Predicting cortical bone adaptation to axial loading in the mouse tibia

The development of predictive mathematical models can contribute to a deeper understanding of the specific stages of bone mechanobiology and the process by which bone adapts to mechanical forces. The objective of this work was to predict, with spatial accuracy, cortical bone adaptation to mechanical load, in order to better understand the mechanical cues that might be driving adaptation. The axial tibial loading model was used to trigger cortical bone adaptation in C57BL/6 mice and provide relevant biological and biomechanical information. A method for mapping cortical thickness in the mouse tibia diaphysis was developed, allowing for a thorough spatial description of where bone adaptation occurs. Poroelastic finite-element (FE) models were used to determine the structural response of the tibia upon axial loading and interstitial fluid velocity as the mechanical stimulus. FE models were coupled with mechanobiological governing equations, which accounted for non-static loads and assumed that bone responds instantly to local mechanical cues in an on–off manner. The presented formulation was able to simulate the areas of adaptation and accurately reproduce the distributions of cortical thickening observed in the experimental data with a statistically significant positive correlation (Kendall's τ rank coefficient τ = 0.51, p < 0.001). This work demonstrates that computational models can spatially predict cortical bone mechanoadaptation to a time variant stimulus. Such models could be used in the design of more efficient loading protocols and drug therapies that target the relevant physiological mechanisms

Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation.

Dexamethasone treatment of F0 pregnant rodents alters F1 placental function and adult cardiometabolic phenotype. The adult phenotype is transmitted to the F2 generation without further intervention, but whether F2 placental function is altered by F0 dexamethasone treatment remains unknown. In the present study, F0 mice were untreated or received dexamethasone (0.2µgg(-1)day(-1), s.c.) over Days 11-15 or 14-18 of pregnancy (term Day 21). Depending on the period of F0 dexamethasone treatment, F1 offspring were lighter at birth or grew more slowly until weaning (P<0.05). Glucose tolerance (1gkg(-1), i.p.) of adult F1 males was abnormal. Mating F1 males exposed prenatally to dexamethasone with untreated females had no effect on F2 placental function on Day 19 of pregnancy. In contrast, when F1 females were mated with untreated males, F2 placental clearance of the amino acid analogue (14)C-methylaminoisobutyric acid was increased by 75% on Day 19 specifically in dams prenatally exposed to dexamethasone on Days 14-18 (P<0.05). Maternal plasma corticosterone was also increased, but F2 placental Slc38a4 expression was decreased in these dams (P<0.05). F0 dexamethasone treatment had no effect on F2 fetal or placental weights, regardless of lineage. Therefore, the effects of F0 dexamethasone exposure are transmitted intergenerationally to the F2 placenta via the maternal, but not paternal, line.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1071/RD14285

An alternative approach to water regulations for public health protection at bathing beaches

This is the final version of the article. Available from Hindawi Publishing Corporation via the DOI in this record.New approaches should be considered as the US Environmental Protection Agency (EPA) moves rapidly to develop new beach monitoring guidelines by the end of 2012, as these guidelines serve as the basis by which states and territories with coasts along the oceans and Great Lakes can then develop and implement monitoring programs for recreational waters. We describe and illustrate one possible approach to beach regulation termed as the "Comprehensive Toolbox within an Approval Process (CTBAP)." The CTBAP consists of three components. The first is a "toolbox" consisting of an inventory of guidelines on monitoring targets, a series of measurement techniques, and guidance to improve water quality through source identification and prevention methods. The second two components are principles of implementation. These include first, "flexibility" to encourage and develop an individualized beach management plan tailored to local conditions and second, "consistency" of this management plan to ensure a consistent national level of public health protection. The results of this approach are illustrated through a case study at a well-studied South Florida recreational marine beach. This case study explores different monitoring targets based on two different health endpoints (skin versus gastrointestinal illness) and recommends a beach regulation program for the study beach that focuses predominately on source prevention.This study was funded in part by the National Science Foundation (NSF) and the National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School (NSF 0CE0432368/0911373) and (NIEHS P50 ES12736); an NSF REU in Oceans and Human Health; and ESF and ERDF Convergence funding to the European Centre for Environment and Human Health (University of Exeter)

Exploiting zinc oxide re-emission to fabricate periodic arrays

The synthesis of hexagonal ring-shaped structures of zinc oxide using nanosphere lithography and metal/metal oxide sputtering is demonstrated. This synthesis exploits the surface re-emission of zinc oxide to deposit material in regions lying out of the line-of-sight of the sputtering source. These rings can nucleate the hydrothermal growth of zinc oxide crystals. Control over the growth could be exercised by varying growth solution concentration or temperature or by applying an external potential. © 2010 American Chemical Society

Nanocapacitive circuit elements

"Natural" lithography was used to prepare arrays of nanoscale capacitors on silicon. The capacitance was verified by a novel technique based on the interaction of a charged substrate with the electron beam of a scanning electron microscope. The "nanocapacitors" possessed a capacitance of ∼1 × 10-16F and were observed to hold charge for over an hour. Our results indicate that fabricating nanostructures using natural lithography may provide a viable alternative for future nanoelectronic devices. © 2008 American Chemical Society

Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development.

Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis

Utilisation of geriatric assessment in oncology - a survey of Australian medical oncologists

© 2018 Elsevier Inc. Introduction: Geriatric assessment (GA) is a multidimensional health assessment of the older person to evaluate their physical and cognitive function, comorbidities, nutrition, medications, psychological state, and social supports. GA may help oncologists optimise care for older patients with cancer. The aim of this study was to explore the views of Australian medical oncologists regarding the incorporation of geriatric screening tools, GA and collaboration with geriatricians into routine clinical practice. Methods: Members of the Medical Oncology Group of Australia were invited to complete an online survey that evaluated respondent demographics, practice characteristics, treatment decision-making factors, use of GA, and access to geriatricians. Results: Sixty-nine respondents identified comorbidities, polypharmacy, and poor functional status as the most frequent challenges in caring for older patients with cancer. Physical function, social supports and nutrition were the most frequent factors influencing treatment decision-making. The majority of respondents perceived value in GA and geriatrician review, although access was a barrier for referral. Such services would need to be responsive, providing reports within two weeks for the majority of respondents. Conclusion: Despite an emerging evidence base for the potential benefits of GA and collaboration with geriatricians, medical oncologists reported a lack of access but a desire to engage with these services

Citizen Science and Open Design: Workshop Findings

An inherent link exists between making things and designing things, often relying on skills, knowledge, and tools, and working together to achieve outcomes. Conventional design and manufac- ture to date has been a closed system requiring professional skills. Traditional manufacture has required a significant initial financial investment for “tooling” to produce large volumes of product (i.e., for “mass production”). In contrast, Digital Manufacture (DM) or Rapid Manufacture (RM) is “the ability to manufacture parts of vir- tually any complexity [and] geometry entirely without the need for tooling.” The latter offers lower financial entry-points and the ability to create bespoke products.1 The following article weaves Open design, Digital Manufacture and Citizen Science together present- ing findings from territory exploring workshops with lay users signposting opportunities and perceived detrimental factors

Rhetoric, organizational category dynamics and institutional change : a study of the UK Welfare State

Accounts of institutional change and categorization conventionally assume that high-status change agents can impose change, even to stable category systems, which lower-status actors accommodate in order to ensure social approval and material resources. By exploring the UK Conservative-Liberal Coalition's rhetorical efforts to reform the welfare state, how welfare providers are categorized and the subsequent response of implicated category members, we offer instead an account of institutional change that exposes the agentic limitations of high-status actors. Whilst governments may well be in a position to impose changes in the formal rules of the game through manipulation of material resources (fiscal contraction, privatization, open markets, deregulation), we find that they cannot necessarily monopolize symbolic resources (identities/cultural features). We also find that deviation from cultural expectations is not only available to large, high-status organizations, low-status actors too have discretion over their responses to institutional pressures regarding how they are categorized and subsequently judged