157 research outputs found
Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus).
No full textWhile younger women with early-stage, oestrogen-sensitive breast cancer are almost invariably treated with surgery plus endocrine therapy, (which deprives the cancer of the hormonal stimulus that induces its growth), women over the age of 70 years are frequently offered endocrine therapy alone. This is known as primary endocrine therapy. Primary endocrine therapy using tamoxifen (a drug which blocks oestrogen receptors on the cancer cell, inhibiting its growth) was first suggested as a treatment for older women in the 1980s. Tamoxifen was given without surgery, radiotherapy or chemotherapy on the basis that older women are more likely to have cancers with oestrogen receptors and will therefore respond well to treatment. In addition they were thought less suitable for major surgery because of other existing health issues. However, a tumour will often only respond to this treatment for between 18 and 24 months, and those women who relapse will have to consider additional hormone treatment or opt for surgery or radiotherapy at a greater age. The long-term data suggest that, at 12 years of follow-up, more elderly women treated by primary tamoxifen alone will suffer a progression of their cancer than those who have had surgery. We undertook this review to assess the evidence for the clinical effectiveness of surgery (with or without endocrine therapy) compared with primary endocrine therapy in the treatment of operable breast cancer in women aged 70 years and over. Based on seven trials and an estimated 1081 deaths in 1571 women, the results of this review showed no benefit in respect to survival for either surgery or primary endocrine therapy. However, women who had surgery were less likely to relapse than women on primary endocrine therapy. The authors conclude that surgery controls breast cancer better than tamoxifen alone in older women but does not extend survival. Both interventions were associated with adverse events. Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included tingling or numbness on the arm on the side of the surgery, and psychosocial problems. On this basis, primary endocrine therapy should only be offered to women with oestrogen receptor (ER)-positive tumours who are unfit for, or who refuse surgery. We need further trials to evaluate the clinical effectiveness of other agents such as aromatase inhibitors for use as primary endocrine therapy for an infirm older population with ER-positive tumours. - See more at: http://summaries.cochrane.org/CD004272/surgery-versus-primary-endocrine-therapy-for-elderly-women-with-operable-primary-breast-cancer#sthash.RRAt9B6f.dpu
Low Variation in the Polymorphic Clock Gene Poly-Q Region Despite Population Genetic Structure across Barn Swallow (Hirundo rustica) Populations
No full textPubMed ID: 22216124This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study.
No full textINTRODUCTION: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. METHODS: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. RESULTS: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. CONCLUSIONS: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified
The learning-decoding approach as a means of overcoming the barriers to growth in small & medium size enterprises
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis explores how small business owners learn to learn' to overcome barriers to
growth or commercial success. This learning takes place within a process which has
been termed the Learning-Decoding Approach. This Approach consists of three main
factors -
(1) how small business owners Scan their environment for signals and cues;
(2) how they Decode any signals and cues; and
(3) how they Test their Mental models and Assumptions - this factor incorporates an analysis of the inclination to be Open to changing or affirming the Mental Models and Assumptions held.
Further, it examines what the small business owner does with the final result from this
process: that is, is it used to influence the design of some strategic plan or does it become part of an emerging one?
Generally, it was found that Strategic Planning is not a function of the Learning-
Decoding Approach. It is not considered a core tool for overcoming barriers to
growth. Its major role is at the task or operational level rather than the business level.
Further, any attempt at Strategy Planning is only used as a guide.
Fifty small firms were investigated within two `knowledge-worker' sectors: the
Management Consulting Sector and the Marketing Consulting Sector. Within these
sectors three sizes of firms were reviewed. Thirty-eight male and twelve female
owner-managers were involved in the interviews.
The research identified a number of similarities and some differences between the sectors; and provided a cultural explanation for them. The daily work practices used by owner-managers showed that the sectors were different but closely aligned.
A tentative Learning-Decoding Approach model was developed and comprised three
spectrums. Firms can be positioned on them according to their predisposition to, and
skills in, Scanning the environment for signals, and Decoding the signals and then
Testing them against their Mental Models and Assumptions. Further, if learning is to
occur the owner-manager must be prepared to be open to changing any Mental Models and Assumptions held. By learning the skills implicit in this process, the owner-manager can move on to learning how to overcome the barriers to growth. This suggests that the Learning- Decoding Approach can provide a helpful model for advisers to enable them to mentor, coach, counsel or facilitate small business owners in a review of their business style and practice.
The main conclusion drawn from the thesis is that Scanning, Decoding and Testing are perceived as valuable activities which influence commercial success. However, a gap is evident between attitude and behaviour. Due to this, it is felt that the aims of the research are only partly met
Vascular Targeted Agents for the Treatment of Angiosarcoma
No full textBackground:
Angiogenesis is the process of new blood vessel formation, and is regulated by angiogenic growth factors including vascular endothelial growth factor (VEGF). Angiosarcomas are rare, aggressive vascular tumours. Studies were performed to investigate the expression of angiogenic growth factors in angiosarcoma, and to assess vascular targeted agents for the treatment of angiosarcoma.
Methods:
In vitro studies compared two human cutaneous angiosarcoma cell lines (ASM and ISO-HAS) with human dermal microvascular endothelial cells (HuDMECs). The cell lines were compared in functional assays, including cell viability, cell differentiaiton and cell migration assays, and protein expression profiled using antibody arrays.
Cell responses to vascular targeted agents were compared, including response to bevacizumab an anti-VEGF antibody, axitinib a VEGF receptor (VEGFR) tyrosine kinase inhibitor, selumetinib a MEK inhibitor, and DMXAA a vascular disrupting agent.
Immunohistochemistry studies measured the expression of angiogenic growth factors in angiosarcoma tumour specimens using benign vascular lesions for comparison, and assessed canine angiosarcoma as a model of human angiosarcoma.
Results:
ASM and ISO-HAS demonstrated accelerated growth kinetics, chaotic tubule formation, and increased cell migration compared to HuDMECs.
ASM and ISO-HAS expressed significantly increased VEGF compared to HuDMECs. Only minor responses were observed to VEGF targeted agents in functional assays
despite western blot studies that showed target inhibition of VEGFR2 phosphorylation,. Striking responses were seen however to selumetinib and DMXAA.
Immunohistochemistry studies demonstrated benign and malignant vascular tumours expressed a range of pro-angiogenic growth factors, however analysis did not distinguish malignant from benign vascular tumours.
The morphology of canine angiosarcoma was similar to human angiosarcoma. VEGF and VEGFR2 expression was significantly increased in canine angiosarcoma compared to benign vascular lesions.
Conclusion:
These studies predict limited in vivo angiosarcoma tumour response to VEGF targeted agents. Selumetinib and DMXAA are suggested for further study. Canine angiosarcomas represent a potential model of human angiosarcoma to be explored in future studies
The dUTPase Enzyme Is Essential in Mycobacterium smegmatis
No full textPubMed ID: 22655049This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Economic strategies for coastal disaster risk reduction: A case study of Exmouth, Western Australia
No full textRecent major natural disasters in Australia have highlighted how some of the economic costs of living in risk-prone areas are borne by the rest of society. This study used the town of Exmouth, in north-western Australia, to investigate economic strategies for coastal disaster risk reduction, as it typifies expanding development in coastal areas prone to extreme weather events. Using a GIS, coastal inundation scenarios from cyclonic storm-surge were investigated relative to coastal property, infrastructure and shire planning. It showed that some areas developed in the past decade are at high risk of storm-surge inundation. There has been a loss of disastermitigating ecosystem functions as well as increased risk to previously unaffected areas. The extent to which risk perceptions of cyclonic storm-surge inundation and flooding influenced the price buyers paid for residential property in Exmouth over the period 1988-2010 was examined using a Hedonic Price Model. This incorporated dwelling variables, proximity to the coast, cyclone Vance storm-surge and 1-in-100 year flood levels and indicated that prices did not reflect the real societal cost of risk. To internalize these costs, a mandatory private insurance scheme for high-risk properties (with a time-phased government subsidy) and penalties for local councils undertaking new high-risk developments are proposed. Further, a hybrid economic instrument aimed at correcting the market failure in coastal land which comprises an environmental offset by developers, a propertyowner tax and special disaster risk mitigation fund, is also proposed. This study is highly relevant in view of the planned revision of the Western Australian Coastal Planning Policy, the expansion of industry along the coast of northern Australia and the predicted effects of climate change on sea levels and extreme weather events
Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease
No full textPrevious studies have shown that Mycobacterium tuberculosis (MTB) Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of tuberculosis (TB) in Uganda. Using a well characterized patient population, this study sought to determine whether there are clinical and patient characteristics associated with the success of the MTB Uganda family in Kampala.; A total of 1,746 MTB clinical isolates collected from1992-2009 in a household contact study were genotyped. Genotyping was performed using Single Nucleotide Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4 strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from patients with detailed clinical data. These data were used to seek associations between MTB lineage/sub-lineage and patient phenotypes.; Three MTB lineages were found to dominate the MTB population in Kampala during the last two decades. Overall, MTB Uganda accounted for 63% (1,092/1,746) of all cases, followed by other Lineage 4 strains accounting for 22% (394/1,746), and Lineage 3 for 11% (187/1,746) of cases, respectively. Seventy-three (4 %) strains remained unclassified. Our longitudinal data showed that MTB Uganda family occurred at the highest frequency during the whole study period, followed by other Lineage 4 strains and Lineage 3. To explore whether the long-term success of MTB Uganda family was due to increased virulence, we used cavitary disease as a proxy, as this form of TB is the most transmissible. Multivariate analysis revealed that even though cavitary disease was associated with known risk factors such as smoking (adjusted odds ratio (aOR) 4.8, 95% confidence interval (CI) 3.33-6.84) and low income (aOR 2.1, 95% CI 1.47-3.01), no association was found between MTB lineage and cavitary TB.; The MTB Uganda family has been dominating in Kampala for the last 18 years, but this long-term success is not due to increased virulence as defined by cavitary disease
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