An exploratory study of help-giving interactions occuring among a selected group of hospitalized mentally ill patients

Thesis (M.S.)--Boston Universit

Gene Therapy Approaches To Immune Tolerance Induction In Canine Hemophilia

A key issue in gene therapy is the immune response to the therapeutic transgene. This is especially important in applications where current treatments often elicit an antibody response, like hemophilia, where protein replacement therapy results in neutralizing antibodies (“inhibitors”) in ~25% of severe hemophilia A and 1-3% of severe hemophilia B patients. To test the ability of skeletal muscle-directed gene therapy to prevent an immune response, we used an inhibitor-prone dog model of severe hemophilia B to express a hyperactive factor IX (FIX) variant from skeletal muscle via adeno-associated viral (AAV) vector and observed curative levels of expression that lasted for \u3e3 years (ongoing observation). There was no evidence of an immune response even after immunological challenge with recombinant FIX protein that would normally provoke high-titer inhibitors in this model. In dogs that had been previously administered vector, we observed stable expression for \u3e8 years, and immune tolerance was maintained upon FIX challenge. Next, we investigated the ability of liver-directed gene therapy to reverse pre-existing inhibitor responses using three novel dog models of severe hemophilia A. We expressed canine factor VIII variants with increased secretion and activity relative to wild-type from the livers of four dogs by AAV vectors. All dogs had baseline high-titer inhibitors and would have a poor prognosis with current clinical protocols. One dog died during a spontaneous bleeding event after his inhibitor titer declined by \u3e90%, but the other dogs completely eradicated their inhibitors and expressed therapeutic levels of factor VIII at the last sample. Unlike protein replacement therapy, gene therapy results in stable, constitutive levels of factor. This constant expression appears crucial to inducing immune tolerance to protein replacement therapy or reversing pre-existing immune responses. Even in the most challenging hemophilia models of immune tolerance induction, expression from the vector was able to prevent an antibody response and induce tolerance to protein replacement therapy or completely eradicate pre-existing inhibitors in three of four dogs (one reduced inhibitor titer by \u3e90%). These results support the use of gene therapy to both induce immune tolerance in high-risk patient populations and provide therapeutic benefit after tolerance is achieved

Old Horse or The Sailor’s Grace

Old Horse is an old sea song (dating at least back to the 1830s, and probably long before that) that expresses sailors\u27 dissatisfaction with the quality of their food.https://digitalcommons.library.umaine.edu/songstorysamplercollection/1052/thumbnail.jp

Canaday-I-O

The major recurring theme in these folksongs from Maine and Maritime Canada is the flow of cultural products and people within the area of New Hampshire, Maine, and eastern Canada. But while this cultural and demographic exchange helped define the region, it did not mean there was no rivalry or animosity between states, provinces, or nations.https://digitalcommons.library.umaine.edu/songstorysamplercollection/1016/thumbnail.jp

The study of teacher morale in secondary schools

It is often argued by the teachers' organisations that salary levels and alterations in working conditions are the dominant factors in any change in the morale of teachers in our schools today However, previous research on 'morale states’, both in schools and other organisations, has indicated the existence of a wide range of factors which affect morale. The research which follows will show the existence of a web of 'social’ relationships which influence teacher morale. Basically, the study focusses on analyses of the views of ten 'mid-career’ teachers from secondary schools in a North of England education authority. Most of these are seen to be peculiar to the schools in which they work, being based on the characteristic structures, processes and organisational problems that they meet there. Often they are to do with 'critical incidents' involving senior personnel. However, it will be indicated that there are variables which are affecting the individual morale of these teachers which are subject to an increasing number of external constraints and issues* These are of a 'political' and/or 'economic' nature and many are linked to central government initiatives and policies on education