A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.

Paul and death : a study in psychological coping

The present investigation looks into the attitudes toward death in Paul’s authentic letters, and puts them in relation to modern theories of psychological coping. Drawing on psychologically-oriented hermeneutic theory, and theories about psychological coping in particular, I argue that each case of psychological coping must be understood in its historical situation as strategies emanating from a specific person’s subjective appraisal (cf. Pargament, Lazarus and Folkman). Paul’s letters frequently refer to persecution and violent death. To aid in psychological coping is often integral to the purpose of the letters, which makes the perspective of psychological coping akin to their genre. In the course of a tentatively assumed chronological order of 1 Thessalonians, Galatians, 1 Corinthians, 2 Corinthians, Romans, Philippians, and Philemon, Paul moves from the perception of Jesus dying for the faithful to the understanding of dying with Jesus. His coping strategies concerning death are gradually transformed from conservative and deferring coping styles, to a more self-directing coping style, to collaborative and transformative coping styles, and finally to a new sense of deferring coping style in prison. The last case of deferring coping carries the traits of generosity and flexibility even in the face of death, which is in contrast to his previous letters. Through his correspondence, we see Paul’s attitude toward death transformed from denial to reaction, to processing, to acceptance (cf. Lindemann, Kübler-Ross, Bowlby, Parkes, among others). His strategies also shift in accordance with these understandings. Denial is accompanied by diversion, threat by aggression, processing by rumination, and acceptance by joy. The study shows the hermeneutic benefits of reading Paul’s letters as the rhetorically framed expressions of a person in a particular historical situation. The letters open small windows through which we can glimpse the coping process of a person of antiquity. In adopting the method of psychological exegesis, the study shows that the variety of attitudes toward death in Paul’s letters makes sense from the perspective of psychological coping. The psychological aspect of these letters is an underexamined richness that can extend into areas of contemporary individual and group identity, and from there to public policy and ethics.

Prenatal management, pregnancy and pediatric outcomes in fetuses with septated cystic hygroma

It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.

Elaboration of biscuits with oatmeal and fat palm with added L-leucine and calcium for sarcopenia

The objective of this study was to evaluate the effect of the addition of oatmeal and palm fat in the elaboration of biscuits with added L-leucine and calcium in order to develop a product for sarcopenia in the elderly. The biscuits, or cookies, were elaborated applying a central composite rotational design with surface response methodology, and the significant linear, quadratic and interaction terms were used in the second order mathematical model. Physical, physicochemical and sensory analyses were performed by a trained panel. Based on the best results obtained, three cookie formulations were selected for sensory evaluation by the target group and physicochemical determinations. The formulations with the highest sensory scores for appearance and texture and medium scores for color and expansion index were selected. The addition of calcium and leucine increased significantly the concentration of these components in the biscuits elaborated resulting in a cookie with more than 30% of DRI (Dietary Reference Intake) for calcium and leucine. The formulations selected showed high acceptance by the target group; therefore, they can be included in the diet of elderly with sarcopenia as a functional food.

Evaluation of a treatment program for individuals with an intellectual disability who have high risk behaviours

In the past two decades numerous programs have emerged to treat individuals with developmental disabilities who have sexual offending behaviours. There has, however been very few studies that systematically examine the effectiveness of long term treatment with this population. The present research examines the therapeutic outcomes of a multi-modal behaviour approach with six individuals with intellectual disabilities previously charged with sexual assault. The participants also exhibited severe behavioural challenges that included verbal aggression, physical aggression, destruction and self-injury. These six participants (5 males, 1 female) were admitted to a Long Term Residential Treatment Program (LTRTP), due to the severity of their behaviours and due to their lack of treatment success in other programs. Individualized treatment plans focused on the reduction of maladaptive behaviours and the enhancing of skills such as positive coping strategies, socio-sexual knowledge, life skills, recreation and leisure skills. The treatment program also included psychiatric, psychological, medical, behavioural and educational interventions. The participants remained in the Long Term Residential Treatment Program (LTRTP) program from 181 to 932 days (average of 1.5 years). Pre and post treatment evaluations were conducted using the following tools: frequency of target behaviours, Psychopathology Inventory for Mentally Retarded Adults (PIMRA), Emotional Problems Scale (EPS), Socio-Sexual Knowledge and Attitudes Assessment Tool (SSKAAT-R) and Quality of Life Questionnaire (QOL-Q). Recidivism rates and the need for re-hospitalization were also noted for each participant. By offering high levels of individualized interventions, all six participants showed a 37 % rate of reduction in maladaptive behaviours with zero to low rates of inappropriate sexualbehaviour, there were no psychiatric hospitalizations, and there was no recidivism for 5 of 6 participants. In addition, medication was reduced. Mental health scores on the PIMRA were reduced across all participants by 25 % and scores on the Quality of Life Questionnaire increased for all participants by an average of 72 %. These findings add to and build upon the existing literature on long term treatment benefits for individuals with a intellectual disability who sexually offend. By utilizing an individualized and multimodal treatment approach to reduce severe behavioural challenges, not only can the maladaptive behaviours be reduced, but adaptive behaviours can be increased, mental health concerns can be managed, and overall quality of life can be improved.

Memory mixed with desire : a preliminary study of philosophy and literature in the works of Friedrich Nietzsche and Milan Kundera

Memory Mixed with Desire: A preliminary study of Philosophy and Literature in the works of Friedrich Nietzsche and Milan Kundera Robert Spinelli Brock University, Department of Philosophy This thesis studies intertextuality in the works of Friedrich Nietzsche and Milan Kundera through the primary themes of memory and forgetting. The thesis starts with two introductory chapters that delineate memory according to Nietzsche and Kundera respectively. From here, I move into a discussion of Nietzsche's Ubermensch as an example of the type of forgetting that Nietzsche sees as a cure for the overabundance of memory that has led to Christian morality. Next, I explore the Kunderan concept of kitsch as the polar opposite of what Nietzsche has sought in his philosophy, finishing the chapter by tying the two thinkers together in a Kunderan critique of Nietzsche. The thesis ends with a chapter devoted to the Eternal Return beginning with an exegesis of Nietzsche's idea and ending with a similar exegesis of Kundera's treatment of this thought. What I suggest in this chapter is that the Eternal Return might itself be a form of kitsch even in its attempt to revalue existence.

Home schooling in view of John Calvin : a study in education and communion of saints /

This study explores the tension that has emerged around the rise of home schooling in a faith-community strongly committed to establishing and maintaining day schools in the tradition of John Calvin. It aims to identify and understand factors that contributed to this tension and to find ways to bridge, diffuse, reduce, or eliminate it. In line with Calvin, personal convictions, and the nature of the community, the study takes a Christian epistemological and axiological stance. Its premise is that the integrity of the commvmity is more important than the manner in which its children are taught. The study reviews relevant literature and several interviews. It considers both secular and Christian literature to understand communities, community breakdown, and community restoration. It also examines literature about the significance of home, school, and community relationships; the attraction of Reformed day schools; and the appeal of home schooling. Interviews were conducted with 4 home schooling couples and 2 focus groups. One focus group included local school representatives, and the other home schoolers and school representatives from an area with reputedly less tension on the issue. Interviews were designed for participants to give their perspectives on reasons for home schooling, the existing tension, and ways to resolve the issues. The study identifies the rise of home schooling in this particular context as the initial issue and the community's deficiency to properly deal with it as the chief cause for the rising tensions. However, I argue that, within the norms the community firmly believes in, home schooling need not jeopardize its integrity. I call for personal, social, and spiritual renewal to restore the covenant community in gratitude to God.

Childlessness in a child-centered environment : the experiences of voluntarily childless female teachers /

In the literature on voluntary childlessness there is a lack of research on the types of occupations held by women who choose not to mother and how their fertility choice influences their occupational experiences. At the same time, the experience ofwomen with regard to the childfree choice has not been adequately addressed in contemporary feminist literature. In the field of education, much has been written about the association between mothering and teaching. Thus, childfree teachers become particularly interesting since they made seemingly paradoxical choices in that they chose not to bear and rear children yet they chose an occupation in which they are surrounded by and responsible for the daily care of many children. To gain an understanding of the work-related experiences of childfree women, in-depth interviews were conducted with 7 voluntarily childless female elementary school teachers from Southern Ontario. In addition, a focus group interview in which 3 of the 7 childfree teachers participated was conducted. Findings revealed that these women's "choice" to be childless was the result of complex circumstances and multiple motivations. Also, despite their decision to forgo the traditional female role of mother, these women held surprisingly conventional beliefs with regard to family and gender roles. In addition, these childfree women at times identified themselves as mother-like when teaching, yet at other times distanced themselves as teachers from mothers. Finally, results showed that these women experienced both direct and indirect pronatalist pressures outside as well as inside the workplace as a result of their childfree status.

Educational issues perceived by expectant lesbian couples /

Despite the increasing public profile of lesbian childbearing, public health resources for expectant women often bear heterosexist assumptions and create barriers to accessing information relevant to lesbian mothering experiences. This descriptive, exploratory study examined one lesbian couple's perceived educational needs for effective support, barriers to access, strategies for locating care, and the impact of childbearing on their lives, as well as their reflections on inviting ways to offer supportive practices in a public health context. A case study approach used feminist ethnographic methodology and purposeful convenience sampling. A prenatal and a postnatal open-ended interview were completed with 1 white, middle-class, able, lesbian childbearing couple, each ofwhom has birthed as coparent and biological mother in this couple relationship. Despite this couple's immense situated privilege, they struggled to locate the support they sought for childbearing in a way that offered optimal emotional and physical care from the preconceptual to postpartum stages and which maintained confidentiality or anonymity as desired. They created meaningful care through personal networks. The findings were framed using invitational and feminist theories: how people, places, programs, processes, policies, and politics contributed to educational support. A three part conceptual framework emerged which identified components of access to support: perceived safety of resources, disclosure status, situated privilege, and public or private availability of information. The consequences of lack of public access to comprehensive childbearing care for lesbian women and their communities are described. Educational possibilities addressed systemic heterosexism through the development of sensitive educators, meaningful curriculum, program planning, explicit policies, community partnerships, and political leadership with respect to both institutional and research venues.

Underemployment and depressive affect : the moderating influence of coping styles /

This study tested a model which predicted the relationship between underemployment and depressive affect as moderated by coping styles. A randomly selected community sample of 574 young adults completed a self-report employment status measure, the Underemployment Scale, the Center for Epidemiological Study Depression Scale, and the Coping^Stralegy Indicator. The interaction model was supported for men only. Results indicated that significant interactions between Perceived Job Requirements Underemployment by avoidance copings and Subjective Underemployment by avoidance coping predicted depressive affect for men. Further, the same results were found even after controlling for prior depressive affect. UsingJhe^ selfreport employment status measure revealed significant group differences between unemployed and underemployed men. Underemployed men who utilized more support seeking coping strategies reported higher depressive affect than unemployed men. The interaction model was not supported for women even though women have consistently reported higher depressive affect rates. These results have implications for underemployment and depressive affect research and practical implications for assisting men who feel subjectively underemployed and need to find an appropriate strategy to cope with the situation.

Transforming curriculum leadership: vice principals in independent Christian elementary schools /

The literature on the vice principalship characterizes the position as one filled with clerical record keeping and student discipline and paints a picture of role conflict and general discontent. Research suggests that vice principals desire to take on a more significant role, specifically a role in curriculum leadership. Using open-ended interviews, a focus group interview, document analysis, and my research journal, I have explored the work ofa group of vice principals who have taken on the role of curriculum leader in independent Christian elementary schools in Ontario. When asked to explain their understanding of curriculum, the participants referred to written programs of study. However, their leadership activities reveal a broader understanding of curriculum as something that is in fact dynamic in nature. This leadership is enabled and shaped by their middle position on staff that combines the authority of an administrator and the credibility of a teacher. Although this dual identity creates tension, it also provides opportunities for genuine curriculum leadership. As middle leaders, the participants in this study often pull together or connect elements of the curriculum (teachers, principals, and programs) that have become separated. Such connective leadership is characterized by transformational (Van Brummelen, 2002) tendencies. This research suggests that the further along the continuum one goes from the understanding of curriculum as planned (Eisner, 1994) to acknowledging a lived curriculum (Aoki, 1993), the more transformational one's leadership style becomes.

The dual role of students with behavioural problems: an analysis of their experiences as bullies and victims /

The present study examined the bullying experiences of a group of students, age 10-14 years, identified as having behaviour problems. A total often students participated in a series of mixed methodology activities, including self-report questionnaires, story telling exercises, and interview style joumaling. The main research questions were related to the prevalence of bully/victims and the type of bullying experiences in this population. Questionnaires gathered information about their involvement in bullying, as well as about psychological risk factors including normative beliefs about antisocial acts, impulsivity, problem solving, and coping strategies. Journal questions expanded on these themes and allowed students to explain their personal experiences as bullies and victims as well as provide suggestions for intervention. The overall results indicated that all of the ten students in this sample have participated in bullying as both a bully and a victim. This high prevalence of bully/victim involvement in students from behavioural classrooms is in sharp contrast with the general population where the prevalence is about 33%. In addition, a common thread was found that indicated that these students who participated in this study demonstrate characteristics of emotionally dysregulated reactive bullies. Theoretical implication and educational practices are discussed.

A model of personality and health : coping styles as a moderator in the perfectionism-health connection

The purpose of this study was to examine a model of personality and health. Specifically, this thesis examined perfectionism as a predictor of health status and health behaviours, as moderated by coping styles. A community sample of 813 young adults completed the Multidimensional Perfectionism Scale, the Coping Strategy Indicator, and measures of health symptoms, health care utilization, and various health behaviours. Multiple regression analyses revealed a number of significant findings. First, perfectionism and coping styles contributed significant main effects in predicting health status and health behaviours, although coping styles were not shown to moderate the perfectionism-health relationship. The data showed that perfectionism did constitute a health risk, both in terms of health status and health behaviours. Finally, an unexpected finding was that perfectionism also included adaptive features related to health. Specifically, some dimensions of perfectionism were also associated with reports of better health status and involvement in some positive health behaviours.

A journey into narrative inquiry : one teacher's lived experience with eating disorders /

In "A Journey Into Narrative Inquiry: One Teacher's Lived Experience With Eating Disorders," an elementary teacher searches for answers regarding how education can help prevent eating disorders by journeying into her own experience of having had such a disorder. This qualitative study is a personal narrative based on an individual's experience, a method appropriate to the sharing of personal voices and stories told in education research. It is an attempt to address the gap found in the research on this topic by offering a subjective and unique perspective of what it is like to live within the nightmare of an eating disorder and by sharing the wisdom gained from having survived such an experience. This narrative inquiry explains how a teacher found herself at a stage where she was willing and ready to share her experience for the sake of research. The story of having had an eating disorder, consisting of both anorexia and bulimia, for over a decade is shared in a genuine, reflective manner. The researcher then shares the analysis of her own story, unpacking the themes of journeying toward voice, self-esteem, self-acceptance, and self and the completion of an M.Ed. degree. Bridges are made which connect these themes to the personal and professional life of the researcher, to the schools in terms of both curriculum and climate, to research directions, and to the larger culture. Suggestions are made for possible changes in educational settings that may help teachers in providing students with some tools and strategies to prevent turning to eating disorders as coping mechanisms. A literature review of eating disorders is included as well, as a guide for others to use when undertaking such qualitative studies.