Competition of stress corrosion crack branches observed in-situ using time-lapse 3D x-ray synchrotron computed tomography

The progress of a stress corrosion crack in a sensitized AA7075 alloy was studied by in-situ x-ray synchrotron computed tomography. A load was applied to a pre-cracked specimen inside an environmental cell containing moist air and the propagation of the stress corrosion crack was observed. Measurements from the 3D image of the crack have already been shown to provide better quantification compared to observations of the crack from the outer surface. In this paper we study in detail the progress of the stress corrosion crack as it propagates through the material. We reveal how the formation of metal ligaments occurs and the competition of the ‘main’ crack and its branches. We have visualized these features to show the complexity of the local variation in crack morphology in a way that brings new insight into the interaction of the stress corrosion crack with the microstructure of the material

Schroedinger equation for joint bidirectional motion in time

The conventional, time-dependent Schroedinger equation describes only unidirectional time evolution of the state of a physical system, i.e., forward or, less commonly, backward. This paper proposes a generalized quantum dynamics for the description of joint, and interactive, forward and backward time evolution within a physical system. [...] Three applications are studied: (1) a formal theory of collisions in terms of perturbation theory; (2) a relativistically invariant quantum field theory for a system that kinematically comprises the direct sum of two quantized real scalar fields, such that one field evolves forward and the other backward in time, and such that there is dynamical coupling between the subfields; (3) an argument that in the latter field theory, the dynamics predicts that in a range of values of the coupling constants, the expectation value of the vacuum energy of the universe is forced to be zero to high accuracy. [...]Comment: 30 pages, no figures. Related material is in quant-ph/0404012. Differs from published version by a few added remarks on the possibility of a large-scale-average negative energy density in spac

Please mind the gap: students’ perspectives of the transition in academic skills between A-level and degree level geography

This paper explores first-year undergraduates’ perceptions of the transition from studying geography at pre-university level to studying for a degree. This move is the largest step students make in their education, and the debate about it in the UK has been reignited due to the government’s planned changes to A-level geography. However, missing from most of this debate is an appreciation of the way in which geography students themselves perceive their transition to university. This paper begins to rectify this absence. Using student insights, we show that their main concern is acquiring the higher level skills required for university learning

First experience with a new negative pressure incision management system on surgical incisions after cardiac surgery in high risk patients

<p>Abstract</p> <p>Background</p> <p>Sternal wound infection remains a serious potential complication after cardiac surgery. A recent development for preventing wound complications after surgery is the adjunctive treatment of closed incisions with negative pressure wound therapy. Suggested mechanisms of preventive action are improving the local blood flow, removing fluids and components in these fluids, helping keep the incision edges together, protecting the wound from external contamination and promoting incision healing. This work reports on our initial evaluation and clinical experience with the Prevena™Incision Management System, a recently introduced new negative pressure wound therapy system specifically developed for treating closed surgical incisions and helping prevent potential complications. We evaluated the new treatment on sternal surgical incisions in patients with multiple co-morbidities and consequently a high risk for wound complications.</p> <p>Methods</p> <p>The Prevena™incision management system was used in 10 patients with a mean Fowler risk score of 15.1 [Range 8-30]. The negative pressure dressing was applied immediately after surgery and left in place for 5 days with a continuous application of -125 mmHg negative pressure. Wounds and surrounding skin were inspected immediately after removal of the Prevena™ incision management system and at day 30 after surgery.</p> <p>Results</p> <p>Wounds and surrounding skin showed complete wound healing with the absence of skin lesions due to the negative pressure after removal of the Prevena™ dressing. No device-related complications were observed. No wound complications occurred in this high risk group of patients until at least 30 days after surgery.</p> <p>Conclusions</p> <p>The Prevena™system appears to be safe, easy to use and may help achieve uncomplicated wound healing in patients at risk of developing wound complications after cardiothoracic surgery.</p

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman

Negative pressure wound therapy: Potential publication bias caused by lack of access to unpublished study results data

<p>Abstract</p> <p>Background</p> <p>Negative pressure wound therapy (NPWT) is widely applied, although the evidence base is weak. Previous reviews on medical interventions have shown that conclusions based on published data alone may no longer hold after consideration of unpublished data. The main objective of this study was to identify unpublished randomised controlled trials (RCTs) on NPWT within the framework of a systematic review.</p> <p>Methods</p> <p>RCTs comparing NPWT with conventional wound therapy were identified using MEDLINE, EMBASE, CINAHL and The Cochrane Library. Every database was searched from inception to May 2005. The search was updated in December 2006. Reference lists of original articles and systematic reviews, as well as congress proceedings and online trial registers, were screened for clues to unpublished RCTs. Manufacturers of NPWT devices and authors of conference abstracts were contacted and asked to provide study information. Trials were considered nonrandomised if concealment of allocation to treatment groups was classified as "inadequate". The study status was classified as "completed", "discontinued", "ongoing" or "unclear". The publication status of completed or discontinued RCTs was classified as "published" if a full-text paper on final study results (completed trials) or interim results (discontinued trials) was available, and "unpublished" if this was not the case. The type of sponsorship was also noted for all trials.</p> <p>Results</p> <p>A total of 28 RCTs referring to at least 2755 planned or analysed patients met the inclusion criteria: 13 RCTs had been completed, 6 had been discontinued, 6 were ongoing, and the status of 3 RCTs was unclear. Full-text papers were available on 30% of patients in the 19 completed or discontinued RCTs (495 analysed patients in 10 published RCTs vs. 1154 planned patients in 9 unpublished RCTs). Most information about conference abstracts and unpublished study information referring to trials that were unpublished at the time these documents were generated was obtained from the manufacturer Kinetic Concepts Inc. (KCI) (19 RCTs), followed by The Cochrane Library (18) and a systematic review (15). We were able to obtain some information on the methods of unpublished RCTs, but results data were either not available or requests for results data were not answered; the results of unpublished RCTs could therefore not be considered in the review. One manufacturer, KCI, sponsored the majority of RCTs (19/28; 68%). The sponsorship of the remaining trials was unclear.</p> <p>Conclusion</p> <p>Multi-source comprehensive searches identify unpublished RCTs. However, lack of access to unpublished study results data raises doubts about the completeness of the evidence base on NPWT.</p

Epilysin (matrix metalloproteinase-28) contributes to airway epithelial cell survival

MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we generated cell lines expressing wild-type or catalytically-inactive mutant MMP28 in two pulmonary epithelial cell lines, A549 and BEAS-2B. We observed that over-expression of MMP28 provided protection against apoptosis induced by either serum-deprivation or treatment with a protein kinase inhibitor, staurosporine. Furthermore, we observed increased caspase-3/7 activity in influenza-infected lungs from Mmp28-/- mice compared to wild-type mice, and this activity localized to the airway epithelium but was not associated with a change in viral load. Thus, we have identified a novel role of MMP28 in promoting epithelial cell survival in the lung

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention

"I try and smile, I try and be cheery, I try not to be pushy. I try to say ‘I’m here for help’ but I leave feeling… worried’’: A qualitative study of perceptions of interactions with health professionals by community-based older adults with chronic pain

Background: Over 50% of community-dwelling older adults experience chronic pain, which threatens their quality of life. Of importance to their pain management is older people’s interaction with health professionals that, if unsatisfactory, may impair the outcome. Aims: To add to the limited research specific to older people living with chronic pain in the community, we explored how they perceive their experiences of interacting with health professionals, seeking factors that might optimise these interactions. Methods: Purposive sampling was used to recruit men and women .65 years with self-reported musculoskeletal chronic pain. Qualitative individual interviews and one group interview were undertaken with 23 participants. Data were transcribed verbatim and underwent Framework Analysis. Results: Three themes were identified. Seeking help illustrates issues around why older people in the community may or may not seek help for chronic pain, and highlights the potential involvement of social comparison. Importance of diagnosis illustrates the desire for professional validation of their condition and an aversion to vague explanations based on the person’s age. Being listened to and being heard illustrates the importance of empathic communication and understanding expectations, with due respect for the person’s age. Conclusions: In common with people of all ages, an effective partnership between an older person in pain and health professionals is essential if pain is to be reported, appropriately assessed and managed, because of the subjective nature of pain and its treatment responses. For older people with pain, perception about their age, by both parties in the partnership, is an additional factor that can unnecessarily interfere with the effectiveness of this partnership. Health professionals should engage with older adults to clarify their expectations about pain and its management, which may be influenced by perceptions about age; and to encourage expression of their concerns, which may also be affected by perceptions about age