechanisms are poorly understood. We hypothesized that the epithelial cell–derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. Objectives: To assess whether rhinovirus induces a type 2 inflammatory response in asthma in vivo and to define a role for IL-33 in this pathway. Methods: We used a human experimental model of rhinovirus infection and novel airway sampling techniques to measure IL-4, IL-5, IL-13, and IL-33 levels in the asthmatic and healthy airways during a rhinovirus infection. Additionally, we cultured human T cells and type 2 innate lymphoid cells (ILC2s) with the supernatants of rhinovirusinfected bronchial epithelial cells (BECs) to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. Measurements and Main Results: IL-4, IL-5, IL-13, and IL-33 are all induced by rhinovirus in the asthmatic airway in vivo and relate to exacerbation severity. Further, induction of IL-33 correlates with viral load and IL-5 and IL-13 levels. Rhinovirus infection of human primary BECs induced IL-33, and culture of human T cells and ILC2s with supernatants of rhinovirus-infected BECs strongly induced type 2 cytokines. This induction was entirely dependent on IL-33. Conclusions: IL-33 and type 2 cytokines are induced during a rhinovirus-induced asthma exacerbation in vivo. Virus-induced IL-33 and IL-33–responsive T cells and ILC2s are key mechanistic links between viral infection and exacerbation of asthma. IL-33 inhibition is a novel therapeutic approach for asthma exacerbation

Construct and face validity of SINERGIA laparoscopic virtual reality simulator

Purpose Laparoscopic techniques have nowadays become a gold standard in many surgical procedures, but they imply a more difficult learning skills process. Simulators have a fundamental role in the formative stage of new surgeons. This paper presents the construct and face validity of SINERGIA laparoscopic virtual reality simulator in order to decide whether it can be considered as an assessment tool. Methods Twenty people participated in this study, 14 were novices and 6 were experts. Five tasks of SINERGIA were included in the study: coordination, navigation, navigation and touch, precise grasping and coordinate traction. For each one of these tasks, a certain number of metrics are automatically recorded. All subjects accomplished each task only once and filled in two questionnaires. A statistical analysis was made and results from both groups were compared with the Mann–Whitney U-test, considering significant differences when P ≤ 0.05. Internal consistency of the system has been analyzed with the Cronbach’s alpha test. Results Novices and experts positively rated SINERGIA characteristics. At least one of the evaluated metrics of each exercise presented significant differences between both groups. Nevertheless, all metrics under study gave a better punctuation to the executions accomplished by experts (lower time, higher efficiency, fewer errors. . .) than to those made by novices. Conclusion SINERGIA laparoscopic virtual reality simulator is able to discriminate subjects according to their level of experience in laparoscopic surgery; therefore, it can be used within a training program as an assessment too