12 research outputs found

    Prognostic factors in prostate cancer: key elements in structured histopathology reporting of radical prostatectomy specimens

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    Prostate cancer is the most common visceral cancer and the second most common cause of cancer death in males. The number of radical prostatectomies performed each year is increasing and accurate data from the histopathological examination of these specimens aid clinicians in stratifying patients for surveillance and adjuvant therapies. This review focuses on the histopathological prognostic factors which should be routinely recorded in pathology reports and complements the Royal College of Pathologists of Australasia Structured Reporting Protocol for Prostate Cancer (Radical Prostatectomy). Such structured pathology reports have been shown to significantly enhance the completeness and quality of data provided to clinicians. The review also discusses the International Society for Urological Pathology Consensus Conference recommendations which were published recently.James G. Kench, David R. Clouston, Warick Delprado, Thomas Eade, David Ellis, Lisa G. Horvath, Hemamali Samaratunga, Jurgen Stahl, Alan M.F. Stapleton, Lars Egevad, John R. Srigley and Brett Delahun

    Further evidence linking urolithiasis and blood coagulation: Urinary prothrombin fragment 1 is present in stone matrix

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    Further evidence linking urolithiasis and blood coagulation: Urinary prothrombin fragment 1 is present in stone matrix. The fact that organic material is always present and distributed throughout each renal calculus suggests that it may play a role in stone formation. The organic matrix of calcium oxalate (CaOx) crystals freshly generated in urine in vitro contains urinary prothrombin fragment 1 (UPTF1) as the principal protein. In this initial study, matrix was extracted from 12 renal calculi and evaluated for the presence of UPTE1 using Western blotting. UPTF1 was present in all eight stones whose principal component was CaOx, and in one of two stones which consisted mainly of calcium phosphate (CaP). UPTE1 was absent from the two struvite calculi examined. The relationship between CaP and UPTF1 was explored further. Matrix harvested from CaP crystals freshly generated in urine in vitro was also shown to contain UPTF1 as its principal component. Our inability to detect UPTF1 in one mixed CaOx/CaP stone may be related to our methods of matrix retrieval, while its absence from two struvite stones argues against it being present in the other stones merely as a consequence of passive inclusion. This absence may be related to the alkaline environment typical of struvite stone growth. The finding that UPTF1 is present in some renal stones provides the first direct evidence that links blood coagulation proteins with urolithiasis

    Immunohistochemical distribution and quantification of crystal matrix protein

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    Immunohistochemical distribution and quantification of crystal matrix protein. The aim of this study was to determine the immunohistochemical distribution and quantification of crystal matrix protein (CMP). CMP, a 31 kDa glycoprotein, is the principal macromolecule found in calcium oxalate crystals generated in human urine, and is a potent inhibitor of crystal aggregation. A polyclonal rabbit anti-human CMP antibody was used to examine renal tissue by immunohistochemical techniques and light microscopy (N = 45). Twenty-five other human organs were similarly assessed. Quantification was performed using a visual analogue scale. CMP was visible as cytoplasmic staining in the epithelial cells of the TALH and the distal convoluted tubule including the macula densa in a subgroup of nephrons. CMP was not identified elsewhere in the urinary tract or in the extrarenal organs examined. Despite a trend indicating that the kidneys of normal men had more CMP than those of normal women, the difference failed to reach significance (P = 0.11). There was, however, more CMP in the stone formers group compared with either normal men (P < 0.01) or normal women (P < 0.01). This protein may be an important determinant of calcium oxalate kidney stone disease

    Single- and Multi-carrier Quadrature Amplitude Modulation: Principles and Applications for Personal Communications, WATM and Broadcasting: 2nd

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    Single- and Multi-carrier Quadrature Amplitude Modulation Principles and Applications for Personal Communications, WLANs and Broadcasting L. Hanzo Department of Electronics and Computer Science, University of Southampton, UK W. Webb Motorola, Arlington Heights, USA formerly at Multiple Access Communications Ltd, Southampton, UK T. Keller Ubinetics, Cambridge Technology Centre, Melbourn, UK formerly at Department of Electronics and Computer Science, University of Southampton, UK Motivated by the rapid evolution of wireless communication systems, this expanded second edition provides an overview of most major single- and multi-carrier Quadrature Amplitude Modulation (QAM) techniques commencing with simple QAM schemes for the uninitiated through to complex, rapidly-evolving areas, such as arrangements for wide-band mobile channels. Targeted at the more advanced reader, the multi-carrier modulation based second half of the book presents a research-orientated outlook using a variety of novel QAM-based arrangements. * Features six new chapters dealing with the complexities of multi-carrier modulation which has found applications ranging from Wireless Local Area Networks (WLAN) to Digital Video Broadcasting (DVB) * Provides a rudimentary introduction for readers requiring a background in the field of modulation and radio wave propagation * Discusses classic QAM transmission issues relevant to Gaussian channels * Examines QAM-based transmissions over mobile radio channels * Incorporates QAM-related orthogonal techniques, considers the spectral efficiency of QAM in cellular frequency re-use structures and presents a QAM-based speech communications system design study * Introduces Orthogonal Frequency Division Multiplexing (OFDM) over both Gaussian and wideband fading channels By providing an all-encompassing self-contained treatment of single- and multi- carrier QAM based communications, a wide range of readers including senior undergraduate and postgraduate students, practising engineers and researchers alike will all find the coverage of this book attractive

    Assessing malaria attributed mortality in west and southern Africa

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    Malaria has persistently remained a serious health and socio-economic problem in developing nations particularly in Sub-Saharan Africa (SSA). There are approximately 500 million cases of malaria each year and close to one million deaths occurring mainly among children under five years. Developing countries spend a reasonable proportion of their gross domestic product (GDP) on malaria which in the end hinders their levels of development. World Health Organizations (WHO) and partners through the Roll Back Malaria initiative (RBM) have targeted vector control, health promotion and case management (using rapid diagnostic tests and treatment with Artemisinin combination therapy) in order reduce malaria morbidity and mortality cases. Since 2002, funds for promoting malaria control activities have increased exponentially in SSA. Major donors include presidential malaria initiative (PMI) and Global fund to fight AIDS, tuberculosis and malaria (GFATM). Countries which have scaled up the recommended malaria control strategies such as insecticides-treat net (ITN) and treatment of confirmed cases have reported a decline in both morbidity and mortality especially among children. However, these statistics are based on health facilities data and yet in most developing countries many deaths occur at home and are never recorded due to inefficient vital registration systems. Monitoring the progress of such interventions requires reliable sources of data on both the transmission and infection outcome. In malaria endemic areas, people acquire natural immunity during the early years of their life after getting exposed to repeated infections. This is observed from the reductions in the number of severe malaria-related morbidity and mortality cases especially in children >5 years. Due to the current undertakings that are aimed at reducing malaria exposure, there are concerns about shifting the disease burden to older children but the required to data to monitor this are not readily available in SSA. Low income countries have resorted to health and demographic surveillance systems (HDSS) to monitor routinely population changes and health outcomes within a defined geographical area. In 2000, the INDEPTH, a network of HDSS integrated the Malaria Transmission Intensity and Mortality Burden Across Africa (MTIMBA) project into selected sites’ routine activities in order to assess the transmission-malaria mortality relationship taking into account the current interventions. Mortality data and other demographic characteristics were extracted from routinely collected HDSS databases. The entomological data were collected every fortnight from randomly sampled compounds over the 3 years MTIMBA period. The MTIMBA project generated large geostatistical data that are correlated in space and time. Furthermore, the project captured longitudinal mosquito data that were characterized by many zeros especially during the dry periods. The zeros are due empty traps from a compound or when all the captured mosquitoes are not infectious. Appropriate data analysis therefore should apply models that account for spatial-temporal correlation and the excess zeros in order to avoid over or underestimation of parameters. Zero-inflated geostatistical models account for spatial-temporal correlation by introducing location-specific and time interval random effects which creates more parameters to estimate. Bayesian models implemented via Markov chain Monte Carlo simulation (MCMC) addresses fit of highly parameterized models. This work applied zero-inflated Bayesian models to estimate malaria attributable mortality across all age-groups using large, correlated and sparse data collected from Navrongo and Manhiça HDSS between 2001 and 2004. The contributions of this thesis were (i) the description of the HDSS data characteristics and relevant methods for analysis; (ii) the spatially explicit estimates of malaria transmission intensity at monthly intervals; and (iii) the relationship between all-cause mortality and malaria transmission intensity across all age categories. Chapter 2 described the characteristics of the MTIMBA data. These are large geostatistical, temporal, seasonal and zero-inflated data. The mortality and mosquito data were misaligned because they were captured at different compounds and time periods. Zero-inflated Bayesian spatio-temporal models are the state-of-art in handling such data. The rigorous statistical process was demonstrated by modelling sporozoite rate (SR) data from Manhiça HDSS. The analysis of the MTIMBA data was used as an avenue for building SSA capacity through course work, seminars and mentorship. Site-specific analyses are still on-going. However, the project generated data that is relevant for assessing within and between site malaria transmission heterogeneity. The Navrongo malaria exposure surfaces described in chapter 3 were obtained from zero-inflated geostatistical models fitting separately the binomial SR data and negative binomial count data by mosquito species. All the models included space and time correlation in addition to the Climate, environmental and seasonality covariates. The entomological inoculation rate (EIR) estimates were derived as a product of predicted man biting rate and SR. Observed EIR in this district was >100 infective bites/person/year. Distance to water to bodies, day temperatures and vegetation were the main predictors of mosquito densities for the two species. The EIR maps clearly indicated that the temporal heterogeneity was stronger than the spatial variation in this area. The same situation was also observed from the analyses of the two MTIMBA sites of Rufiji (Tanzania) and Kisumu (Kenya). Monthly malaria exposure surfaces (chapter 3) were linked to the nearest compounds where mortality was observed as described in chapter 4. Time to death data were split at monthly intervals in order to generate Bernoulli and binomial data that were modelled via logistic regression formulations. Spatio-temporal models were fitted to obtain age-specific mortality risk estimates. The model considered 2 covariates; natural logarithm transformed EIR estimates with their measurement errors and age. ITN variable was only included in neonates, post-neonates and child models. The analysis showed a positive log-linear relationship between all-cause mortality and malaria exposure in all the age groups but the association was only important among children (1-4 years) and people >= 60 years. ITN use showed a protective effect among all the under five children, confirming what was observed in Rufiji and Kisumu HDSS. The methods used in estimating malaria exposure surfaces and mortality risks in chapters 3 and 4 were extended to Manhiça HDSS (Mozambique) data to describe the mortality-malaria transmission relationship for this area (chapter 5). The spatio-temporal age-specific models considered EIR estimates with their measurement errors (to account for the predictive uncertainty) and age as model covariates. The distance to the nearest water bodies was the only important common predictor of An. funestus and An. gambiae mosquito densities. Malaria transmission intensity declined consistently in this area. The Model-based results indicated a positive log-linear relationship between all-cause mortality and malaria exposure across all age groups namely; the neonates (0-28 days), post-neonates (1-11months), children (1-4years), young people (5-14 years), adults (15- 59years) and old age (>=60 years). This work contributes to further understand of malaria-mortality relationships. A positive association between mortality and malaria exposure among the under fives is consistent with what was reported from the MTIMBA sites of Rufiji and Kisumu. Completion of the remaining site-specific analyses followed by a meta-analysis will make a great contribution to malaria epidemiology. Further work however, should consider cohort analysis in order to ascertain whether malaria control interventions have caused a shift in the age of acquired immunity

    Valuing adaptation under rapid change

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    AbstractThe methods used to plan adaptation to climate change have been heavily influenced by scientific narratives of gradual change and economic narratives of marginal adjustments to that change. An investigation of the theoretical aspects of how the climate changes suggests that scientific narratives of climate change are socially constructed, biasing scientific narratives to descriptions of gradual as opposed rapid, non-linear change. Evidence of widespread step changes in recent climate records and in model projections of future climate is being overlooked because of this. Step-wise climate change has the potential to produce rapid increases in extreme events that can cross institutional, geographical and sectoral domains.Likewise, orthodox economics is not well suited to the deep uncertainty faced under climate change, requiring a multi-faceted approach to adaptation. The presence of tangible and intangible values range across five adaptation clusters: goods; services; capital assets and infrastructure; social assets and infrastructure; and natural assets and infrastructure. Standard economic methods have difficulty in giving adequate weight to the different types of values across these clusters. They also do not account well for the inter-connectedness of impacts and subsequent responses between agents in the economy. As a result, many highly-valued aspects of human and environmental capital are being overlooked.Recent extreme events are already pressuring areas of public policy, and national strategies for emergency response and disaster risk reduction are being developed as a consequence. However, the potential for an escalation of total damage costs due to rapid change requires a coordinated approach at the institutional level, involving all levels of government, the private sector and civil society.One of the largest risks of maladaptation is the potential for un-owned risks, as risks propagate across domains and responsibility for their management is poorly allocated between public and private interests, and between the roles of the individual and civil society. Economic strategies developed by the disaster community for disaster response and risk reduction provide a base to work from, but many gaps remain.We have developed a framework for valuing adaptation that has the following aspects: the valuation of impacts thus estimating values at risk, the evaluation of different adaptation options and strategies based on cost, and the valuation of benefits expressed as a combination of the benefits of avoided damages and a range of institutional values such as equity, justice, sustainability and profit.The choice of economic methods and tools used to assess adaptation depends largely on the ability to constrain uncertainty around problems (predictive uncertainty) and solutions (outcome uncertainty). Orthodox methods can be used where both are constrained, portfolio methodologies where problems are constrained and robust methodologies where solutions are constrained. Where both are unconstrained, process-based methods utilising innovation methods and adaptive management are most suitable. All methods should involve stakeholders where possible.Innovative processes methods that enable transformation will be required in some circumstances, to allow institutions, sectors and communities to prepare for anticipated major change.Please cite this report as: Jones, RN, Young, CK, Handmer, J, Keating, A, Mekala, GD, Sheehan, P 2013 Valuing adaptation under rapid change, National Climate Change Adaptation Research Facility, Gold Coast, pp. 192.The methods used to plan adaptation to climate change have been heavily influenced by scientific narratives of gradual change and economic narratives of marginal adjustments to that change. An investigation of the theoretical aspects of how the climate changes suggests that scientific narratives of climate change are socially constructed, biasing scientific narratives to descriptions of gradual as opposed rapid, non-linear change. Evidence of widespread step changes in recent climate records and in model projections of future climate is being overlooked because of this. Step-wise climate change has the potential to produce rapid increases in extreme events that can cross institutional, geographical and sectoral domains.Likewise, orthodox economics is not well suited to the deep uncertainty faced under climate change, requiring a multi-faceted approach to adaptation. The presence of tangible and intangible values range across five adaptation clusters: goods; services; capital assets and infrastructure; social assets and infrastructure; and natural assets and infrastructure. Standard economic methods have difficulty in giving adequate weight to the different types of values across these clusters. They also do not account well for the inter-connectedness of impacts and subsequent responses between agents in the economy. As a result, many highly-valued aspects of human and environmental capital are being overlooked.Recent extreme events are already pressuring areas of public policy, and national strategies for emergency response and disaster risk reduction are being developed as a consequence. However, the potential for an escalation of total damage costs due to rapid change requires a coordinated approach at the institutional level, involving all levels of government, the private sector and civil society.One of the largest risks of maladaptation is the potential for un-owned risks, as risks propagate across domains and responsibility for their management is poorly allocated between public and private interests, and between the roles of the individual and civil society. Economic strategies developed by the disaster community for disaster response and risk reduction provide a base to work from, but many gaps remain.We have developed a framework for valuing adaptation that has the following aspects: the valuation of impacts thus estimating values at risk, the evaluation of different adaptation options and strategies based on cost, and the valuation of benefits expressed as a combination of the benefits of avoided damages and a range of institutional values such as equity, justice, sustainability and profit.The choice of economic methods and tools used to assess adaptation depends largely on the ability to constrain uncertainty around problems (predictive uncertainty) and solutions (outcome uncertainty). Orthodox methods can be used where both are constrained, portfolio methodologies where problems are constrained and robust methodologies where solutions are constrained. Where both are unconstrained, process-based methods utilising innovation methods and adaptive management are most suitable. All methods should involve stakeholders where possible.Innovative processes methods that enable transformation will be required in some circumstances, to allow institutions, sectors and communities to prepare for anticipated major change
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