Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist

Observing convective aggregation

Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad a distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network

Evaluation of the model representation of the evolution of convective systems using satellite observations of outgoing longwave radiation

We introduce a technique for assessing the diurnal development of convective storm systems based on outgoing longwave radiation fields. Using the size distribution of the storms measured from a series of images, we generate an array in the lengthscale-time domain based on the standard score statistic. It demonstrates succinctly the size evolution of storms as well as the dissipation kinematics. It also provides evidence related to the temperature evolution of the cloud tops. We apply this approach to a test case comparing observations made by the Geostationary Earth Radiation Budget instrument to output from the Met Office Unified Model run at two resolutions. The 12km resolution model produces peak convective activity on all lengthscales significantly earlier in the day than shown by the observations and no evidence for storms growing in size. The 4km resolution model shows realistic timing and growth evolution although the dissipation mechanism still differs from the observed data

Intercomparison of methods of coupling between convection and large-scale circulation: 1. Comparison over uniform surface conditions

As part of an international intercomparison project, a set of single column models (SCMs) and cloud-resolving models (CRMs) are run under the weak temperature gradient (WTG) method and the damped gravity wave (DGW) method. For each model, the implementation of the WTG or DGW method involves a simulated column which is coupled to a reference state defined with profiles obtained from the same model in radiative-convective equilibrium. The simulated column has the same surface conditions as the reference state and is initialized with profiles from the reference state. We performed systematic comparison of the behavior of different models under a consistent implementation of the WTG method and the DGW method and systematic comparison of the WTG and DGW methods in models with different physics and numerics. CRMs and SCMs produce a variety of behaviors under both WTG and DGW methods. Some of the models reproduce the reference state while others sustain a large-scale circulation which results in either substantially lower or higher precipitation compared to the value of the reference state. CRMs show a fairly linear relationship between precipitation and circulation strength. SCMs display a wider range of behaviors than CRMs. Some SCMs under the WTG method produce zero precipitation. Within an individual SCM, a DGW simulation and a corresponding WTG simulation can produce different signed circulation. When initialized with a dry troposphere, DGW simulations always result in a precipitating equilibrium state. The greatest sensitivities to the initial moisture conditions occur for multiple stable equilibria in some WTG simulations, corresponding to either a dry equilibrium state when initialized as dry or a precipitating equilibrium state when initialized as moist. Multiple equilibria are seen in more WTG simulations for higher SST. In some models, the existence of multiple equilibria is sensitive to some parameters in the WTG calculations

Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: study design and baseline characteristics of the IMPACT SHPT study

Background. Paricalcitol and cinacalcet are common therapies for patients on haemodialysis with secondary hyperparathyroidism (SHPT). We conducted a multi-centre study in 12 countries to compare the safety and efficacy of paricalcitol and cinacalcet for the treatment of SHPT

Scientific imperatives, clinical implications, and theoretical underpinnings for the investigation of the relationship between genetic variables and patient-reported quality-of-life outcomes

Objectives There is emerging evidence for a genetic basis of patient-reported quality-of-life (QOL) outcomes that can ultimately be incorporated into clinical research and practice. Objectives are (1) to provide arguments for the timeliness of investigating the genetic basis of QOL given the scientific advances in genetics and patient-reported QOL research; (2) to describe the clinical implications of such investigations; (3) to present a theoretical foundation for investigating the genetic underpinnings of QOL; and (4) to describe a series of papers resulting from the GENEQOL Consortium that was established to move this work forward. Methods Discussion of scientific advances based on relevant literature. Results In genetics, technological advances allow for increases in speed and efficiency and decreases in costs in exploring the genetic underpinnings of disease processes, drug metabolism, treatment response, and survival. In patient-based research, advances yield empirically based and stringent approaches to measurement that are scientifically robust. Insights into the genetic basis of QOL will ultimately allow early identification of patients susceptible to QOL deficits and to target care. The Wilson and Cleary model for patient-reported outcomes was refined by incorporating the genetic underpinnings of QOL. Conclusions This series of papers provides a path for QOL and genetics researchers to work together to move this field forward and to unravel the intricate interplay of the genetic underpinnings of patient-reported QOL outcomes. The ultimate result will be a greater understanding of the process relating disease, patient, and doctor that will have the potential to lead to improved survival, QOL, and health services deliver

The tropical rain belts with an annual cycle and a continent model intercomparison project: TRACMIP

This paper introduces the Tropical Rain belts with an Annual cycle and a Continent Model Intercomparison Project (TRACMIP). TRACMIP studies the dynamics of tropical rain belts and their response to past and future radiative forcings through simulations with 13 comprehensive and one simplified atmosphere models coupled to a slab ocean and driven by seasonally-varying insolation. Five idealised experiments, two with an aquaplanet setup and three with a setup with an idealized tropical continent, fill the space between prescribed-SST aquaplanet simulations and realistic simulations provided by CMIP5/6. The simulations reproduce key features of present-day climate and expected future climate change, including an annual-mean intertropical convergence zone (ITCZ) that is located north of the equator and Hadley cells and eddy-driven jets that are similar to present-day climate. Quadrupling CO2 leads to a northward ITCZ shift and preferential warming in Northern high-latitudes. The simulations show interesting CO2-induced changes in the seasonal excursion of the ITCZ and indicate a possible state-dependence of climate sensitivity. The inclusion of an idealized continent modulates both the control climate and the response to increased CO2; for example, it reduces the northward ITCZ shift associated with warming and, in some models, climate sensitivity. In response to eccentricity-driven orbital seasonal insolation changes, seasonal changes in oceanic rainfall are best characterized as a meridional dipole, while seasonal continental rainfall changes tend to be symmetric about the equator. This survey illustrates TRACMIP's potential to engender a deeper understanding of global and regional climate and to address questions on past and future climate

Tropical intraseasonal variability in 14 IPCC AR4 climate models. Part I: Convective signals

This study evaluates the tropical intraseasonal variability, especially the fidelity of The results show that current state-of-the-art GCMs still have significant problems and display a wide range of skill in simulating the tropical intraseasonal variability. The total intraseasonal (2-128 day) variance of precipitation is too weak in most of the models. About half of the models have signals of convectively coupled equatorial waves, with Kelvin and MRG-EIG waves especially prominent. However, the variances are generally too weak for all wave modes except the EIG wave, and the phase speeds are generally too fast, being scaled to excessively deep equivalent depths. An interesting result is that this scaling is consistent within a given model across modes, in that both the symmetric and antisymmetric modes scale similarly to a certain equivalent depth. Excessively deep equivalent depths suggest that these models may not have a large enough reduction in their "effective static stability" due to diabatic heating. 3 The MJO variance approaches the observed value in only two of the 14 models, but is less than half of the observed value in the other 12 models. The ratio between the eastward MJO variance and the variance of its westward counterpart is too small in most of the models, which is consistent with the lack of highly coherent eastward propagation of the MJO in many models. Moreover, the MJO variance in 13 of the 14 models does not come from a pronounced spectral peak, but usually is associated with an overreddened spectrum, which in turn is associated with a too strong persistence of equatorial precipitation. The two models that arguably do best at simulating the MJO are the only ones having convective closures/triggers linked in some way to moisture convergence