Generation and Characterization of Mice Carrying a Conditional Allele of the Wwox Tumor Suppressor Gene

WWOX, the gene that spans the second most common human chromosomal fragile site, FRA16D, is inactivated in multiple human cancers and behaves as a suppressor of tumor growth. Since we are interested in understanding WWOX function in both normal and cancer tissues we generated mice harboring a conditional Wwox allele by flanking Exon 1 of the Wwox gene with LoxP sites. Wwox knockout (KO) mice were developed by breeding with transgenic mice carrying the Cre-recombinase gene under the control of the adenovirus EIIA promoter. We found that Wwox KO mice suffered from severe metabolic defect(s) resulting in growth retardation and all mice died by 3 wk of age. All Wwox KO mice displayed significant hypocapnia suggesting a state of metabolic acidosis. This finding and the known high expression of Wwox in kidney tubules suggest a role for Wwox in acid/base balance. Importantly, Wwox KO mice displayed histopathological and hematological signs of impaired hematopoeisis, leukopenia, and splenic atrophy. Impaired hematopoeisis can also be a contributing factor to metabolic acidosis and death. Hypoglycemia and hypocalcemia was also observed affecting the KO mice. In addition, bone metabolic defects were evident in Wwox KO mice. Bones were smaller and thinner having reduced bone volume as a consequence of a defect in mineralization. No evidence of spontaneous neoplasia was observed in Wwox KO mice. We have generated a new mouse model to inactivate the Wwox tumor suppressor gene conditionally. This will greatly facilitate the functional analysis of Wwox in adult mice and will allow investigating neoplastic transformation in specific target tissues

Meditation on the Soles of the Feet Practice Provides Some Control of Aggression for Individuals with Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative condition that affects cognition, mental and physical health, and functionality of older people. As the disease progresses from the mild to moderate stage, there is a concomitant increase in several behavioral variables, chiefly agitation, anger, and aggression. Currently, there are no evidence-based treatments for these behaviors in this population. Three individuals with moderate Alzheimer’s disease were taught an informal mindfulness practice, meditation on the Soles of the Feet (SoF), as a self-management strategy within a multiple-baseline design across participants. All three were able to learn and use the SoF practice to manage their verbal and physical aggression. Their use of the SoF practice was correlated with decreased perceived psychological stress for their spouses and caregivers, as well as for the participants, but to a much smaller degree. In terms of social validity, the participants, their spouses, and caregivers rated the SoF practice as acceptable, effective, with no unintended effects, and indicated that they would recommend the practice to others. However, they also rated SoF as effortful for the participants because it involves the participants remembering to use the practice with rising anger, a requirement particularly challenging for those with memory problems. The SoF practice may enable individuals in the early stages of dementia to manage their anger and aggression. The data were derived from an internally valid experimental design, suggestive of initial proof-of-concept, but needs to be replicated before any clinical implications can be imputed from this study

The development of accounting in UK universities:an oral history

This article reports on the development of the accounting discipline in universities in England and Scotland from the 1960s. Drawing on the oral history narratives of six distinguished accounting scholars who played a significant role in the discipline, this article documents (1) the initial influences on the teaching of accounting in English universities, (2) the different influences on the teaching of accounting in Scottish universities and (3) the influence of US universities and their scholars on the development of academic accounting in the United Kingdom. With a focus on the second wave of accounting professoriate who followed the London School of Economics (LSE) ‘Triumvirate’ of William Baxter, Harold Edey and David Solomons, this article provides first-hand insights into the shape and spread of university accounting education at a crucial stage of its development. This, in turn, develops an understanding of the contemporary academic accounting discipline in the United Kingdom.PostprintPeer reviewe

The precarious supply of physical therapists across Canada: exploring national trends in health human resources (1991 to 2005)

<p>Abstract</p> <p>Background</p> <p>Health Human Resource (HHR) ratios are one measure of workforce supply, and are often expressed as a ratio in the number of health professionals to a sub-set of the population. In this study, we explore national trends in HHR among physical therapists (PTs) across Canada.</p> <p>Methods</p> <p>National population data were combined with provincial databases of registered physical therapists in order to estimate the HHR ratio in 2005, and to establish trends between 1991 and 2005.</p> <p>Results</p> <p>The national HHR ratio was 4.3 PTs per 10,000 population in 1991, which increased to 5.0 by 2000. In 2005, the HHR ratios varied widely across jurisdictions; however, we estimate that the national average dropped to 4.8 PTs per 10,000. Although the trend in HHR between 1991 and 2005 suggests positive growth of 11.6%, we have found negative growth of 4.0% in the latter 5-years of this study period.</p> <p>Conclusion</p> <p>Demand for rehabilitation services is projected to escalate in the next decade. Identifying benchmarks or targets regarding the optimal number of PTs, along with other health professionals working within inter professional teams, is necessary to establish a stable supply of health providers to meet the emerging rehabilitation and mobility needs of an aging and increasingly complex Canadian population.</p

Titanium dioxide engineered for near-dispersionless high terahertz permittivity and ultra-low-loss

Realising engineering ceramics to serve as substrate materials in high-performance terahertz(THz) that are low-cost, have low dielectric loss and near-dispersionless broadband, high permittivity, is exceedingly demanding. Such substrates are deployed in, for example, integrated circuits for synthesizing and converting nonplanar and 3D structures into planar forms. The Rutile form of titanium dioxide (TiO2) has been widely accepted as commercially economical candidate substrate that meets demands for both low-loss and high permittivities at sub-THz bands. However, the relationship between its mechanisms of dielectric response to the microstructure have never been systematically investigated in order to engineer ultra-low dielectric-loss and high value, dispersionless permittivities. Here we show TiO2 THz dielectrics with high permittivity (ca. 102.30) and ultra-low loss (ca. 0.0042). These were prepared by insight gleaned from a broad use of materials characterisation methods to successfully engineer porosities, second phase, crystallography shear-planes and oxygen vacancies during sintering. The dielectric loss achieved here is not only with negligible dispersion over 0.2-0.8 THz, but also has the lowest value measured for known high-permittivity dielectrics. We expect the insight afforded by this study will underpin the development of subwavelength-scale, planar integrated circuits, compact high Q-resonators and broadband, slow-light devices in the THz band

Formative evaluation of the telecare fall prevention project for older veterans

<p>Abstract</p> <p>Background</p> <p>Fall prevention interventions for community-dwelling older adults have been found to reduce falls in some research studies. However, wider implementation of fall prevention activities in routine care has yielded mixed results. We implemented a theory-driven program to improve care for falls at our Veterans Affairs healthcare facility. The first project arising from this program used a nurse advice telephone line to identify patients' risk factors for falls and to triage patients to appropriate services. Here we report the formative evaluation of this project.</p> <p>Methods</p> <p>To evaluate the intervention we: 1) interviewed patient and employee stakeholders, 2) reviewed participating patients' electronic health record data and 3) abstracted information from meeting minutes. We describe the implementation process, including whether the project was implemented according to plan; identify barriers and facilitators to implementation; and assess the incremental benefit to the quality of health care for fall prevention received by patients in the project. We also estimate the cost of developing the pilot project.</p> <p>Results</p> <p>The project underwent multiple changes over its life span, including the addition of an option to mail patients educational materials about falls. During the project's lifespan, 113 patients were considered for inclusion and 35 participated. Patient and employee interviews suggested support for the project, but revealed that transportation to medical care was a major barrier in following up on fall risks identified by nurse telephone triage. Medical record review showed that the project enhanced usual medical care with respect to home safety counseling. We discontinued the program after 18 months due to staffing limitations and competing priorities. We estimated a cost of $9194 for meeting time to develop the project.</p> <p>Conclusions</p> <p>The project appeared feasible at its outset but could not be sustained past the first cycle of evaluation due to insufficient resources and a waning of local leadership support due to competing national priorities. Future projects will need both front-level staff commitment and prolonged high-level leadership involvement to thrive.</p

Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy

Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours

Evidence for a Minimal Eukaryotic Phosphoproteome?

BACKGROUND: Reversible phosphorylation catalysed by kinases is probably the most important regulatory mechanism in eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS: We studied the in vitro phosphorylation of peptide arrays exhibiting the majority of PhosphoBase-deposited protein sequences, by factors in cell lysates from representatives of various branches of the eukaryotic species. We derived a set of substrates from the PhosphoBase whose phosphorylation by cellular extracts is common to the divergent members of different kingdoms and thus may be considered a minimal eukaryotic phosphoproteome. The protein kinases (or kinome) responsible for phosphorylation of these substrates are involved in a variety of processes such as transcription, translation, and cytoskeletal reorganisation. CONCLUSIONS/SIGNIFICANCE: These results indicate that the divergence in eukaryotic kinases is not reflected at the level of substrate phosphorylation, revealing the presence of a limited common substrate space for kinases in eukaryotes and suggests the presence of a set of kinase substrates and regulatory mechanisms in an ancestral eukaryote that has since remained constant in eukaryotic life

Tweet reach : a research protocol for using Twitter to increase information exchange in people with communication disabilities

Objective: To (a) outline the background to research evaluating Twitter use by people with severe physical and communication disabilities participating actively in online communication forums for increasing information exchange and (b) illustrate a range of potential methods that might be applied in furthering research on the use of social media by people with developmental and acquired communication disabilities. Methods: The literature on communication disabilities, augmentative and alternative communication, and social media research informed the rationale for and design of three studies investigating the use of Twitter by people with communication disabilities. Results: To date, there is little information in the literature about how people with a range of communication disabilities might use Twitter to increase their access to information and help them to feel knowledgeable and in control of their own lives. In this paper, three studies are proposed to investigate the use of Twitter by people with communication disabilities