Controversies in the Management of Endometrial Carcinoma: An Update

Endometrial carcinoma is the commonest type of female genital tract malignancy in the developed countries. Endometrial carcinoma is usually confined to the uterus at the time of diagnosis and as such usually carries an excellent prognosis with high curability. Our understanding and management of endometrial cancer have continuously developed. Current controversies focus on screening and early detection, the extent of nodal surgery, and the changing roles of radiation therapy and chemotherapy and will be discussed in this paper

The Application of a Residual Risk Evaluation Technique Used for Expendable Launch Vehicles

This presentation provides a Residual Risk Evaluation Technique (RRET) developed by Kennedy Space Center (KSC) Safety and Mission Assurance (S&MA) Launch Services Division. This technique is one of many procedures used by S&MA at KSC to evaluate residual risks for each Expendable Launch Vehicle (ELV) mission. RRET is a straight forward technique that incorporates the proven methodology of risk management, fault tree analysis, and reliability prediction. RRET derives a system reliability impact indicator from the system baseline reliability and the system residual risk reliability values. The system reliability impact indicator provides a quantitative measure of the reduction in the system baseline reliability due to the identified residual risks associated with the designated ELV mission. An example is discussed to provide insight into the application of RRET

Modeling large scale species abundance with latent spatial processes

Modeling species abundance patterns using local environmental features is an important, current problem in ecology. The Cape Floristic Region (CFR) in South Africa is a global hot spot of diversity and endemism, and provides a rich class of species abundance data for such modeling. Here, we propose a multi-stage Bayesian hierarchical model for explaining species abundance over this region. Our model is specified at areal level, where the CFR is divided into roughly $37{,}000$ one minute grid cells; species abundance is observed at some locations within some cells. The abundance values are ordinally categorized. Environmental and soil-type factors, likely to influence the abundance pattern, are included in the model. We formulate the empirical abundance pattern as a degraded version of the potential pattern, with the degradation effect accomplished in two stages. First, we adjust for land use transformation and then we adjust for measurement error, hence misclassification error, to yield the observed abundance classifications. An important point in this analysis is that only $28$ of the grid cells have been sampled and that, for sampled grid cells, the number of sampled locations ranges from one to more than one hundred. Still, we are able to develop potential and transformed abundance surfaces over the entire region. In the hierarchical framework, categorical abundance classifications are induced by continuous latent surfaces. The degradation model above is built on the latent scale. On this scale, an areal level spatial regression model was used for modeling the dependence of species abundance on the environmental factors.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS335 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Final Summary Report to the Narragansett Bay Project Office: Assessment of Organic Contaminants in Narragansett Bay Sediments and Hard Shell Clams

As part of a multidisciplinary investigation on the sediments of Narragansett Bay, sediment trap materials, surface sediments, hard shell clams (Mercenaria mercenaria) and sediment cores from throughout the bay were analyzed for organic contaminants including: polychlorinated biphenyls (PCBs), petroleum hydrocarbons (PHCs). polycyclic aromatic hydrocarbons (PAHs), substituted benzotriazoles (BZTs), bis (2-ethylhexyl) phthalate (DEHP) and coprostanol (COP). The objectives of this particular study were to provide information on the source, transport and biogeochemical fate of organic contaminants in the bay: while the overall goals of the investigation were to characterize the sediments and sedimentary processes of the Narragansett Bay system based on the results of integrated biological, chemical and geological studies. Sediment Trap Materials The sediment trap samples showed a trend of decreasing concentration for most components from Fox Point to Ohio Ledge, suggesting that the source(s) of these contaminants were pollution discharges (e.g., industrial and municipal effluents, CSOs. spills and runoff,) to the upper Providence River and its tributaries. In general, the agreement between the results from the present sediment trap study and older suspended solids data (1985-86) was quite good. However, the PHC concentrations reponed in 1977 were considerably higher than the more recent values. But it is difficult, if not impossible, to determine if changes have really occurred based on the limited number of samples analyzed and procedural variations in the different studies. In the case of BZT concentrations and their ratios (C10-BZT/Cl-BZT), there was a maximum amount of both BZTs and a minimum ratio in trap material at a Providence River station about 7 km south of Fox Point (i.e., adjacent to the Pawtuxet Cove entrance). This trend with distance is probably due to the source of the BZTs to the Providence River which is the Pawtuxet River via Pawtuxet Cove. The BZT ratio indicates a change in the relative amounts of the two compounds over the distance from the point of entry, i.e., there is a trend of increasing values with distance from Pawtuxet Cove (ratio = 1.5) to Ohio Ledge (ratio = 3.2). The ratio for sediment trap material from the Pawtuxet River was 1.0 - 2.0; since these values are generally lower than any others reported, it suggests that the river is the major source of the material in the Pawtuxet Cove traps. The relationships between contaminant concentrations in sediment trap material and surface sediments were quite good. For Ar 1254, the sediment levels were about twice the trap values. Conversely, the hydrocarbon concentrations in trap material were about 1.5 times as high for PHCs and about equal in pyrene, relative to the surface sediments. (In all cases, the correlations were significant at the 95% confidence level). In general, these data support the concept that the chemical composition of particulate material and surf ace sediments are closely related, and that the former could be a major source of contaminants to the underlying surface sediments. It is also possible that resuspended surface sediments could contribute to the particulate material in the water column depending on a number of factors such as bottom currents and extent of bioturbation. There was a significant relationship between the concentration of Cl-BZT in trap material and surface sediments; however, the relationship for the C10-BZT was not as good. and there is presently no explanation for these differences other than that the production of C-BZT started in 1963 and ceased in 1972, while that of the C10-BZT started in 1970 and continued to 1985. (The log Kow for both BZTs are essentially the same, Pruell & Quinn, 1985.) Perhaps, the former BZTs more uniformally distributed in particulate material and sediments than the more recently discharged C10-BZT. Changes in the BZT ratio (C10/Cl) of trap material may be due to a number of reasons including: the preferential retention of the C10-BZT and/or loss of Cl-BZT due to various biogeochemical reactions, and the resuspension of more recent sediments containing higher concentrations of the C10-BZT. This trend would be in agreement with the low ratio in Pawtuxet River surface sediments relative to sediment from the other locations where the ratios generally increase as found in the trap material. For example, the BZT ratio in surface sediments from Ohio Ledge is 7.2, in the mid-bay it is 8.2 and at the west passage the ratio is 9.5 (significant at the 9S% confidence level). Surface Sediments and Clams In general, the levels of all contaminants were highest in the Providence River sediments and decreased exponentially with distance downbay, with the lowest values usually found at the mouth of the bay. The major exception was a station in Newport Harbor in the lower east passage, where the concentrations of PHCs, PCBs and COP were relatively high and similar to some of the upper bay stations. The sources of the contaminants at this station may be related to sewage effluent, CSO discharges and runnoff to the harbor area. One way of evaluating the distribution of various contaminants in surface sediments is to compare the half distances for these components (defined as the distance in which the highest contaminant concentration decreases by 50%). A comparison of values for the east and west transects obtained in this study showed some small differences. For most components (exceptions are BZTs) the half distances were longer in the cast transect, suggesting additional sources of contaminants to that area. This may be due to several reasons including the influence of Newport effluents etc., different water circulation patterns in the two passages, and possible influences from Mount Hope Bay. Organic carbon had the longest half distance due to a large number of sources throughout the bay, and the BZTs had the lowest values since their only source is the Providence River via the Pawtuxct River. Finally, the PH Cs, P AHs. PCBs (sometimes measured as specific chlorobiphenyl (CB) cogeners) and coprostanol had similar half distances, suggesting major sources in the Providence River as well as smaller additional inputs throughout the bay. Five of the contaminants (CB 101, CB 138, PHCs, C10-BZT) showed significant correlations (95% confidence level or better) between sediment and clam concentrations, and all values decreased with distance from the Providence River. These sediment components are hydrophobic and are strongly partitioned into the clams\u27 lipids. Based on the data from this study, it may be possible to identify areas of the bay from which clams are harvested for commercial use. For example, clams suspected of being taken from areas closed to shellfishing could be analyzed for, these 5 contaminants and the results converted to sediment location using the relationships developed in this investigation. Trends from older investigations were generally similar to those observed in the present study; namely, highest concentrations in Providence River sediments and clams with decreasing amounts downbay. The range of previous values brackets those obtained in this study. Given then variations in station location, collection procedures, processing techniques and analytical methods, it is impossible to determine at the present time, if the concentrations have significantly changed over the past 15-20 years. Sediment Cores Highest levels and deepest penetration of PCBs (measured as CB 138) were in the Fox Point core which had a fairly uniform concentration down to 72 cm, but increased at 110 cm and remained about the same at the bottom of the core (147 cm). The other cores showed less penetration ranging from 42 cm (bottom of core) at Conimicut Point to 13 cm at Fields Point where the CB 138 values reached background (\u3c 0.1 ng/g) concentration. Apparently, the latter core site is a non-depositional area in contrast to Fox Point which has a relatively high sedimentation rate. The distribution of PHCs and pyrene were similar in some respects. In both cases, Fox Point had the highest level and deepest penetration with relatively constant values down to 147 cm. The PHCs never quite reached background levels in these cores (Ohio Ledge and Fields Point were the closest to background), but the pyrene did reach this level in two cores including the Fields Point core which again had the shallowest penetration (18 cm). Similar distributions were shown by COP and DEHP in that the Fox Point core had the highest levels and deepest penetration - a slight increase down to 110 cm followed by a prominent decrease to 147 cm. None of the cores reached background values for DEHP, but Ohio Ledge and Conimicut Point came very close. The COP reached background in only the Fields Point core but it rapidly increased again. It is impossible to adequately explain all of the trends in sediment core distributions with only the organic contaminant results. However, a detailed evaluation of all of the data (i.e., trace metals, organic components, biological species, pollen and geochemical analyses and radiometric dating) is currently being prepared in order to provide information on historical trends as recorded in the bay sediment cores (King et al., 1992). [Text taken from report summary.

Explaining species distribution patterns through hierarchical modeling

Understanding spatial patterns of species diversity and the distri- butions of individual species is a consuming problem in biogeography and con- servation. The Cape Floristic Region (CFR) of South Africa is a global hotspot of diversity and endemism, and the Protea Atlas Project, with some 60,000 site records across the region, provides an extraordinarily rich data set to analyze bio- diversity patterns. Analysis for the region is developed at the spatial scale of one minute grid-cells ( 37; 000 cells total for the region). We report on results for 40 species of a owering plant family Proteaceae (of about 330 in the CFR) for a de ned subregion. Using a Bayesian framework, we develop a two stage, spatially explicit, hierar- chical logistic regression. Stage one models the suitability or potential presence for each species at each cell, given species attributes along with grid cell (site-level) climate, precipitation, topography and geology data using species-level coe cients, and a spatial random e ect. The second level of the hierarchy models, for each species, observed presence=absence at a sampling site through a conditional speci- cation of the probability of presence at an arbitrary location in the grid cell given that the location is suitable. Because the atlas data are not evenly distributed across the landscape, grid cells contain variable numbers of sampling localities. Indeed, some grid cells are entirely unsampled; others have been transformed by human intervention (agriculture, urbanization) such that none of the species are there though some may have the potential to be present in the absence of distur- bance. Thus the modeling takes the sampling intensity at each site into account by assuming that the total number of times that a particular species was observed within a site follows a binomial distribution.In fact, a range of models can be examined incorporating di erent rst and second stage speci cations. This necessitates model comparison in a misaligned multilevel setting. All models are tted using MCMC methods. A best" model is selected. Parameter summaries o er considerable insight. In addition, results are mapped as the model-estimated potential presence for each species across the domain. This probability surface provides an alternative to customary empiri- cal \range of occupancy" displays. Summing yields the predicted species richness over the region. Summaries of the posterior for each environmental coe cient show which variables are most important in explaining species presence. Other biodi- versity measures emerge as model unknowns. A considerable range of inference is available. We illustrate with only a portion of the analyses we have conducted, noting that these initial results describe biogeographical patterns over the modeled region remarkably well

Diffusion kurtosis MRI as a predictive biomarker of response to neoadjuvant chemotherapy in high grade serous ovarian cancer

Abstract: This study assessed the feasibility of using diffusion kurtosis imaging (DKI) as a measure of tissue heterogeneity and proliferation to predict the response of high grade serous ovarian cancer (HGSOC) to neoadjuvant chemotherapy (NACT). Seventeen patients with HGSOC were imaged at 3 T and had biopsy samples taken prior to any treatment. The patients were divided into two groups: responders and non-responders based on Response Evaluation Criteria In Solid Tumours (RECIST) criteria. The following imaging metrics were calculated: apparent diffusion coefficient (ADC), apparent diffusion (Dapp) and apparent kurtosis (Kapp). Tumour cellularity and proliferation were quantified using histology and Ki-67 immunohistochemistry. Mean Kapp before therapy was higher in responders compared to non-responders: 0.69 ± 0.13 versus 0.51 ± 0.11 respectively, P = 0.02. Tumour cellularity correlated positively with Kapp (rho = 0.50, P = 0.04) and negatively with both ADC (rho = −0.72, P = 0.001) and Dapp (rho = −0.80, P < 0.001). Ki-67 expression correlated with Kapp (rho = 0.53, P = 0.03) but not with ADC or Dapp. In conclusion, Kapp was found to be a potential predictive biomarker of NACT response in HGSOC, which suggests that DKI is a promising clinical tool for use oncology and radiology that should be evaluated further in future larger studies

Participant recruitment into a randomised controlled trial of exercise therapy for people with multiple sclerosis

The success of a clinical trial is often dependant on whether recruitment targets can be met in the required time frame. Despite an increase in research into the benefits of exercise in people with multiple sclerosis (PwMS), no trial has reported detailed data on effective recruitment strategies for large-scale randomised controlled trials. The main purpose of this report is to provide a detailed outline of recruitment strategies, rates and estimated costs in the Exercise Intervention for Multiple Sclerosis (ExIMS) trial to identify best practices for future trials involving multiple sclerosis (MS) patient recruitment

Individualized Cost-Effectiveness Analysis

John Ioannidis and Alan Garber discuss how to use incremental cost-effectiveness ratios (ICER) and related metrics so they can be useful for decision-making at the individual level, whether used by clinicians or individual patients

A review of survival analysis methods used in NICE technology appraisals of cancer treatments: consistency, limitations and areas for improvement

Objectives: In June 2011, the National Institute for Health and Care Excellence (NICE) Decision Support Unit published a Technical Support Document (TSD) providing recommendations on survival analysis for NICE technology appraisals (TAs). Survival analysis outputs are influential inputs into economic models estimating the cost-effectiveness of new cancer treatments. Hence, it is important that systematic and justifiable model selection approaches are used. This study investigates the extent to which the TSD recommendations have been followed since its publication. Methods: We reviewed NICE cancer TAs completed between July 2011 and July 2017. Information on survival analyses undertaken and associated critiques for overall survival (OS) and progressionfree survival were extracted from the company submissions, Evidence Review Group (ERG) reports and final appraisal determination documents. Results: Information was extracted from 58 TAs. Only four (7%) followed all TSD recommendations for OS outcomes. The vast majority (91%) compared a range of common parametric models and assessed their fit to the data (86%). Only a minority of TAs included an assessment of the shape of the hazard function (38%) or proportional hazards assumption (40%). Validation of the extrapolated portion of the survival function using external data was attempted in a minority of TAs (40%). Extrapolated survival functions were frequently criticised by ERGs (71%). Conclusions: Survival analysis within NICE TAs remains sub-optimal, despite publication of the TSD. Model selection is not undertaken in a systematic way resulting in inconsistencies between TAs. More attention needs to be given to assessing hazard functions and validation of extrapolated survival functions. Novel methods not described in the TSD have been used, particularly in the context of immuno-oncology, suggesting that an updated TSD may be of value