Controls on the CO2 seasonal cycle

Surface pressure measurement performed by the Viking landers show substantial variations in pressure on seasonal timescales that are characterized by two local minima and two local maxima. These variations have widely been attributed to the seasonal condensation and sublimation of CO2 in the two polar regions. It has been somewhat of a surprise that the amplitude of the minimum and maximum that is dominated by the CO2 cycle in the north was much weaker than the corresponding amplitude of the south-dominated extrema. Another surprise was that the seasonal pressure cycle during years 2 and 3 of the Viking mission was so similar to that for year 1, despite the occurrence of two global dust storms during year 1 and none during years 2 and 3. An energy balance model that incorporates dynamical factors from general circulation model (GCM) runs in which the atmospheric dust opacity and seasonal date were systematically varied was used to model the observed seasonal pressure variations. The energy balance takes account of the following processes in determining the rates of CO2 condensation and sublimation at each longitudinal and latitudinal grid point: solar radiation, infrared radiation from the atmosphere and surface, subsurface heat conduction, and atmospheric heat advection. Condensation rates are calculated both at the surface and in the atmosphere. In addition, the energy balance model also incorporates information from the GCM runs on seasonal redistribution of surface pressure across the globe. Estimates of surface temperature of the seasonal CO2 caps were used to define the infrared radiative losses from the seasonal polar caps. The seasonal pressure variations measured at the Viking lander sites were closely reproduced

A Cloud Greenhouse Effect on Mars: Significant Climate Change in the Recent Past

The large variations in Mars orbit parameters are known to be significant drivers of climate change on the Red planet. The recent discovery of buried CO2 ice at the South Pole adds another dimension to climate change studies. In this paper we present results from the Ames GCM that show within the past million years it is possible that clouds from a greatly intensified Martian hydrological cycle may have produced a greenhouse effect strong enough to raise global mean surface temperatures by several tens of degrees Kelvin. It is made possible by the ability of the Martian atmosphere to transport water to high altitudes where cold clouds form, reduce the outgoing longwave radiation, and drive up surface temperatures to maintain global energy balance

Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model.

Purpose Despite documented oncologic benefit, use of postoperative adjuvant radiotherapy (aRT) in patients with prostate cancer is still limited in the United States. We aimed to develop and internally validate a risk-stratification tool incorporating the Decipher score, along with routinely available clinicopathologic features, to identify patients who would benefit the most from aRT. Patient and Methods Our cohort included 512 patients with prostate cancer treated with radical prostatectomy at one of four US academic centers between 1990 and 2010. All patients had ≥ pT3a disease, positive surgical margins, and/or pathologic lymph node invasion. Multivariable Cox regression analysis tested the relationship between available predictors (including Decipher score) and clinical recurrence (CR), which were then used to develop a novel risk-stratification tool. Our study adhered to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for development of prognostic models. Results Overall, 21.9% of patients received aRT. Median follow-up in censored patients was 8.3 years. The 10-year CR rate was 4.9% vs. 17.4% in patients treated with aRT versus initial observation ( P \u3c .001). Pathologic T3b/T4 stage, Gleason score 8-10, lymph node invasion, and Decipher score \u3e 0.6 were independent predictors of CR (all P \u3c .01). The cumulative number of risk factors was 0, 1, 2, and 3 to 4 in 46.5%, 28.9%, 17.2%, and 7.4% of patients, respectively. aRT was associated with decreased CR rate in patients with two or more risk factors (10-year CR rate 10.1% in aRT v 42.1% in initial observation; P = .012), but not in those with fewer than two risk factors ( P = .18). Conclusion Using the new model to indicate aRT might reduce overtreatment, decrease unnecessary adverse effects, and reduce risk of CR in the subset of patients (approximately 25% of all patients with aggressive pathologic disease in our cohort) who benefit from this therapy

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

Nonlinear inverse perturbation method in dynamic analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76092/1/AIAA-8245-515.pd

Standard survey methods for estimating colony losses and explanatory risk factors in Apis mellifera

This chapter addresses survey methodology and questionnaire design for the collection of data pertaining to estimation of honey bee colony loss rates and identification of risk factors for colony loss. Sources of error in surveys are described. Advantages and disadvantages of different random and non-random sampling strategies and different modes of data collection are presented to enable the researcher to make an informed choice. We discuss survey and questionnaire methodology in some detail, for the purpose of raising awareness of issues to be considered during the survey design stage in order to minimise error and bias in the results. Aspects of survey design are illustrated using surveys in Scotland. Part of a standardized questionnaire is given as a further example, developed by the COLOSS working group for Monitoring and Diagnosis. Approaches to data analysis are described, focussing on estimation of loss rates. Dutch monitoring data from 2012 were used for an example of a statistical analysis with the public domain R software. We demonstrate the estimation of the overall proportion of losses and corresponding confidence interval using a quasi-binomial model to account for extra-binomial variation. We also illustrate generalized linear model fitting when incorporating a single risk factor, and derivation of relevant confidence intervals

Characterization of 1577 primary prostate cancers reveals novel biological and clinicopathologic insights into molecular subtypes.

BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests. OBJECTIVE: To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping. DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model was trained and validated. Outlier expression analysis was used to predict other mutually exclusive non-ERG ETS gene rearrangements (ETS(+)) or SPINK1 overexpression (SPINK1(+)). OUTCOME MEASUREMENTS: Associations with clinical features and outcomes by multivariate logistic regression analysis and receiver operating curves. RESULTS AND LIMITATIONS: The m-ERG classifier showed 95% accuracy in an independent validation subset (155 samples). Across cohorts, 45% of PCas were classified as m-ERG(+), 9% as m-ETS(+), 8% as m-SPINK1(+), and 38% as triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Gene expression profiling supports three underlying molecularly defined groups: m-ERG(+), m-ETS(+), and m-SPINK1(+)/triple negative. On multivariate analysis, m-ERG(+) tumors were associated with lower preoperative serum prostate-specific antigen and Gleason scores, but greater extraprostatic extension (p CONCLUSIONS: A clinically available prognostic test (Decipher) can also assess PCa molecular subtypes, obviating the need for additional testing. Clinicopathologic differences were found among subtypes based on global expression patterns. PATIENT SUMMARY: Molecular subtyping of prostate cancer can be achieved using extra data generated from a clinical-grade, genome-wide expression-profiling prognostic assay (Decipher). Transcriptomic and clinical analysis support three distinct molecular subtypes: (1) m-ERG(+), (2) m-ETS(+), and (3) m-SPINK1(+)/triple negative (m-ERG(-)/m-ETS(-)/m-SPINK1(-)). Incorporation of subtyping into a clinically available assay may facilitate additional applications beyond routine prognosis

The transition to Earth-like torsional oscillations in magnetoconvection simulations

Evidence for torsional oscillations (TOs) operating within the Earth's fluid outer core has been found in the secular variation of the geomagnetic field. These waves arise via disturbances to the predominant (magnetostrophic) force balance believed to exist in the core. The coupling of the core and mantle allow TOs to affect the length-of-day of the Earth via angular momentum conservation. Encouraged by previous work, where we were able to observe TOs in geodynamo simulations, we perform 3-D magnetoconvection simulations in a spherical shell in order to reach more Earth-like parameter regimes that proved hitherto elusive. At large Ekman numbers we find that TOs can be present but are typically only a small fraction of the overall dynamics and are often driven by Reynolds forcing at various locations throughout the domain. However, as the Ekman number is reduced to more Earth-like values, TOs become more apparent and can make up the dominant portion of the short timescale flow. This coincides with a transition to regimes where excitation is found only at the tangent cylinder, is delivered by the Lorentz force and gives rise to a periodic Earth-like wave pattern, approximately operating on a 4 to 5 year timescale. The core travel times of our waves also become independent of rotation at low Ekman number with many converging to Earth-like values of around 4 years

Thin ice, deep snow and surface flooding in Kotzebue Sound: landfast ice mass balance during two anomalously warm winters and implications for marine mammals and subsistence hunting

The inaugural data from the first systematic program of sea ice observations in Kotzebue Sound, Alaska, in 2018 coincided with the first winter in living memory when the Sound was not choked with ice. The following winter of 2018-19 was even warmer and characterized by even less ice. Here we discuss the mass balance of landfast ice near Kotzebue (Qikiktagruk) during these two anomalously warm winters. We use in-situ observations and a 1-D thermodynamic model to address three research questions developed in partnership with an Indigenous Advisory Council. In doing so, we improve our understanding of connections between landfast ice mass balance, marine mammals, and subsistence hunting. Specifically, we show: i) Ice growth stopped unusually early due to strong vertical ocean heat flux, which also likely contributed to early start to bearded seal hunting; ii) Unusually thin ice contributed to widespread surface flooding. The associated snow ice formation partly offset the reduced ice growth, but the flooding likely had a negative impact on ringed seal habitat; iii) Sea ice near Kotzebue during the winters of 2017-18 and 2018-19 was likely the thinnest since at least 1945, driven by a combination of warm air temperatures and a persistent ocean heat flux.