Aspect-Switching and Subordination: the Role of It-Clefts in Discourse

this paper, we explore a proposal, first put forward by Prince [1978], to the effect that it-clefts serve an apparently subordinating function in discourse. In addition to the cause-and-effect subordination noted by Prince, our own data reveals that clefts are also involved in temporal subordination, where the clefted material appears dissociated from the main time line. Using Scha and Polanyi's [1988] notation, we can draw a local discourse structure that illustrates the general subordination relation involved. However, this does not constitute an explanation of why subordination is effected by/t-cleft

Significance of Medicare and Medicaid Programs for the Practice of Medicine

The 1965 legislation that established Medicare and Medicaid declared that the Federal Government would not interfere in clinical medicine. Despite the original intent, Medicare and Medicaid have had tremendous influence on medical practice. In this article, we focus on four policy areas that illustrate the influence of CMS (and its predecessor agencies) on medical practice. We discuss the implications of the relationship between CMS and clinical medicine and how this relationship has changed over time. We conclude with thoughts about potential future efforts at CMS

User-centred design of flexible hypermedia for a mobile guide: Reflections on the hyperaudio experience

A user-centred design approach involves end-users from the very beginning. Considering users at the early stages compels designers to think in terms of utility and usability and helps develop the system on what is actually needed. This paper discusses the case of HyperAudio, a context-sensitive adaptive and mobile guide to museums developed in the late 90s. User requirements were collected via a survey to understand visitors’ profiles and visit styles in Natural Science museums. The knowledge acquired supported the specification of system requirements, helping defining user model, data structure and adaptive behaviour of the system. User requirements guided the design decisions on what could be implemented by using simple adaptable triggers and what instead needed more sophisticated adaptive techniques, a fundamental choice when all the computation must be done on a PDA. Graphical and interactive environments for developing and testing complex adaptive systems are discussed as a further step towards an iterative design that considers the user interaction a central point. The paper discusses how such an environment allows designers and developers to experiment with different system’s behaviours and to widely test it under realistic conditions by simulation of the actual context evolving over time. The understanding gained in HyperAudio is then considered in the perspective of the developments that followed that first experience: our findings seem still valid despite the passed time

Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity

Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance

Two treatments, one disease: childhood malaria management in Tanga, Tanzania

<p>Abstract</p> <p>Background</p> <p>In the Tanga District of coastal Tanzania, malaria is one of the primary causes of mortality for children under the age of five. While some children are treated with malaria medications in biomedical facilities, as the World Health Organization recommends, others receive home-care or treatment from traditional healers. Recognition of malaria is difficult because symptoms can range from fever with uncomplicated malaria to convulsions with severe malaria. This study explores why caregivers in the Tanga District of Tanzania pursue particular courses of action to deal with malaria in their children.</p> <p>Methods</p> <p>Qualitative data were collected through interviews with three samples: female caregivers of children under five (N = 61), medical practitioners (N = 28), and traditional healers (N = 18) in urban, peri-urban, and rural areas. The female caregiver sample is intentionally stratified to reflect the greater population of the Tanga District in level of education, marital status, gender of household head, religion, and tribal group affiliation. Qualitative data were counted, coded and analysed using NVivo7 software.</p> <p>Results</p> <p>Results indicate that a variety of factors influence treatment choice, including socio-cultural beliefs about malaria symptoms, associations with spiritual affliction requiring traditional healing, knowledge of malaria, and fear of certain anti-malaria treatment procedures. Most notably, some caregivers identified convulsions as a spiritual condition, unrelated to malaria. While nearly all caregivers reported attending biomedical facilities to treat children with fever (N = 60/61), many caregivers stated that convulsions are best treated by traditional healers (N = 26/61). Qualitative interviews with medical practitioners and traditional healers confirmed this belief.</p> <p>Conclusion</p> <p>Results offer insight into current trends in malaria management and have implications in healthcare policy, educational campaigns, and the importance of integrating traditional and biomedical approaches.</p

Understanding caretakers' dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate

BACKGROUND: Malaria kills. A single rectal dose of artesunate before referral can reduce mortality and prevent permanent disability. However, the success of this intervention depends on caretakers' adherence to referral advice for follow-up care. This paper explores the dilemma facing caretakers when they are in the process of deciding whether or not to transit their child to a health facility after pre-referral treatment with rectal artesunate. METHODS: Four focus group discussions were held in each of three purposively selected villages in Mtwara rural district of Tanzania. Data were analysed manually using latent qualitative content analysis. RESULTS: The theme "Caretakers dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate" depicts the challenge they face. Caretakers' understanding of the rationale for going to hospital after treatment--when and why they should adhere--influenced adherence. Caretakers, whose children did not improve, usually adhered to referral advice. If a child had noticeably improved with pre-referral treatment however, caretakers weighed whether they should proceed to the facility, balancing the child's improved condition against other competing priorities, difficulties in reaching the health facilities, and the perceived quality of care at the health facility. Some misinterpretation were found regarding the urgency and rationale for adherence among some caretakers of children who improved which were attributed to be possibly due to their prior understanding. CONCLUSION: Some caretakers did not adhere when their children improved and some who adhered did so without understanding why they should proceed to the facility. Successful implementation of the rectal artesunate strategy depends upon effective communication regarding referral to clinic

Establishment of a New Cell Line from Lepidopteran Epidermis and Hormonal Regulation on the Genes

When an insect molts, old cuticle on the outside of the integument is shed by apolysis and a new cuticle is formed under the old one. This process is completed by the epidermal cells which are controlled by 20-hydroxyecdysone (20E) and juvenile hormone. To understand the molecular mechanisms of integument remolding and hormonal regulation on the gene expression, an epidermal cell line from the 5th instar larval integument of Helicoverpa armigera was established and named HaEpi. The cell line has been cultured continuously for 82 passages beginning on June 30, 2005 until now. Cell doubling time was 64 h. The chromosomes were granular and the chromosome mode was from 70 to 76. Collagenase I was used to detach the cells from the flask bottom. Non-self pathogen AcMNPV induced the cells to apoptosis. The cell line was proved to be an epidermal cell line based on its unique gene expression pattern. It responded to 20E and the non-steroidal ecdysone agonist RH-2485. Its gene expression could be knocked down using RNA interference. Various genes in the cell line were investigated based on their response to 20E. This new cell line represents a platform for investigating the 20E signaling transduction pathway, the immune response mechanism in lepidopteran epidermis and interactions of the genes

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record