bluuebunny/crossref_metadata_2025_split huggingface dataset:
The experiences of ethnic minority MSM using NHS sexual health clinics in Britain
Authors: McKeown Eamonn , Doerner Rita , Nelson Simon , Low Nicola , Robinson Angela , Anderson Jane , Elford Jonathan 
Published: June 2012

ObjectiveTo compare the experiences of ethnic minority and white British men who have sex with men (MSM) who attend NHS sexual health clinics in Britain.MethodsIn 2007–2008, a national sample of MSM living in Britain was recruited through websites, in sexual health clinics, bars, clubs and other venues. Men completed an online survey, which included questions about their experience of attending an NHS sexual health clinic.ResultsAnalysis is restricted to 363 ethnic minority MSM and 4776 white British MSM who had attended an NHS sexual health clinic in the 12 months before the survey. Compared with white British men, men from an Indian, Pakistani or Bangladeshi background were more likely to be very anxious about attending the clinic (adjusted OR (aOR) 2.58, 95% CI 1.63 to 4.07), express concerns about being overheard at reception (aOR 1.68, 95% CI 1.10 to 2.58), be uncomfortable in the waiting area (aOR 2.08, 95% CI 1.35 to 3.22) or be afraid that people in their community would find out that they have sex with men (aOR 7.70, 95% CI 4.49 to 13.22). The adjusted ORs for being afraid that people in their community would find out that they have sex with men were also elevated for black Caribbean, black African, Chinese and other Asian men.ConclusionSexual health clinics should be aware that some ethnic minority MSM, particularly those from an Indian, Pakistani or Bangladeshi background, have heightened concerns about clinic attendance and confidentiality compared with white British MSM.
Modeling contaminant transport through composite liner with a hole in the geomembrane
Authors: Rowe R. Kerry , Abdelatty Khaled 
Published: June 2012

Contaminant transport through a single hole in a geomembrane (GM) that forms part of composite liner with a geosynthetic clay liner (GCL) for applied heads (0.3 and 1 m) and an applied pressure of about 100 kPa is modeled and compared with experimental results. The system was first permeated with distilled water until a steady state was reached. The permeant was then switched to an NaCl solution. The inferred interface transmissivity at steady state (after 280 days) is about 2.3 × 10−11 m2/s for both heads examined. After 800 days permeation with an 0.14 mol/L NaCl solution, the interface transmissivity between the geomembrane and GCL was inferred to have decreased from 2.3 × 10−11 to 1.1 × 10−11 m2/s for experiments with heads of both 0.3 and 1 m. Modeling of the flow and changes in the GCL hydraulic conductivity arising from interaction between the bentonite and the 0.14 mol/L NaCl permeant is shown to give excellent agreement with the observed leakage. The differences between modeling a uniform and nonuniform interface transmissivity is found to be small — with the leakage being dominated by the interface transmissivity 0.1 to 0.15 m from the hole in the GM. Typical published values for the diffusion coefficient for both the GCL and sandy soil are shown to give good predictions of effluent concentration with time and chloride distribution in the silty sand in contact with the composite liners at the end of the test.
Failure analysis of the breached levee at the 17th Street Canal in New Orleans during Hurricane Katrina
Authors: Wang X. , Castay Mark 
Published: June 2012

The breached levee system at the 17th Street Canal has been independently studied by conducting total and effective stress analyses. Performance of the levee system during the hurricane duration was investigated with special attention focused on the formation of a gap between the levee fills and the floodwall, and on the localized shear strain in the lacustrine clay layer. In contrast to the total stress analyses conducted by the Interagency Performance Evaluation Task Force (IPET) and the Independent Levee Investigation Team (ILIT), the effective stress analysis presented in this paper considered the soil – pore water interaction, and demonstrated evidences of initiation and mobilization of the localized shear strain.
The geodynamic province of transitional lithosphere adjacent to magma-poor continental margins
Authors: Sibuet Jean-Claude , Tucholke Brian E. 
Published: June 2012

Abstract
Two different types of ‘transitional lithosphere’ have been documented along magma-poor rifted margins. One consists of apparently subcontinental mantle that has been exhumed, brittlely deformed, and serpentinized during late stages of rifting. A second is thinned (<10 km) continental crust, which in some cases is known to have been supported near sea level at least early in the rift history and thus is interpreted to reflect depth-dependent extension. In both cases, it is typically assumed that oceanic crust forms at the time that the brittle continental crust is breached or soon thereafter, and thus that transitional lithosphere has relatively limited width. Here three representative cases of transitional lithosphere are examined: one in the Newfoundland–Iberia rift and one at Goban Spur (both exhumed mantle), and one off the Angola–Congo margin (thin continental crust flanked seaward by apparently exhumed lower continental crust±exhumed mantle). Considering the geological and geophysical evidence, it appears that depth-dependent extension (riftward flow of weak lower continental crust and/or upper mantle) may be a common phenomenon on magma-poor margins and that this can result in a much broader zone of transitional lithosphere than has hitherto been assumed. Transitional lithosphere in this wide zone may consist of subcontinental mantle, lower continental crust or some combination thereof, depending on the strength profile of the pre-rift continental lithosphere. Transitional lithosphere ceases to be emplaced (i.e. ‘final break-up’ occurs) only when emplacement of heat and melt from the rising asthenosphere becomes dominant over lateral flow of the weak lower lithosphere. This model implies a two-stage break-up: first, the rupture of the brittle continental crust; and, second, the eventual separation of the ductile subcontinental lithosphere which is coincident with emplacement of normal oceanic crust. Well defined magnetic anomalies can form in transitional lithosphere that consists of highly serpentinized, exhumed mantle, and such anomalies therefore are not diagnostic of oceanic crust. Where present, the anomalies can be helpful in interpreting and dating the rifting history.
Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells
Authors: Hertwig Falk , Meyer Katharina , Braun Sebastian , Ek Sara , Spang Rainer , Pfenninger Cosima V. , Artner Isabella , Prost Gaëlle , Chen Xinbin , Biegel Jaclyn A. , Judkins Alexander R. , Englund Elisabet , Nuber Ulrike A. 
Published: June 2012

Abstract
Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381–92. ©2012 AACR.
Outcome of Patients with Platelet-Derived Growth Factor Receptor Alpha–Mutated Gastrointestinal Stromal Tumors in the Tyrosine Kinase Inhibitor Era
Authors: Cassier Philippe A. , Fumagalli Elena , Rutkowski Piotr , Schöffski Patrick , Van Glabbeke Martine , Debiec-Rychter Maria , Emile Jean-François , Duffaud Florence , Martin-Broto Javier , Landi Bruno , Adenis Antoine , Bertucci François , Bompas Emmanuelle , Bouché Olivier , Leyvraz Serge , Judson Ian , Verweij Jaap , Casali Paolo , Blay Jean-Yves , Hohenberger Peter ,   for the European Organisation for Research and Treatment of Cancer
Published: June 2012

Abstract
Purpose: Platelet-derived growth factor receptor-alpha (PDGFRA) mutations are found in approximately 5% to 7% of advanced gastrointestinal stromal tumors (GIST). We sought to extensively assess the activity of imatinib in this subgroup.
Experimental Design: We conducted an international survey among GIST referral centers to collect clinical data on patients with advanced PDGFRA-mutant GISTs treated with imatinib for advanced disease.
Results: Fifty-eight patients were included, 34 were male (59%), and median age at treatment initiation was 61 (range, 19–83) years. The primary tumor was gastric in 40 cases (69%). Thirty-two patients (55%) had PDGFRA-D842V substitutions whereas 17 (29%) had mutations affecting other codons of exon 18, and nine patients (16%) had mutation in other exons. Fifty-seven patients were evaluable for response, two (4%) had a complete response, eight (14%) had a partial response, and 23 (40%) had stable disease. None of 31 evaluable patients with D842V substitution had a response, whereas 21 of 31 (68%) had progression as their best response. Median progression-free survival was 2.8 [95% confidence interval (CI), 2.6–3.2] months for patients with D842V substitution and 28.5 months (95% CI, 5.4–51.6) for patients with other PDGFRA mutations. With 46 months of follow-up, median overall survival was 14.7 months for patients with D842V substitutions and was not reached for patients with non-D842V mutations.
Conclusions: This study is the largest reported to date on patients with advanced PDGFRA-mutant GISTs treated with imatinib. Our data confirm that imatinib has little efficacy in the subgroup of patients with D842V substitution in exon 18, whereas other mutations appear to be sensitive to imatinib. Clin Cancer Res; 18(16); 4458–64. ©2012 AACR.
ATP Citrate Lyase Knockdown Induces Growth Arrest and Apoptosis through Different Cell- and Environment-Dependent Mechanisms
Authors: Zaidi Nousheen , Royaux Ines , Swinnen Johannes V. , Smans Karine 
Published: June 2012

Abstract
ATP citrate lyase (ACLY) is a cytosolic enzyme that catalyzes generation of acetyl-CoA, which is a vital building block for fatty acid, cholesterol, and isoprenoid biosynthesis. ACLY is upregulated in several types of cancer, and its inhibition induces proliferation arrest in certain cancer cells. As ACLY is involved in several pathways, its downregulation may affect multiple processes. Here, we have shown that short hairpin RNA-mediated ACLY silencing in cell lines derived from different types of cancers induces proliferation, cell-cycle arrest, and apoptosis. However, this antiproliferative effect of ACLY knockdown was observed only when cells were cultivated under lipid-reduced growth conditions. Proliferation arrest induced by ACLY silencing was partially rescued by supplementing the media with fatty acids and/or cholesterol. This indicates that the ACLY knockdown-mediated growth arrest might be the result of either fatty acid or cholesterol starvation or both. In the absence of ACLY, the cancer cells displayed elevated expression of sterol regulatory element binding protein–regulated downstream genes involved in de novo fatty acid and cholesterol biosynthesis. Furthermore, ACLY suppression resulted in elevated expression of acyl-CoA synthetase short-chain family member 2 (ACSS2), an enzyme that also produces acetyl-CoA using acetate as a substrate. Acetate supplementation partially rescued the cancer cells from ACLY suppression–induced proliferation arrest. We also observed that the absence of ACLY enhanced ACSS2-dependent lipid synthesis. These findings provide new insights into the role of ACLY in cancer cell growth and give critical information about the effects of ACLY silencing on different pathways. This information is crucial in understanding the possible application of ACLY inhibition in cancer therapeutics. Mol Cancer Ther; 11(9); 1925–35. ©2012 AACR.
Vitamin D May Not Improve Lipid Levels
Authors: Ponda Manish P. , Huang Xiaohua , Odeh Mouneer A. , Breslow Jan L. , Kaufman Harvey W. 
Published: June 2012

Background—
Vitamin D deficiency is highly prevalent and is associated with dyslipidemia and cardiovascular disease. The impact of correcting vitamin D deficiency on blood lipids, strong cardiovascular disease prognostic factors, is unknown.

Methods and Results—

To determine relationships between 25-hydroxyvitamin D levels and lipids, we analyzed 4.06 million deidentified patient laboratory test results from September 2009 through February 2011. We performed a cross-sectional study of this population to determine associations between 25-hydroxyvitamin D levels and lipids across clinically defined strata. We also conducted a retrospective cohort study of vitamin D deficient patients to investigate how changes in 25-hydroxyvitamin D levels relate to changes in lipid levels. After exclusions, 107 811 patients with serial testing were selected for cross-sectional analysis. Compared with vitamin D deficient patients (<20 ng/mL), those with optimal levels (≥30 ng/mL) had lower mean total cholesterol (−1.9 mg/dL; 95% confidence interval [95% CI], −1.2 to −2.7;
P
<0.0001), lower low-density lipoprotein cholesterol (−5.2 mg/dL; 95% CI, −4.5 to −5.8;
P
<0.0001), higher high-density lipoprotein cholesterol (4.8 mg/dL; 95% CI, 4.5–5.0;
P
<0.0001), and lower triglycerides (−7.5 mg/dL; 95% CI, −6.2 to −8.7;
P
<0.0001). For the retrospective cohort analysis, raising vitamin D levels from <20 to ≥30 ng/mL (n=6260), compared with remaining at <20 ng/mL (n=2332), was associated with a mean increase in total cholesterol (0.77 mg/dL; 95% CI, 0.18–1.36;
P
=0.01) and high-density lipoprotein cholesterol (0.42 mg/dL; 95% CI, 0.08–0.76;
P
=0.02) but nonsignificant changes in low-density lipoprotein cholesterol (0.32 mg/dL; 95% CI, −0.01 to 0.66;
P
=0.06) and triglycerides (0.04 mg/dL; 95% CI, −2.16 to 2.23 mg/dL;
P
=0.97).

Conclusions—
Although vitamin D deficiency is associated with an unfavorable lipid profile in cross-sectional analyses, correcting for a deficiency might not translate into clinically meaningful changes in lipid concentrations; however, data from intervention trials are required to confirm these findings.
Independent Representations of Verbs and Actions in Left Lateral Temporal Cortex
Authors: Peelen Marius V. , Romagno Domenica , Caramazza Alfonso 
Published: June 2012

Abstract
Verbs and nouns differ not only on formal linguistic grounds but also in what they typically refer to: Verbs typically refer to actions, whereas nouns typically refer to objects. Prior neuroimaging studies have revealed that regions in the left lateral temporal cortex (LTC), including the left posterior middle temporal gyrus (pMTG), respond selectively to action verbs relative to object nouns. Other studies have implicated the left pMTG in action knowledge, raising the possibility that verb selectivity in LTC may primarily reflect action-specific semantic features. Here, using functional neuroimaging, we test this hypothesis. Participants performed a simple memory task on visually presented verbs and nouns that described either events (e.g., “he eats” and “the conversation”) or states (e.g., “he exists” and “the value”). Verb-selective regions in the left pMTG and the left STS were defined in individual participants by an independent localizer contrast between action verbs and object nouns. Both regions showed equally strong selectivity for event and state verbs relative to semantically matched nouns. The left STS responded more to states than events, whereas there was no difference between states and events in the left pMTG. Finally, whole-brain group analysis revealed that action verbs, relative to state verbs, activated a cluster in pMTG that was located posterior to the verb-selective pMTG clusters. Together, these results indicate that verb selectivity in LTC is independent of action representations. We consider other differences between verbs and nouns that may underlie verb selectivity in LTC, including the verb property of predication.
Ventral and Dorsal Stream Interactions during the Perception of the Müller-Lyer Illusion: Evidence Derived from fMRI and Dynamic Causal Modeling
Authors: Plewan Thorsten , Weidner Ralph , Eickhoff Simon B. , Fink Gereon R. 
Published: June 2012

Abstract
The human visual system converts identically sized retinal stimuli into different-sized perceptions. For instance, the Müller-Lyer illusion alters the perceived length of a line via arrows attached to its end. The strength of this illusion can be expressed as the difference between physical and perceived line length. Accordingly, illusion strength reflects how strong a representation is transformed along its way from a retinal image up to a conscious percept. In this study, we investigated changes of effective connectivity between brain areas supporting these transformation processes to further elucidate the neural underpinnings of optical illusions. The strength of the Müller-Lyer illusion was parametrically modulated while participants performed either a spatial or a luminance task. Lateral occipital cortex and right superior parietal cortex were found to be associated with illusion strength. Dynamic causal modeling was employed to investigate putative interactions between ventral and dorsal visual streams. Bayesian model selection indicated that a model that involved bidirectional connections between dorsal and ventral stream areas most accurately accounted for the underlying network dynamics. Connections within this network were partially modulated by illusion strength. The data further suggest that the two areas subserve differential roles: Whereas lateral occipital cortex seems to be directly related to size transformation processes, activation in right superior parietal cortex may reflect subsequent levels of processing, including task-related supervisory functions. Furthermore, the data demonstrate that the observer's top–down settings modulate the interactions between lateral occipital and superior parietal regions and thereby influence the effect of illusion strength.
Temporal Dynamics of Neural Activity at the Moment of Emergence of Conscious Percept
Authors: Noguchi Yasuki , Yokoyama Takemasa , Suzuki Megumi , Kita Shinichi , Kakigi Ryusuke 
Published: June 2012

Abstract
From which regions of the brain do conscious representations of visual stimuli emerge? This is an important but controversial issue in neuroscience because some studies have reported a major role of the higher visual regions of the ventral pathway in conscious perception, whereas others have found neural correlates of consciousness as early as in the primary visual areas and in the thalamus. One reason for this controversy has been the difficulty in focusing on neural activity at the moment when conscious percepts are generated in the brain, excluding any bottom–up responses (not directly related to consciousness) that are induced by stimuli. In this study, we address this issue with a new approach that can induce a rapid change in conscious perception with little influence from bottom–up responses. Our results reveal that the first consciousness-related activity emerges from the higher visual region of the ventral pathway. However, this activity is rapidly diffused to the entire brain, including the early visual cortex. These results thus integrate previous “higher” and “lower” views on the emergence of neural correlates of consciousness, providing a new perspective for the temporal dynamics of consciousness.
Incidental Thyroid Cancer Found during Surgery for Head and Neck Squamous Cell Carcinoma
Authors: Gilbert Mark R. , Kim Seungwon 
Published: June 2012

ObjectiveTo quantify the incidence of occult thyroid cancer encountered during neck dissection in patients with head and neck squamous cell carcinoma (HNSCC), to discuss the management of these patients, and to assess the need for further treatment of the incidentally discovered thyroid cancer.Study DesignCase series with chart review.SettingUniversity‐based tertiary care hospital.MethodsThe authors retrospectively reviewed 2538 neck dissections performed at their institution over a 15‐year period. Twenty‐nine patients had an incidental pathologic finding of thyroid cancer at surgery. The authors reviewed demographics, diagnoses, histopathology, initial and subsequent management, and outcome.ResultsWell‐differentiated thyroid cancer (WDC) was found in every case in this cohort. Fifteen patients died during the period of the study (2.4‐year follow‐up), with 14 patients still alive (4.3‐year follow‐up). Seven patients, all of whom are still alive, received further treatment for their thyroid cancer: 2 with completion thyroidectomy, 2 with I‐131 ablation, and 3 with both. There was no clinical evidence of recurrence of thyroid cancer in any of the patients who died, and none died as a result of thyroid cancer. In addition, none of the patients still alive have biopsy‐proven evidence of thyroid cancer recurrence.ConclusionNone of the patients in this cohort died as a result of their thyroid disease, and none of the patients had evidence of recurrence of their WDC during the follow‐up period. The results suggest that further management of occult WDC discovered in patients receiving neck dissections for HNSCC is not necessary.
The B-cell receptor signaling pathway as a therapeutic target in CLL
Authors: Woyach Jennifer A. , Johnson Amy J. , Byrd John C. 
Published: June 2012

AbstractTargeted therapy with imatinib and other selective tyrosine kinase inhibitors has transformed the treatment of chronic myeloid leukemia. Unlike chronic myeloid leukemia, chronic lymphocytic leukemia (CLL) lacks a common genetic aberration amenable to therapeutic targeting. However, our understanding of normal B-cell versus CLL biology points to differences in properties of B-cell receptor (BCR) signaling that may be amenable to selective therapeutic targeting. The applica-tion of mouse models has further expanded this understanding and provides information about targets in the BCR signaling pathway that may have other important functions in cell development or long-term health. In addition, overexpression or knockout of selected targets offers the potential to validate targets genetically using new mouse models of CLL. The initial success of BCR-targeted therapies has promoted much excitement in the field of CLL. At the present time, GS-1101, which reversibly inhibits PI3Kδ, and ibrutinib (PCI-32765), an irreversible inhibitor of Bruton tyrosine kinase, have generated the most promising early results in clinical trials including predominately refractory CLL where durable disease control has been observed. This review provides a summary of BCR signaling, tools for studying this pathway relevant to drug development in CLL, and early progress made with therapeutics targeting BCR-related kinases.