Oral particle uptake and organ targeting drives the activity of amphotericin B nanoparticles

There are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and stability. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure (relevant to nephrotoxic drugs). Our work demonstrates, for the first time, that oral particle uptake and translocation to specific organs may be used to achieve a beneficial therapeutic response. We have illustrated this using amphotericin B, a nephrotoxic drug encapsulated within <i>N</i>-palmitoyl-<i>N</i>-methyl-<i>N</i>,<i>N</i>-dimethyl-<i>N</i>,<i>N</i>,<i>N</i>-trimethyl-6-<i>O</i>-glycol chitosan (GCPQ) nanoparticles, and have evidenced our approach in three separate disease states (visceral leishmaniasis, candidiasis, and aspergillosis) using industry standard models of the disease in small animals. The oral bioavailability of AmB-GCPQ nanoparticles is 24%. In all disease models, AmB-GCPQ nanoparticles show comparable efficacy to parenteral liposomal AmB (AmBisome). Our work thus paves the way for others to use nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index

Theme of rootlessness in West Indian fiction

This thesis acknowledges that a combination of circumstances has produced in the West Indies an almost wholly-immigrant population whose fundamental condition is one of rootlessness. It attempts to show that rootlessness manifests itself negatively in the literature in an inability to regard the West Indies as home, in the placelessness that is brought about by emigration, in an uncertainty as to identity, allegiances and origins, and in an existential self-alienation produced by acculturation. Chapter One is a selective account of relevant historical and sociological data that demonstrates how the condition of rootlessness and the accompanying feeling of loss and deprivation arose. It ends by trying to draw a parallel between the particular West Indian condition of rootlessness that sprang from a slave society and existential rootlessness as generally understood by Western philosophy. Chapters Two, Three and Four are studies of selected prose texts which treat this theme. The texts are grouped according to their setting. Chapter Two attempts a detailed analysis of three novels set in the West Indies which depict the rootlessness of an individual or sector of society against a larger uncreated society. They reflect two fundamental reactions to the condition of rootlessness — refusal to come to terms with the environment, and its opposite, the attempt to ground one's existence meaningfully. The novels that have been selected are: Patterson’s The Children of Sisyphus, Naipaul’s A House For Mr. Biswas and Lamming’s Season of Adventure. The world of the immigrant is explored in Chapter Three. Austin Clarke’s The Meeting Point is set in Canada while Selvon’s The Lonely Londoners and Salkey’s The Adventures of Catullus Kelly are set in England. In these novels, the characters are cut adrift of any moorings and their rootlessness exacerbated in an even more alien environment in which they are totally disoriented. The Afro/Asian/European search for origins in the ancestral homeland and the chasm that separates the West Indian from his origins form the subject of Chapter Four. Naipaul’s Area of Darkness, Dennis Williams’ Other Leopards, and Jean Rhys’ Wide Sargasso Sea and Voyage In The Dark demonstrate the impossibility of return, and the irreconcilability of the two worlds and the sensibilities born of them.Arts, Faculty ofEnglish, Department ofGraduat

An exploratory study aimed to determine the efficacy of an assessment battery designed to examine oral English language acquisition in refugee and migrant children.

The process of migration has resulted in population growth and contributed to the transformation of New Zealand. Migrant and refugee children face many adjustment factors and their ease in resettling in New Zealand is largely dependent on their ability to learn English. Migration stress, change, trauma and loss may result in psychological difficulties which in turn may affect their resettling and learning. The Ministry of Education and other professionals work together to enhance the quality of their service provision to facilitate easier adjustment, resettlement and effective learning for these children. An adequate assessment battery for speech language therapists to assess migrant and refugee children, is presently lacking in New Zealand. Therapists currently use various assessments, with the assistance of interpreters. The New Zealand Speech Therapists’ Association (NZSTA), in accordance with speech therapists in Group Special Education (GSE), strongly supports the need for research with these groups and the development of an appropriate assessment battery. This exploratory study aimed to determine an assessment battery for use in examining English language acquisition in refugee and migrant children and to highlight the benefit of using measurement tools that determine incremental change over time in contrast to the use of monolingual psychometric tests. The study explored a selected assessment battery and gathered data in five main focus areas, namely: cognition, language, trauma, classroom behaviour, developmental and birth information. Eligible children were those who did not have physiologically - impaired cognitive abilities. Eight cases, four refugee and four migrant students, were selected by convenience sampling. All participants were children selected from primary school 1 (three refugees and three migrants) and primary school 2 (one refugee and one migrant) primary schools, aged approximately (5-8 years). Participants included four male and four females, refugee and migrant children, and those with both high and low English ability. Based on the study’s results, recommendations were made to refine the test battery, which included test modification. For example, the use of the trauma measurement tool only if there is prior evidence of trauma, the inclusion of a larger test population who have a common primary language to allow for cost effective interpreter use and to also allow for generalisations to be made, the inclusion of an assessment of the children’s primary language in order to determine the relationship, development and acquisition of the child’s second language with reference to his/her development and skills in his native language. All of the refugee children and 3 migrant children displayed slower processing time during the administration of the tests. Migrant parents were quicker in test completion as compared to refugee parents. They displayed differences in family size, contact with extended family, socioeconomic status and educational level. Migrant children produced sentences that included correct word order and sequence whilst refugee children produced sentences that lacked adequate word order or lacked articles and determiners. The study found the proposed test battery was an effective choice for use in the assessment of both migrant and refugee children, as the battery allows for dynamic assessment of children from diverse groups and this proved to be an unbiased means of assessing their English language and cognitive skills. Recommendations are made for future, more-extensive research. These findings provide information about appropriate and reliable language acquisition tests that measure incremental change with time. This study will contribute to a developing knowledge base for speech-language therapists who work with migrant or refugee children. Effective assessment on which to base tailored language programmes will assist them to optimise their experience in New Zealand schools and enhance their English language skills

L'inconfort des passagers causé par les moteurs dans un avion

Dans la cabine d’un avion, l’une des raisons d’inconfort des passagers est due aux bruits et aux vibrations générés par la rotation des moteurs. En effet, les moteurs engendrent des excitations sinusoïdales mono-fréquentielles liées à un équilibrage imparfait. La fréquence (entre 25 et 55 Hz) et l’amplitude des stimuli varient en fonction des paramètres de vol. Cette étude traite de l’influence de la fréquence et du niveau de bruit et de vibration sur l’évaluation de l’inconfort. L’objectif est de construire un modèle d’inconfort global. Des expériences de perception ont été réalisées dans un laboratoire, sur un moyen d’essai permettant de contrôler des stimuli sonores et vibratoires. Les participants ont évalué séparément l’inconfort vibratoire, sonore et global. Pour chaque participant et pour chaque stimulus l’accélération au pied, au dossier, à l’assise et aux accoudoirs a été mesurée. Les résultats ont montré, comme attendu, que l’inconfort sonore ou vibratoire dépend du niveau ; en revanche, aucune influence de la fréquence n’a été détectée. De plus, l’inconfort global semble fortement dépendre de l’inconfort vibratoire

Global and local temporal processing in audition, and the influence of musical expertise

International audienc