933 resultados para Malignant underlying disease
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This thesis examined the relationship between firms' corporate reputation and their future financial performance. Corporate reputation was represented by measuring the level of senior executives' attention to a number of intangible firm' resources (e.g. financial reputation, service culture) within firms' annual reports over a 17 year period. Initial findings suggested there was only a small relationship between reputation and future performance which lead to a reformulation of the problem. Reputation was posited to be a source of corporate resilience that helped firms with stronger reputations to sustain superior financial performance in times of difficulty, as well as allowing them to rebound more quickly from performance decline. Results suggest this interpretation of corporate reputation as well as indicating that industry sectors operate in different reputational 'domains' in which the relative importance of financial versus stakeholder aspects of corporate reputation varies.
Immunity against a Chlamydia infection and disease may be determined by a balance of IL-17 signaling
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Most vaccines developed against Chlamydia using animal models provide partial protection against a genital tract infection. However, protection against the oviduct pathology associated with infertility is highly variable and often has no defining immunological correlate. When comparing two adjuvants (CTA1-DD and a combination of Cholera toxin plus CpG- oligodeoxynucleotide–CT/CpG) combined with the chlamydial major outer membrane protein (MOMP) antigen and delivered via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, we identified two vaccine groups with contrasting outcomes following infection. SL immunization with MOMP/CTA1-DD induced a 70% reduction in the incidence of oviduct pathology, without significantly altering the course of infection. Conversely, IN immunization with MOMP/CT/CpG prevented an ascending infection, but not the oviduct pathology. This anomaly presented a unique opportunity to study the mechanisms by which vaccines can prevent oviduct pathology, other than by controlling the infection. The IL-17 signaling in the oviducts was found to associate with both the enhancement of immunity to infection and the development of oviduct pathology. This conflicting role of IL-17 may provide some explanation for the discordance in protection between infection and disease and suggests that controlling immunopathology, as opposed to the rapid eradication of the infection, may be essential for an effective human chlamydial vaccine that prevents infertility.
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Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.
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Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far.
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Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer related deaths in Australian men. Treatment in the early stages of the disease involves surgery, radiation and/or hormone therapy. However, in late stages of the disease these treatments are no longer effective and only palliative care is available. Therefore, there is a focus on exploration of novel therapies to increase survival and treatment efficacy. Advanced prostate cancer is characterised by bone or other distant metastasis. Spreading of the primary tumour to a secondary location is a complex process requiring an initial loss in cell-cell adhesion followed by increased cell migration and invasion. One gene family that has been known to affect cell-to-cell contact in other model systems are the Eph receptor tyrosine kinases. They are the largest family of receptor tyrosine kinases made up of 14 vertebrate Eph receptors that bind to nine cell membrane bound ephrin ligands. Eph-ephrin interaction is crucial in regulating cell behaviour in developmental processes and it is now thought that the underlying mechanisms involved in development may also be involved in cancer. Aberrant expression has been reported in many human malignancies including prostate cancer. Furthermore, expression has been linked with metastasis and poor prognosis in other tumour models. This study explores the potential role of the Eph receptor family in prostate cancer, in particular the roles of EphA2, EphA3 and ephrin-A5. Gene expression profiles were established for the Eph family in a series of prostate cancer cell lines using quantitative real time RT-PCR. A smaller subset of the most prominently expressed genes was chosen to screen a cohort of clinical samples. Elevated levels of EphA2, EphA3 and their ligands, ephrin-A1 and ephrin-A5 were observed in individual cell lines. Interestingly high EphA3 expression was observed in the androgen responsive cell lines while EphA2 was more prominent in the androgen independent cell lines. However, studies using 5-dihydrotestosterone suggest that EphA3 expression in not regulated by androgen. Cells expressing EphA2 showed a greater ability for migration and invasion while cells expressing EphA3 showed poor migration and invasion. Forced expression of EphA2 in the LNCaP cell line resulted in a more invasive phenotype while forced expression of EphA3 in the PC-3 cell line suggests a possible negative effect for EphA3 on cell migration and invasion. Cell signalling studies show activation of EphA2 decreases activity of proteins thought to be involved in pathways regulating cell movement including Akt, Src and FAK. Changes to the activation status of Rho family members, including RhoA and Rac1, associated with reorganisation of the actin cytoskeleton, an important part of cell migration was also observed. As a result, activation of EphA2 in PC-3 cells resulted in a less invasive phenotype. A novel finding in this study was the discovery of a combination of two EphA2 Mabs able to activate EphA2. Preliminary results show a potential for this antibody combination to reduce prostate cancer invasion in vitro. A unique aspect of Eph-ephrin interaction is the resulting bi-directional signalling that occurs through both the receptor and ligand. In this study a potential role for ephrin-A5 mediated signalling in prostate cancer was observed. LNCaP cells express high levels of EphA3 and its high affinity ligand ephrin-A5. In stripe assays, used to study guidance cues, LNCaP cells show strong attraction/migration to EphA3-Fc stripes but not ephrin-A5-Fc stripes suggesting ephrin-A5 mediated reverse cell signalling is involved. Knockdown of ephrin-A5 using shRNA resulted in a decrease in attraction/migration to EphA3-Fc stripes. Furthermore a reduction in proliferation was also observed in vitro. A subcutaneous xenograft model using ephrin-A5 shRNA cells versus controls showed a decrease in tumour formation. This study demonstrates a difference in EphA2 and EphA3 function in prostate cancer migration/invasion and a potential role for ephrin-A5 in prostate cancer cell adhesion and growth.
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The Chinese government should be commended for its open, concerted, and rapid response to the recent H7N9 influenza outbreak. However, the first known case was not reported until 48 days after disease onset.1 Although the difficulties in detecting the virus and the lack of suitable diagnostic methods have been the focus of discussion,2 systematic limitations that may have contributed to this delay have hardly been discussed. The detection speed of surveillance systems is limited by the highly structured nature of information flow and hierarchical organisation of these systems. Flu surveillance usually relies on notification to a central authority of laboratory confirmed cases or presentations to sentinel practices for flu-like illness. Each step in this pathway presents a bottleneck at which information and time can be lost; this limitation must be dealt with...
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Background & Aims Nutrition screening and assessment enable early identification of malnourished people and those at risk of malnutrition. Appropriate assessment tools assist with informing and monitoring nutrition interventions. Tool choice needs to be appropriate to the population and setting. Methods Community-dwelling people with Parkinson’s disease (>18 years) were recruited. Body mass index (BMI) was calculated from weight and height. Participants were classified as underweight according to World Health Organisation (WHO) (≤18.5kg/m2) and age specific (<65 years,≤18.5kg/m2; ≥65 years,≤23.5kg/m2) cut-offs. The Mini-Nutritional Assessment (MNA) screening (MNA-SF) and total assessment scores were calculated. The Patient-Generated Subjective Global Assessment (PG-SGA), including the Subjective Global Assessment (SGA), was performed. Sensitivity, specificity, positive predictive value, negative predictive value and weighted kappa statistic of each of the above compared to SGA were determined. Results Median age of the 125 participants was 70.0(35-92) years. Age-specific BMI (Sn 68.4%, Sp 84.0%) performed better than WHO (Sn 15.8%, Sp 99.1%) categories. MNA-SF performed better (Sn 94.7%, Sp 78.3%) than both BMI categorisations for screening purposes. MNA had higher specificity but lower sensitivity than PG-SGA (MNA Sn 84.2%, Sp 87.7%; PG-SGA Sn 100.0%, Sp 69.8%). Conclusions BMI lacks sensitivity to identify malnourished people with Parkinson’s disease and should be used with caution. The MNA-SF may be a better screening tool in people with Parkinson’s disease. The PG-SGA performed well and may assist with informing and monitoring nutrition interventions. Further research should be conducted to validate screening and assessment tools in Parkinson’s disease.
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Many health professionals in Vietnam have limited knowledge and experience in coordinating care for victims of Domestic Violence (DV). This qualitative study aimed to elicit the beliefs of nurses and doctors that are influencing the care of victims of DV. Data were collected by semistructured interviews with nineteen nurses and doctors. Data were analyzed by content analysis and organized by three main themes; behavioral beliefs, normative beliefs and control beliefs. The outcomes of this study will inform the development of intervention strategies that will enable health professionals to better respond to and manage care for women who experience domestic violence in Vietnam.
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Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141(hi) and CD1c(+) myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141(hi) DCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c(+) DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141(hi) and CD1c(+) blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A(+) and CD1c(+) cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.
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This cross-sectional study of a 45 to 60 year old Brisbane population examined socioeconomic differences in campaign reach, understanding of health language, and effectiveness, of a recent mass media health promotion campaign. Lower socioeconomic groups were reached significantly less and understood significantly less of the health language than higher socioeconomic groups thus contributing to the widening of the health inequality gap.
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Background/Aims: Coronary heart disease (CHD) and coronary events have been strongly linked to psychological symptoms in patients during hospitalisation and post-discharge. Within Australia CHD average length of stay is decreasing and symptoms often do not present until discharge. Early screening and treatment of psychological symptoms has been recommended to reduce mortality and identify anxiety and depression. This literature review was undertaken to evaluate and describe current screening practices to identify psychological symptoms in these patients.
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The book is mostly designed for students of echocardiography, teachers of echocardiography and cardiac sonographers working in routine clinical practice, but will also be very useful to echocardiologists and cardiac registrars. The goal of the text is to provide a comprehensive review of transthoracic echocardiography in the assessment of various cardiac pathologies. Refresher notes on cardiac anatomy and the relevant cardiac physiology and pathophysiology are included to expand the cardiac sonographer’s knowledge in this area and further their understanding of various diseases, disease processes and associated findings.
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In 2009 the world experienced an influenza pandemic caused by the H1N1 virus. While the pandemic was milder then expected, it nonetheless provided the world with an opportunity to do real-time testing of pandemic preparedness. This paper examines the threats to human health posed by infectious diseases and the challenges for the global community in development of effective surveillance systems for emerging infectious diseases. In 2005 a new revised version of the International Health Regulations (IHR) was adopted. The requirements of the IHR (2005) are outlined and considered in light of the constraints facing resource-poor countries. Finally, the paper addresses the role of domestic law-making in supporting public health preparedness and articulates a number of ethical principles that should be considered when developing new public health laws.
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Ross River virus (RRV) infection is a debilitating disease which has a significant impact on population health, economic productivity and tourism in Australia. This study examined epidemiological patterns of the RRV disease in Queensland, Australia between January 2001 and December 2011 at a statistical local area level. Spatial-temporal analyses were used to identify the patterns of the disease distribution over time stratified by age, sex and space. The results show that the mean annual incidence was 54 per 100,000 people, with a male: female ratio of 1:1.1. Two space-time clusters were identified: the areas adjacent to Townsville, on the eastern coast of Queensland; and the south east areas. Thus, although public health intervention should be considered across all areas in which RRV occurs, it should specifically focus on these high risk regions, particularly during the summer and autumn to reduce the social and economic impacts of RRV.
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Based on the characterization by Atomic Force Microscopy (AFM), we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young’s moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton (CSK) and the intracellular fluid when the fixed chondrocytes is mainly governed by their intracellular fluid which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic (PHE) constitutive material model which can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.