A Sub-Type of Familial Pancreatic Cancer: Evidence and Implications of Loss-of-Function Polymorphisms in Indoleamine-2,3-Dioxygenase-2.

BACKGROUND: Variation in an individual\u27s genetic status can impact the development of pancreatic ductal adenocarcinoma; however, the majority of familial pancreatic cancers (FPC) cannot yet be attributed to a specific inherited mutation. We present data suggesting a correlation between loss-of-function single nucleotide polymorphisms (SNPs) in an immune regulator gene, indoleamine-2,3-dioxygenase-2 (IDO2), and an increased risk of FPC. STUDY DESIGN: Germline DNA from patients who underwent resection for pancreatic ductal adenocarcinoma (n = 79) was sequenced for the IDO2 SNPs R248W and Y359Stop. Genotypes resulting in inactivation of IDO2 (Y325X homozygous, R248W homozygous) were labeled as homozygous, and the other genotypes were grouped as wild-type or heterozygous. Genotype distributions of each SNP were analyzed for Hardy-Weinberg deviation. A genotype frequency set from the 1000 Genomes Project (n = 99) was used as a genetic control for genotype distribution comparisons. RESULTS: A significant 2-fold increase in the overall prevalence of the Y359Stop homozygous genotype compared with the expected Hardy-Weinberg equilibrium was noted (p \u3c 0.05). Familial pancreatic cancer was noted in 15 cases (19%) and comparison of the FPC cohort set to the genetic control set showed a 3-fold increase in Y359Stop homozygous rates (p = 0.054). Overall in our cohort, the homozygous genotype group was associated with increased risk of FPC (odds ratio 5.4; 95% CI 1.6 to 17.6; p \u3c 0.01). Sex, age at diagnosis, and history of tobacco use were not found to be significantly associated with FPC. CONCLUSIONS: Our preliminary data suggest a strong association between the IDO2 inactivating Y359Stop SNP and an increased risk of FPC when compared with the control group. Future studies will evaluate the value of IDO2 genotyping as a prognostic, early detection marker for pancreatic ductal adenocarcinoma and a predictive marker for novel immune checkpoint therapies

Procedural Rights and Remedies under the Texas Property Tax Code - A Guide to the Code, Recent Amendments, and Developing Case Law.

Abstract Forthcoming

Variability of Surface Pigment Concentrations in the South Atlantic Bight

A 1‐year time sequence (November 1978 through October 1979) of surface pigment images from the South Atlantic Bight (SAB) was derived from the Nimbus 7 coastal zone color scanner. This data set is augmented with in situ observations of hydrographic parameters, freshwater discharge, sea level, coastal winds, and currents for the purpose of examining the coupling between physical processes and the spatial and temporal variability of the surface pigment fields. The SAB is divided into three regions: the east Florida shelf, the Georgia‐South Carolina shelf and the Carolina Capes. Six‐month seasonal mean pigment fields and time series of mean values within subregions were generated. While the seasonal mean isopleths were closely oriented along isobaths, significant differences between seasons in each region were found to exist. These differences are explained by correlating the pigment time series with physical parameters and processes known to be important in the SAB. Specifically, summertime concentrations between Cape Romain and Cape Canaveral were greater than those in winter, but the opposite was true north of Cape Romain. It is suggested that during the abnormally high freshwater discharge in the winter‐spring of 1979, Cape Romain and Cape Fear were the major sites of cross‐shelf transport, while the cross‐shelf exchange during the fall of 1979 occurred just north of Cape Canaveral. Finally, the alongshore band of high pigment concentrations increased in width throughout the year in the vicinity of Charleston, but near Jacksonville it exhibited a minimum width in the summer and a maximum width in the fall of 1979

Ozone Depletion from Nearby Supernovae

Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time, improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made in theoretical modeling of supernovae and of the resultant gamma-ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma-rays and cosmic rays. We find that for the combined ozone depletion roughly to double the ``biologically active'' UV flux received at the surface of the Earth, the supernova must occur at <8 pc. Based on the latest data, the time-averaged galactic rate of core-collapse supernovae occurring within 8 pc is ~1.5/Gyr. In comparing our calculated ozone depletions with those of previous studies, we find them to be significantly less severe than found by Ruderman (1974), and consistent with Whitten et al. (1976). In summary, given the amplitude of the effect, the rate of nearby supernovae, and the ~Gyr time scale for multicellular organisms on Earth, this particular pathway for mass extinctions may be less important than previously thought.Comment: 24 pages, 4 Postscript figures, to appear in The Astrophysical Journal, 2003 March 10, vol. 58

Europe's rare earth element resource potential: an overview of REE metallogenetic provinces and their geodynamic setting

Security of supply of a number of raw materials is of concern for the European Union; foremost among these are the rare earth elements (REE), which are used in a range of modern technologies. A number of research projects, including the EURARE and ASTER projects, have been funded in Europe to investigate various steps along the REE supply chain. This paper addresses the initial part of that supply chain, namely the potential geological resources of the REE in Europe. Although the REE are not currently mined in Europe, potential resources are known to be widespread, and many are being explored. The most important European resources are associated with alkaline igneous rocks and carbonatites, although REE deposits are also known from a range of other settings. Within Europe, a number of REE metallogenetic belts can be identified on the basis of age, tectonic setting, lithological association and known REE enrichments. This paper reviews those metallogenetic belts and sets them in their geodynamic context. The most well-known of the REE belts are of Precambrian to Palaeozoic age and occur in Greenland and the Fennoscandian Shield. Of particular importance for their REE potential are the Gardar Province of SW Greenland, the Svecofennian Belt and subsequent Mesoproterozoic rifts in Sweden, and the carbonatites of the Central Iapetus Magmatic Province. However, several zones with significant potential for REE deposits are also identified in central, southern and eastern Europe, including examples in the Bohemian Massif, the Iberian Massif, and the Carpathians

Clustering of childhood mortality in the Kintampo Health and Demographic Surveillance System in Ghana

Background: Childhood mortality in Ghana has generally declined in the last four decades. However, estimates tend to conceal substantial variability among regions and districts. The lack of population-based data in Ghana, as in other less developed countries, has hindered the development of effective programmes targeted specifically at clusters where mortality levels are significantly higher. Objective: This paper seeks to test for the existence of statistically significant clusters of childhood mortality within the Kintampo Health and Demographic Surveillance System (KHDSS) between 2005 and 2007. Design: In this study, mortality rates were generated using mortality data extracted from the health and demographic surveillance database of the KHDSS and exported into STATA. The spatial and spatio-temporal scan statistic by Kulldorff was used to identify significant clusters of childhood mortality within the KHDSS. Results: A significant cluster of villages with high under-five mortality in the south-eastern part of the KHDSS in 2006 was identified. This is a remote location where poverty levels are relatively higher, health facilities are more sparse and these are compounded by poor transport services in case of emergencies. Conclusion: This study highlights the potential of the surveillance platform to demonstrate the spatial dimensions of childhood mortality clustering. It is apparent, though, that further studies need to be carried out in order to explore the underlying risk factors for potential mortality clusters that could emerge later

Towards a Critique of Educative Violence: Walter Benjamin and ‘Second Education’

Although modern systems of mass education are typically defined in their opposition to violence, it has been argued that it is only through an insistent and critical focus upon violence that radical thought can be sustained. This article seeks to take up this challenge in relation to Walter Benjamin’s lesser-known writings on education. Benjamin retained throughout his life a deep suspicion about academic institutions and about the pedagogic, social and economic violence implicated in the idea of cultural transmission. He nonetheless remained committed to the possibility of another kind of revolutionary potential inherent to true education and, when he comes to speak of this in his Critique of Violence, it is remarkable that he describes it as manifesting an educative violence. This article argues that Benjamin’s philosophy works toward a critique of educative violence that results in a distinction between a ‘first’ and ‘second’ kind of education and asks whether destruction might have a positive role to play within pedagogical theories in contrast to current valorisations of creativity and productivity

Nucleation of vortex arrays in rotating anisotropic Bose-Einstein condensates

The nucleation of vortices and the resulting structures of vortex arrays in dilute, trapped, zero-temperature Bose-Einstein condensates are investigated numerically. Vortices are generated by rotating a three-dimensional, anisotropic harmonic atom trap. The condensate ground state is obtained by propagating the Gross-Pitaevskii equation in imaginary time. Vortices first appear at a rotation frequency significantly larger than the critical frequency for vortex stabilization. This is consistent with a critical velocity mechanism for vortex nucleation. At higher frequencies, the structures of the vortex arrays are strongly influenced by trap geometry.Comment: 5 pages, two embedded figures. To appear in Phys. Rev. A (RC