bluuebunny/crossref_metadata_2025 huggingface dataset:
Tectonic setting and regional significance of the ‘Port aux Basques Gneiss’, SW Newfoundland
Authors: SCHOFIELD D. I. , VAN STAAL C. R. , WINCHESTER J. A.
Published: December 2007

The ‘Port aux Basques Gneiss’ of southwest Newfoundland comprises three paragneiss and schist assemblages: the Grand Bay and Port aux Basques complexes, and the Harbour le Cou Group. They are intruded by large volumes of basic sheets and coeval Middle Ordovician granitoids: the Margaree and Kelby Cove orthogneiss, which also cut a tectonic slice of earlier ultrabasic to basic rocks within the Grand Bay Complex: the Big Barachois assemblage. The Grand Bay and Port aux Basques complexes are juxtaposed by the Late Silurian Isle aux Morts Fault Zone against the Harbour le Cou Group to the east, which dominantly comprises sillimanite and garnet-bearing, pyritiferous metasediments with amphibolitic intrusions and meta-pillow basalts in its lower stratigraphic units.

Geochemical studies have shown that metabasites of the Grand Bay Complex, Port aux Basques Complex, Margaree and Kelby Cove orthogneiss comprise fractionated and crustally contaminated MORB-like and within plate tholeiites, suggestive of an ensialic Okinawa type back-arc basin. These have comparable characteristics to metabasites in the Harbour le Cou Group and suggest that these units comprise remnants of an extensive Mid-Ordovician marginal basin developed within a promontory on the peri-Gondwanan continental margin. In contrast, the Big Barachois assemblage in part comprises a distinct suite of pre-Mid-Ordovician Island Arc Tholeiites
The Proterozoic–Cambrian transition within the ‘Charnian Supergroup’ of central England and the antiquity of the Ediacara fauna
Authors: McILROY D. , BRASIER M. D. , MOSELEY J. B.
Published: December 2007

A revised interpretation for the ‘Charnian Supergroup’ is suggested from ichnological and lithological comparisons with the Cambrian of Nuneaton and other parts of the Avalonian superterrane. Late Neoproterozoic volcaniclastic sediments contain an Ediacara fauna in the Maplewell Group. These are succeeded by one or more inferred erosional breaks and overlain by passive margin sediments (quartzarenites, glauconitic greywackes, pelites) of the Brand Group which yield Cambrian trace fossils, including abundant large
Teichichnus
. This transformation is compared with that between the Neoproterozoic Caldecote Volcanic Formation and the Cambrian Hartshill Formation at Nuneaton. The Hanging Rocks Formation of the Brand Group lies above a major erosional break but shares a volcanogenic island arc petrology with the underlying Maplewell Group. Conglomeratic sandstones at the base of the Brand Hills Formation contain purple pelite clasts comparable with underlying lithologies, plus clasts of weathered diorite showing granophyric textures identical to those seen in the enigmatic South Charnwood Diorites. Nd–Sm isotope studies confirm the geochemical similarity between these diorites and those that intruded the Caldecote Volcanics at Nuneaton, previously U–Pb zircon dated at 603±2 Ma. These strong similarities with the Nuneaton succession suggest that deposition of the Brand Hills Formation in the Cambrian was preceded by the local unroofing of diorite and erosion of underlying mudrocks, much as seen in other parts of Avalonia. A date of 603±2 Ma for the South Charnwood Diorites provides a minimum age for the local Ediacara fauna but this is in need of substantiation.
The Great Glen Fault: a major vertical lithospheric boundary
Authors: CANNING J. C. , HENNEY P. J. , MORRISON M. A. , VAN CALSTEREN P. W. C. , GASKARTH J. W. , SWARBRICK A.
Published: December 2007

Two lamprophyre suites are used to constrain sub-continental lithospheric mantle domains in Late Caledonian Northern Britain (at 400 Ma). A Northern Highlands and a Southern domain are resolved. The first has low (ɛNd (−6.4 to − 12.8); the latter has higher (+3.9 to −3.4). The boundary between them is coincident with the surface expression of the Great Glen Fault. The two mantle domains tightly bracket the fault. The lamprophyre magmas were generated at depths of at least 100 km. At the end of the Caledonian Orogeny the Great Glen Fault was a major vertical discontinuity that transected the sub-continental lithospheric mantle.
Slumps, debris flows and sandy deep-water channel systems: implications for the application of sequence stratigraphy to deep water clastic sediments
Authors: CRONIN B. , OWEN D. , HARTLEY A. , KNELLER B.
Published: December 2007

The Hecho Group is a classic sedimentary system from which turbidite classifications have been defined. This study of mudstone-rich intervals from this group suggests that published models in which Type 2 and 3 systems develop in response to changes in relative sea level or tectonic activity need to be reassessed. Intervals developed between channel/lobe sandstones comprise mud-matrix supported conglomeratic debris flows and/or slump deposits which blanket the underlying sand-rich channel-fills. They record periods of major disturbance and re-organization of the sedimentary regime. The sandstone bodies are not strongly incised and have high aspect ratios. Previous interpretations of these intervening muddy intervals as overbank wedge/levee deposits, developed during a relative rise in sea level (Type 3) are considered inappropriate for the sections studied.
Fossil plants record an atmospheric
12
CO
2
and temperature spike across the Palaeocene-Eocene transition in NW Europe
Authors: BEERLING D. J. , JOLLEY D. W.
Published: December 2007

The large negative excursion of carbon-isotope composition (δ
13
C) recorded from foraminifera and bulk carbonates indicates a major anomaly in the operation of the global carbon cycle across the Palaeocene-Eocene boundary. Therefore, we sought terrestrial evidence for the transfer of isotopically light carbon (
12
CO
2
) from the ocean to the atmosphere by making systematic δ
13
C measurements or well-dated sequences of fossil pollen from NW Europe. The results indicate an atmospheric
12
CO
2
spike of
c.
2 % between 58 and 55 Ma coincident with the ocean isotopic anomalies. Pollen spectra from these sequences suggest a marked shift in dominance from mixed mesophytic to paratropical forests synchronous with the terrestrial isotope excursion.
U–Pb geochronology and Sm–Nd isotopic composition of Proterozoic gneisses,Channel Islands, UK
Authors: SAMSON SCOTT D. , D’LEMOS RICHARD S.
Published: December 2007

Gneissic units of the Channel Islands, United Kingdom, have traditionally been considered to be Palaeoproterozoic basement to the late Neoproterozoic Cadomia terrane, based on lithological correlations and imprecise or ambiguous isotopic data. A new precise U–Pb date of 2061&2 Ma, based on analyses of single zircons, for the Icart granitic orthogneiss of Guernsey confirms a Palaeoproterozoic age of its igneous protolith. The Nd depleted mantle model age (
T
DM
)of this gneiss is 2220 Ma, only slightly older than its crystallization age, indicating that it represents juvenile crust. Other gneisses from Guernsey have similar
T
DM
ages ranging from 2210 to 2370 Ma, suggesting that they are also exposures of juvenile Palaeoproterozoic crust. A component from a penetratively deformed orthogneiss from Sark, previously correlated with Icartian gneisses on Guernsey, yields a U–Pb zircon date of 616
+4
-2 Ma. This crystallization age demonstrates that the protolith was a Cadomian intrusion and that penetrative deformation and amphibolite-facies metamorphism in the northern Channel Islands were Cadomian in age. The use of gneissic features as a means of invoking the antiquity of many other undated gneissic units in the region is thus considered unreliable. The presence of 2170 ± 7 Ma zircon xenocrysts within the Sark orthogneiss, combined with its initial ε
Nd
(615)= − 9.5, are strong evidence that pre-Cadomian basement was a significant source component, and that documenting the extent and age of pre-Cadomian basement may be possible by indirect geochemical methods.
Geochemical and Sr–Nd–Pb isotopic data bearing on the origin of Pan-Africangranitoids in the Kid area, southeast Sinai, Egypt
Authors: MOGHAZI A. M. , ANDERSEN T. , OWEISS G. A. , EL BOUSEILY A. M.
Published: December 2007

The Kid plutonic suite in southeast Sinai, Egypt is composed of: (1) a gabbro–diorite complex; (2) quartz monzodiorite; (3) granodiorite–monzogranite association; (4) syenogranite. Major- and traceelement analyses and radiogenic isotope data (Rb/Sr, Sm/Nd and Pb/Pb) are presented for these rocks. Rb–Sr isochrons indicate ages of 581±11 Ma, 576±11 Ma and 570±4 Ma for the quartz monzodiorite–granodiorite–monzogranite association and syenogranite, respectively. The gabbro–diorite complex is a layered intrusion varying in SiO2 from 42 to 59 wt%. It shows a calc-alkaline trend, and the trace element characteristics of arc lavas. Subsequently, this magma fractionated to give quartz monzodiorite andsyenogranite magmas. The quartz monzodiorite has low initial
87
Sr/
86
Sr ratios (0.703) and high ɛ
Nd
values (+4.4±0.3), with trace element characteristics of volcanic-arc granites. The granodiorite–monzograniteassociation has higher initial Sr ratio (0.7044), lower ɛ
Nd
(+1.5–+2.7) and relatively high
207
Pb/
204
Pb and
208
Pb/
204
Pb, significantly different from those of the older rocks. Isotopic data and REE modelling suggestthat it formed by partial melting of an early Pan-African amphibolitic lower crust. The syenogranite isa typical highly fractionated post-orogenic granite, with a deep negative Eu anomaly, HFSE and REEenrichment, a
87
Sr/
86
Sr initial ratio of 0.7033, ɛ
Nd
of 4.5
&
0.5 and distinct variations in the
206
Pb/
204
Pbratio. The isotopic compositions of Sr, Nd and Pb indicate that the syenogranite and the quartzmonzodiorite are comagmatic. Increasing fluorine concentration from the quartz monzodiorite to thesyenogranite suggests that fluid fractionation involving fluorine complexing played an important role inthe genesis of the syenogranite. This process led to the enrichment of HFSE and HREE, to extensivefractional crystallization, to changes in the U/Pb ratios and a distinct variation in
206
Pb/
204
Pb.
A reassessment of the age of the Cockburn Island Formation, northern Antarctic Peninsula, and its palaeoclimatic implications
Authors: JONKERS H. A. , KELLEY S. P.
Published: December 2007

New constraints on the age of the Cockburn Island Formation, northern Antarctic Peninsula, resulting from whole rock laser-stepped heated
40
Ar–
39
Ar dating of associated basalt and palaeomagnetic re-calibration of the ranges of the formation’s fossil diatom taxa, suggest that interglacial conditions existed around 3 million years ago. The refined age of the deposit supports continent-wide Late Pliocene warming in Antarctica, and makes more likely the occurrence of extensive marine incursions in East Antarctica at that time.
An upper Dalradian microfossil reassessed
Authors: MOLYNEUX S. G.
Published: December 2007

An acritarch from the highest Dalradian Macduff Slate of northeast Scotland is confirmed as
Veryhachium
cf.
lairdii
. Its presence implies that the Macduff Slate is Ordovician. This conclusion is compatible with the view that there is stratigraphical and structural continuity between the Dalradian and Lower Palaeozoic rocks in the vicinity of the Highland Border (e.g. the Lower Cambrian Keltie Water Grit Formation), but runs counter to other lines of evidence, notably biotite cooling ages, which suggest that the Dalradian had undergone metamorphism by the Late Cambrian. Further investigations are needed to reproduce and confirm the biostrati-graphical evidence for the age of the Macduff Slate.
The erosional and uplift history of NE Atlantic passive margins: constraints on a passing plume
Authors: CLIFT P. D. , CARTER A. , HURFORD A. J.
Published: December 2007

New apatite fission-track analyses from NW Britain indicate that a maximum of 2.5 km of erosion has occurred there during the Cenozoic, similar to values for SE Greenland and the east Greenland coast north of Scoresby Sund. The erosion may have been facilitated by magmatic underplating during break-up. However, at Kangerdlugssuaq, East Greenland, 4–6 km of erosion is measured since 45 Ma. Lower–mid-Eocene marine sedimentary rocks overlying the lavas on the Blosseville Coast indicate that magmatic underplating on the central Greenland coast substantially post-dated flood volcanism and break-up, behaviour not predicted by simple plume-rift models. Subsidence reconstructions of the Hebrides Shelf, and the east and west Greenland coasts, show that rapid, dynamic uplift was effectively synchronous at 63 Ma and preceded volcanism by <1.6 million years. The magnitude of uplift on the Hebrides Shelf (
c
. 400 m) is compatible with a mantle temperature anomaly of
c
. 100
°
C. These data suggest very rapid lateral flow of the impacting Iceland plume head. The predicted crossing of the plume by the east Greenland coast in the mid–late Eocene would account for post-rift magmatic underplating and dynamic support on the Greenland but not the European side of the North Atlantic basin.
A precise late Neoproterozoic U-Pb zircon age for the syntectonic Perelle quartz diorite, Guernsey, Channel Islands, UK
Authors: SAMSON SCOTT D. , D'LEMOS RICHARD S.
Published: December 2007

A precise U-Pb zircon age of 611.4
+2.0
–1.1
Ma has been determined for the foliated quartz diorite at Perelle Bay, Guernsey, UK Channel Islands. The age is based on the analysis of single zircons, half of a single grain, and groups of two and three zircons. The age is nearly 100 Ma younger than that suggested by other workers, based on
207
Pb/
206
Pb dates of large, multi-grain fractions of zircon, and thus rules out this intrusion as the earliest marker of the onset of Cadomian magmatism in the North Armorican Massif. A 611 Ma crystallization age for the Perelle quartz diorite is consistent with previous detailed fabric development studies that suggested magmatic fabrics within the pluton are largely overprinted by similarly oriented solid-state deformation fabrics resulting from syntectonic emplacement during Cadomian orogenesis. The U-Pb age is approximately 8–15 Ma older than
40
Ar/
39
Ar hornblende dates for the pluton, consistent with the emplacement of the intrusion followed by slow cooling in a region of moderate to high ambient crustal temperatures. These new data emphasize the fact that periods of pluton emplacement are considerably briefer than periods of deformation and thus syntectonic intrusions do not date regional deformational events, but only mark events within a period of regional tectonism. The ability to analyse single zircons, and selected portions of single zircons, using ultra-low blank U-Pb analytical techniques documents the feasibility of determining precise emplacement ages of other Neoproterozoic granitoids that contain a significant percentage of xenocrystic zircon.
Characterizing and producing from reservoirs in landslides: challenges and opportunities
Authors: Welbon A. I. F. , Brockbank P. J. , Brunsden D. , Olsen T. S.
Published: December 2007

Landslides can consist of rotational slips, translational glide blocks, topples, talus slopes, debris flows, mudslides and compressional toes which can combine in different proportions to form complex landslides. The mass movement can be subaerial or submarine, occur over wide ranges of scale and can vary in rate from creep to catastrophic failure. Complexity of the landslide reflects the controlling factors including the strength of the deforming material and triggering mechanisms such as earthquakes, imposed load, increasing topographic relief and removal of toe material.

Processes of landslide deformation include slip on discrete surfaces, distributed shear within the landslide, vertical thinning and lateral spreading through shear, fluidization, porosity collapse and loss of material from the top or toe of the complex. These processes control the quality of the resultant reservoirs. This leads to a greater range of reservoir types than conventional faulted reservoirs, with a proportionate upside and downside potential and difficulty in quantifying uncertainty.

This paper uses examples from the literature, outcrops and subsurface datasets (including the Statfjord Field and the Halten Terrace in Norway) to outline the complexity of reservoirs in landslides and the challenges and opportunities in finding and producing them. We present workflows for seismic and subseismic characterization for exploration and reservoir scale based on geomorphological principles. Seismic mapping is achieved by classifying the form of the reflectors (both slip surfaces and the bounding envelope of the landslide) from an atlas of geometric and structural styles and is applied to both the Halten Terrace example and the Statfjord Field. We present a new workflow for reservoir characterization in which integration of structural, biostratigraphic, sedimentological and dynamic data gives key information on process, timing and heterogeneity of the reservoir. For the Statfjord field, important maps of the landslide block stratigraphy derived from a subcrop map and communication maps based on a
c
. 130 well dataset can be correlated to outcrop analogues and used to develop a predictive tool for landslide reservoir extent and quality, both in this field and others.
Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus
Authors: Perfume Guadalupe , Nabhen Sabrina L. , Riquelme Barrera Karla , Otero María G. , Bianciotti Liliana G. , Vatta Marcelo S.
Published: December 2007

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETBreceptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETCreceptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.
Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic syndrome
Authors: Nakhoul Farid , Khankin Eliyahu , Yaccob Afif , Kawachi Hiroshi , Karram Tony , Awaad Huda , Nakhoul Nakhoul , Hoffman Aaron , Abassi Zaid
Published: December 2007

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and edema. It is believed that nephrin and podocin are involved in the development of proteinuria. The proteinuria and effects of eplerenone alone or combined with enalapril on nephrin/podocin abundance in rats with NS have not yet been studied. Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 wk after NS induction) effects of eplerenone and enalapril, alone or combined, on proteinuria and nephrin/podocin abundance in rats with adriamycin-induced NS. Adriamycin caused a significant increase in daily protein excretion (UprV; from 26.96 ± 3.43 to 958.57 ± 56.7 mg/day, P < 0.001) and cumulative proteinuria [from 900.33 ± 135.5 to 22,490.62 ± 931.26 mg ( P < 0.001)] during 6 wk. Early treatment with enalapril significantly decreased UprV from 958.6 ± 56.7 to 600.31 ± 65.13 mg/day ( P < 0.001) and cumulative proteinuria to 12,842.37 ± 1,798.17 mg/6 wk ( P < 0.001). Similarly, early treatment with eplerenone produced a profound antiproteinuric effect: UprV decreased from 958.57 ± 56.7 to 593.38 ± 21.83 mg/day, P < 0.001, and cumulative proteinuria to 16,601.84 ± 1,334.31 mg/6 wk; P < 0.001. An additive effect was obtained when enalapril and eplerenone were combined: UprV decreased from 958.57 ± 56.69 to 424.17 ± 38.54 mg/day, P < 0.001, and cumulative protein excretion declined to 10,252.88 ± 1,011.3 mg/6 wk, P < 0.001. These antiproteinuric effects were associated with substantial preservation of glomerular nephrin and podocin. In contrast, late treatment with either enalapril or eplerenone alone or combined mildly decreased UprV and cumulative proteinuria. Thus pretreatment with eplerenone or enalapril is effective in reducing daily and cumulative protein excretion and preservation of nephrin/podocin. More profound antiproteinuric effects were obtained when enalapril and eplerenone were combined.
Gene Expression-Based Molecular Diagnostic System for Malignant Gliomas Is Superior to Histological Diagnosis
Authors: Shirahata Mitsuaki , Iwao-Koizumi Kyoko , Saito Sakae , Ueno Noriko , Oda Masashi , Hashimoto Nobuo , Takahashi Jun A. , Kato Kikuya
Published: December 2007

Purpose: Current morphology-based glioma classification methods do not adequately reflect the complex biology of gliomas, thus limiting their prognostic ability. In this study, we focused on anaplastic oligodendroglioma and glioblastoma, which typically follow distinct clinical courses. Our goal was to construct a clinically useful molecular diagnostic system based on gene expression profiling.

Experimental Design: The expression of 3,456 genes in 32 patients, 12 and 20 of whom had prognostically distinct anaplastic oligodendroglioma and glioblastoma, respectively, was measured by PCR array. Next to unsupervised methods, we did supervised analysis using a weighted voting algorithm to construct a diagnostic system discriminating anaplastic oligodendroglioma from glioblastoma. The diagnostic accuracy of this system was evaluated by leave-one-out cross-validation. The clinical utility was tested on a microarray-based data set of 50 malignant gliomas from a previous study.

Results: Unsupervised analysis showed divergent global gene expression patterns between the two tumor classes. A supervised binary classification model showed 100% (95% confidence interval, 89.4-100%) diagnostic accuracy by leave-one-out cross-validation using 168 diagnostic genes. Applied to a gene expression data set from a previous study, our model correlated better with outcome than histologic diagnosis, and also displayed 96.6% (28 of 29) consistency with the molecular classification scheme used for these histologically controversial gliomas in the original article. Furthermore, we observed that histologically diagnosed glioblastoma samples that shared anaplastic oligodendroglioma molecular characteristics tended to be associated with longer survival.

Conclusions: Our molecular diagnostic system showed reproducible clinical utility and prognostic ability superior to traditional histopathologic diagnosis for malignant glioma.
Pharmacodynamic Markers of Perifosine Efficacy
Authors: Hennessy Bryan T. , Lu Yiling , Poradosu Enrique , Yu Qianghua , Yu Shuangxing , Hall Hassan , Carey Mark S. , Ravoori Murali , Gonzalez-Angulo Ana Maria , Birch Robert , Henderson I. Craig , Kundra Vikas , Mills Gordon B.
Published: December 2007

Purpose: It is critical to develop methods to quantify the early pharmacodynamic effects of targeted therapeutics in vivo to make drug development more efficient and ensure biologically relevant dosing. Furthermore, an ability to identify patients likely to respond to targeted therapeutics would decrease the size, duration, and cost of clinical trials, resulting in more efficient translation to improved patient outcomes. Recent studies suggest that perifosine inhibits the phosphatidylinositol-3′-kinase (PI3K) pathway by preventing cell membrane recruitment of the AKT pleckstrin homology domain.

Experimental Design: A novel functional proteomics technology, reverse phase protein array, was used to establish and quantify pharmacodynamic markers of perifosine efficacy.

Results: Perifosine selectively prevents AKT recruitment to the membrane and blocks activation of downstream effectors. Perifosine inhibited breast, ovarian, and prostate cancer models. Growth inhibition was associated with apoptosis. Activation of AKT as a consequence of genomic aberrations predicted perifosine efficacy. In cell lines and xenografts, there was a highly statistically significant correlation between the degree of antitumor efficacy of different perifosine doses and quantified down-regulation of phosphorylation of AKT and of its downstream targets, particularly S6.

Conclusions: Because of a strong correlation between proportional modulation of PI3K pathway biomarkers and quantified perifosine efficacy, it is likely that early measurement of such pharmacodynamic biomarkers with reverse phase protein array will optimize selection of responding patients and guide perifosine dosing. Furthermore, PI3K pathway activation status may allow baseline selection of patients most likely to respond to perifosine alone or in combination with other therapies.
A Novel Set of DNA Methylation Markers in Urine Sediments for Sensitive/Specific Detection of Bladder Cancer
Authors: Yu Jian , Zhu Tongyu , Wang Zhirou , Zhang Hongyu , Qian Ziliang , Xu Huili , Gao Baomei , Wang Wei , Gu Lianping , Meng Jun , Wang Jina , Feng Xu , Li Yixue , Yao Xuebiao , Zhu Jingde
Published: December 2007

Purpose: This study aims to provide a better set of DNA methylation markers in urine sediments for sensitive and specific detection of bladder cancer.

Experimental Design: Fifty-nine tumor-associated genes were profiled in three bladder cancer cell lines, a small cohort of cancer biopsies and urine sediments by methylation-specific PCR. Twenty-one candidate genes were then profiled in urine sediments from 132 bladder cancer patients (8 cases for stage 0a; 68 cases for stage I; 50 cases for stage II; 4 cases for stages III; and 2 cases for stage IV), 23 age-matched patients with noncancerous urinary lesions, 6 neurologic diseases, and 7 healthy volunteers.

Results: Despite six incidences of four genes reported in 3 of 23 noncancerous urinary lesion patients analyzed, cancer-specific hypermethylation in urine sediments were reported for 15 genes (P < 0.05). Methylation assessment of an 11-gene set (SALL3, CFTR, ABCC6, HPR1, RASSF1A, MT1A, RUNX3, ITGA4, BCL2, ALX4, MYOD1, DRM, CDH13, BMP3B, CCNA1, RPRM, MINT1, and BRCA1) confirmed the existing diagnosis of 121 among 132 bladder cancer cases (sensitivity, 91.7%) with 87% accuracy. Significantly, more than 75% of stage 0a and 88% of stage I disease were detected, indicating its value in the early diagnosis of bladder cancer. Interestingly, the cluster of reported methylation markers used in the U.S. bladder cancers is distinctly different from that identified in this study, suggesting a possible epigenetic disparity between the American and Chinese cases.

Conclusions: Methylation profiling of an 11-gene set in urine sediments provides a sensitive and specific detection of bladder cancer.
Clinical and Biological Significance of Vascular Endothelial Growth Factor in Endometrial Cancer
Authors: Kamat Aparna A. , Merritt William M. , Coffey Donna , Lin Yvonne G. , Patel Pooja R. , Broaddus Russell , Nugent Elizabeth , Han Liz Y. , Landen Charles N. , Spannuth Whitney A. , Lu Chunhua , Coleman Robert L. , Gershenson David M. , Sood Anil K.
Published: December 2007

Purpose: Vascular endothelial growth factor (VEGF) is critical for angiogenesis and tumor progression; however, its role in endometrial cancer is not fully known. Therefore, we examined the clinical and therapeutic significance of VEGF in endometrial carcinoma using patient samples and an endometrioid orthotopic mouse model.

Experimental Design: Following Institutional Review Board approval, VEGF expression and microvessel density (MVD) counts were evaluated using immunohistochemistry in 111 invasive endometrioid endometrial cancers by two independent investigators. Results were correlated with clinicopathologic characteristics. For the animal model, Ishikawa or Hec-1A cancer cell lines were injected directly into the uterine horn. Therapy experiments with bevacizumab alone or in combination with docetaxel were done and samples were analyzed for markers of angiogenesis and proliferation.

Results: Of 111 endometrial cancers, high expression of VEGF was seen in 56% of tumors. There was a strong correlation between VEGF expression and MVD (P < 0.001). On multivariate analysis, stage (P = 0.04), grade (P = 0.003), VEGF levels (P = 0.03), and MVD (P = 0.037) were independent predictors of shorter disease-specific survival. In the murine model, whereas docetaxel and bevacizumab alone resulted in 61% to 77% tumor growth inhibition over controls, combination therapy had the greatest efficacy (85-97% inhibition over controls; P < 0.01) in both models. In treated tumors, combination therapy significantly reduced MVD counts (50-70% reduction over controls; P < 0.01) and percent proliferation (39% reduction over controls; P < 0.001).

Conclusions: Increased levels of VEGF and angiogenic markers are associated with poor outcome in endometrioid endometrial cancer patients. Using a novel orthotopic model of endometrioid endometrial cancer, we showed that combination of antivascular therapy with docetaxel is highly efficacious and should be considered for future clinical trials.
NKG2D-Mediated Antitumor Activity by Tumor-Infiltrating Lymphocytes and Antigen-Specific T-Cell Clones Isolated from Melanoma Patients
Authors: Maccalli Cristina , Nonaka Daisuke , Piris Adriano , Pende Daniela , Rivoltini Licia , Castelli Chiara , Parmiani Giorgio
Published: December 2007

Purpose: The role of NKG2D receptor in antitumor immunosurveillance has not been completely clarified. We addressed this issue by investigating the involvement of this receptor in tumor-specific immunologic response in melanoma patients.

Experimental Design: We determined the presence of NKG2D+ T cells among tumor-infiltrating lymphocytes (TIL) of 10 (one primary and 9 metastatic) melanoma samples and the expression of NKG2D ligands (NKG2DL) by these tumor cells. Moreover, the expression of NKG2D was assessed in a panel of antigen-specific T lymphocytes isolated from melanoma patients and the engagement of NKG2D in antitumor activity mediated by these T cells was determined.

Results: TILs located either in the periphery or within the tumor mass of melanoma samples expressed NKG2D and the expression of this receptor by T cells was retained after in vitro culture. However, NKG2DLs were weakly expressed, or not expressed, by most metastatic lesions with only the primary tumor being positive for all these molecules. In contrast, these ligands were expressed, although heterogeneously, by all in vitro established melanoma lines. Moreover, the engagement of NKG2D occurred in antitumor activity by both freshly isolated and in vitro cultured TILs. However, this receptor was involved to a different extent in the antitumor activity of antigen-specific T-cell clones.

Conclusions: These findings indicate that NKG2D+ T cells have a role in the immunologic response against tumor. Thus, new immunotherapeutic treatments for melanoma patients should be designed aimed at augmenting the NKG2D+ T lymphocyte–mediated immune response.
Depression Vulnerable and Nonvulnerable Smokers After a Failure Experience
Authors: Scott Walter D. , Beevers Christopher G. , Mermelstein Robin J.
Published: December 2007

The present study extended previous tests of cognitive priming theories of depression by examining cognitive self-regulatory, motivational, and affective functioning of depression-vulnerable and nonvulnerable individuals after a failure experience. Participants were enrolled in a clinic-based smoking cessation program that consisted of seven group meetings. Major findings show that compared to the nonvulnerable group, depression-vulnerable individuals were less motivated to quit and experienced more negative affect, but only after a failure to quit smoking. However, after controlling for actual smoking rate, depression-vulnerable individuals did not evaluate their success any more negatively, nor did they indicate lower self-efficacy for quitting. Results are discussed in terms of cognitive self-regulatory and affect temperament models of motivation and depression.
Organizational Justice and Organizational Citizenship Behavior: A Mediated Multifoci Model †
Authors: Karriker Joy H. , Williams Margaret L.
Published: December 2007

This research explores the differential effects of multifoci organizational justice perceptions on organizational citizenship behavior. Based on data collected from 217 employee—supervisor dyads, our findings clarify the bi-focal nature of distributive and procedural justice, illuminate the mono-focus of interpersonal justice, and support the premise that justice investments yield exponential behavioral responses that are sometimes mediated by the quality of the employee— supervisor relationship.
Supporting Economic Migrants in the North West of England
Authors: Pemberton Simon
Published: December 2007

This article considers the characteristics and experiences of economic migrants arriving in the UK from the `A8' Accession countries following the enlargement of the EU in 2004. Through case study analysis focused on the north west of England, the article attempts to fill gaps in knowledge of A8 migrant worker communities and their local and regional impact. This is particularly pertinent given that the vast majority of research to date in the UK has been on economic migrants in London, the East and the South East. Consequently the article focuses on the role of A8 migrants in contributing towards regional economic objectives. It is highlighted that a number of issues appear to be impacting upon the most `effective' use of skilled A8 migrant labour in the North West, including (1) recruitment and selection procedures by employers and foreign recruitment agencies and (2) language barriers and access to relevant information/support services. The implications for regional and local policies are subsequently discussed.
Towards a Viable and Just Global Nursing Ethics
Authors: Crigger Nancy J.
Published: December 2007

Globalization, an outgrowth of technology, while informing us about people throughout the world, also raises our awareness of the extreme economic and social disparities that exist among nations. As part of a global discipline, nurses are vitally interested in reducing and eliminating disparities so that better health is achieved for all people. Recent literature in nursing encourages our discipline to engage more actively with social justice issues. Justice in health care is a major commitment of nursing; thus questions in the larger sphere of globalization, justice and ethics, are our discipline's questions also. Global justice, or fairness, is not an issue for some groups or institutions, but a deeper human rights issue that is a responsibility for everyone. What can we do to help reduce or eliminate the social and economic disparities that are so evident? What kind of ethical milieu is needed to address the threat that globalization imposes on justice and fairness? This article enriches the conceptualization of globalization by investigating recent work by Schweiker and Twiss. In addition, I discuss five qualities or characteristics that will facilitate the development of a viable and just global ethic. A global ethic guides all people in their response to human rights and poverty. Technology and business, two major forces in globalization that are generally considered beneficial, are critiqued as barriers to social justice and the common good.

To turn human nature into humanity and righteousness is like turning the willow into cups and bowls.

The book of Mencius
Supporting Sexual Activity in Long-Term Care
Authors: Everett Bethan
Published: December 2007

Although nurses in almost every long-term care facility face daily challenges involving issues related to residents' sexual lives, guidelines for ethically supporting sexual activity are rare and inadequate. A decision-making framework was developed to guide care providers in responding to the sexual expression of residents in long-term care. The framework recommends that nurses should weigh the documented substantial benefits of having a sexual life against harm to the resident and others, and against offence to others. This article illustrates the use of this ethical decision-making framework by using the example of nurses supporting a resident's expression of his sexuality. It is suggested that nurses use this framework to guide their practice when related ethical issues arise.
Nurses' and Doctors' Perspectives on Slow Codes
Authors: Kelly Jacinta
Published: December 2007

The aim of this study was to ascertain nurses' and doctors' perspectives on the practice of slow codes, which are cardiopulmonary resuscitative efforts that are intentionally performed too slowly for resuscitation to occur. A Heideggerian phenomenological study was conducted in 2005, during which data were gathered in the Republic of Ireland from three nurses and two doctors (via unstructured interviews) and analysed using Colaizzi's reductive procedure. Slow codes do occur in Ireland and are intended as beneficent acts. However, slow codes were identified as pointless and undignified when intrusive measures were employed. There is a need for discussion on the topic of slow codes in Ireland, and for aids to cardiopulmonary resuscitation decision making to be developed, such as advance directives, communication training, clinical guidelines and an explanatory leaflet for patients and families.
Align, Don't Necessarily Follow
Authors: Wittmann Eveline
Published: December 2007

In the face of globalization, states around the world have tried to regain legitimacy by using a policy framework known as new public management (NPM). In education, it promises to improve quality and competitiveness, by means of increasing control over educational institutions, implementing managerial techniques and submitting educational institutions to increased competitiveness. This article presents evidence from an exploratory study comparing senior college administrators' attitudes in the Canadian province of British Columbia and those of vocational school administrators in two German subjurisdictions toward NPM. Questions addressed include: (1) how NPM-related measures were perceived by those administrators; and (2) how differences in the way reform discourses are framed in the different subjurisdictions impact the administrators' attitudes towards NPM. Findings show that the level of agreement on different aspects of NPM was comparatively similar across countries and subjurisdictions. Correlational analysis, however, revealed differences between the administrators' semantic constructions of the reform policy. Interpretive analysis indicated that semantic constructions were linked to the varying policy discourses of the subjurisdictions. The article concludes that discourse is an important aspect when introducing NPM in educational institutions, since it lays the groundwork for the conceptualization of future policy discourses.
Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood–derived mononuclear cell cultures
Authors: Liu Anquan , Claesson Hans-Erik , Mahshid Yilmaz , Klein George , Klein Eva
Published: December 2007

Epstein-Barr virus (EBV)–specific cellular memory is not transferred from mother to child. Therefore, EBV-induced B-cell proliferation in in vitro–infected cord blood mononuclear cell cultures is not inhibited. However, by addition of immunomodulators, polysaccharide K (PSK) or truncated thioredoxin (Trx80) that activate monocytes, EBV-specific T-cell response could be generated in such cultures. Presently, we demonstrate that leukotriene B4 (LTB4) is involved in the effect of the immunomodulators. LTB4 was detected in the medium, and T-cell activation was compromised by addition of leukotriene biosynthesis inhibitors. Moreover, we found that LTB4 added to infected cultures, which did not receive the immunomodulators, induced functional activation of the T cells. LTB4 activated the monocytes and acted directly on the T cells. In consequence, addition of LTB4 inhibited the EBV-induced proliferation of B lymphocytes. Specific cytotoxicity could be generated by restimulation of the T cells. The experiments showed successive stages of T-cell activation in acquisition of their immunologic effector function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors—here interferon (IFN)-γ, interleukin (IL)-15, IL-12, and LTB4. Importantly, the results indicate that endogenous LTB4 can induce T-cell activation that inhibits the EBV-induced proliferation of B lymphocytes.
Standardised PCR-based molecular epidemiology of tuberculosis
Authors: Allix-Béguec C. , Supply P. , Wanlin M. , Bifani P. , Fauville-Dufaux M.
Published: December 2007

A population-based molecular epidemiology investigation has been undertaken to evaluate tuberculosis transmission and control in the Brussels-Capital Region (Belgium).

All tuberculosis cases reported from January 2003 to December 2004 were investigated. In total, 536Mycobacterium tuberculosisisolates (89% of culture-positive samples) were genotyped by the newly standardised 24 loci-based mycobacterial interspersed repetitive unit-variable number tandem-repeat typing, spoligotyping and IS6110fingerprinting.

Of all the patients, 30% were grouped based on strain clusters, suggesting a transmission index of 20%. An unsuspected outbreak entailing ≥23 patients was evidenced by molecular typing analysis and confirmed by contact tracing. Foreign-born status accounted for 79% of the studied patients, including 37.9% illegal immigrants and asylum seekers. Among foreign-born patients, asylum seekers and illegal immigrants were significantly less abundant in strain clusters than settled residents.

Tuberculosis in the Brussels-Capital Region is a bi-faceted problem, comprising both persisting recent transmission and “imported diseases”. Molecular epidemiology based on real-time genotyping techniques has proven invaluable in better understanding tuberculosis transmission. However, it will most efficiently contribute to tuberculosis control when implemented in an integrated public health system.
Phosphodiesterase-4 inhibition attenuates pulmonary inflammation in neonatal lung injury
Authors: de Visser Y. P. , Walther F. J. , Laghmani E. H. , van Wijngaarden S. , Nieuwland K. , Wagenaar G. T. M.
Published: December 2007

Phosphodiesterase-4 (PDE4) inhibitors may offer novel therapeutic strategies in respiratory diseases, including asthma and chronic obstructive pulmonary disease. Therefore, selective PDE4 inhibitors may also provide a therapeutic option for very pre-term infants with bronchopulmonary dysplasia (BPD). The anti-inflammatory effect of two PDE4 inhibitors was investigated in a pre-term rat model of hyperoxia-induced lung injury.

Pre-term rat pups were exposed to room air, hyperoxia, or hyperoxia and one of two PDE4 inhibitors: rolipram and piclamilast. The anti-inflammatory effects of prolonged PDE4 inhibitor therapy were investigated by studying survival, histopathology, fibrin deposition, alveolar vascular leakage and differential mRNA expression (real-time RT-PCR) of key genes involved in inflammation, alveolar enlargement, coagulation and fibrinolysis.

PDE4 inhibitor therapy prolonged median survival by up to 7 days and reduced alveolar fibrin deposition, lung inflammation and vascular leakage by decreasing the influx of monocytes and macrophages and protein efflux in bronchoalveolar lavage fluid. Analysis of mRNA expression of key genes involved in experimental BPD revealed a significant PDE4 inhibitor-induced improvement of genes involved in inflammation, fibrin deposition and alveolarisation.

In conclusion, phosphodiesterase-4 inhibition prolongs survival by inhibiting inflammation and reducing alveolar fibrin deposition in pre-term rat pups with neonatal hyperoxic lung injury, whereby piclamilast outperformed rolipram.
Effectiveness of pharmacist intervention for asthma control improvement
Authors: Mehuys E. , Van Bortel L. , De Bolle L. , Van Tongelen I. , Annemans L. , Remon J. P. , Brusselle G.
Published: December 2007

Education on optimal medication use is an essential strategy to improve asthma control. The current authors investigated whether pharmacist interventions, focused on appropriate use of asthma medication and tailor-made to the patient's current asthma control, would improve asthma control in adult patients.

A 6-month randomised, controlled, parallel-group trial was conducted in 66 community pharmacies in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 94) or a pre-defined pharmacist intervention (n = 107). This intervention mainly focused on improving inhalation technique and medication adherence. Primary outcome was the level of asthma control, as assessed by the Asthma Control Test® (ACT).

Mean ACT scores did not change from baseline for both study groups. However, a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care. The intervention also reduced, for the complete study group, reliever medication use and the frequency of night-time awakenings due to asthma. Inhalation technique and adherence to controller medication were significantly better in the intervention group.

In conclusion, pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients.
Sildenafil treatment in COPD does not affect stroke volume or exercise capacity
Authors: Rietema H. , Holverda S. , Bogaard H. J. , Marcus J. T. , Smit H. J. , Westerhof N. , Postmus P. E. , Boonstra A. , Vonk-Noordegraaf A.
Published: December 2007

In chronic obstructive pulmonary disease (COPD) patients, stroke volume response to exercise is impaired. The aim of the present study was to investigate whether 3 months of sildenafil treatment improves stroke volume and, if so, whether this improvement is related to the pulmonary artery pressure and translated into an improved exercise capacity.

A total of 15 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) underwent right heart catheterisation at rest and during exercise. Stroke volume was assessed by magnetic resonance imaging (MRI) at rest and during submaximal exercise in the supine position and compared with eight age-matched controls. Additionally, a cardiopulmonary exercise test and a 6-min walking distance test were performed. Exercise tests and MRI were repeated after 12 weeks of oral therapy with 50 mg sildenafil three times daily.

Stroke volume in COPD patients was significantly lower than in healthy controls (62±12versus81±22 mL at rest and 70±15versus101±28 mL during exercise). Pulmonary hypertension (PH) was diagnosed in nine patients and was absent in six. Treatment with sildenafil had no effect on stroke volume or exercise capacity. Although the stroke volume was lower in COPD patients with associated PH in comparison with non-PH patients, there was no difference in treatment response between both groups.

In the present group of 15 chronic obstructive pulmonary disease patients, a reduced stroke volume was found at rest and during exercise. Neither stroke volume nor exercise capacity were improved by 3 months of sildenafil therapy.