Summary
Background: Castration‐resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. However, characterisation of the disease epidemiology is ...hampered by use of varying terminology, definition and disease management. The aim of this review was to conduct a systematic review to provide greater clarity on the sum of the available epidemiologic evidence and to guide future research into the disease prevalence, progression, characteristics and outcome.
Methods: Systematic searches of PubMed and Embase were performed in March 2010 to identify relevant observational studies relating to the epidemiology, progression and outcomes of CRPC. Further studies were identified for inclusion in our review through manual searches of the authors’ bibliographical databases and the reference lists of the included articles.
Results: We identified 12 articles (10 full papers and 2 s) reporting studies that included a total of 71,179 patients observed for up to 12 years for evaluation in our review. Five studies looked at the prevalence of CRPC in patients with prostate cancer. Together, the data indicate that 10–20% of prostate cancer patients develop CRPC within approximately 5 years of follow‐up. Two studies reported the prevalence of bone metastases present at diagnosis of CRPC. Together, ≥ 84% were shown to have metastases at diagnosis. Of those patients with no metastases present at diagnosis of CRPC, 33% could expect to develop them within 2 years. The median survival of patients with CRPC was reported in five studies, with values varying from 9 to 30 months. A pooled, sample‐weighted survival estimate calculated from the survival data included in this review is 14 months. Very few studies that met our inclusion criteria evaluated treatment patterns in CRPC. One study reported that only 37% of patients with CRPC received chemotherapy, with the remainder receiving only steroids and supportive care. The most common palliative therapies administered to patients with skeletal symptoms were radiotherapy, radionuclide therapy, bisphosphonates and opioids.
Conclusions: This review highlights the poor prognosis of patients with CRPC, and demonstrates a survival of 9–13 months in those patients with metastatic CRPC. Furthermore, progression to CRPC is associated with deterioration in quality of life, and few therapeutic options are currently available to patients with CRPC. However, epidemiologic study of these patients is hampered by differing terminology, definitions and treatment paradigms. Our review highlights the need for further well‐designed, epidemiological studies of CRPC, using standardised definitions and methods.
The SAXS/WAXS beamline at the Australian Synchrotron is an advanced and flexible undulator X‐ray scattering beamline used for small‐ and wide‐angle X‐ray scattering analysis on a wide variety of ...solids, fluids and surfaces across a diverse range of research and development fields. The beamline has numerous features that minimize the intensity of the instrument background, provide automated stable optics, and allow accurate analysis of very weakly scattering samples. The geometric and intensity requirements of a three‐slit collimation system are described in detail for conventional metal and single‐crystal germanium slits. Straightforward ray tracing and simple linear projections describe the observed direct beam as well as parasitic background scattering geometry of the beamline at its longest camera length, providing a methodology for the design and operation of similar beamlines. As an aid to instrument design, the limit of background intensity determined by the intensity incident on single‐crystal germanium guard slit edges and its q dependence was quantified at 11 keV. Details of the beamline's implementation, underlying optical concept and measured performance are given.
This article surveys the history and current state of the art of visualization in meteorology, focusing on visualization techniques and tools used for meteorological data analysis. We examine ...characteristics of meteorological data and analysis tasks, describe the development of computer graphics methods for visualization in meteorology from the 1960s to today, and visit the state of the art of visualization techniques and tools in operational weather forecasting and atmospheric research. We approach the topic from both the visualization and the meteorological side, showing visualization techniques commonly used in meteorological practice, and surveying recent studies in visualization research aimed at meteorological applications. Our overview covers visualization techniques from the fields of display design, 3D visualization, flow dynamics, feature-based visualization, comparative visualization and data fusion, uncertainty and ensemble visualization, interactive visual analysis, efficient rendering, and scalability and reproducibility. We discuss demands and challenges for visualization research targeting meteorological data analysis, highlighting aspects in demonstration of benefit, interactive visual analysis, seamless visualization, ensemble visualization, 3D visualization, and technical issues.
Gaussian processes (GP) form a well-established predictive tool which provides a natural platform for tackling high-dimensional random input data in challenging simulations. This paper introduces a ...generic framework for integrating Gaussian Processes with risk-based structural optimization. We solve robust and reliability-based design problems in the context of stress-based topology optimization under imperfections in geometry and material properties, and loading variability. We construct independent GPs for primal and adjoint quantities, namely the global maximum von Mises stress and its sensitivity where we enhance the computational efficiency by leveraging the information from multiresolution finite element simulations. The GP framework naturally lends itself to modeling noise in data. We investigate the effect of numerical modeling error in high-fidelity simulations via a noisy GP emulator and provide a pareto curve that shows the robustness of optimal design with respect to the noise level. We provide a posteriori error estimates that quantify the discrepancy between the noisy emulator and true simulations, and verify them with a numerical study. We demonstrate our approach on a benchmark L-shape structure which exhibits stress concentration, a compliant mechanism design and a heat sink design. We also provide practical guidelines for estimation of failure probability and its sensitivity to facilitate reliability-based topology optimization.
The probable effect of climate change on the water available for use in Bangladesh is not well known. We calculate monthly water balances for five main regions of Bangladesh to examine the likely ...impacts of climate change to 2050. We also examine the impact of past and potential future irrigation development. Climate change projections for rainfall in Bangladesh are uncertain, with increased rain in the wet season likely, but decreased rain also possible. Runoff is projected to vary in a manner similar to rainfall. However, assuming no change to the area of crops, all projections result in increases in irrigation water use, which leads to groundwater level declines. The impact of change (whether climate change or development) on water availability and use is greater in the Northwest region than elsewhere. For most water balance terms in most regions, irrigation development (both historic and future) is calculated to have a larger impact than climate change. Climate change is calculated to have a larger impact than irrigation development only on evapotranspiration and runoff, and possibly on groundwater levels. Model sensitivity tests suggest that model uncertainty is less than climate change uncertainty. To reverse lowered groundwater levels, Bangladesh’s policy includes greater use of surface water. While we calculate groundwater levels will rise, the viability of the policy may be affected by future changes to upstream use.
Enhancing crop production, particularly by growing a crop in the typically-fallow dry season is a key strategy for alleviating poverty in the Ganges delta region. We used a polder water and salt ...balance model to examine the impact of several crop management, salt management and climate change scenarios on salinity and crop evapotranspiration at Dacope and Amtali in Bangladesh and Gosaba in India. A key (and unsurprising) finding is that salt management is very important, particularly at the two drier sites, Dacope and Gosaba. Good salt management lowers salinity in the shallow groundwater, soil and water storage ponds, and leads to more irrigation. Climate change is projected to alter rainfall, and this in turn leads to modelled increases or decreases in runoff from the polders, and thence affect salt concentrations in the soil and ponds and canals. Thus, the main impacts of climate change are through the indirect impacts on salt concentrations, rather than the direct impacts of the amount of water supplied as rainfall. Management practices to remove salt from polders are therefore likely to be effective in combatting the impacts of projected climate change particularly at Dacope and Gosaba.
Tick populations are dependent on a complex interplay of abiotic and biotic influences, many of which are influenced by anthropic factors including climate change. Dermacentor variabilis, the wood ...tick or American dog tick, is a hardy tick species that feeds from a wide range of mammals and birds that can transmit pathogens of medical and agricultural importance. Significant range expansion across North America has been occurring over the past decades;this study documents northwards range expansion in the Canadian Maritime provinces. Tick recoveries from passive surveillance between 2012 and 2021 were examined to assess northward population expansion through Atlantic Canada. At the beginning of this period, D. variabilis was abundant in the most southerly province, Nova Scotia, but was not considered established in the province to the north, New Brunswick. During the 10-year span covered by this study, an increasing number of locally acquired ticks were recovered in discrete foci, suggesting small established or establishing populations in southern and coastal New Brunswick. The pattern of population establishment follows the climate-driven establishment pattern of Ixodes scapularis to some extent but there is also evidence of successful seeding of disjunct populations in areas identified as sub-optimal for tick populations. Dogs were the most common host from which these ticks were recovered, which raises the possibility of human activity, via movement of companion animals, having a significant role in establishing new populations of this species. Dermacentor variabilis is a vector of several pathogens of medical and agricultural importance but is not considered to be a competent vector for Borrelia burgdorferi, the etiological agent of Lyme disease; our molecular analysis of a subset of D. variabilis for both B. burgdorferi and B. miyamotoi did not confirm any with Borrelia. This study spans the initial establishment of this tick species and documents the pattern of introduction, providing a relatively unique opportunity to examine the first stages of range expansion of a tick species.
We present a quantum algorithm for simulation of quantum field theory in the light-front formulation and demonstrate how existing quantum devices can be used to study the structure of bound states in ...relativistic nuclear physics. Specifically, we apply the Variational Quantum Eigensolver algorithm to find the ground state of the light-front Hamiltonian obtained within the Basis Light-Front Quantization (BLFQ) framework. The BLFQ formulation of quantum field theory allows one to readily import techniques developed for digital quantum simulation of quantum chemistry. This provides a method that can be scaled up to simulation of full, relativistic quantum field theories in the quantum advantage regime. As an illustration, we calculate the mass, mass radius, decay constant, electromagnetic form factor, and charge radius of the pion on the IBM Vigo chip. This is the first time that the light-front approach to quantum field theory has been used to enable simulation of a real physical system on a quantum computer.
Chronic cellular stress has a profound impact on the brain, leading to degeneration and accelerated aging. Recent work has revealed the vital role of RNA modifications, and the proteins responsible ...for regulating them, in the stress response. In our study, we defined the role of CG14618/dTrmt10A, the Drosophila counterpart of human TRMT10A a N1-methylguanosine methyltransferase, on m6A regulation and heat stress resilience in the Drosophila brain. By m6A-IP RNA sequencing on Drosophila head tissue, we demonstrated that manipulating dTrmt10A levels indirectly regulates m6A levels on polyA + RNA. dTrmt10A exerted its influence on m6A levels on transcripts enriched for neuronal signaling and heat stress pathways, similar to the m6A methyltransferase Mettl3. Intriguingly, its impact primarily targeted 3' UTR m6A, setting it apart from the majority of Drosophila m6A-modified transcripts which display 5' UTR enrichment. Upregulation of dTrmt10A led to increased resilience to acute heat stress, decreased m6A modification on heat shock chaperones, and coincided with decreased decay of chaperone transcripts and increased translation of chaperone proteins. Overall, these findings establish a potential mechanism by which dTrmt10A regulates the acute brain stress response through m6A modification.
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