A qualitative study of trends in patient preferences for the management of partial dentition

Objective: To identify factors influencing attitudes of partially dentate adults towards dental treatment in Ireland. Background: People are retaining more teeth later in life than ever before. Management of partially dentate older adults will be a major requirement for the future and it is important to determine factors which may influence patients’ attitudes to care. Methods: Subjects: A purposive sample of 22 partially dentate patients was recruited; 12 women and 12 men, ranging in age from 45 to 75 years. Data Collection: Semi-structured individual interviews. Results: Dental patients have increasing expectations in relation to (i) a more sophisticated approach to the management of missing teeth and (ii) their right to actively participate in decision making regarding the management of their tooth loss. There is some evidence of a cohort effect with younger patients (45–64 years) having higher expectations. Conclusions: The evidence of a cohort effect within this study in relation to higher patient expectations indicates that both contemporary and future patients are likely to seek a service based on conservation and restoration of missing teeth by fixed prostheses.

The reproductive biology of the soft shell clam Mya arenaria in Ireland and the possible impacts of climate variability

Little is known about the biology of the softshell clam in Europe, despite it being identified as a potential species to culture for food in the future. Monthly samples of the softshell clam, Mya arenaria, were collected intertidally from Co. Wexford, Ireland, over a period of sixteen months. The mean weight of sampled individuals was 7 4 ± 4 . 9  g and mean length was 8 . 2 ± 0 . 2  cm. Histological examination revealed a female-to-male ratio of 1 : 1.15. In 2010, M. arenaria at this site matured over the summer months, with both sexes either ripe or spawning by August. A single spawning event was recorded in 2010, completed by November. Two unusually cold winters, followed by a warmer-than-average spring, appear to have affected M. arenaria gametogenesis in this area, potentially affecting the time of spawning, fertilisation success, and recruitment of this species. No hermaphrodites were observed in the samples collected, nor were any pathogens observed. Timing of development and spawning is compared with the coasts of eastern North America and with other European coasts.

“Something isn’t right here”: American exceptionalism and the creative nonfiction of the Vietnam War

In this thesis, I argue that few attempts were as effective in correcting the exceptionalist ethos of the United States than the creative nonfiction written by the veterans and journalists of the Vietnam War. Using critical works on creative nonfiction, I identify the characteristics of the genre that allowed Paul John Eakin to call it ‘a special kind of fiction.’ I summarise a brief history of creative nonfiction to demonstrate how it became a distinctly American form despite its Old World origins. I then claim that it was the genre most suited to the kind of ideological transformation that many hoped to instigate in U.S. society in the aftermath of Vietnam. Following this, the study explores how this “new” myth-making process occurred. I use Tim O’Brien’s If I Die in a Combat Zone and Philip Caputo’s A Rumor of War to illustrate how autobiography/memoir was able to demonstrate the detrimental effect that America’s exceptionalist ideology was having on its population. Utilising narrative and autobiographical theory, I contend that these accounts represented a collective voice which spoke for all Americans in the years after Vietnam. Using Neil Sheehan’s A Bright Shining Lie and C.D.B. Bryan’s Friendly Fire, I illustrate how literary journalism highlighted the hubris of the American government. I contend that while poiesis is an integral attribute of creative nonfiction, by the inclusion of extraneous bibliographic material, authors of the genre could also be seen as creating a literary context predisposing the reader towards an empirical interpretation of the events documented within. Finally, I claim that oral histories were in their essence a synthesis of “everyman” experiences very much in keeping with the American zeitgeist of the early Eighties. Focussing solely on Al Santoli’s Everything We Had, I demonstrate how such polyphonic narratives personalised the history of the Vietnam War.

"I have nothing to say, only to show": appropriation in the poetries of Trevor Joyce, Alan Halsey, and Susan Howe

This thesis studies contemporary poetry’s innovations in textual borrowing and the range and scope of its appropriative practices. The restrictions of the inherited definitions of appropriation include a limited capacity for expression and meaningfulness, a partial concept of appropriation’s critical capacity, and an inadequate sense of the poet’s individual and unique practice of appropriation. This thesis resolves the problematic constraints limiting contemporary definitions of appropriation by tracing the history of the practice to reveal an enduring relation between appropriation and poetic expression. Close readings of Trevor Joyce’s, Alan Halsey’s, and Susan Howe’s poetry serve as evidence of contemporary poetry’s development of appropriation beyond the current ascriptions and offer some direction on how the critical understanding of appropriation might be extended and redefined. Here, appropriation is recognized as another source of lyric expression, critical innovation, and conceptual development in contemporary poetry. This thesis encourages a new perspective on the purpose and processes of poetic appropriation and the consequences of its declarative potential for both poet and poem.

A nation preferring visions: moving statues, apparitions and vernacular religion in contemporary Ireland

This thesis examines important issues of Irish vernacular Catholicism, Irish religious and cultural identities, the impacts of modernity plus socio-religious and economic change on traditional religiosity, sacred landscape and topophilia, religious material culture, folk and individual creativity, gender roles and expectations, and devotional subcultures through the vehicle of Marian apparitions and their aftermath in the Republic of Ireland in the late 20th and early 21st centuries. This thesis examines in detail five Irish Marian shrines as case studies; Knock shrine (Co. Mayo), Ballinspittle and Mitchelstown grottoes (Co. Cork), Mount Melleray grotto (Co. Waterford) and the Marian shrines of Inchigeela in West Cork and the attached houses of prayer. Key themes include; vernacular religious theory; the nature of Irish indigenous Catholicism; local, global and transnational trends in contemporary Irish devotional life; areas of individual creativity, fluidity and agency in Marian devotion; and the vital role and influence of material culture in and on local and individual religiosity.

Monstrative acts and becoming-monster: on identity, bodies, and the feminine other

Using two examples of literary monsters, the Creature in Mary Shelley’s Frankenstein (1818), and Grendel’s Mother in Beowulf, this thesis demonstrates the bearing fictional identities have on “real” bodies, through an examination of two further literary texts, David Henry Hwang’s play, M. Butterfly (1986) and J. M. Coetzee’s novel, Disgrace (1999). Western definitions of Being have historically divided body and mind, favouring the mind as formative of subjective experience and denigrating the body as secondary and impure. This thesis demonstrates that this mind/body binary is symptomatic of the masculine ontological imperative to disown the body and its effects on Being, simultaneously ridding itself of the feminine it believes is its irrational opposite. Using recent feminist reviews of the canon, which emphasise the body’s importance to ontology and demonstrate the conceptual association between the feminine and the corporeal, this thesis links performative identity practices to theories of monstrosity, explaining how fictional qualities adhere to monstrous bodies by proposing a new theoretical category, the “monstrative.” The monstrative is a performative force that makes the Other into a living sign of Otherness; however, unlike earlier theories of Othering, the monstrative accounts for the Other’s being other to herself. This thesis also attempts to read the misrepresented body of the Other as a possible site for more empowered identity performances, where the monstrous “I” is interpreted as a potentially positive model for identity practice, through the conceptualisation of identity as a process of Becoming rather than Being. The transferal from a noun to a verb not only emphasises the performativity of identity, but also suggests fluidity and multiplicity in identity practice, which always already indicates a monstrosity at work. Thus, while monstrative acts constitute bodies as monstrous, Becoming-monster is an empathetic response to the Other’s monstrosity.

Biogas production from novel substrates

Biogas production is the conversion of the organic material into methane (CH4) and carbon dioxide (CO2) under anaerobic conditions. Anaerobic digestion (AD) is widely used in continental and Scandinavian communities as both a waste treatment option and a source of renewable energy. Ireland however lags behind this European movement. Numerous feedstocks exist which could be digested and used to fuel a renewable transport fleet in Ireland. An issue exists with the variety of feedstocks; these need to be assessed and quantified to ascertain their potential resource and application to AD. From literature the ideal C:N ratio is between 25 and 30:1. Low levels of C:N (<15) can lead to problems with ammonia inhibition. Within the digester a plentiful supply of nutrients and a balanced C:N is required for stable performance. Feedstocks were sampled from a range of over 100 different substrates in Ireland including for first, second and third generation feedstocks. The C:N ranged from 81:1 (Winter Oats) to 7:1 (Silage Effluent). The BMP yields were recorded ranging from 38 ± 2.0 L CH4 kg−1 VS for pig slurry (weaning pigs) to 805 ± 57 L CH4 kg−1 VS for used cooking oil (UCO). However the selection of the best preforming feedstock in terms of C:N ratio or BMP yield alone is not sufficiently adequate. A total picture has to be created which includes C:N ratio, BMP yield, harvest yield and availability. Potential feedstocks which best meet these requirements include for Grass silage, Milk processing waste (MPW) and Saccharina latissima. MPW has a potential of meeting over 6 times the required energy for Ireland’s 2020 transport in energy targets. S. Latissima recorded a yield of over 10,000 GJ ha-1 yr-1 which out ranks traditional second generation biofuels by a factor of more than 4.

Self-neglect: a case study and implications for clinical practice

Self-neglect is a worldwide and serious public health issue that can have serious adverse outcomes and is more common in older people. Cases can vary in presentation but typically present as poor self-care, poor care of the environment and service refusal. Community nurses frequently encounter self-neglect cases and health and social care professionals play a key role in the identification, management and prevention of self-neglect. Self-neglect cases can give rise to ethical, personal and professional challenges. The aim of this article is to create a greater understanding of the concept of self-neglect among community nurses.

Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist.

Interleukin-1 beta (IL1β) is a proinflammatory cytokine that mediates arthritic pathologies. Our objectives were to evaluate pain and limb dysfunction resulting from IL1β over-expression in the rat knee and to investigate the ability of local IL1 receptor antagonist (IL1Ra) delivery to reverse-associated pathology. IL1β over-expression was induced in the right knees of 30 Wistar rats via intra-articular injection of rat fibroblasts retrovirally infected with human IL1β cDNA. A subset of animals received a 30 µl intra-articular injection of saline or human IL1Ra on day 1 after cell delivery (0.65 µg/µl hIL1Ra, n = 7 per group). Joint swelling, gait, and sensitivity were investigated over 1 week. On day 8, animals were sacrificed and joints were collected for histological evaluation. Joint inflammation and elevated levels of endogenous IL1β were observed in knees receiving IL1β-infected fibroblasts. Asymmetric gaits favoring the affected limb and heightened mechanical sensitivity (allodynia) reflected a unilateral pathology. Histopathology revealed cartilage loss on the femoral groove and condyle of affected joints. Intra-articular IL1Ra injection failed to restore gait and sensitivity to preoperative levels and did not reduce cartilage degeneration observed in histopathology. Joint swelling and degeneration subsequent to IL1β over-expression is associated limb hypersensitivity and gait compensation. Intra-articular IL1Ra delivery did not result in marked improvement for this model; this may be driven by rapid clearance of administered IL1Ra from the joint space. These results motivate work to further investigate the behavioral consequences of monoarticular arthritis and sustained release drug delivery strategies for the joint space.

Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model.

Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1beta overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models.

Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.

The autosomal recessive kidney disease nephronophthisis (NPHP) constitutes the most frequent genetic cause of terminal renal failure in the first 3 decades of life. Ten causative genes (NPHP1-NPHP9 and NPHP11), whose products localize to the primary cilia-centrosome complex, support the unifying concept that cystic kidney diseases are "ciliopathies". Using genome-wide homozygosity mapping, we report here what we believe to be a new locus (NPHP-like 1 [NPHPL1]) for an NPHP-like nephropathy. In 2 families with an NPHP-like phenotype, we detected homozygous frameshift and splice-site mutations, respectively, in the X-prolyl aminopeptidase 3 (XPNPEP3) gene. In contrast to all known NPHP proteins, XPNPEP3 localizes to mitochondria of renal cells. However, in vivo analyses also revealed a likely cilia-related function; suppression of zebrafish xpnpep3 phenocopied the developmental phenotypes of ciliopathy morphants, and this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal. Consistent with a role for XPNPEP3 in ciliary function, several ciliary cystogenic proteins were found to be XPNPEP3 substrates, for which resistance to N-terminal proline cleavage resulted in attenuated protein function in vivo in zebrafish. Our data highlight an emerging link between mitochondria and ciliary dysfunction, and suggest that further understanding the enzymatic activity and substrates of XPNPEP3 will illuminate novel cystogenic pathways.

Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer.

BACKGROUND: The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy. METHODS/DESIGN: Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk⁻¹ of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO₂peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO₂peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO₂peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks). DISCUSSION: EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO₂peak and other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy. TRIAL REGISTRATION: NCT01186367.

Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy.

Transgenic mice were generated by using the alpha-myosin heavy chain promoter coupled to the coding sequence of a constitutively active mutant alpha 1B-adrenergic receptor (AR). These transgenic animals demonstrated cardiac-specific expression of this alpha 1-AR with resultant activation of phospholipase C as shown by increased myocardial diacylglycerol content. A phenotype consistent with cardiac hypertrophy developed in adult transgenic mice with increased heart/body weight ratios, myocyte cross-sectional areas, and ventricular atrial natriuretic factor mRNA levels relative to nontransgenic controls. These transgenic animals may provide insight into the biochemical triggers that induce hypertrophy in cardiac disease and serve as a convenient experimental model for studies of this condition.

Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein kinase is mediated by G beta gamma activation of p21ras.

Stimulation of Gi-coupled receptors leads to the activation of mitogen-activated protein kinases (MAP kinases). In several cell types, this appears to be dependent on the activation of p21ras (Ras). Which G-protein subunit(s) (G alpha or the G beta gamma complex) primarily is responsible for triggering this signaling pathway, however, is unclear. We have demonstrated previously that the carboxyl terminus of the beta-adrenergic receptor kinase, containing its G beta gamma-binding domain, is a cellular G beta gamma antagonist capable of specifically distinguishing G alpha- and G beta gamma-mediated processes. Using this G beta gamma inhibitor, we studied Ras and MAP kinase activation through endogenous Gi-coupled receptors in Rat-1 fibroblasts and through receptors expressed by transiently transfected COS-7 cells. We report here that both Ras and MAP kinase activation in response to lysophosphatidic acid is markedly attenuated in Rat-1 cells stably transfected with a plasmid encoding this G beta gamma antagonist. Likewise in COS-7 cells transfected with plasmids encoding Gi-coupled receptors (alpha 2-adrenergic and M2 muscarinic), the activation of Ras and MAP kinase was significantly reduced in the presence of the coexpressed G beta gamma antagonist. Ras-MAP kinase activation mediated through a Gq-coupled receptor (alpha 1-adrenergic) or the tyrosine kinase epidermal growth factor receptor was unaltered by this G beta gamma antagonist. These results identify G beta gamma as the primary mediator of Ras activation and subsequent signaling via MAP kinase in response to stimulation of Gi-coupled receptors.

G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity.

The alpha 1B-adrenergic receptor (alpha 1B-ADR) is a member of the G-protein-coupled family of transmembrane receptors. When transfected into Rat-1 and NIH 3T3 fibroblasts, this receptor induces focus formation in an agonist-dependent manner. Focus-derived, transformed fibroblasts exhibit high levels of functional alpha 1B-ADR expression, demonstrate a catecholamine-induced enhancement in the rate of cellular proliferation, and are tumorigenic when injected into nude mice. Induction of neoplastic transformation by the alpha 1B-ADR, therefore, identifies this normal cellular gene as a protooncogene. Mutational alteration of this receptor can lead to activation of this protooncogene, resulting in an enhanced ability of agonist to induce focus formation with a decreased latency and quantitative increase in transformed foci. In contrast to cells expressing the wild-type alpha 1B-ADR, focus formation in "oncomutant"-expressing cell lines appears constitutively activated with the generation of foci in unstimulated cells. Further, these cell lines exhibit near-maximal rates of proliferation even in the absence of catecholamine supplementation. They also demonstrate an enhanced ability for tumor generation in nude mice with a decreased period of latency compared with cells expressing the wild-type receptor. Thus, the alpha 1B-ADR gene can, when overexpressed and activated, function as an oncogene inducing neoplastic transformation. Mutational alteration of this receptor gene can result in the activation of this protooncogene, enhancing its oncogenic potential. These findings suggest that analogous spontaneously occurring mutations in this class of receptor proteins could play a key role in the induction or progression of neoplastic transformation and atherosclerosis.