bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term Prognosis and Psychosocial Outcomes after Surgery for MTLE
Authors: Dupont Sophie , Tanguy Marie‐Laure , Clemenceau Stephane , Adam Claude , Hazemann Paule , Baulac Michel
Published: November 2006

Summary:  Purpose: To assess the seizure‐freedom rates and self‐perceived psychosocial changes associated with the long‐term outcome of epilepsy surgery in patients with refractory medial temporal lobe epilepsy associated with hippocampal sclerosis.

Methods: A standard questionnaire was given to 183 patients who underwent surgery between 1988 and 2004, and 110 were completed.

Results: The mean duration of follow‐up after surgery was 7 years, with a maximum of 17 years. The probability that patients were seizure‐free after surgery was dependent on the definition of the seizure freedom. For the patients who were seizure‐free since surgery (Engel's class Ia), the probability was 97.6% at 1 year after surgery, 85.2% at 2 years after surgery, 59.5% at 5 years after surgery, and 42.6% at 10 years after surgery. For the patients who still experienced rare disabling seizures after surgery but were seizure‐free at least 1 year before the time of assessment, the probability was of 97.6% at 1 year after surgery, 95% at 2 years after surgery, 82.8% at 5 years after surgery, and 71.1% at 10 years after surgery.

The psychosocial long‐term outcome, as measured by indices of driving, employment, familial and social relationships, and marital status, was similar to the psychosocial short‐term outcome. It did not depend on seizure freedom or on follow‐up time interval and was not influenced statistically by seizure frequency in cases of persisting seizures. Most but not all patients noticed a substantial overall improvement in their psychosocial condition; 48% drove (increased by 7%), 47% improved (14% worsened) in their employment status, and 68% improved (5% worsened) in their familial and social relationships. Overall, 91% of patients were satisfied with the surgery, and 92% did not regret their decision.

Conclusions: The results of this study suggest that temporal lobe surgery has real long‐term benefits. Two specific conclusions emerge: (a) the long‐term rates of freedom from seizure depend on how seizure freedom is defined, and (b) the psychosocial long‐term outcome does not change dramatically over years and does not depend on seizure freedom.
Development of Performance Indicators for the Primary Care Management of Pediatric Epilepsy: Expert Consensus Recommendations Based on the Available Evidence
Authors: Caplin Deirdre A. , Rao Jaya K. , Filloux Francis , Bale James F. , Van Orman Colin
Published: November 2006

Summary: Purpose:To use available evidence and expert consensus to develop performance indicators for the evaluation and management of pediatric epilepsy.

Methods:We used a three‐step process to develop the performance indicators. First, research findings were compiled into evidence tables focusing on different clinical issues. Second, an advisory panel of clinicians, educational and public health experts, and families of children with epilepsy reviewed the evidence. The advisory group used the evidence to draft a preliminary set of performance indicators for pediatric epilepsy management. Third, 13 internationally recognized experts in pediatric neurology or epilepsy rated the value of these indicators on a 5‐point scale [1 (essential) to 5 (not necessary)] in a two‐round Delphi process. Positive consensus was reached if ≥80% of experts gave an indicator a “1” rating and negative consensus if >80% gave an indicator a “5” rating. Indicators that achieved positive consensus during either round of the Delphi process constituted the final set of indicators.

Results:Of the 68 draft performance indicators, the expert panel members achieved positive consensus on 30 performance indicators: eight indicators related to diagnostic strategies and seizure classification, nine related to antiepileptic drug use, six related to cognitive and behavioral issues, six related to quality of life, and three related to specialty referrals.

Conclusions:We identified 30 potential indicators for evaluating the care provided to pediatric patients with epilepsy. The next step is to examine the relation of these performance indicators to clinical outcomes and health care utilization among pediatric patients with epilepsy.
Mesial Temporal Lobe Epilepsy Impairs Advanced Social Cognition
Authors: Schacher Martina , Winkler Rebecca , Grunwald Thomas , Kraemer Guenter , Kurthen Martin , Reed Victoria , Jokeit Hennric
Published: November 2006

Summary:  Purpose: Although memory, language, and executive functions have been extensively studied in patients with mesial temporal lobe epilepsy (MTLE), investigations into advanced social cognitive abilities have been neglected. In the present study, we investigated the ability to detect social faux pas and studied possible mediating clinical and demographic variables in patients with MTLE compared with patients with an epilepsy not originating within the MTLE and healthy controls.

Methods: The 27 MTLE patients (16 were investigated pre‐ and 11 postoperatively), 27 patients with an extramesiotemporal epilepsy (except frontal lobe epilepsy), and 12 healthy controls performed a shortened version of the faux‐pas test. Additionally, we used standardized tests to measure intelligence. Only patients with intact reading‐comprehension abilities were included in the study.

Results: MTLE patients, both pre‐ and postoperative, performed the faux‐pas test significantly worse than patients with extramesiotemporal lobe epilepsy and healthy controls. The latter two groups showed comparable performance. No statistical association was found between the MTLE patients' deficit in recognizing a faux pas and the variables IQ, age, age at seizure onset, and duration of epilepsy.

Conclusions: We report for the first time that patients with MTLE are specifically impaired in recognizing faux pas, suggesting that MTLE as such is a specific etiology of deficits in higher‐order social cognition.
Seizures and Antiepileptic Drugs: Does Exposure Alter Normal Brain Development?
Authors: Marsh Eric D. , Brooks‐Kayal Amy R. , Porter Brenda E.
Published: November 2006

Summary:  Seizures and antiepileptic drugs (AEDs) affect brain development and have long‐term neurological consequences. The specific molecular and cellular changes, the precise timing of their influence during brain development, and the full extent of the long‐term consequences of seizures and AEDs exposure have not been established. This review critically assesses both the basic and clinical science literature on the effects of seizures and AEDs on the developing brain and finds that evidence exists to support the hypothesis that both seizures and antiepileptic drugs influence a variety of biological process, at specific times during development, which alter long‐term cognition and epilepsy susceptibility. More research, both clinical and experimental, is needed before changes in current clinical practice, based on the scientific data, can be recommended.
State Courts, the U.S. Supreme Court, and the Protection of Civil Liberties
Authors: Howard Robert M. , Graves Scott E. , Flowers Julianne
Published: November 2006

Advocates of federalism, both in the United States and elsewhere, often cite the potential for enhanced protection of individual civil liberties as an emerging rationale for a federal system dividing governmental responsibilities between central and regional governments and central and regional judiciaries. Echoing this, some judicial officials and scholars, confronting an increasingly conservative U.S. Supreme Court, have called for state supreme courts to use the state constitutional grounds to preserve and increase the protections of the Bill of Rights. Using event count analysis, we examine state search-and-seizure cases for 1981 to 1993 to ascertain under what circumstances state courts would use this opportunity to eliminate Supreme Court review. We find that the relative ideological position of the state supreme courts and the U.S. Supreme Court often prevents, or does away with the need for, liberal courts to use the adequate and independent state grounds doctrine to expand the rights of criminal defendants and that state supreme court justices react more predictably in the assertion of constitutional protection law than the general consensus suggests.
Organizational Interpretations of Drug Test Results
Authors: Paik Leslie
Published: November 2006

The U.S. courts consistently have upheld the constitutionality of laws regarding mandatory drug testing policies in the workplace and schools; these policies were designed to detect individuals' drug use that could compromise public safety. Yet looking at the uses of drug test results in another setting—the justice system—reveals one aspect that goes largely unaddressed in these laws and prior research on drug testing: the organizational context surrounding the administration of drug tests that shapes how their results are understood. In response, this article uses ethnographic methods to analyze the ways that staff at a juvenile drug court in southern California interprets drug test results. The article demonstrates that the staff's understandings of drug testing results involve interactional and institutional processes, dependent upon meanings constructed and situated in local organizational contexts.
Regeneration of the epithelium in organ‐cultured donor corneas with extended post‐mortem time
Authors: Slettedal Jon Klokk , Lyberg Torstein , Ramstad Hanne , Beraki Kahsai , Nicolaissen Bjørn
Published: November 2006

Purpose:  The maximum post‐mortem time limit for obtaining donor corneas varies between eye banks. It is not known for how long a time the epithelial cells survive post‐mortem, nor is it known if donor corneas with extended post‐mortem time are able to regenerate the epithelium. Therefore, we wanted to examine the epithelium in donor corneas for regenerative ability during storage in an eye bank organ culture system.

Methods:  Twenty‐four paired donor corneas with post‐mortem time from 28 to 163 hr were obtained. One cornea of a pair was fixed immediately to serve as a control, and the second was cultured in eye bank medium at 32°C for 3 days. Examination of the specimens was performed with light and scanning electron microscopy. Immunohistochemical staining methods with antibodies against K 3, K 19, vimentin and p63 were used to further characterize the cells.

Results:  The control corneas showed decreasing amounts of epithelial cells with increasing post‐mortem time. All the cultured corneas demonstrated rapid regeneration of the epithelium. After 3 days in organ culture, 10 of 12 donor corneas were covered with epithelium.

Conclusion:  Even up to 7 days post‐mortem, viable cells reside in the corneal epithelium. The study demonstrates the hardiness and enormous regenerative potential of peripheral corneal cells. Donor corneas processed in an eye bank organ culture storage system will obtain an intact epithelial layer within a few days.
Hook2 Localizes to the Centrosome, Binds Directly to Centriolin/CEP110 and Contributes to Centrosomal Function
Authors: Szebenyi Györgyi , Hall Branden , Yu Rosa , Hashim Arig Ibrahim , Krämer Helmut
Published: November 2006

Centrosomes serve as microtubule‐organizing centers. However, centrosome function depends on microtubule organization and protein transport because the formation, positioning and maintenance of centrosomes require microtubule‐dependent retrograde transport. Linker proteins that associate with the motor protein dynein, organelles and microtubules facilitate loading of cargos for retrograde transport and thus contribute to the composition and placement of the centrosome and other juxtanuclear protein complexes. Members of the hook family of proteins may function as adaptors to link various organelle cargos to dynein for transport and have also been implicated directly in centrosome positioning. Here, we show that mammalian hook2, a previously uncharacterized member of the hook family, localizes to the centrosome through all phases of the cell cycle, the C‐terminal domain of hook2 directly binds to centriolin/CEP110, the expression of the C‐terminal domain of centriolin/CEP110 alters the distribution of endogenous hook2 and mislocalized wild‐type or mutant hook2 proteins perturb endogenous centrosomal and pericentrosomal proteins in cultured mammalian cells. In addition, interference with hook2 function results in the loss of the radial organization of microtubules and a defect in regrowth of microtubules following their nocodazole‐induced depolymerization. Thus, we propose that hook2 contributes to the establishment and maintenance of centrosomal structure and function.
Dynamic Interaction of HIV‐1 Nef with the Clathrin‐Mediated Endocytic Pathway at the Plasma Membrane
Authors: Burtey Anne , Rappoport Joshua Z. , Bouchet Jérôme , Basmaciogullari Stéphane , Guatelli John , Simon Sanford M. , Benichou Serge , Benmerah Alexandre
Published: November 2006

The HIV‐1 Nef protein perturbs the trafficking of membrane proteins such as CD4 by interacting with clathrin–adaptor complexes. We previously reported that Nef alters early/recycling endosomes, but its role at the plasma membrane is poorly documented. Here, we used total internal reflection fluorescence microscopy, which restricts the analysis to a ∼100 nm region of the adherent surface of the cells, to focus on the dynamic of Nef at the plasma membrane relative to that of clathrin. Nef colocalized both with clathrin spots (CS) that remained static at the cell surface, corresponding to clathrin‐coated pits (CCPs), and with ∼50% of CS that disappeared from the cell surface, corresponding to forming clathrin‐coated vesicles (CCVs). The colocalization of Nef with clathrin required the di‐leucine motif essential for Nef binding to AP complexes and was independent of CD4 expression. Furthermore, analysis of Nef mutants showed that the capacity of Nef to induce internalization and downregulation of CD4 in T lymphocytes correlated with its localization into CCPs. In conclusion, this analysis shows that Nef is recruited into CCPs and into forming CCVs at the plasma membrane, in agreement with a model in which Nef uses the clathrin‐mediated endocytic pathway to induce internalization of some membrane proteins from the surface of HIV‐1‐infected T cells.
Dopaminergic deficiency in mice with reduced levels of the dual‐specificity tyrosine‐phosphorylated and regulated kinase 1A, Dyrk1A+/−
Authors: Martinez de Lagran M. , Bortolozzi A. , Millan O. , Gispert J. D. , Gonzalez J. R. , Arbones M. L. , Artigas F. , Dierssen M.
Published: November 2006

The dual‐specificity tyrosine‐phosphorylated and regulated kinase 1A (DYRK1A) gene encodes a protein kinase known to play a critical role in neurodevelopment. Mice with one functional copy of Dyrk1A (Dyrk1A+/−) display a marked hypoactivity and altered gait dynamics in basal conditions and in novel environments. Dopamine (DA) is a key neurotransmitter in motor behavior and genetic deletion of certain genes directly related to the dopaminergic system has a strong impact on motor activity. We have studied the effects of reduced Dyrk1A expression on the function of the nigrostriatal dopaminergic system. To characterize the dopaminergic system in DYRK1A+/− mice, we have used behavioral, pharmacological, histological, neurochemical and neuroimaging (microPET) techniques in a multidisciplinary approach. Dyrk1A+/− mice exhibited decreased striatal DA levels, reduced number of DA neurons in the substantia nigra pars compacta, as well as altered behavioral responses to dopaminergic agents. Moreover, microdialysis experiments revealed attenuated striatal DA release and positron emission tomography scan display reduced forebrain activation when challenged with amphetamine, in Dyrk1A+/− compared with wild‐type mice. These data indicate that Dyrk1A is essential for a proper function of nigrostriatal dopaminergic neurons and suggest that Dyrk1A+/− mice can be used to study the pathogenesis of motor disorders involving dopaminergic dysfunction.
The Synoptic Problem and Statistics
Authors: Abakuks Andris
Published: November 2006

In New Testament studies, the gospels of Matthew, Mark and Luke are known as the synoptic gospels. They contain much common material, and this is particularly clear when their texts are laid out side by side. The gospel of John has a very different style, and there is not such a close correspondence between it and the synoptic gospels. Andris Abakuks focuses on the synoptic problem, hypotheses that attempt to explain the relationships between the synoptic gospels.
Bayes Factors
Authors: O'Hagan Tony
Published: November 2006

Bayes factors are somewhat essential to Bayesian statistics. Tony O'Hagan explains their basics.
Association of the sponge Tethya orphei (Porifera, Demospongiae) with filamentous cyanobacteria
Authors: Gaino Elda , Sciscioli Margherita , Lepore Elena , Rebora Manuela , Corriero Giuseppe
Published: November 2006

Abstract. Specimens of the sponge Tethya orphei, collected in February 2005 on the underside of coral stones on Arì Athol (Maldives), have been processed for histological and ultrastructural investigations. The cortical layer of the sponge was found to be permeated by filamentous cyanobacteria, the trichomes of which measured 45–63 μm on average and were composed of 10–14 cells. The fine organization of the filaments was consistent with their taxonomic identification as Oscillatoria spongeliae. These filaments filled the cortical region of the sponge and penetrated inward into the upper choanosomal region, where they sometimes overlapped the siliceous spicule bundles. A budding specimen of T. orphei showed that the filaments were also present in the single bud protruding from the sponge surface, demonstrating that asexual reproduction can vertically transmit these symbionts from sponge to sponge. The occurrence of filaments in all the specimens studied is consistent with the assumption that filamentous cyanobacteria are not mere intruders but mutualistic symbionts with members of T. orphei.
Systematic significance of tridentate pedicellariae in the echinoid genera Diadema and Echinothrix
Authors: Coppard Simon E. , Campbell Andrew C.
Published: November 2006

Abstract. The tridentate pedicellariae in all species of Diadema and Echinothrix recognized by Mortensen, plus species described later (to include D. palmeri and two color morphs of E. calamaris) were examined to identify diagnostic species characters, and to determine whether such characters are useful in inferring phylogenetic relationships between species. Nineteen morphological characters were measured and analyzed, and species‐specific characters were identified. The morphometric data were then transformed using gap coding and a parsimony analysis was undertaken. The resulting cladogram for the tridentate pedicellariae present in species of Diadema was compared with the mitochondrial DNA phylogeny of Lessios et al., with a good level of congruence observed. Very narrow forceps‐like tridentate pedicellariae were found to be basal among Recent species, present only in D. setosum and D. palmeri. Members of D. palmeri were found to be unique within the genus, having both the forceps‐like form and a broad form of tridentate pedicellaria. The very narrow forceps‐like form is absent in all subsequent divergent species, while the broad form of tridentate pedicellaria in D. palmeri is basal to the broad forms in D. antillarum, D. mexicanum, D. paucispinum, and both the broad and narrow forms of tridentate pedicellaria of D. savignyi. The greatest similarity was found between the broad forms of tridentate pedicellaria in D. antillarum and D. mexicanum. These species were also found to have narrow forms of tridentate pedicellaria that showed a reasonable level of association to one another and to the rostrate form in D. ascensionis. Since the work of Mortensen, D. ascensionis has been shown, using mitochondrial DNA, to be nested within D. antillarum. The results of this study show that the tridentate pedicellaria in D. ascensionis are distinctly different from all other forms within the genus, to the extent that they belong to a rostrate subclass. This indicates that, among Diadema species, the tridentate pedicellariae are one of the first morphological characters to diverge in genetically isolated populations. Unlike the tridentate pedicellariae in Diadema, the different forms of tridentate pedicellariae in E. calamaris and E. diadema showed a stronger association intraspecifically than between forms interspecifically. The small forms of tridentate pedicellaria of the white and brown color morphs in E. calamaris showed a high level of association, while the large forms showed only a moderate association, far lower than would be expected between color morphs of the same species. This suggests that they are either subspecies or recently diverged separate species. This study demonstrates the taxonomic value contained within the characters of the tridentate pedicellariae for both differentiating species (even subspecies) and inferring phylogenetic relationships between species.
The iron K feature in narrow line Seyfert 1 galaxies: evidence for a P Cygni profile?
Authors: Done Chris , Sobolewska Małgorzata A. , Gierliński Marek , Schurch Nicholas J.
Published: November 2006

Narrow line Seyfert 1 galaxies are generally accreting at high fractions of the Eddington limit. They can show complex X-ray spectra, with a strong ‘soft excess’ below 2 keV and a sharp drop at ∼7 keV. There is strong evidence linking the soft excess to either reflection or absorption from relativistic, partially ionized material close to the black hole. The reflection models can also simultaneously produce the 7-keV feature from fluorescent iron Kα line emission from the disc. Here we show that absorption can also produce a sharp feature at 7 keV from the P Cygni profile which results from absorption/scattering/emission of He- and H-like iron Kα resonance lines in the wind. We demonstrate this explicitly by fitting the iron feature seen in XMM–Newton data from 1H 0707-495 to a P Cygni profile. The resulting column and ionization required to produce this feature are probably larger than those needed to produce the soft excess. Nonetheless, the absorbing material could still be a single structure with stratified ionization such as that produced by the ionization instability.
Synthesis of Novel Peptide Inhibitors of Thrombin‐induced Platelet Activation
Authors: Burke Fernanda M. , Warnock Mark , Schmaier Alvin H. , Mosberg Henry I.
Published: November 2006

Inhibitors of the activation of platelet aggregation have promise as important therapeutic agents for the management of acute coronary syndrome (ACS). Platelet activation by thrombin, a serine protease, occurs by binding to and cleavage of the extracellular N‐terminal domains of protease‐activated receptors 1 and 4 (PAR1 and PAR4). The proteolysis of the PARs exposes new tethered ligands that then signal through transmembrane domains to initiate platelet activation as a downstream effect. A pentapeptide cleavage product of bradykinin with the sequence Arg‐Pro‐Pro‐Gly‐Phe serves as a thrombin inhibitor by blockingα‐ andγ‐thrombin‐induced platelet aggregation. Analogs of RPPGF have been prepared that result in improved inhibition of thrombin activation of platelets. Specific amino acid residues required for activity against platelet aggregation have been identified, and a lead compound, rOicPaPhe(p‐Me)‐NH2(FM19), has been developed.FM19, which completely inhibits thresholdγ‐thrombin‐induced platelet aggregation at a concentration of 16 ± 4 μm, represents an important lead compound in the development of inhibitors of thrombin‐mediated platelet aggregation for treatment of ACS.
Convenient Method for Monitoring Aβ Aggregation by Quartz‐Crystal Microbalance
Authors: Okuno Hiroaki , Mori Kanae , Jitsukawa Tomofumi , Inoue Hiromi , Chiba Shinya
Published: November 2006

We have found that a quartz‐crystal microbalance is a facile and useful tool for detecting the specific aggregation of the amyloid‐β peptides responsible for Alzheimer's disease. This method greatly reduces the time and samples (corresponds to 1 Hz frequency decrease per 30 pg mass increase on a 4.9 mm2 electrode) that are needed in the aggregation assay, and is also applicable to molecular interactions between smaller amyloid‐β fragment peptides such as the pentapeptide KLVFF.
1.5 Generation Internal Migration in the U.S.: Dispersion from States of Immigration?
Authors: Ellis Mark , Goodwin-White Jamie
Published: November 2006

The issue of immigrant spatial concentration and the possibilities for immigrant dispersion through migration features in at least three interrelated debates about immigration. First, the ethnic enclave literature centers on the question of whether spatial concentration improves or harms the economic well-being of immigrants. Second, spatial assimilation theory links immigrant relocation away from residential enclaves to socioeconomic gains. Although framed at an intra-urban scale, we suggest that similar assimilation logics infuse thinking and expectations about immigrant settlement and spatial mobility at other scales. And third, immigrant clustering links to anxieties about the threats posed by non-European origin newcomers to the traditional cultural fabric of the nation. In the current wave of immigration, research on questions of settlement geography and spatial mobility has so far been restricted to the first generation. But as the current wave of immigration matures there is a growing population of adults who are the children of immigrants. This article investigates the migration behavior of these adult children, specifically the 1.5 generation, seeking to answer the question of whether they will remain in the states in which their parent's generation settled or move on. It also assesses whether the out-migration response of the 1.5 generation in states of immigrant concentration is similar to that of their parent's generation or the U.S.-born population.
Focal metatarsal sinus tracts in a Weimaraner successfully managed with ciclosporin
Authors: Oliveira A. M. , Obwolo M. J. , Van Den Broek A. H. M. , Thoday K. L.
Published: November 2006

Focal metatarsal sinus tracts (‘fistulation’) are, to the authors knowledge, reported for the first time in a Weimaraner. The six‐year‐old, entire male had a five‐month history of two symmetrical, well‐demarcated sinuses on the plantar aspect of each metatarsus. The area surrounding each pair of sinuses was slightly fluctuant and a serosanguineous discharge could be expressed. Cytological examination of the discharge was characteristic of pyogranulomatous inflammation. Bacterial culture showed the material to be sterile. Examination of a skin biopsy revealed a severe inflammatory reaction involving the dermal collagen, with an infiltrate of neutrophils, macrophages, lymphocytes, plasma cells and multi‐nucleated giant cells, with some micro‐pustule formation. Treatment with ciclosporin induced total remission. Reduction of the dose of ciclosporin resulted in recurrence of the physical signs with further remission on re‐introduction of the original dosage. This is the first report of the use of ciclosporin to control this condition.
Partial tarsal arthrodesis and botulinum toxin A injection for correction of tarsal arthrogryposis in a cat
Authors: Bright S. R. , Girling S. L. , O’Neill T. , Innes J. F.
Published: November 2006

An 11‐week‐old, domestic shorthair cat was presented for evaluation of a congenital right tarsal deformity. The cat was non‐weightbearing lame on the right hindlimb. There was severe tarsal hyperextension and concurrent spasticity/contracture/shortening of the gastrocnemius muscle‐tendon. The cat was otherwise healthy. Radiographically there was luxation of the proximal intertarsal joint and talocrural hyperextension. Treatment with 10 mu/kg botulinum toxin A (Botox; Allergan) intramuscular injections directly into the gastrocnemius muscle and passive physiotherapy marginally improved the range of motion in the talocrural joint. Definitive surgical treatment with partial tarsal arthodesis produced an excellent clinical outcome. This case report demonstrates the successful treatment of a severe congenital tarsal abnormality and also documents the first clinical use of botulinum toxin in a feline patient.
Gene Expression Pattern in Human Brain Endothelial Cells in Response to
Neisseria meningitidis
Authors: Schubert-Unkmeir Alexandra , Sokolova Olga , Panzner Ursula , Eigenthaler Martin , Frosch Matthias
Published: November 2006

To extend our knowledge of target proteins in endothelial cells infected with the meningitis-causing pathogen
Neisseria meningitidis
, we characterized the interaction between the bacterial and human brain microvascular endothelial cell (HBMEC) monolayers. By use of human cDNA microarrays, transcriptional analysis revealed distinct responses to 4 and 8 h of infection. We also addressed the question of whether the major virulence factor of meningococci, i.e., the capsule, influences the host cell response. Of the 1,493 (at 4 h postinfection) and 1,246 (at 8 h postinfection) genes with altered expression upon bacterial contact, about 49.4% and 45%, respectively, depended on capsule expression. In particular, we identified an increase of expression for genes encoding proteins involved in bacterial adhesion and invasion. High levels of apoptosis-related gene (
bad
,
bak
,
asp
, and immediate-early response gene 1) expression could also be detected in infected cells. Further analyses confirmed that HBMECs displayed several hallmarks of apoptosis in response to
N. meningitidis
infection, namely, phosphatidylserine translocation and activation of caspase 3 and AMP-activated protein kinase α. Moreover, several differentially regulated genes not previously known to respond to meningococcal infection were identified. Of these, genes encoding cell adhesion proteins (CD44, CD98, and CD99), genes involved in downstream signaling of integrins (integrin-linked kinase, mitogen-activated protein kinase kinase 1, and mitogen-activated protein kinase kinase kinase 10) as well as negative regulators of these pathways (dual-specificity phosphatases 1, 5, and 14 and G protein pathway suppressor 2), and genes involved in cytoskeleton reorganization (those encoding Arp2/3, p34-arc, actinin alpha 1, vasodilatator-stimulated protein, and Wiskott-Aldrich syndrome protein) were the most prominent. This global transcriptional analysis creates a new platform for further molecular and cellular analysis of the interaction between
N. meningitidis
and target cells.
Perceptions of industry responsibility and tobacco control policy by US tobacco company executives in trial testimony
Authors: Chaiton Michael , Ferrence Roberta , LeGresley Eric
Published: November 2006

Objective:Trial testimony from the United States provides a unique opportunity to examine strategies of the American tobacco industry. This paper examines congruence between the arguments for tobacco control policy presented by representatives of the American tobacco industry at trial and the stages of responsibility associated with corporate social responsibility principles in other industries.

Data sources:Trial testimony collected and coded by the Deposition and Trial Testimony Archive (DATTA).

Study selection:All available testimony was gathered from representative senior staff from major tobacco companies: Brown & Williamson, Philip Morris, RJ Reynolds, and Liggett.

Data extraction:Transcripts from each witness selected were collected and imported in text format into WinMax, a qualitative data program. The documents were searched for terms relating to tobacco control policies, and relevant terms were extracted. A hand search of the documents was also conducted by reading through the testimony. Inferred responsibility for various tobacco control policies (health information, second-hand smoking, youth smoking) was coded.

Data synthesis:The level of responsibility for tobacco control policy varied according to the maturity of the issue. For emerging issues, US tobacco company representatives expressed defensiveness while, for more mature issues, such as youth smoking, they showed increased willingness to deal with the issue. This response to social issues is consistent with corporate social responsibility strategies in other industries.

Conclusion:While other industries use corporate social responsibility programmes to address social issues to protect their core business product, the fundamental social issue with tobacco is the product itself. As such, the corporate nature of tobacco companies is a structural obstacle to reducing harm caused by tobacco use.
“Stay away from them until you’re old enough to make a decision”: tobacco company testimony about youth smoking initiation
Authors: Wakefield Melanie , McLeod Kim , Perry Cheryl L
Published: November 2006

Objective:To determine common themes used by US tobacco industry witnesses pertaining to youth smoking initiation during litigation in the United States.

Methods:Qualitative thematic analysis of transcripts from 29 tobacco litigation cases dating from 1992 to 2002.

Results:Youth smoking is portrayed by the tobacco industry as a source of great concern to them. Youth smoking prevention programmes developed by US tobacco companies are supposedly intended to delay decision-making about smoking until age 18, when individuals are then seen to be of an age where they are able to “choose to smoke”. Tobacco industry media campaigns, youth access, community and school-based programmes are predicated on peer influence, parental factors, and commercial access being the primary influences on youth smoking uptake, rather than tobacco marketing, inaccurate risk appraisal, price and other factors known to influence youth smoking. Despite substantial financial investment in tobacco industry programmes, their witnesses were able to describe only weak evaluation methods, being preoccupied with measures of message comprehension, programme reach and uptake, and the associated costs of their efforts, rather than any evaluation designed to assess effects on youth smoking behaviour.

Conclusion:Stated concerns about youth smoking and youth smoking prevention programmes are put forward in litigation as evidence that the tobacco industry is “serious” about tackling youth smoking, and serve as a primary strategy to improve the tobacco industry’s public image. The tobacco industry’s evaluation of the effectiveness of their youth smoking prevention programmes is demonstrably insufficient under current public health evaluation standards. Public health and welfare agencies should avoid engagement with tobacco industry-sponsored programmes.
Historians’ testimony on “common knowledge” of the risks of tobacco use: a review and analysis of experts testifying on behalf of cigarette manufacturers in civil litigation: Table 1
Authors: Kyriakoudes Louis M
Published: November 2006

A qualitative analysis of the trial and deposition testimony of professional historians who have testified on behalf of the tobacco industry shows that defence historians present a view of past knowledge about tobacco in which the public was frequently warned that cigarettes were both deadly and addictive over the broad historical period. While defence historians testify to conducting significant levels of independent research, they also draw upon a common body of research conducted by industry counsel to support its litigation efforts. Defence historians unduly limit their research materials, ignoring industry records and, therefore, critically undermine their ability to evaluate industry activity in the smoking and health controversy as it unfolded in historical time. A consequence is that defence historians present a skewed history of the cigarette in which the tobacco industry all but ceases to exist.
The association of retail promotions for cigarettes with the Master Settlement Agreement, tobacco control programmes and cigarette excise taxes
Authors: Loomis Brett R , Farrelly Matthew C , Mann Nathan H
Published: November 2006

Background:Retail stores are the primary medium for marketing cigarettes to smokers in the US. The prevalence and characteristics of cigarette retail advertising and promotions have been described by several investigators. Less is known about the proportion of cigarette sales occurring as part of a retail promotion and about the effects of tobacco control policies on cigarette promotions.

Objective:To estimate the effect of the Master Settlement Agreement (MSA), state tobacco control programme funding and cigarette taxes on retail promotions for cigarettes in supermarkets in the US.

Outcome measures:Proportion of cigarette sales occurring under a retail promotion and the value of multipack promotions (eg, buy one pack, get one pack free) and cents-off promotions, measured using scanner data in supermarkets from 50 retail market areas from 1994 to 2004.

Results:Promoted cigarette sales have increased significantly since the MSA (p<0.01), and are higher in market areas with high tobacco control programme funding (p<0.01) and high cigarette tax (p<0.01). The value of a multipack promotion is higher since the MSA (p<0.01) and in market areas with high cigarette tax (p<0.01). The value of a cents-off promotion is negatively related to the MSA (p<0.01), with mixed results for tobacco control programme funding (p<0.05), and is unassociated with tax.

Conclusions:Higher promoted cigarette sales and increased promotional values in market areas with strong tobacco control policies, compared with market areas with weaker tobacco control policies, may partially offset the decline in smoking achieved in those areas.
Tobacco manufacturers’ defence against plaintiffs’ claims of cancer causation: throwing mud at the wall and hoping some of it will stick
Authors: Milberger Sharon , Davis Ronald M , Douglas Clifford E , Beasley John K , Burns David , Houston Thomas , Shopland Donald
Published: November 2006

Background:In the late 1990s and the early part of this decade, the major US cigarette manufacturers admitted, to varying degrees, that smoking causes cancer and other diseases.

Objective:To examine how tobacco manufacturers have defended themselves against charges that their products caused cancer in plaintiffs in 34 personal injury lawsuits, all but one of which were litigated between the years 1986 and 2003.

Methods:Defence opening and closing statements, trial testimony, and depositions for these cases were obtained from the Tobacco Deposition and Trial Testimony Archive (http://tobaccodocuments.org/datta/). All available defence-related transcripts from these cases were reviewed and a content analysis was conducted to identify common themes in the defendants’ arguments.

Results:After review of the transcripts, defendants’ arguments were grouped into seven categories: (1) there is no scientific proof that cigarette smoking causes lung cancer; (2) the plaintiff did not have lung cancer as claimed; (3) the plaintiff had a type of lung cancer not associated with cigarette smoking; (4) the plaintiff had cancer that may have been associated with cigarette smoking or smokeless tobacco use, but tobacco products were not to blame in this particular case; (5) the plaintiff had cancer that may have been associated with cigarette smoking, but the defendant’s cigarette brands were not to blame; (6) the defendant’s cigarettes (or smokeless tobacco) may have played a role in the plaintiff’s illness/death, but other risk factors were present that negate or mitigate the defendant’s responsibility; and (7) the defendant’s cigarettes may have been a factor in the plaintiff’s illness/death, but the plaintiff knew of the health risks and exercised free will in choosing to smoke and declining to quit. Use of the argument that smoking is not a proven cause of lung cancer declined in frequency during and after the period when tobacco companies began to publicly admit that smoking causes disease. Corresponding increases occurred over time in the use of other arguments (namely, presence of other risk factors and “free will”).

Conclusions:Despite the vast body of literature showing that cigarette smoking causes cancer, and despite tobacco companies’ recent admissions that smoking causes cancer, defendants used numerous arguments in these cases to deny that their products had caused cancer in plaintiffs. The cigarette companies, through their public admissions and courtroom arguments, seem to be saying, “Yes, smoking causes lung cancer, but not in people who sue us”.
Finite element modeling of transient saline hydrothermal fluids in multifaulted sedimentary basins: implications for ore-forming processes
Authors: Yang Jianwen
Published: November 2006

A finite element algorithm is presented to simulate fully coupled transient fluid flow, heat, and solute transport in discretely fractured porous media, and yield the regional-scale free thermohaline convection patterns for the McArthur Basin in northern Australia. Numerical results indicate that salinity variation throughout the basin has an important influence on fluid migration and the thermal regime. The spatial and temporal distribution of saline fluids can either promote or impede free convection. Relatively saline conditions (10 wt.%) at the basin floor favour free convection; whereas, high salinities at depth suppress the development of convective hydrothermal systems. When salinity increases with depth, a higher geothermal gradient is required to induce and maintain significant fluid circulation. The implication is that sedimentary-exhalative ore deposits are more easily formed when evaporation first produces surface brines, and then these brines sink and displace pore waters in the basin.
Evidence for a second species of the ichthyosaur Platypterygius in North America: a new record from the Loon River Formation (Lower Cretaceous) of northwestern Canada
Authors: Maxwell E E , Caldwell M W
Published: November 2006

To date, all Cretaceous ichthyosaur material from North America has been referred to the species Platypterygius americanus. This species is generally identified based on skull and paddle morphology, but all non-diagnostic material from North America has been assigned to this species. A new Lower Cretaceous ichthyosaur from the Loon River Formation at Hay River, Northwest Territories, Canada, is described here. The specimen in question consists of the anterior portion of a large ichthyosaur, of which only the pectoral girdle is well preserved. It is assignable to Platypterygius, but is inconsistent with P. americanus based on paddle morphology. It shares most similarities with European and Australian species; unfortunately, it cannot be definitively assigned to any one taxon because of poor preservation of the skull. This specimen increases our knowledge of the diversity of North American Cretaceous ichthyosaurs, and suggests that the Cretaceous Western Interior Seaway was capable of sustaining a large taxonomic diversity of these marine reptiles, similar to the high numbers of Platypterygius species known from Europe.
A new geological framework for the Middle Ordovician Carillon Formation (uppermost Beekmantown Group, Ottawa Embayment): onset of Taconic foreland deposition and tectonism within the Laurentian platform interior
Authors: Dix George R , Rodhan Zuhor Al
Published: November 2006

The Carillon Formation underlies the Ottawa Embayment, a craton-interior extension of the regional Laurentian paleoshelf, defined today by the Ottawa–Bonnechere Graben. Facies within the embayment during the Middle Ordovician identify a mixed-sediment (carbonate, siliciclastic), tide-influenced, peritidal and schizohaline basin, host to a mosaic of dolomitic tidal mudflats, shallow lagoons or ponds, and channels. Skeletal metazoans were rare, but bioturbation increased with episodic influx of less saline water carrying sand and mud, possibly in response to regional climate change. Stratigraphic analysis reveals that the formation coincides with a third-order eustatic sea level cycle, but higher order stratigraphic patterns show no obvious eustatic link. Instead, a stepwise onlap geometry coincided with local faulting that produced widespread syndepositional sediment deformation. In particular, stages of faulting and post-Carillon erosion are mapped along the present-day trace of a northwest–southeast-oriented lineament, the Gloucester Fault, within the present graben. Other present-day northwest–southeast-oriented faults of the graben may also possess Middle Ordovician histories. Platform-interior tectonism and development of the Carillon Formation coincided with the onset of Taconic deformation along the outer paleoshelf (western Newfoundland). The formation defines the initial stage of foreland basin sedimentation in the embayment. Platform-interior faulting identifies a predisposed structural weakness associated with underlying Neoproterozoic structure, possibly enhanced by a regional structural connection (an ocean-to-onland transform fault system) with the distal (~1200 km), convergent, plate boundary.
Improving T Cell Therapy for Cancer
Authors: Leen Ann M. , Rooney Cliona M. , Foster Aaron E.
Published: November 2006

Adoptive transfer of antigen-specific T lymphocytes is a powerful therapy for the treatment of opportunistic disease and some virus-associated malignancies such as Epstein-Barr virus–positive post-transplant lymphoproliferative disease. However, this strategy has been less successful in patients with nonviral cancers owing to their many and varied immune evasion mechanisms. These mechanisms include downregulation of target antigens and antigen-presenting machinery, secretion of inhibitory cytokines, and recruitment of regulatory immune cells to the tumor site. With increased understanding of the tumor microenvironment and the behavior and persistence of ex vivo–manipulated, adoptively transferred T cells, two novel approaches for increasing the efficacy of T cell therapy have been proposed. The first involves genetic modification of tumor-specific T cells to improve their biological function, for example by augmenting their ability to recognize tumor cells or their resistance to tumor-mediated immunosuppression. The second requires modifications to the host environment to improve the homeostatic expansion of infused T cells or to eliminate inhibitory T cell subsets. In this review, we discuss current, promising strategies to improve adoptive T cell therapy for the treatment of cancer.
Intracellular Targets of Matrix Metalloproteinase-2 in Cardiac Disease: Rationale and Therapeutic Approaches
Authors: Schulz Richard
Published: November 2006

A new paradigm of matrix metalloproteinase-2 (MMP-2) action in the heart undergoing oxidative stress has emerged. Although best known for its role in the proteolysis of extracellular protein targets, MMP-2 is also localized to the sarcomere within the cardiomyocyte. Oxidative stress activates full-length MMP-2 without need for proteolytic processing and inactivates an endogenous inhibitor, tissue inhibitor of metalloproteinase-4. MMP-2 proteolyzes specific targets within the cell to cause acute, reversible contractile dysfunction. Inhibitors of MMPs are discussed and their possible use for the therapy of acute heart injury caused by oxidative stress is examined.
Effect of Nitridation on Ge/HfO2 Interface
Authors: Garg Reenu , Misra D. , Guha Supratik
Published: November 2006

Effect of Ge surface nitridation, prior to HfO2 deposition, on Ge/HfO2 interface has been studied using low temperature measurements. C-V characteristics at room temperature show significant dispersion in nitrided devices compared to non-nitrided devices as a function of frequency. Electron trapping is found to be dominant as temperature was reduced to 140K. Estimated activation energies in nitrided and non-nitrided devices indicate that surface nitridation is introducing new trap levels in bulk oxide. Constant voltage stress shows hole trapping being dominant in non-nitrided devices. In nitrided devices, effect of both hole and electron trapping is observed at higher stress level and higher charge injection.