Retinal sensitivity loss in third-generation n-3 PUFA-deficient rats

A previous study conducted in guinea pigs suggested that ingestion of diets high in EPA and DHA may result in suboptimal retinal function. The aim of the present study was to evaluate retinal function in pigmented (Long-Evans) rats, raised to a third generation on diets that were either deficient in n-3 PUFA or adequate (with the addition of DHA). Electroretinographic assessment employed full-field white flash stimulation. Photoreceptor responses were evaluated in terms of peak amplitudes and implicit times (a-wave, b-wave), intensity-response functions (Naka-Rushton), and the parameters of a model of transduction (P3). Retinal phospholipid FA composition was measured by capillary GLC. DHA levels were reduced by 55% in n-3-deficient animals compared with the n-3-adequate group, whereas the levels of docosapentaenoic acid n-6 were 44 times higher in n-3-deficient animals. The level of arachidonic acid was marginally higher (12.8%) in n-6-adequate animals. The n-3-deficient animals exhibited significantly reduced retinal sensitivity (σ and S values were both affected by 0.29 log units) and increased b-wave implicit times compared with those fed the n-3-adequate diet. These data suggest that n-3 PUFA are required for development of retinal sensitivity, more so than other indices of retinal function assessed by current methods, such as maximal response amplitude. However, the benefit for retinal function of adding preformed DHA to diets already replete in n-3 PUFA remains unclear.

Third-generation responses to holocaust video-testimony

This research investigated responses of grandchildren of Holocaust survivors ("third generation") to Holocaust video-testimony. The analysis revealed that video-testimony can transmit memories of survival experiences to viewers, enabling them to "work through" their positions as witnesses and make active decisions relating to remembrance.

The effects of testing procedure on critical fall height determination for third-generation synthetic turf

Test procedures and their accuracy in determining critical fall height (CFH) on sporting grounds are paramount to player safety. The procedure currently adopted for synthetic turf in Australian football [1] consists of four consecutive drops at various drop heights at three test locations on the sample. The quantity and packing of the infill in third-generation turf and the pooling effect of the rubber particles with consecutive drops suggests that the current standard protocol may need re-assessment. Therefore, the purpose of this pilot study was to investigate whether current methods of testing for CFH are appropriate for third-generation synthetic turf or whether an alternative or adapted method needs to be developed. CFH was measured, using a HISUN Uniaxe-II Impact Tester, on 12 combinations of synthetic turf samples (four different products with three shock pad options). Three conditions were investigated on each sample; the existing protocol; an alternative 12 single-drop protocol and four single drops from the CFH determined from the existing protocol. A significant difference was found for both absolute and percentage difference between the existing and 12 single-drop protocol, with p = 0.001 and t = 4.33 and p < 0.001 and t = 6.03, respectively. There was also a significant difference between the CFH reached with and without a shock pad for both the existing protocol and the 12 single-drop protocol. The results of this pilot study demonstrate that differences do occur with alterations to the existing protocol and highlight the need for a more detailed characterisation of testing methods on third-generation synthetic turf and the response of surfaces to them.

Session initiation protocol (SIP) based event notification system architecture for telemedicine applications

Mobility service for hospital technicians involved in telemedicine applications is one of the key issues in providing more flexible and efficient in-house or remote health care services. Today, the Internet based communication has widened the opportunity of event monitoring systems in the medical field. The session initiation protocol (SIP) can work on a variety of devices and can be used to create a medical event notification system. Its adoption as the protocol of choice for third generation wireless networks allows for a robust and scalable environment. One of the advantages of SIP is that it supports personal mobility through the separation of user addressing and device addressing. In this paper, the authors propose a possible solution framework for telemedicine alert notification system based SIP-specific event notification.

An exploration of the impact of celebrity on the HIV/AIDS pandemic

The framework we present in this article separates into three generations the celebrity/personality involvement in the AIDS movement that has been steadily building momentum over the past 25 years. We analyze the celebrification of HIV/AIDS and the role of the media in the process. We contend the relationship between celebrity, the public and HIV/AIDS is multipurpose: celebrities maintain a positive public presence between projects while allowing themselves and their supporting fans to feel good about taking on and affecting a meaningful cause. Celebrities are vehicles and embodiments of concern that act as proxies for their various audiences. And this is their power–celebrities are embodiments of their audiences. The awareness that celebrities have brought to the HIV/AIDS epidemic has resulted in better treatment for victims and increased government support for medical research, and yet has also distracted the public’s attention from the scope of the epidemic. It is the third generation of celebrities who are refocusing efforts on worldwide prevention and a cure for HIV/AIDS.

Anterior knee symptoms after S-ROM hinge implantation

Purpose: To evaluate the performance of a canal filling hinge device for complex knee arthroplasty. Methods: Thirty-seven (4 primary hinge implantation and 33 revision cases) patients who had undergone arthroplasty with the S-ROM third generation hinge device for a combination of massive bone loss or ligamentous insufficiency were prospectively examined with a minimum of 5-year follow-up. Median age at surgery was 72 years (range: 43 to 87 years). Principal indications included aseptic loosening or massive osteolysis (24 cases), infection (8 cases) and periprosthetic fracture (4 cases). All patients exhibited either grade 2 (N = 12) or grade 3 (N = 25) AORI bone loss or a grade 3 medial ligament deficiency. Results: One patient experienced implant failure (71 months), and one patient suffered late deep infection (36 months). Mean WOMAC score improved from 27 to 62. Four patients required patellar resurfacing for persistent pain. The 5-year survivorship was 86%. Conclusions: While the S-ROM device may offer satisfactory medium term outcome for complex end stage knee disease, we report a high rate of debilitating anterior knee symptoms.

The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells

Danusertib (Danu) is a pan-inhibitor of Aurora kinases and a third-generation breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (Bcr-Abl) tyrosine kinase inhibitor, but its antitumor effect and underlying mechanisms in the treatment of human breast cancer remain elusive. This study aimed to investigate the effects of Danu on the growth, apoptosis, autophagy, and epithelial-to-mesenchymal transition (EMT) and the molecular mechanisms in human breast cancer MCF7 and MDA-MB-231 cells. The results demonstrated that Danu remarkably inhibited cell proliferation, induced apoptosis and autophagy, and suppressed EMT in both breast cancer cell lines. Danu arrested MCF7 and MDA-MB-231 cells in G2/M phase, accompanied by the downregulation of cyclin-dependent kinase 1 and cyclin B1 and upregulation of p21 Waf1/Cip1, p27 Kip1, and p53. Danu significantly decreased the expression of B-cell lymphoma-extra-large (Bcl-xl) and B-cell lymphoma 2 (Bcl-2), but increased the expression of Bcl-2-associated X protein (Bax) and p53-upregulated modulator of apoptosis (PUMA), and promoted the cleavage of caspases 3 and 9. Furthermore, Danu significantly increased the expression levels of the membrane-bound microtubule-associated protein 1A/1B-light chain 3 (LC3-II) and beclin 1 in breast cancer cells, two markers for autophagy. Danu induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases 1 and 2 (Erk1/2) and inhibited the activation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways in breast cancer cells. Treatment with wortmannin (a phosphatidylinositol 3-kinase inhibitor) markedly inhibited Danu-induced activation of p38 MAPK and conversion of cytosolic LC3-I to membrane-bound LC3-II. Pharmacological inhibition and small interfering RNA-mediated knockdown of p38 MAPK suppressed Akt activation, resulting in LC3-II accumulation and enhanced autophagy. Pharmacological inhibition and small interfering RNA-mediated knockdown of Erk1/2 also remarkably increased the level of LC3-II in MCF7 cells. Moreover, Danu inhibited EMT in both MCF7 and MDA-MB-231 cells with upregulated E-cadherin and zona occludens protein 1 (ZO-1) but downregulated N-cadherin, zinc finger E-box-binding homeobox 1 (TCF8/ZEB1), snail, slug, vimentin, and β-catenin. Notably, Danu showed lower cytotoxicity toward normal breast epithelial MCF10A cells. These findings indicate that Danu promotes cellular apoptosis and autophagy but inhibits EMT in human breast cancer cells via modulation of p38 MAPK/Erk1/2/Akt/mTOR signaling pathways. Danu may represent a promising anticancer agent for breast cancer treatment. More studies are warranted to fully delineate the underlying mechanisms, efficacy, and safety of Danu in breast cancer therapy.

Temperature and grain orientation dependence of mechanical twinning in a high manganese TWIP steel

 This thesis contains fundamental studies of the deformation mechanisms of the third generation steel at different deformation temperatures. To analyse the microstructure of the steel a unique characterisation technique was implemented for the first time. These analyses provided with vital parameters for modelling the stress-strain behaviour of the steel at different deformation temperatures.

Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial

BACKGROUND: Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.

METHODS/DESIGN: The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.

Collective cultural rights in Asia: recognition and enforcement

This paper focuses particularly on how the notion of collective cultural rights is understood in Asia and how such rights are recognized in law and enforced through governmental policy. The discussion links the notions of cultural rights and cultural heritage, drawing inspiration from Comment No. 21 of the Committee on Economic, Social and Cultural Rights (2009) which asserts that everyone has the right to take part in cultural life and that “the obligations to respect and to protect freedoms, cultural heritage and cultural diversity are interconnected.” Efforts to protect and enhance human rights can only take place within states, and the record in Asian countries is very mixed. First and second generation human rights, with their emphasis on the individual, are sometimes regarded as Western in origin and character, while third generation collective cultural rights have been closely associated with Indigenous peoples, commonly living as minorities within European settler societies in the New World. Unlike Europe, Africa and the Americas, Asia does not have a regional intergovernmental human rights charter. Using case studies of China, Myanmar, Thailand and Vietnam the paper seeks to show why there is no Asian charter and asks what would it look like if there was one.

From local to national: aspects of mapping the welfare third sector in Australia

The paper charts the authors' research experiences in various types of sociological mapping ofc ommunity or third sector organisations. Specifically this was a search for a way of understanding how third sector organisations dealing with welfare issues were operating in Australia in the mid I990s.

The paper tells the story of how the researchers worked through the implications of being faced initially with a dearth of information about their subject and of how lessons were learnt about the disjunctions between what is formally given as textbook knowledge about research practice and what actually can and does happen: that is, the relationship between the theory and the practice of research.

In discussing the creation of a database of organisations, conducting focus groups and a national sample survey, the paper comments on some of the practical problems facing third sector researchers as well as looking at concept generation and typology building as analytical tools.

Generation of total runoff hydrographs using a method derived from a digital filter algorithm

A reliable prediction of the total runoff hydrograph is necessary for water resources management. This study investigates two approaches to generate total runoff hydrograph by adding baseflow to direct runoff hydrographs. The first approach uses a method, derived from a digital filter algorithm for hydrograph separation, to generate baseflow hydrographs from direct runoff hydrographs. The method appears to perform well in producing the overall shape of the total runoff hydrographs and the acceptable mass balance errors for a year of water cycle. For application, the recession baseflow constant needs to be estimated reliably and the initial baseflow could be approximated to the long-term mean dry weather flow. The second approach assumes a constant baseflow rate. Although this approach is still capable of producing the overall hydrograph shape, it yields high mass balance errors in the total runoff hydrographs for both monthly and long-term periods. Further analysis shows that two-third of the mass balance errors are contributed from periods with direct runoff, implying that the constant baseflow assumption could introduce significant errors into the computations of total runoff hydrograph