Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Barriers to Influenza Immunization: The Role of Physician Training on Influenza Vaccine Utilization in Six to Twenty-Three Month Old Infants

Digital Preservation

A focused ethnographic study of community social capital

Social capital, a relatively new public health concept, represents the intangible resources embedded in social relationships that facilitate collective action. Current interest in the concept stems from empirical studies linking social capital with health outcomes. However, in order for social capital to function as a meaningful research variable, conceptual development aimed at refining the domains, attributes, and boundaries of the concept are needed. An existing framework of social capital (Uphoff, 2000), developed from studies in India, was selected for congruence with the inductive analysis of pilot data from a community that was unsuccessful at mobilizing collective action. This framework provided the underpinnings for a formal ethnographic research study designed to examine the components of social capital in a community that had successfully mobilized collective action. The specific aim of the ethnographic study was to examine the fittingness of Uphoff's framework in the contrasting American community. A contrasting context was purposefully selected to distinguish essential attributes of social capital from those that were specific to one community. Ethnographic data collection methods included participant observation, formal interviews, and public documents. Data was originally analyzed according to codes developed from Uphoff's theoretical framework. The results from this analysis were only partially satisfactory, indicating that the theoretical framework required refinement. The refinement of the coding system resulted in the emergence of an explanatory theory of social capital that was tested with the data collected from formal fieldwork. Although Uphoff's framework was useful, the refinement of the framework revealed, (1) trust as the dominant attribute of social capital, (2) efficacy of mutually beneficial collective action as the outcome indicator, (3) cognitive and structural domains more appropriately defined as the cultural norms of the community and group, and (4) a definition of social capital as the combination of the cognitive norms of the community and the structural norms of the group that are either constructive or destructive to the development of trust and the efficacy of mutually beneficial collective action. This explanatory framework holds increased pragmatic utility for public health practice and research. ^

Endogenous Financing and the Long Run Impact of Money Growth on Output and Prices

Most monetary models make use of the quantity theory of money along with a Phillips curve. This implies a strong correlation between money growth and output in the short run (with little or no correlation between money and prices) and a strong long run correlation between money growth and inflation and inflation (with little or no correlation between money growth and output). The empirical evidence between money and inflation is very robust, but the long run money/output relationship is ambiguous at best. This paper attempts to explain this by looking at the impact of money growth on firm financing.

Technology, Investment, and Economic Fluctuations

Since 1854, the United States has experienced 32 business cycles. While the average length of these cycles (trough-to-trough) has been 51 months, there has been significant variation across different subperiods. This paper attempts to explore the relationship between capital accumulation, technology accumulation, and the business cycle.

Expectations, and Credibility in a Model of Monetary Policy

Recent monetary history has been characterized by monetary authorities which have been, alternatively hard and soft on inflation. In a vintage capital framework, investment decisions are not easily reversed. Therefore, expectations of policy as well as current policy are important to the investment decision. Here, a vintage capital model is used to assess the value of central bank credibility for a policy change. Policy in this model is assumed to be private information of the central banker. Agents learn about that policy which to study the ensuing transitional dynamics following a change in monetary policy regime.

Technology Creation, Diffusion, and Growth Cycles

Standard macroeconomic models that assume an exogenous stochastic process for multifactor productivity offer the interpretation that recessions are the result of ''bad news'' (technological regress) and expansions are the result of ''good news'' (technological advancement). The view taken here is that both expansions and recessions are the result of ''good news'' in the sense that in both cases, aggregate production possibilities have increased. Recessions can be thought of as the transition from one technological frontier to the next.

Water Infiltration following Land Rolling of Soybeans

Land rolling of soybean fields has become a popular practice in north central and northwest Iowa during the past five years. Although this technique was first utilized to push rocks into the ground to avoid combine damage and aid in harvesting lodged crops in Canada, producers in Iowa quickly learned that pushing corn root-balls flat at the time of planting and pushing small rocks into the ground can increase harvest efficiency. Typically fields are rolled shortly after planting. One disturbing trend that was noticed, however, was that rolled fields tended to have more water standing between the rows after moderate or heavy rain events. This would imply that water infiltration was slower in fields that had been rolled compared with fields that had not been rolled. Infiltration measurements were taken on a few plots in 2010 at the ISU Northern Research Farm. It seemed that water infiltration was less on the rolled plots. However, we wanted more measurements before publishing any results. In 2011 infiltration measurements were taken on the research farm and on neighboring farms where soybeans had been rolled. The goal was to determine if water infiltration had been reduced by land rolling.

Noble metal abundances in ODP Leg 115 basalts (Table 1)

A comparison of 50 basalts recovered at Sites 706, 707, 713, and 715 along the Reunion hotspot trace during Ocean Drilling Program Leg 115 in the Indian Ocean shows that seafloor alteration had little effect on noble metal concentrations (Au, Pd, Pt, Rh, Ru, and Ir), determined by inductively coupled plasma-mass spectrometry (ICP-MS), which generally tend to decrease with magma evolution. Their compatible-element behavior may be related to the precipitation of Ir-Os-based alloys, chromite, sulfides, and/or olivine and clinopyroxene in some combination. The simplest explanation indicates silicate control of concentrations during differentiation. Basalts from the different sites show varying degrees of alkalinity. Noble metal abundances tend to increase with decreasing basalt alkalinity (i.e., with increasing percentages of mantle melting), indicating that the metals behave as compatible elements during mantle melting. The retention of low-melting-point Au, Pd, and Rh in mantle sulfides, which mostly dissolve before significant proportions of Ir-Os-based alloys melt, explains increasing Pd/Ir ratios with decreasing alkalinity (increasing melting percentages) in oceanic basalts. High noble metal concentrations in Indian Ocean basalts (weighted averages of Au, Pd, Rh, Pt, Ru, and Ir in Leg 115 basalts are 3.2, 8.1, 0.31, 7.3, 0.22, and 0.11 ppb, respectively), compared with basalts from some other ocean basins, may reflect fundamental primary variations in upper- mantle noble metal abundances

(Table 2) Stratigraphic position of midpoints of reddish and beige layers of lithologic cycles in the Loulja-A Section and their astronomical ages after tuning to the ETP and Summer Insolation Curves of the La2004 solution

An integrated high-resolution stratigraphy and orbital tuning is presented for the Loulja sections located in the Bou Regreg area on the Atlantic side of Morocco. The sections constitute the upward continuation of the upper Messinian Ain el Beida section and contain a well-exposed, continuous record of the interval straddling the Miocene-Pliocene (M-P) boundary. The older Loulja-A section, which covers the interval from ~5.59 to 5.12 Ma, reveals a dominantly precession-controlled color cyclicity that allows for a straightforward orbital tuning of the boundary interval and for detailed cyclostratigraphic correlations to the Mediterranean; the high-resolution and high-quality benthic isotope record allows us to trace the dominantly obliquity-controlled glacial history. Our results reveal that the M-P boundary coincides with a minor, partly precession-related shift to lighter "interglacial" values in d18O. This shift and hence the M-P boundary may not correlate with isotope stage TG5, as previously thought, but with an extra (weak) obliquity-controlled cycle between TG7 and TG5. Consequently, the M-P boundary and basal Pliocene flooding of the Mediterranean following the Messinian salinity crisis are not associated with a major deglaciation and glacio-eustatic sea level rise, indicating that other factors, such as tectonics, must have played a fundamental role. On the other hand, the onset of the Upper Evaporites in the Mediterranean marked by hyposaline conditions coincides with the major deglaciation step between marine isotope stage TG12 and TG11, suggesting that the associated sea level rise is at least partly responsible for the apparent onset of intermittently restricted marine conditions following the main desiccation phase. Finally, the Loulja-A section would represent an excellent auxiliary boundary stratotype for the M-P boundary as formally defined at the base of the Trubi marls in the Eraclea Minoa section on Sicily.