Children Affected by AIDS: A Review of the Literature on Orphaned and Vulnerable Children

This paper presents a systematic review of the literature pertaining to orphans and vulnerable children in sub-Saharan Africa, with a particular focus on research in countries heavily impacted by HIV/AIDS. Despite study and data limitations, the literature provides evidence of growing orphan-based disparities, difficulties within households providing care, and insufficient capacity among social services. Still, additional research is urgently needed, including better OVC surveillance methods, qualitative data than answers persisting questions, the inclusion of more useful indicators in national household surveys, and longitudinal studies to determine the mechanisms by which parental HIV status and death impacts children, caregiving impacts households, and the orphan epidemic impacts communities and social systems.

Effects of synbiotics on cancer risk biomarkers

Colorectal cancer (CRC) is the fourth most common cause of death from cancer in the world and second most common (behind lung cancer) in developed countries. In recent years there has been much interest in the potential use of prebiotics, probiotics and synbiotics in the prevention and treatment of CRC. We have previously shown that synbiotic consumption in Azoxymethane treated rats modulates the immune system, influences the genotoxic potential of caecal contents and reduces the number of colonic tumours compared to control rats who did not receive the synbiotic. The aim of the current study was to identify biomarkers suitable for use as cancer risk markers and as intervention markers. A second aim was to determine the influence of synbiotic consumption on cancer risk biomarkers such as in vivo colonic mucosal proliferation and genotoxic damage along with examining the genotoxic, cytotoxic and tumour promoting potential of faecal water (FW). Synbiotic consumption altered the composition of the gastrointestinal flora and reduced in vivo genotoxic damage and the genotoxic potential of FW in cancer and polyp subjects. Synbiotic consumption also reduced the proliferative activity in the colonic mucosa in polyp subjects. In both cancer and polyp subjects gene expression in the colonic mucosa was modulated in synbiotic consuming subjects. In this and other studies the activity of natural killer cells, the level of PGE2 in FW, IL-12 production by PBMCs, genotoxic damage in the colonic mucosa and the tumour promoting activities of FW have been identified as possible biomarkers of cancer risk. Future large scale studies investigating these parameters in healthy and diseased individuals are needed to confirm the suitability of these markers in assessing cancer risk and the role of synbiotics in modulating them.

The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells

Neurogenesis occurs in two distinct regions of the adult brain; the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the subventricular zone (SVZ) lining the lateral ventricles. It is now well-known that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors e.g. local signalling molecules, exercise, environmental enrichment and learning. Moreover, levels of adult hippocampal neurogenesis decrease with age, at least in rodents, and alterations in hippocampal neurogenesis have been reported in animal models and human studies of neuropsychiatric and neurodegenerative conditions. Neuroinflammation is a common pathological feature of these conditions and is also a potent modulator of adult hippocampal neurogenesis. Recently, the orphan nuclear receptor TLX has been identified as an important regulator of adult hippocampal neurogenesis as its expression is necessary to maintain the neural precursor cell (NPC) pool in the adult DG. Likewise, exposure of animals to voluntary exercise has been consistently demonstrated to promote adult hippocampal neurogenesis. Lentivirus (LV)- mediated gene transfer is a useful tool to elucidate gene function and to explore potential therapeutic candidates across an array of conditions as it facilitates sustained gene expression in both dividing and post-mitotic cell populations. Both intrinsic and extrinsic factors are important regulators of adult hippocampal neurogenesis. Examining how these factors are affected by an inflammatory stimulus, and the subsequent effects on adult hippocampal neurogenesis provides important information for the development of novel treatment strategies for neuropsychiatric and neurodegenerative conditions in which adult hippocampal neurogenesis is impaired. The aims of the series of experiments presented in this thesis were to examine the effect of the pro-inflammatory cytokine interleukin-1β (IL-1β) on adult hippocampal NPCs both in vitro and in vivo. In vitro, we have shown that IL-1β reduces proliferation of adult hippocampal NPCs in a dose and time-dependent manner. In addition, we have demonstrated that TLX expression is reduced by IL-1β. Blockade of IL-1β signalling prevented both the IL-1β-induced reduction in cell proliferation and TLX expression. In vivo, we examined the effect of short term and long term exposure to LV-IL-1β in sedentary mice and in mice exposed to voluntary running. We demonstrated that impaired hippocampal neurogenesis is only evident after long term exposure to IL-1β. In mice exposed to voluntary running, hippocampal neurogenesis is significantly increased following short-term but not long-term exposure to running. Moreover, short-term running effectively prevents any IL-1β-induced effects on hippocampal neurogenesis; however, no such effects are seen following long-term exposure to running.

'Muchos Méxicos': widening the lens in Rulfo's cinematic texts

It is difficult to overstate the importance of Juan Rulfo’s two major pieces of fictional narrative work—his haunting, enigmatic novel Pedro Páramo (1955) and his unrelenting depictions of the failures of post-revolutionary Mexico in his short story collection El Llano en llamas (1953). In her foreword to the Margaret Sayers Peden English translation, Susan Sontag hails Pedro Páramo as ‘not only one of the masterpieces of 20th Century world literature, but one of the most influential of the century’s books’. García Márquez has compared the influence of Rulfo on 20th Century world literature to that of Sophocles: ‘No son más de 300 páginas, pero son casi tantas y creo tan perdurables como las que conocemos de Sófocles’ and, completing this oftrepeated triumvirate of recommendations, Jorge Luis Borges has referred to Pedro Páramo as: ‘una de las mejores novelas de las literaturas de lengua hispánica, y aun de la literatura.’ Despite the praise heaped upon Rulfo’s two most famous books, when his third book of fiction, El gallo de oro y otros textos para cine, was finally published in 1980, just six years before his death, it was greeted with almost critical silence. It is precisely this publication that provides the focus of this investigation. The collection contains three texts—El despojo, La fórmula secreta and El gallo de oro. Constituting a third of the fictional work he published in his lifetime, expanding upon themes present in El Llano en llamas and Pedro Páramo while, at the same time, examining new ground, no thematic discussion of Rulfo’s written output is complete without including these texts. Yet they are frequently dismissed. In this way this investigation attempts to go some way towards filling this critical gap in the work of one of the most influential writers of the twentieth century

Afterwords: reparative queer death and the contemporary Irish novel, 1960-2000

Given that an extant comprehensive study of homosexuality and the twentieth century Irish novel has yet to produced, this thesis is an attempt at rectifying such a gap in research by way of close textual analysis of writing from the latter half of the century—that is, from 1960-2000. Analysis of seven novels by four male authors – John Broderick, Desmond Hogan, Colm Tóibín and Keith Ridgway – lead to one overarching feature common to all four writers becoming clear: the homosexual or queer is always dying or already ‘dead’. ‘Dead’ is placed in inverted commas here as it is not only biological death that characterises the fate of gay men in the aforementioned literature. In the first instance, such men are also always already ‘dead’—that is, by light of their disenfranchisement as homosexual or queer, they are, in socialized terms, examples of the ‘living’ dead. Secondly, biological death neither fully obliterates the queer body nor its disruptive influence. Consequently, one of the overarching ways in which I read queer death in the late twentieth century Irish novel is through the prism of its reparative ‘afterw(a)ord’. On the one hand, such readings are temporally based (that is, reading from a point beyond the death of the protagonist - or their ‘afterward’); while, on the other hand, such readings are stylistically premised (that is, reading or interpreting the narrative itself as an ‘afterword’). The current project thus constitutes an original contribution to knowledge by establishing variant ways of reading the contemporary Irish novel from the point of view of the queer ‘unliving’. In assessing such heterogeneous aspects of contemporary queer death, the project a) contributes to recent, largely Anglo-American-based literary theoretical research on the queer and the eschatological, and b) provides a more contemporized literary base upon which future research can uncover a continuum of Irish queer writing in the twentieth century, one concerned with writing prior to 1960 and not limited to writing my men, in which death and same-sex desire are at parallel angles to one another.

Totality of experience: sound, music and mythology in Gus Van Sant’s “Death Quartet”

Reflecting on Gus Van Sant’s films Gerry (2003) Elephant (2004) and Last Days (2005), the director’s long-term sound-designer Leslie Shatz observed that “You have to get into the totality of the experience and not just the dialogue”. Shatz’s comment expresses something fundamental about the experimental approach to cinema and to soundscapes undertaken by Van Sant in these three films, unofficially known as the “Death Trilogy”. This thesis contends that Van Sant makes deliberate aesthetic choices which do indicate a distinctly “auteurist” leaning. However, I also argue that intertextual elements, prior knowledge, and audience participation in meaningmaking enhance the experience of, and reveal the nuances in, the soundtracks themselves. This thesis aims to contribute to a growing body of work within filmmusic scholarship concerned with resisting a traditional bias in the field: that film music should be understood as a means of characterisation and as emotional signifier. The films of the “Death Quartet”, which includes Paranoid Park (2007), I believe, offer fertile ground on which to explore these new approaches. It is my contention that these films deconstruct the traditional approach to soundtracking and the relationship between soundtrack and character, and that only an approach sensitive to the aesthetic and philosophical functions of music and sound can adequately acknowledge their unique cinematic qualities.

From the demise of theory to its resurgence. A retrospective on the postmodern turn to rethink the 'desire for narrative' and the sublime untimeliness of emancipation

Cultural Marxist Theory, commonly known as theory, enjoyed a moment of extraordinary success in the 1970s, when the works of leading post-war French philosophers were published in English. After relocating to Anglophone academia, however, theory disavowed its original concerns and lost its ambition to understand the world as a whole, becoming the play of heterogeneities associated with postcolonialism, multiculturalism and identity politics, commonly referred to as postmodern theory. This turn, which took place during a period that seemed to have spelt the death of Marxism, the 1990s, induced many of its supporters to engage in an ongoing funeral wake designating the merits of theory and dreaming its resurgence. According to them, had theory been resurrected in historical circumstances completely different from those which had led to its rise, it would have never reacquired the significance that had originally connoted it. This thesis demonstrates how theory has survived its demise and entirely regained its prominence in our socio-political context marked by the effects of the latest crisis of capitalism and by the global threat of terrorisms rooted in messianic eschatologies. In its current form theory does no longer need to show allegiance to certain intellectual stances or political groupings in order to produce important reformulations of the projects it once gave life to. Though less overtly radical and epistemologically bounded, theory remains a necessary form of enquiry justified by the political commitment which originated it in the first place. Its voice continues to speak to us about justice ‘where it is not yet, not yet there, where it is no longer’ (Derrida, 1993, XVIII).

Reflections on Children

In the Fall 2004, while preparing my dissertation project “Reflections on children,” I realized that whether art songs, operatic arias or scenes, the classical repertory offers a wide variety of masterpieces regarding all aspects of children’s life. My first dissertation recital is called “Journeys” and was performed on December 6th 2004 at 8:00pm in the Tawes Recital Hall. Change is the only inevitable condition in life and as such, it has been thought-provoking to many poets and composers. The narrator in Mahler’s Wayfarer Songs experiences the pain of love for the first time and emerges transformed into an adult. The narrator in Barber’s Knoxville is an adult looking back at his journey in an attempt to understand himself. The mothers in Britten’s Charm of Lullabies each make every effort to accept the changes in their own life after the birth of her baby. Finally, both Brahms’ songs are about risks and losses. “Destinies” is the title of the second dissertation recital as it attempts to capture the dark fate of Mignon and of Rückert/Mahler’s children. It was performed on April 8th 2005 in the Tawes Recital Hall. Mignon’s grief is portrayed through songs full of sadness and hopelessness in mourning of a long lost childhood. Rückert wrote 425 Kindertotenlieder in memory of his children’s deaths over a period of twenty years and Mahler orchestrated five of them. Mahler’s choices deal with light and darkness, symbolizing eternal life and hope versus despair and death, in both the literal and the literary sense. Finally, the third dissertation recital called “Blessings” was performed on May 19th 2005 in the Tawes Recital Hall. It relies on the evocation of moods and scenes created by a variety of composers and poets. Poulenc’s La Courte Paille are brief works in the style of a child’s song with unrelated and unexpected images juxtaposed, creating a sense of inner monologues. John Greer’s House of Tomorrow, Guastavino’s Cradle Songs and the rest of the composers offer wonderful pieces of immense power and expression in their directness and sensitive contour.

Impact of simian immunodeficiency virus infection on chimpanzee population dynamics.

Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002-2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of -6.5% to -7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002-2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen.

Effects of 17-α-ethynylestradiol on Hybrid Striped Bass Sperm

Gemstone Team FISH

Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.

BACKGROUND: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. MATERIALS AND METHODS: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. RESULTS: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. CONCLUSION: Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.

Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk.

Genome-wide association studies (GWASs) have characterized 13 loci associated with melanoma, which only account for a small part of melanoma risk. To identify new genes with too small an effect to be detected individually but which collectively influence melanoma risk and/or show interactive effects, we used a two-step analysis strategy including pathway analysis of genome-wide SNP data, in a first step, and epistasis analysis within significant pathways, in a second step. Pathway analysis, using the gene-set enrichment analysis (GSEA) approach and the gene ontology (GO) database, was applied to the outcomes of MELARISK (3,976 subjects) and MDACC (2,827 subjects) GWASs. Cross-gene SNP-SNP interaction analysis within melanoma-associated GOs was performed using the INTERSNP software. Five GO categories were significantly enriched in genes associated with melanoma (false discovery rate ≤ 5% in both studies): response to light stimulus, regulation of mitotic cell cycle, induction of programmed cell death, cytokine activity and oxidative phosphorylation. Epistasis analysis, within each of the five significant GOs, showed significant evidence for interaction for one SNP pair at TERF1 and AFAP1L2 loci (pmeta-int  = 2.0 × 10(-7) , which met both the pathway and overall multiple-testing corrected thresholds that are equal to 9.8 × 10(-7) and 2.0 × 10(-7) , respectively) and suggestive evidence for another pair involving correlated SNPs at the same loci (pmeta-int  = 3.6 × 10(-6) ). This interaction has important biological relevance given the key role of TERF1 in telomere biology and the reported physical interaction between TERF1 and AFAP1L2 proteins. This finding brings a novel piece of evidence for the emerging role of telomere dysfunction into melanoma development.

A noisy linear map underlies oscillations in cell size and gene expression in bacteria.

During bacterial growth, a cell approximately doubles in size before division, after which it splits into two daughter cells. This process is subjected to the inherent perturbations of cellular noise and thus requires regulation for cell-size homeostasis. The mechanisms underlying the control and dynamics of cell size remain poorly understood owing to the difficulty in sizing individual bacteria over long periods of time in a high-throughput manner. Here we measure and analyse long-term, single-cell growth and division across different Escherichia coli strains and growth conditions. We show that a subset of cells in a population exhibit transient oscillations in cell size with periods that stretch across several (more than ten) generations. Our analysis reveals that a simple law governing cell-size control-a noisy linear map-explains the origins of these cell-size oscillations across all strains. This noisy linear map implements a negative feedback on cell-size control: a cell with a larger initial size tends to divide earlier, whereas one with a smaller initial size tends to divide later. Combining simulations of cell growth and division with experimental data, we demonstrate that this noisy linear map generates transient oscillations, not just in cell size, but also in constitutive gene expression. Our work provides new insights into the dynamics of bacterial cell-size regulation with implications for the physiological processes involved.

Birth-death processes with mass annihilation and state-dependent immigration

A birth-death process is subject to mass annihilation at rate β with subsequent mass immigration occurring into state j at rateα j . This structure enables the process to jump from one sector of state space to another one (via state 0) with transition rate independent of population size. First, we highlight the difficulties encountered when using standard techniques to construct both time-dependent and equilibrium probabilities. Then we show how to overcome such analytic difficulties by means of a tool developed in Chen and Renshaw (1990, 1993b); this approach is applicable to many processes whose underlying generator on E\{0} has known probability structure. Here we demonstrate the technique through application to the linear birth-death generator on which is superimposed an annihilation/immigration process.

Birth-death processes with an instantaneous reflection barrier

A new structure with the special property that an instantaneous reflection barrier is imposed on the ordinary birth-death processes is considered. An easy-checking criterion for the existence of such Markov processes is first obtained. The uniqueness criterion is then established. In the nonunique case, all the honest processes are explicitly constructed. Ergodicity properties for these processes are investigated. It is proved that honest processes are always ergodic without necessarily imposing any extra conditions. Equilibrium distributions for all these ergodic processes are established. Several examples are provided to illustrate our results.