315 research outputs found
Investigating novel therapies for osteosarcoma using advanced medical imaging
No full text© 2012 Dr. Matthew L. BroadheadPublications included in thesis:Dowsey, M. M., Broadhead, M. L., Stoney, J. D. & Choong, P. F. (2009). Outcomes of total knee arthroplasty in English-versus non-English-speaking patients. Journal of Orthopaedic Surgery, 17(3), 305–309.Broadhead, M. L., Dass, C. R. & Choong, P. F. M. (2011). Systemically administered PEDF against primary and secondary tumours in a clinically relevant osteosarcoma model. British Journal of Cancer, 105(10), 1503–1511. DOI: 10.1038/bjc.2011.410Broadhead, M. L., Choong, P. F. M. & Dass, C. R. (2012). Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis. Journal of Biomedicine and Biotechnology, 2012. DOI: 10.1155/2012/230298Broadhead, M. L., Dass, C. R. & Choong, P. F. M. (2009). Cancer cell apoptotic pathways mediated by PEDF: prospects for therapy. Trends in Molecular Medicine, 15(10), 461–467. DOI: 10.1016/j.molmed.2009.08.003Broadhead, M. L., Dass, C. R. & Choong, P. F. M. (2009). In vitro and in vivo biological activity of PEDF against a range of tumours. Expert Opinion on Therapeutic Targets, 13(12), 1429–1438. DOI: 10.1517/14728220903307475Broadhead, M. L., Clark, J. C. M., Choong, P. F. M. & Dass, C. R. (2010). Making gene therapy for osteosarcoma a reality. Expert Review of Anticancer Therapy, 10(4), 477–480. DOI: 10.1586/ERA.10.18Broadhead, M. L., Akiyama, T., Choong, P. F. M. & Dass, C. R. (2010). The pathophysiological role of PEDF in bone diseases. Current Molecular Medicine, 10(3), 296–301.Broadhead, M. L., Becerra, S. P., Choong, P. F. M. & Dass, C. R. (2010). The applied biochemistry of PEDF and implications for tissue homeostasis. Growth Factors, 28(4), 280–285. DOI: 10.3109/08977191003604513Broadhead, M. L., Clark, J. C. M., Dass, C. R. & Choong, P. F. M. (2010). Microarray: an instrument for cancer surgeons of the future? ANZ Journal of Surgery, 80(7-8), 531–536. DOI: 10.1111/j.1445-2197.2010.05379.xBroadhead, M. L., Clark, J. C. M., Myers, D. E., Dass, C. R. & Choong, P. F. M. (2011). The molecular pathogenesis of osteosarcoma: a review. Sarcoma, 2011. DOI: 10.1155/2011/959248Broadhead, M. L., Clark, J. C. M., Dass, C. R., Choong, P. F. M. & Myers, D. E. (2011). Therapeutic targeting of osteoclast function and pathways. Expert Opinion on Therapeutic Targets, 15(2), 169–181. DOI: 10.1517/14728222.2011.546351Babazadeh, S., Broadhead, M. L., Slavin, J. L. & Choong, P. F. M. (2009). An interesting diagnosis for a presacral mass: case report. International Seminars in Surgical Oncology, 6(18). DOI: 10.1186/1477-7800-6-18Babazadeh, S., Broadhead, M. L., Slavin, J. L., Schlicht, S. M. & Choong, P. F. M. (2010). Giant cell tumour of metacarpal diaphysis. European Journal of Radiology Extra, 75(1), e31–e36. DOI: 10.1016/j.ejrex.2010.04.008Broadhead, M. L., Babazadeh, S., O'Brien, B. & Choong, P. F. M. (2010). Thigh enlargement and the art of misdirection. ANZ Journal of Surgery, 80(11), 839–840. DOI: 10.1111/j.1445-2197.2010.05503.xBroadhead, M. L., Babazadeh, S., Goldwasser, M. & Choong, P. F. M. (2011). Waxing and waning of joint motion. Grand Rounds, 11, 44–47. DOI: 10.1102/1470-5206.2011.0011Babazadeh, S., Broadhead, M. L. & Choong, P. F. M. (2011). If you are called to lead, you are called to serve. ANZ Journal of Surgery, 81(6), 401–403. DOI: 10.1111/j.1445-2197.2011.05782.xBroadhead, M. L., Babazadeh, S., Ng, K. W., Choong, P. F. M. & Stoney, J. D. (2011). Atraumatic bilateral femoral neck fractures during pregnancy: a missed diagnosis. Australian and New Zealand Journal of Obstetrics and Gynaecology, 51(6), 563-564. DOI: 10.1111/j.1479-828X.2011.01366.xBabazadeh, S., Broadhead, M. L., Schlicht, S. M., Powell, G. J. & Tymms, G. M. (2011). Pathologic fracture of a calcaneal aneurysmal bone cyst. The Journal of Foot and Ankle Surgery, 50(6), 727–732. DOI: 10.1053/j.jfas.2011.04.036Osteosarcoma is the most common primary cancer of bone. Current best treatment consists of chemotherapy and surgery, however many tumours are chemoresistant. Spread of osteosarcoma to the lungs is frequent and is the most common cause of death. This thesis examines the role of pigment epithelium-derived factor (PEDF) in the processes of osteosarcoma growth, invasion and metastasis. In order to evaluate this potential role, both in vitro and in vivo studies have been performed.
In vitro studies have examined the biological effects and mechanisms of PEDF. PEDF exhibits a multifaceted ability to inhibit osteosarcoma tumorigenicity. PEDF inhibits proliferation, induces apoptosis and reduces cell cycling of osteosarcoma cells in vitro. Additionally, the metastatic capacity of osteosarcoma cell lines is diminished by PEDF. Osteosarcoma cells treated with PEDF demonstrate an enhanced capacity for adhesion and a reduced ability for invasion through collagen I, the most abundant protein in bone.
An established murine model of orthotopic osteosarcoma has been optimised for the evaluation of novel therapeutic agents in vivo. This model allowed for an evaluation of systemically delivered PEDF and PEDF-derived peptides, both as sole treatments and in combination with doxorubicin. Systemic administration of PEDF causes a reduction in both primary tumour volume and pulmonary metastatic disease. PEDF-derived peptides, StVOrth-2 (residues 78-102) and StVOrth-3 (residues 90-114) were also delivered systemically. StVOrth-2 primarily restricts growth of primary osteosarcoma while StVOrth-3 restricts pulmonary metastatic disease.
Finally, advanced medical imaging techniques have been applied to this murine model of orthotopic osteosarcoma for the study of tumour growth, invasion and metastasis; in vivo bioluminescent imaging, [18F]-Fluoride-PET, [18F]-FDG-PET and micro-computed tomography provide novel information about this model. Use of these imaging modalities has improved osteosarcoma modelling and allowed closer monitoring of disease progression. This is the first time that in vivo imaging has been used in the assessment of PEDF’s anti-osteosarcoma properties and is a major advance from previously published studies demonstrating direct effects on osteosarcoma growth and metastasis
NATO Conference on Materials for Advanced Batteries
No full textThe idea of a NATO Science Committee Institute on "Materials for Advanced Batteries" was suggested to JB and DWM by Dr. A. G. Chynoweth. His idea was to bring together experts in the field over the entire spectrum of pure research to applied research in order to familiarize everyone with potentially interesting new systems and the problems involved in their development. Dr. M. C. B. Hotz and Professor M. N. Ozdas were instrumental in helping organize this meeting as a NATO Advanced Science Institute. An organlzlng committee consisting of the three of us along with W. A. Adams, U. v Alpen, J. Casey and J. Rouxel organized the program. The program consisted of plenary talks and poster papers which are included in this volume. Nearly half the time of the conference was spent in study groups. The aim of these groups was to assess the status of several key aspects of batteries and prospects for research opportunities in each. The study groups and their chairmen were: Current status and new systems J. Broadhead High temperature systems W. A. Adams Interface problems B. C. H. Steele Electrolytes U. v Alpen Electrode materials J. Rouxel These discussions are summarized in this volume. We and all the conference participants are most grateful to Professor J. Rouxel for suggesting the Aussois conference site, and to both he and Dr. M. Armand for handling local arrangements
I+E Illumination and Emanation; Light as Body Adornment and the Implications of Wearable Light
Get PDFI+E Illumination and Emanation; Light As Body Adornment and the Implications of Wearable Light is practice-based research that exploits advances in miniature light sources in order to establish new forms of aesthetic expression through wearable light.
I+E investigates how wearable light interacts with the body and its environment; it explores how this interaction shapes the visual perception of the body and establishes a critical framework for the description and evaluation of wearable light.
Practice working with light and body crosses disciplines from jewellery and fashion to fine art, performance and lens-based media. Wearable light, however, is a new field with few precedents and potential for future applications in sportswear, therapeutic rehabilitation and personal safety.
A reflexive, and adaptive methodology characterized the research process in which practice was the main vehicle, informed by the selection of critical context and continuous external feedback. Due to the cross-disciplinary nature of wearable light collaborative projects with practitioners in art & design and technological experts were balanced with experimental solo projects.
The research outcome is a body of work that investigates wearable light in a variety of applications such as light jewellery, performance and lens-based media.
Original contributions to knowledge are: in developing an experimental, practice-based research methodology with a particular focus on the role of collaborations vis-à-vis solo projects, and the expansion of the role of the practitioner from designer-maker to ‘auteur’, the focus and conduit in the practice of a new and complex performance art based on wearable light; in developing a critical vocabulary for the description and evaluation of wearable light and in investigating the mechanics of placing light on the body and its effects on the perception of the body in its environment
High-prevalence and high-estimated incidence of HIV infection among new injecting drug users in Estonia: need for large scale prevention programs.
Get PDFOBJECTIVE: To examine HIV risk behavior and HIV infection among new injectors in Tallinn, Estonia. Design and methods Data from two cross-sectional surveys of injecting drug users (IDUs) recruited from a syringe exchange program (N = 162, Study 1) or using respondent driven sampling (N = 350, Study 2). Behavioral surveys were administered; serum samples were collected for HIV testing. Subjects were categorized into new injectors (injecting 3 years). RESULTS: Twenty-eight of 161 (17%, Study 1) and 73/350 (21%, Study 2) of the study subjects were new injectors. HIV infection was substantial among the newer injectors: HIV prevalence was 50% (Study 1) and 34% (Study 2), and estimated HIV incidence 31/100 PY and 21/100 PY, respectively. In Study 2, new injectors were more likely to be female and ethnic Estonian and less likely to be injecting daily compared with long-term injectors. No significant difference was found among two groups on sharing injecting equipment or reported number of sexual partners. CONCLUSIONS: A continuing HIV epidemic among new injectors is of critical public health concern. Interventions to prevent initiation into injecting drug use and scaling up HIV prevention programs for IDUs in Estonia are of utmost importance
Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species
Get PDFAntigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections
University of Nebraska College of Medicine Class of 2005
No full textBenjamin Aaker, Daniel J. Albertson, Mikala M. Albertson, William J. Andrews, Laura A. Arndorfer, Ryan M. Arnold, Nathan G. Asher, Elizabeth M. Augustine, Mathue M. Baker, Amy R. Barker, Matthew P. Behrens, Aaron T. Benner, Casey D. Beran, Margaret M. Beran, Shreenath Bishu, Kimberly A. Borke, Robert E. Bowen, Jess L. Boysen, Allyson L. Braasch, Sarah K. Broadhead, Michael A. Burson, Jesica A. Christensen, Paul J. Cluff, Chris A. Cornett, Chandra E. Cullen, Kwanza N. Devlin, Travis W. Dierks, Erik T. Ehlers, Justin O. Endo, David J. Ensz, Brian T. Fay, Michael R. Feilmeier, Michael P. Fullenkamp, Joseph J. Gard, Kristina A. Garnett, Kristine M. Gerbus, David C. Griffin, Joseph E. Hansler, Katherine A. Hanson, David J. Haralson, Charles H. Harper, Dana J. Hess, Carrie Anne Hoarty, Alastair T. Hoyt, Terry Huang, Ryan C. Hurd, Kate E. Hutchens, Andrew S. Itkin, Todd A. Jensen, Anya A. Johansen, Phillip I. Jones, Adam T. Kafka, Robyn M. Kaiser, Susan D. Keasling, Christopher T. Koch, Lori M. Krajicek, Taryn Q. Lambrecht, William J. Lawton, Louis Lin, Todd R. Lovgren, Clancy E. McNally, David J. Meduna, Melissa B. Meier, Laura R. Millemon, Mathew J. Miller, Natalya K. Miller, Tara J. Missoi, Joseph J. Mueller, Casey G. Nekl, Oluyemisi M. Odugbesan, Kimberlee J. Olsen, Dana M. Olson, Preston S. Omer, John M. Park, Nicole N. Paulman, Roger A. Paulman, Joshua D. Phillips, Nathan A. Pitts, Rebecca E. Rawalt, Lindsey M. Rentschler, Staci L. Rosche, Erik J. Sather, Stephanie R. Schardt, Stephen M. Schinker, John R. Schneider, Clayton B. Schroeder, James H. Sederberg, Tracie I. Shea, Ryan C. Shelstad, Nicole M. Sherman, Mohsin Q. Soliman, Kristin J. Somers, Thomas F. Spiegel, Alvin J. Stosich, Matthew T. Stritt, Regan M. Taylor, Monique A. Tolston, Anna K. Trauernicht, Chris A. Unterseher, Christine A. VanBeek, Kelly S. Wagoner, Shannon E. Wakeley, Aaron J. Ward, Dustin J. Weiss, Debra K. Whaley, Nicholas P. Wilson, Lucille R. Woodard, Hadi Zahra, Elizabeth A. Ziembahttps://digitalcommons.unmc.edu/comclass/1086/thumbnail.jp
Experimental and natural abrasion of conodonts in marine and eolian environments
No full textSmall skeletal sediment particles, by virtue of their size, experience physical sedimentological conditions different from those affecting large (i.e., > 4 mm) particles. In shallow, high-energy marine carbonate environments with an overall fine-grained (< 4 mm) sediment composition, grain-to-grain impacts are probably of insufficient magnitude to overcome the cushioning effect of water and cause abrasive wear. Very large skeletal grains within such a setting will promote physical degradation, but biological activity (microboring, bioerosion) is more effective in modifying particle surfaces and diminishing grain size. Only in eolian environments are collisions between small grains effective in causing abrasion. Quartz sand, a particularly important abrasive agent in the destruction of large skeletal parts under even moderate energy regimes, also appears to be appreciably important for the degradation of small skeletons only under eolian conditions.Conodonts are small (0.2–2.0 mm), phosphatic teeth, which may have belonged to an extinct (Cambrian-Triassic) group of jawless fish. They occur principally in marine and marginal marine sedimentary rocks; most specimens probably were deposited as discrete particles or as components of fecal masses. Because the extent and nature of degradation of a skeleton reflects its taphonomic history, evaluation of the susceptibility of conodonts to physical abrasion is important. Bioerosion, probably the principal cause of degradation of calcareous skeletons, was probably insignificant in alteration of conodonts. Their mineralogical composition made conodonts unlikely substrates for endoliths, and they were insufficiently abundant to serve as a recyclable source of phosphate for larger metazoans. Chemical breakdown of skeletal apatite would not have occurred, although atmospheric exposure may have promoted degradation of organic laminae, causing exfoliation.Experimental studies of abrasion (elements of Palmatolepis sp., Polygnathus sp. - U. Devonian, Iowa) plus petrographic examination of conodont bearing marine, marginal marine, and eolian facies of the Morgan Formation (M. Pennsylvanian, Utah and Colorado) suggests that abrasion of conodonts is insignificant in aqueous environments, and likely to occur to a major degree only under eolian conditions. High-energy (25.6 cm/sec) conditions were simulated in a tumbler containing quartz sand (4Φ − 2Φ), artificial sea water and moderate conodont abundances (50 specimens/kg). Abrasion produced under these artificially extreme conditions (e.g., continuous motion for up to 20 km travel distance) was at a scale detectable only with SEM. “Dry” tumbling experiments were ineffective, as noted by other authors simulating conditions for abrasion of mineral grains. Eolian conditions were simulated in a glass “wind tube” (see Kuenen, 1960, Journal of Geology) using a similar range of quartz sand sizes. Air velocity of approximately 100 cm/sec produced subtle visually detectable abrasion following 5 hours of exposure/transport in 2Φ quartz sand (1667 specimens/kg), but exhibited no visual evidence of abrasion under similar conditions with 3Φ sand.The Morgan Formation is a mixed carbonate/siliciclastic sequence that reflects repeated episodes of submergence and exposure of a carbonate shelf and laterally adjacent siliciclastic eolian “sand sea.” It represents a virtually ideal ancient example for the interpretation of the effects of natural sedimentary processes because of its well-documented environmental heterogeneity and contains both abraded and unabraded conodonts. Conodonts sampled from high-energy subtidal carbonate facies of the Morgan are unabraded, irrespective of the presence of quartz sand; platform and delicate ramiform elements are all represented. Conodonts sampled from mixed siliciclastic/carbonate eolian facies are extremely abraded; only the most durable Pa elements of Adetognathus sp. and Idiognathodus sp. are preserved, although fine surface details and denticles are worn and anterior blades are missing. Laboratory simulations confirm the interpretation that marine processes are generally insufficient to physically abrade small phosphatic skeletal grains and that highly abraded Morgan conodonts experienced extremely long residence times in the eolian environment where they were transported, repeatedly buried, and exposed to bombardment and abrasion by quartz sand.Supported by NSF EAR9004300</jats:p
Creativity and Embodied Fluid Movements
No full textThere is an increasing body of evidence suggesting that the embodiment of certain movements can stimulate creative idea formation. Embodied Creativity suggests that embodying particular movements, often fluid, free movements can improve creative thinking over the embodiment of nonfluid movements. In the first of two experiments participants were required to navigate a character through a bespoke virtual environment while (a) following a fluid, free flowing pathway, (b) a nonfluid pathway, or (c) a straight, linear pathway. Movements were performed on a flat, horizontal axial plane. Participants completed a series of Divergent thinking tasks (Torrence Test of Creative Thinking, TTCT; Torrence, 1974) and a series of Convergent thinking tasks (Remote Associations Test, RAT; Mednick, 1962).
The first experiment results suggest a contradiction with previous findings, displaying an increase in creativity scores for participants embodying both fluid and non-fluid movements when compared to the straight pathway. It was discussed that aspects of the virtual pathway design may explain the result. Though the first experiment showed support for the idea that individuals can embody movements when immersed within virtual environments. In a similar yet revised second experiment, participants embodied fluid, non-fluid and linear movements through an altered virtual pathway. The movements were performed on a variable vertical axis, participants embodied up and down fluid and non-fluid movements. The results indicated increased divergent thinking scores for those completing both a fluid pathway and a linear free moving straight pathway over a non-fluid pathway in line with previous research (Slepian & Ambady, 2012; Leung et al., 2012). Results were discussed in terms of virtual environments, axis and embodied metaphors
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