Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians

PURPOSE: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians. METHODS: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays. Chi square analysis was used to test for association of allele and genotype with overall AIH, and with severe fibrosis and ALT levels at 6 months. RESULTS: Significant risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI 1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed that rs2187668 was independently associated with type 1 AIH susceptibility (OR = 2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of FAS SNP rs1800682 was associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI 1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015). CONCLUSIONS: This is the first population-based study to investigate genetic risk loci for type 1 AIH in New Zealand Caucasians. We report significant independent association of HLA-DRB1*03:01 with overall susceptibility to type 1 AIH, as well as FAS with a more aggressive disease phenotype

Harnessing mental imagery and enhancing memory specificity: Developing a brief early intervention for depressive symptoms in adolescence

Background Treatment innovation for depressive symptoms in adolescence is urgently needed. Adult research suggests interventions targeting underlying cognitive mechanisms, such as dysfunctional mental imagery and overgeneral memory, are promising. Here, we describe and evaluate in a case series a brief imagery-based intervention for depressive symptoms that targets these cognitive mechanisms. Methods Nine participants completed the four-session intervention, whose principle components were imagery rescripting and memory specificity training. Questionnaires and experimental tasks (assessing symptomatology and cognitive mechanisms) were administered at three time points: pre-intervention, post-intervention and 3-month follow-up. Results The intervention was feasible to deliver and acceptable to participants. There was a large reduction in depression symptom scores from pre to post intervention (d = 1.32; 67% showed reliable improvement, RI) and this was maintained at follow-up (d = 1.46; RI = 75%). There were also reductions in anxiety (post: d = 1.15, RI = 44%; follow-up: d = 1.67, RI = 63%), increases in self-esteem (post: d = − 0.70, RI = 44%; follow-up: d = − 1.20, RI = 50%) and noteworthy changes in memory specificity (post: d = − 1.80, RI = 67%; follow-up: d = − 0.94, RI = 63%). Conclusions This is the first study to use imagery rescripting and memory specificity training in adolescence. Initial evidence is provided that the intervention is acceptable and may have clinical utility. Future randomised controlled trials are needed to further assess the intervention

"On the Spot": travelling artists and Abolitionism, 1770-1830

Until recently the visual culture of Atlantic slavery has rarely been critically scrutinised. Yet in the first decades of the nineteenth century slavery was frequently represented by European travelling artists, often in the most graphic, sometimes voyeuristic, detail. This paper examines the work of several itinerant artists, in particular Augustus Earle (1793-1838) and Agostino Brunias (1730–1796), whose very mobility along the edges of empire was part of a much larger circulatory system of exchange (people, goods and ideas) and diplomacy that characterised Europe’s Age of Expansion. It focuses on the role of the travelling artist, and visual culture more generally, in the development of British abolitionism between 1770 and 1830. It discusses the broad circulation of slave imagery within European culture and argues for greater recognition of the role of such imagery in the abolitionist debates that divided Britain. Furthermore, it suggests that the epistemological authority conferred on the travelling artist—the quintessential eyewitness—was key to the rhetorical power of his (rarely her) images. Artists such as Earle viewed the New World as a boundless source of fresh material that could potentially propel them to fame and fortune. Johann Moritz Rugendas (1802-1858), on the other hand, was conscious of contributing to a global scientific mission, a Humboldtian imperative that by the 1820s propelled him and others to travel beyond the traditional itinerary of the Grand Tour. Some artists were implicated in the very fabric of slavery itself, particularly those in the British West Indies such as William Clark (working 1820s) and Richard Bridgens (1785-1846); others, particularly those in Brazil, expressed strong abolitionist sentiments. Fuelled by evangelical zeal to record all aspects of the New World, these artists recognised the importance of representing the harsh realities of slave life. Unlike those in the metropole who depicted slavery (most often in caustic satirical drawings), many travelling artists believed strongly in the evidential value of their images, a value attributed to their global mobility. The paper examines the varied and complex means by which visual culture played a significant and often overlooked role in the political struggles that beset the period

Towards a method for cryopreservation of mosquito vectors of human pathogens

Mosquito-borne diseases are responsible for millions of human deaths every year, posing a massive burden on global public health. Mosquitoes transmit a variety of bacteria, parasites and viruses. Mosquito control efforts such as insecticide spraying can reduce mosquito populations, but they must be sustained in order to have long term impacts, can result in the evolution of insecticide resistance, are costly, and can have adverse human and environmental effects. Technological advances have allowed genetic manipulation of mosquitoes, including generation of those that are still susceptible to insecticides, which has greatly increased the number of mosquito strains and lines available to the scientific research community. This generates an associated challenge, because rearing and maintaining unique mosquito lines requires time, money and facilities, and long-term maintenance can lead to adaptation to specific laboratory conditions, resulting in mosquito lines that are distinct from their wild-type counterparts. Additionally, continuous rearing of transgenic lines can lead to loss of genetic markers, genes and/or phenotypes. Cryopreservation of valuable mosquito lines could help circumvent these limitations and allow researchers to reduce the cost of rearing multiple lines simultaneously, maintain low passage number transgenic mosquitoes, and bank lines not currently being used. Additionally, mosquito cryopreservation could allow researchers to access the same mosquito lines, limiting the impact of unique laboratory or field conditions. Successful cryopreservation of mosquitoes would expand the field of mosquito research and could ultimately lead to advances that would reduce the burden of mosquito-borne diseases, possibly through rear-and-release strategies to overcome mosquito insecticide resistance. Cryopreservation techniques have been developed for some insect groups, including but not limited to fruit flies, silkworms and other moth species, and honeybees. Recent advances within the cryopreservation field, along with success with other insects suggest that cryopreservation of mosquitoes may be a feasible method for preserving valuable scientific and public health resources. In this review, we will provide an overview of basic mosquito biology, the current state of and advances within insect cryopreservation, and a proposed approach toward cryopreservation of Anopheles stephensi mosquitoes

Challenges experienced with early introduction and sustained consumption of allergenic foods in the Enquiring About Tolerance (EAT) study: A qualitative analysis.

BACKGROUND: The early introduction group participants of the Enquiring About Tolerance study were asked to undertake a proscriptive regimen of early introduction and sustained consumption of 6 allergenic foods. It was envisaged that this might be challenging, and early introduction group families were presented with an open-text question to express any problems they were experiencing with the regimen in recurring online questionnaires. OBJECTIVE: We sought to analyze these open-text questionnaire responses with the aim of identifying challenges associated with the introduction and regular consumption of allergenic foods. METHODS: Three combinations of interim questionnaire responses were selected for analysis, representing the early period (4, 5, and 6 months), middle period (8 and 12 months), and late period (24 and 36 months) of participation in the Enquiring About Tolerance study. Responses were assigned a code to describe their content and subsequently grouped into themes to portray key messages. A thematic content analysis allowed for conversion of qualitative codes into quantitative summaries. RESULTS: Three main challenges to allergenic food consumption were identified. First, some children refused the allergenic food, causing a sense of defeat among caregivers. Second, caregivers were concerned that allergenic foods might be causing a reaction, triggering a need for reassurance. Third, practical problems associated with the regimen compromised caregivers' capacity to persist. CONCLUSION: Understanding the challenges experienced with allergenic food introduction and sustained consumption is the necessary precursor to developing specific communication and support strategies that could be used by caregivers, practitioners, policymakers, and key stakeholders to address these problems

Efficacy of the Enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy.

BACKGROUND: The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction of allergenic solids into the infant diet from 3 months of age. The intervention effect did not reach statistical significance in the intention-to-treat analysis of the primary outcome. OBJECTIVE: We sought to determine whether infants at high risk of developing a food allergy benefited from early introduction. METHODS: A secondary intention-to-treat analysis was performed of 3 groups: nonwhite infants; infants with visible eczema at enrollment, with severity determined by SCORAD; and infants with enrollment food sensitization (specific IgE ≥0.1 kU/L). RESULTS: Among infants with sensitization to 1 or more foods at enrollment (≥0.1 kU/L), early introduction group (EIG) infants developed significantly less food allergy to 1 or more foods than standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P = .03), and among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02). CONCLUSION: Early introduction was effective in preventing the development of food allergy in specific groups of infants at high risk of developing food allergy: those sensitized to egg or to any food at enrollment and those with eczema of increasing severity at enrollment. This efficacy occurred despite low adherence to the early introduction regimen. This has significant implications for the new national infant feeding recommendations that are emerging around the world

Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen.

BACKGROUND: The influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain. OBJECTIVE: We sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance. METHODS: We performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age. RESULTS: One thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age). CONCLUSION: Early introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies

Rethinking the fall of the planter class

This issue of Atlantic Studies began life as a one-day conference held at Chawton House Library in Hampshire, UK, and funded by the University of Southampton. The conference aimed, like this issue, to bring together scholars currently working on the history of the British West Indian planter class in the eighteenth and nineteenth centuries and to discuss how, when, and why the fortunes of the planters went into decline. As this introduction notes, the difficulties faced by the planter class in the British West Indies from the 1780s onwards were an early episode in a wider drama of decline for New World plantation economies. The American historian Lowell Ragatz published the first detailed historical account of their fall. His work helped to inform the influential arguments of Eric Williams, which were later challenged by Seymour Drescher. Recent research has begun to offer fresh perspectives on the debate about the decline of the planters, and this collection brings together articles taking a variety of new approaches to the topic, encompassing economic, political, cultural, and social histor