LITERARY DESTINATIONS: MARK TWAIN'S HOUSES AND LITERARY TOURISM

Mark Twain has been commemorated for more than eighty-five years at his various houses. His birthplace in Florida, Missouri, his boyhood home in Hannibal, Missouri, his adult home in Hartford, Connecticut, and his summer retreat at Quarry Farm in Elmira, New York have all come to celebrate very different versions of the most iconic of American writers. This study examines the history of these four houses to illustrate how our memory of Twain has been shaped by sites of literary tourism. At each house, museum staffs have struggled to balance Samuel Clemens's biography with his literature and mythic persona. Though these literary house museums provide access to the famous homes that are associated with Clemens, they are mediated objects. The houses cannot display Clemens's domestic life without managerial interpretation. Clemens's birthplace, for example, has long been the subject of disputed authenticity. His boyhood home has, until very recently, substituted Hannibal's past for Tom Sawyer's story. His adult home is a Gilded Age museum that so perfectly recreated the "Mark Twain period," it sometimes overlooked Twain's literary contributions. Quarry Farm is a Twain scholar's paradise that actually allows visitors to write and live where Clemens did. Mark Twain's houses are places where local people have contributed to his popular canonization through preservation efforts and tourism. Clemens's place in the American canon was uncertain at the founding of three of these four sites. These house museums, in the end, may have done as much for Clemens as he did for them. However, to remain viable literary houses have to explain compellingly how they are central to understanding a writer's literary creativity. They have to articulate a connection to a literary text, to a specific writerly space, or to an atmosphere that was particular to the writer's literary production. They mediate a relationship between author, text, and tourists. This study contributes to literary studies and Mark Twain studies by explaining how visitation to and preservation of literary places influence the way we remember Mark Twain

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British Lung Foundation/United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51)

Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial

Background An estimated 15% of girls aged 9-14 years worldwide have been vaccinated against human papillomavirus (HPV) with the recommended two-dose or three-dose schedules. A one-dose HPV vaccine schedule would be simpler and cheaper to deliver. We report immunogenicity and safety results of different doses of two different HPV vaccines in Tanzanian girls. Methods In this open-label, randomised, phase 3, non-inferiority trial, we enrolled healthy schoolgirls aged 9-14 years from Government schools in Mwanza, Tanzania. Eligible participants were randomly assigned to receive one, two, or three doses of either the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart) or the 9-valent vaccine (Gardasil-9, Sanofi Pasteur MSD, Lyon). The primary outcome was HPV 16 specific or HPV 18 specific seropositivity following one dose compared with two or three doses of the same HPV vaccine 24 months after vaccination. Safety was assessed as solicited adverse events up to 30 days after each dose and unsolicited adverse events up to 24 months after vaccination or to last study visit. The primary outcome was done in the per-protocol population, and safety was analysed in the total vaccinated population. This study was registered in ClinicalTrials.gov, NCT02834637. Findings Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility. 72 girls were excluded. 930 girls were enrolled and randomly assigned to receive one dose of Cervarix (155 participants), two doses of Cervarix (155 participants), three doses of Cervarix (155 participants), one dose of Gardasil-9 (155 participants), two doses of Gardasil-9 (155 participants), or three doses of Gardasil-9 (155 participants). 922 participants received all scheduled doses within the defined window (three withdrew, one was lost to follow-up, and one died before completion; two received their 6-month doses early, and one received the wrong valent vaccine in error; all 930 participants were included in the total vaccinated cohort). Retention at 24 months was 918 (99%) of 930 participants. In the accordingto-protocol cohort, at 24 months, 99% of participants who received one dose of either HPV vaccine were seropositive for HPV 16 IgG antibodies, compared with 100% of participants who received two doses, and 100% of participants who received three doses. This met the prespecified non-inferiority criteria. Anti-HPV 18 seropositivity at 24 months did not meet non-inferiority criteria for one dose compared to two doses or three doses for either vaccine, although more than 98% of girls in all groups had HPV 18 antibodies. 53 serious adverse events (SAEs) were experienced by 42 (4.5%) of 930 girls, the most common of which was hospital admission for malaria. One girl died of malaria. Number of events was similar between groups and no SAEs were considered related to vaccination. Interpretation A single dose of the 2-valent or 9-valent HPV vaccine in girls aged 9-14 years induced robust immune responses up to 24 months, suggesting that this reduced dose regimen could be suitable for prevention of HPV infection among girls in the target age group for vaccination. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

The effectiveness of classroom vocabulary intervention for adolescents with language disorder

Purpose Phonological-semantic intervention has been shown to be effective in enhancing the vocabulary skills of children with language disorder in small-group or individual settings. Less is known about vocabulary interventions for adolescents with language disorder in whole-class models of delivery. The current study investigated the effectiveness of phonological-semantic vocabulary intervention for adolescents with language disorder, delivered by secondary school teachers within science lessons. Methods Seventy-eight adolescents with language disorder, aged 11 – 13 years, were taught science curriculum words by teachers in class, under two conditions: 1) 10 words taught through usual teaching practice; and 2) 10 matched words taught using an experimental intervention known as Word Discovery, which embedded phonological-semantic activities into the teaching of the syllabus. Ten similar control words received no intervention. Word knowledge was assessed pre-intervention, post-intervention, and follow-up. Results At pre-intervention, measures of depth of word knowledge and expressive word use did not differ between usual teaching practice and experimental words. At post-intervention, depth of knowledge of experimental words was significantly greater than that of usual teaching practice words. This significant advantage was not maintained at follow-up, although depth of knowledge for experimental words remained significantly higher at follow-up than at preintervention. At post-intervention, expressive use of experimental words was significantly greater than that of usual teaching practice words, and this significant difference was maintained at follow-up. There was no change in students’ depth of knowledge or expressive use of no-intervention words over time, confirming that the findings were not due to maturity or practice effects. Conclusion The experimental intervention was more effective than usual teaching practice in increasing the word knowledge of participants. Clinical and teaching implications include the importance of intervening during the adolescent years, with classroom vocabulary intervention being a viable option for collaborative teacher and speech and language therapy/pathology practice

Using dengue epidemics and local weather in Bali, Indonesia to predict imported dengue in Australia.

BACKGROUND: Although the association between dengue in Bali, Indonesia, and imported dengue in Australia has been widely asserted, no study has quantified this association so far. METHODS: Monthly data on dengue and climatic factors over the past decade for Bali and Jakarta as well as monthly data on imported dengue in Australia underwent a three-stage analysis. Stage I: a quasi-Poisson regression with distributed lag non-linear model was used to assess the associations of climatic factors with dengue in Bali. Stage II: a generalized additive model was used to quantify the association of dengue in Bali with imported dengue in Australia with and without including the number of travelers in log scale as an offset. Stage III: the associations of mean temperature and rainfall (two climatic factors identified in stage I) in Bali with imported dengue in Australia were examined using stage I approach. RESULTS: The number of dengue cases in Bali increased with increasing mean temperature, and, up to a certain level, it also increased with increasing rainfall but dropped off for high levels of rainfall. Above a monthly incidence of 1.05 cases per 100,000, dengue in Bali was almost linearly associated with imported dengue in Australia at a lag of one month. Mean temperature (relative risk (RR) per 0.5 °C increase: 2.95, 95% confidence interval (CI): 1.87, 4.66) and rainfall (RR per 7.5 mm increase: 3.42, 95% CI: 1.07, 10.92) in Bali were significantly associated with imported dengue in Australia at a lag of four months. CONCLUSIONS: This study suggests that climatic factors (i.e., mean temperature and rainfall) known to be conducive of dengue transmission in Bali can provide an early warning with 4-month lead time for Australia in order to mitigate future outbreaks of local dengue in Australia. This study also provides a template and framework for future surveillance of travel-related infectious diseases globally

Double-blind, 12 month follow-up, placebo-controlled trial of mifepristone on cognition in alcoholics: the MIFCOG trial protocol

Background: Increased levels of cortisol during acute alcohol withdrawal have been linked to cognitive deficits and depression. Preclinical research found that the glucocorticoid Type II receptor antagonist, mifepristone, prevented some of the neurotoxic effects of withdrawal and memory loss. Clinical trials have shown mifepristone effective in the treatment of depression. This study aims to examine the extent to which the glucocorticoid Type II receptor antagonist, mifepristone, when given to alcohol dependent males during the acute phase of alcohol withdrawal, will protect against the subsequent memory loss and depressive symptoms during abstinence from alcohol. Methods/Design: The study is a Phase 4 therapeutic use, “Proof of Concept” trial. The trial is a double-blind randomised controlled clinical trial of mifepristone versus inactive placebo. The trial aims to recruit 120 participants referred for an inpatient alcohol detoxification from community alcohol teams, who meet the inclusion criteria; 1) Male, 2) Aged 18–60 inclusive, 3) alcohol dependent for 5 or more years. A screening appointment will take place prior to admission to inpatient alcohol treatment units to ensure that the individual is suitable for inclusion in the trial in accordance with the inclusion and exclusion criteria. On admission participants are randomised to receive 600 mg a day of mifepristone (200 mg morning, afternoon and evening) for 7 days and 400 mg for the subsequent 7 days (200 mg morning and evening) or the equivalent number of placebo tablets for 14 days. Participants will remain in the trial for 4 weeks (at least 2 weeks as an inpatient) and will be followed up at 3, 6 and 12 months post randomisation. Primary outcome measures are cognitive function at week 3 and 4 after cessation of drinking and symptoms of depression over the 4 weeks after cession of drinking, measured using the Cambridge Neuropsychological Test Automated battery and Beck Depression Inventory, respectively. Secondary outcome measures are severity of the acute phase of alcohol withdrawal, alcohol craving, symptoms of protracted withdrawal and maintenance of abstinence and levels of relapse drinking at follow-up. Discussion: The current trial will provide evidence concerning the role of glucocorticoid Type II receptor activation in cognitive function and depression during acute alcohol withdrawal and the efficacy of treatment with mifepristone