The mTOR Pathway in Breast Cancer

There is currently a wealth of information regarding the mutations that contribute to cancer development. Most of these mutations alter the expression and activity of signal transduction proteins. The current goal in cancer therapy is to use our knowledge of the molecular alterations in a cancer cell to choose the most appropriate signal transduction inhibitor for an individual patient. The topic of this review is the mammalian target of rapamycin (mTOR) kinase signaling pathway, which is aberrantly activated in many types of human cancer. We will discuss the mTOR pathway and the potential mechanisms that contribute to its activation in cancer, together with data relating to the potential for inhibitors targeting the mTOR-signaling pathway to impact on breast cancer therap

National Study of Individual Chapter 11 Bankruptcies

Article published in the ABI Law Review

Research ethics in practice: Lessons from studies exploring intimate partner violence in different contexts

Studies researching interpersonal violence (IPV) are associated with a range of ethical challenges. In this paper, lessons are drawn from three case studies exploring the experiences of different groups of survivors and perpetrators of IPV in diverse contexts: refugees in the Thailand-Burma border area; partner-violent adult men and female survivors in Ireland; and, school children in five European countries. The ethical – and associated methodological - challenges faced, and the ways in which they were overcome, are presented. Drawing on the case studies presented, the paper concludes that three key areas require special attention when conducting research in this field: accessing and recruiting participants, researcher skills and experience, and appropriate use of data

Promoting Resilience amongst Young People Transitioning from Care to Independent Living: Experiences of Residential Social Care Workers

The capacity for a young adult to develop and overcome obstacles in life underpins the concept of resilience building (Gilligan, 1997). A key role of the social care worker is to ensure that young adults growing up in the care system are afforded the best possible outcomes. This includes social care workers helping young people build their resilience in preparation for the transition into independent living and aftercare. The research reported here examines the experiences and perspectives of two residential social care workers regarding the promotion of resilience amongst young people transitioning from residential care to independent living. From analysis of the data collected, three themes were identified: the importance of a secure base, maintaining consistent and long-term relationships and challenges faced by social care workers in building the resilience of care leavers. Findings concur with previous research, which identified the importance of young people having a secure base in their lives as well as long-term relationships as a source of support to aid them in their transition from care to independence. This research in exploring some of the challenges of helping build the resilience of care leavers highlights the possible value of allowing young people to engage in positive risk taking opportunities in order to build important life skills for independent livin

Contrasts in Tick Innate Immune Responses to Borrelia burgdorferi challenge: Immuno-tolerance in Ixodes scapularis versus Immunocompetence in Dermacentor variabilis (Acari: Ixodidae).

The blacklegged tick, Ixodes scapularis Say, transmits the Lyme disease spirochete (Borrelia burgdorferi), whereas the American dog tick, Dermacentor variabilis (Say), is unable to transmit the bacterium. We compared the innate immune response of these ticks against spirochetes directly inoculated into the hemocoel cavity of ticks. In I. scapularis, some Borrelia were found associated with hemocytes, while numerous other spiral-shaped, intact bacteria remained free in the hemolymph. In contrast, in D. variabilis only remnants of the bacteria were evident in the hemolymph, indicating lysis; intact spirochetes were rare. Spirochetes were observed bound to or within the organs of both tick species, although many more spirochetes were found associated with the I. scapularis organs. The few spirochetes observed with the D. variabilis organs appeared to be dead because D. variabilis tissues rarely contained culturable bacteria, unlike I. scapularis tissues. When spirochetes were incubated with I. scapularis hemolymph plasma in vitro, bacterial survival and motility were not reduced. In contrast, incubation of spirochetes with D. variabilis hemolymph plasma resulted in \u3e 50% of the spirochetes becoming nonmotile by 45 min. The differences in the responses of the two different tick species indicate that I. scapularis is immunotolerant when challenged with B. burgdorferi and dependent on a slow phagocytic response to clear Borrelia from the hemolymph. In contrast, D. variabilis is highly immunocompetent (i.e., innate immunity), using plasma borreliacidal factors and a rapid increase in phagocytic cells to clear the infection and limit tissue invasion

Glass Capillary Tube Feeding: A Method for Infecting Nymphal Ixodes scapularis (Acari: Ixodidae) with the Lyme Disease Spirochete Borrelia burgdorferi

We evaluated an artificial capillary feeding method to infect nymphal Ixodes scapularis (Say) ticks with Borrelia burgdorferi, the causative agent of Lyme disease. Thirty to 70% of the nymphs were infected after feeding for 2.5 h from glass capillary tubes filled with a solution of spirochetes. Capillary infection was stable and persisted in the nymphs for at least 10 d after feeding. Capillary feeding also maintained natural vector competence patterns because I. scapularis ticks acquired infection unlike Dermacentor variablis (Say), which did not become infected. Capillary infected I. scapularis nymphs were capable of transmitting the infection to naive mice although not as efficiently as naturally infected nymphs. The capillary infection method is convenient and is a better alternative to syringe inoculation as a means of infecting animals with B. burgdorferi

National Study of Individual Chapter 11 Bankruptcies

Article published in the ABI Law Review

Biological and anthropogenic predictors of metal concentration in the Eurasian otter, a sentinel of freshwater ecosystems

Toxic metals have been linked to a range of adverse health effects in freshwater organisms. However, for higher vertebrates, there is little understanding of the large-scale drivers of exposure. We quantified toxic metal/semi-metal concentrations in a sentinel freshwater top predator, the Eurasian otter (Lutra lutra), across England and Wales, and determined how this varied with key natural and anthropogenic factors. We related liver concentrations in 278 otters that died between 2006 and 2017 to habitat biogeochemistry, proximity to point source contamination and to biological characteristics (length, sex, condition). Evidence for any positive association with putative anthropogenic sources (mining, human population, known discharges) was weak or lacking in nearly all cases, with the exception of a positive association between lead and human population density. Despite concerns that burgeoning use of nanosilver in consumer products might increase silver concentrations in waste waters, there was no increase over time. Spatial variation in soil/sediment pH, precipitation, and soil calcium oxide are indicated as significant predictors of metal concentrations in otters (higher cadmium and silver in areas with lower pH and higher rainfall, and higher chromium and lead in areas of lower calcium oxide). Liver chromium and nickel concentrations declined significantly over time (Cr 0.030 ± 1.2 to 0.015 ± 1.3 μg/g dry weight, Ni 0.0038 ± 1.2 to 0.00068 ± 1.5 μg/g, between 2006–2009 and 2014–2017), but other metals showed no temporal change. Biotic associations were important, with age related accumulation indicated for mercury and cadmium (as well as interactions with body condition). Our results suggest that larger-scale geochemical and hydrological processes are important in determining metal exposure in otters, and we provide an indication of risk factors that may be of relevance for freshwater vertebrates in other countries with well-developed water pollution management

The &Spaces Library

Capstone project for LIS 2005 involving the redesign of public library institutions with a focus on physical space. Conference poster, PowerPoint, and paper attached

Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells

We show that elevated levels of Ret receptor are found in different sub-types of human breast cancers and that high Ret correlates with decreased metastasis-free survival. The role of Ret in ER+ breast cancer models was explored combining in vitro and in vivo approaches. Our analyses revealed that ligand-induced Ret activation: (i) stimulates migration of breast cancer cells; (ii) rescues cells from anti-proliferative effects of endocrine treatment and (iii) stimulates expression of cytokines in the presence of endocrine agents. Indeed, we uncovered a positive feed-forward loop between the inflammatory cytokine IL6 and Ret that links them at the expression and the functional level. In vivo inhibition of Ret in a metastatic breast cancer model inhibits tumour outgrowth and metastatic potential. Ret inhibition blocks the feed-forward loop by down-regulating Ret levels, as well as decreasing activity of Fak, an integrator of IL6-Ret signalling. Our results suggest that Ret kinase should be considered as a novel therapeutic target in subsets of breast cancer