A study of fifteen female patients with chronic diseases in a public welfare hospital in Massachusetts.

Thesis (M.S.)--Boston Universit

Genetic contribution to radiographic severity in osteoarthritis of the knee

Objective Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10–8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases. Methods 3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index. Results No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011). Conclusions Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors

Our image of the child

Our image of the child influences our view of children, our relationship with, and expectations of them. An image of the child as unique, self-assured, capable, secure, loving, joyful, competent, the protagonist of their own learning and discovery, sets the parameters of engagement with children. The adult's role in promoting and consolidating this image begins with adults who intentionally build and models respectful relationships. Thus bullying, power over behaviours, are unacceptable and discouraged. One research question was examined in this online study: Is an adults' positive image of the child aligned with an authoritative paradigm of teaching and learning? Findings from this study form part of a larger study examining the adults' role in building young children's social capacity. Findings are intended to fill the gap in the research literature by identifying the positive image of the child with authoritatively teaching young children social behaviour. Participants in this study are staff and parents of the Indooroopilly Montessori Children's Centre, Brisbane, Australia. A total of 25 participants responded to an online survey: 7 staff (Female = 7, Male = 0) and 18 parents (Females = 17, Males = 1). Respondents recorded their image of the child as a lifelong learner, active, curious, capable and confident individual. Findings identified children as lifelong learners in supportive relationships with trustworthy adults. Findings further identified that adults teach in ways that enable children to develop a positive sense of identity, by fostering wellbeing and connectedness with others in the social world. This teaching is based on secure, respectful, responsive, and reciprocal relationships between adults and children, and is enacted within teaching and learning environments that promote justice, beneficence, and peace

State-Funded Fictions: The NEA and the Making of American Literature After 1965

This dissertation studies the effects of a patronage institution, the National Endowment for the Arts Literature Program, on American literary production in the postwar era. Though American writers had long cultivated informal relationships with government patrons, the National Endowment for the Arts (NEA) reflected a new investment in the aesthetic life of the nation. By awarding grants to citizens without independent resources for work yet to be produced, it changed both the demographics of authorship and the idea of the “professional” writer. The grants also generated new themes for fiction as well as new civic roles for writers themselves. The central argument of “State-Funded Fictions” is literary-historical: state funding resulted in the development of what I call the compromise aesthetic: fiction that combines realism and experimentalism in order to appeal to readers across the educational (and political) spectrum. This is the resolution of a set of dynamic tensions inherent in welfare state liberalism and enacted by writers involved in the agency’s initiatives. Ralph Ellison, a public servant and an architect of the NEA Literature Program, championed the artist’s individual freedom as a way of advancing the collective good. Tillie Olsen advocated for a more democratic literary world with more accessible resources, but her rhetoric and writing preserved the ideas of meritocracy and literary excellence. Raymond Carver and the writers of minimalist short fiction—Bobbie Ann Mason among them—produced fiction that navigated between populism and elitism in an increasingly polarized political climate. Contemporary writers achieve a different kind of compromise, both aesthetically and politically, in realist fiction that acknowledges critiques of state power without suggesting revolutionary action. Taken together, the literary products of federal patronage attest to the intimate relationship between aesthetics and politics in the twentieth century and beyond.Englis

Imported falciparum malaria among adults requiring intensive care: analysis of the literature.

BACKGROUND: Malaria is the most important imported tropical disease. Infection with Plasmodium falciparum is responsible for most of the morbidity and mortality. There are differences in both the epidemiology of imported malaria and in the facilities available to treat travellers with severe malaria between different parts of the world. There are limited data to guide clinicians caring for adults with imported malaria in an intensive care unit (ICU). Available data from the English-speaking literature concerning such patients was reviewed. METHODS: PubMed was searched for studies on adults with imported malaria treated in an ICU. Data were extracted on the epidemiology, management, rates of concomitant community-acquired bacterial infection and outcomes. RESULTS: Thirteen studies were identified, which between them included 1,001 patients over more than 40 years. Forty-one per cent were born and often still resident in an endemic country and were assumed to have at least partial immunity to the disease. Acute kidney injury (AKI) (36%), acute respiratory distress syndrome (ARDS) (31%) and impaired consciousness (25%) were common. Hyperparasitaemia (more than 2%) was seen in 57%. Thirty-four per cent required mechanical ventilation and 22% required renal replacement therapy. Community-acquired bacterial co-infection was seen in 8%; 2% had gram-negative bacteraemia at admission. Overall the case fatality rate was 9%. CONCLUSIONS: Many patients who require admission to ICU were originally from malaria-endemic countries and many did not have hyperparasitaemia. Gram-negative bacteraemia was uncommon among adults with severe malaria. The case fatality rate remains high; however, improvements in ICU care and increasing use of artemisinins may reduce this in the future

Gametocyte carriage in Plasmodium falciparum-infected travellers.

BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease

The genetic contribution to severe post-traumatic osteoarthritis

Objective: to compare the combined role of genetic variants loci associated with risk of knee or hip osteoarthritis (OA) in post-traumatic (PT) and non-traumatic (NT) cases of clinically severe OA leading to total joint replacement. Methods: A total of 1590 controls, 2168 total knee replacement (TKR) cases (33.2% PT) and 1567 total hip replacement (THR) cases (8.7% PT) from 2 UK cohorts were genotyped for 12 variants previously reported to be reproducibly associated with risk of knee or hip OA. A genetic risk score was generated and the association with PT and NT TKR and THR was assessed adjusting for covariates. Results: For THR, each additional genetic risk variant conferred lower risk among PT cases (OR=1.07, 95% CI 0.96 to 1.19; p=0.24) than NT cases (OR 1.11, 95% CI 1.06 to 1.17; p=1.55×10−5). In contrast, for TKR, each risk variant conferred slightly higher risk among PT cases (OR 1.12, 95% CI 1.07 to 1.19; p=1.82×10−5) than among NT cases (OR 1.08, 95% CI 1.03 to 1.1; p=0.00063). Conclusions: Based on the variants reported to date PT TKR cases have at least as high a genetic contribution as NT cases

Geographical and temporal trends in imported infections from the tropics requiring inpatient care at the Hospital for Tropical Diseases, London - a 15 year study.

BACKGROUND: Understanding geographic and temporal trends in imported infections is key to the management of unwell travellers. Many tropical infections can be managed as outpatients, with admission reserved for severe cases. METHODS: We prospectively recorded the diagnosis and travel history of patients admitted between 2000 and 2015. We describe the common tropical and non-tropical infectious diseases and how these varied based on region, reason for travel and over time. RESULTS: A total of 4362 admissions followed an episode of travel. Falciparum malaria was the most common diagnosis (n=1089). Among individuals who travelled to Africa 1206/1724 (70.0%) had a tropical diagnosis. The risk of a tropical infection was higher among travellers visiting friends and relatives than holidaymakers (OR 2.8, p<0.001). Among travellers to Asia non-tropical infections were more common than tropical infections (349/782, 44.6%), but enteric fever (117, 33.5%) of the tropical infections and dengue (70, 20.1%) remained important. The number of patients admitted with falciparum malaria declined over the study but those of enteric fever and dengue did not. CONCLUSIONS: Most of those arriving from sub-Saharan Africa with an illness requiring admission have a classical tropical infection, and malaria still predominates. In contrast, fewer patients who travelled to Asia have a tropical diagnosis but enteric fever and dengue remain relatively common. Those visiting friends and relatives are most likely to have a tropical infection

Preferential Th1 Cytokine Profile of Phosphoantigen-Stimulated Human Vγ9Vδ2 T Cells

Human Vγ9Vδ2 T cells recognise pyrophosphate-based antigens (phosphoantigens) and have multiple functions in innate and adaptive immunity, including a unique ability to activate other cells of the immune system. We used flow cytometry and ELISA to define the early cytokine profiles of Vγ9Vδ2 T cells stimulated in vitro with isopentenyl pyrophosphate (IPP) and (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP) in the absence and presence of IL-2 and IL-15. We show that fresh Vγ9Vδ2 T cells produce interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) within 4 hours of stimulation with phosphoantigen, but neither IL-10, IL-13, nor IL-17 was detectable up to 72 hours under these conditions. Cytokine production was not influenced by expression or lack, thereof, of CD4 or CD8. Addition of IL-2 or IL-15 caused expansion of IFN-γ-producing Vγ9Vδ2 T cells, but did not enhance IFN-γ secretion after 24–72 hours. Thus, phosphoantigen-stimulated Vγ9Vδ2 T cells have potential as Th1-biasing adjuvants for immunotherapy