bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Tinnitus With a Customized, Dynamic Acoustic Neural Stimulus: Underlying Principles and Clinical Efficacy
Authors: Hanley Peter J. , Davis Paul B.
Published: July 2008

Tinnitus has been challenging to treat with consistently positive results. The Neuromonics Tinnitus Treatment is a newly available approach to the treatment of clinically significant, problematic tinnitus (and reduced sound tolerance) that was developed with the intention of simultaneously addressing the auditory, attentional, and emotional processes underlying the condition. It uses a prescribed acoustic stimulus, customized for each patient's individual audiometric profile, which provides a broad frequency stimulus to address the effects of auditory deprivation, promotes relief and relaxation with the intention of reducing engagement of the limbic system/amygdala and autonomic nervous system, and applies the principles of systematic desensitization to address the attentional processes. This article describes the underlying principles behind this approach. It also summarizes evidence for clinical efficacy from controlled clinical studies and from a private practice clinical setting, where it has been shown to provide consistently positive outcomes for patients meeting suitability criteria.
NOTES: Transvaginal for Cancer Diagnostic Staging: Preliminary Clinical Application
Authors: Zorrón Ricardo , Soldan Monica , Filgueiras Marcos , Maggioni Luis Carlos , Pombo Luciana , Lacerda Oliveira Andre
Published: July 2008

Laparoscopy is now a reliable method for staging gastrointestinal cancer, orienting the therapy, and avoiding unnecessary laparotomy. Natural orifice transluminal endoscopic surgery (NOTES) is an emerging concept with potential advantages for patient recovery. The first case of clinical diagnostic application of transvaginal NOTES for diagnostic cancer staging is presented. Informed consent and Institutional Commission approval were obtained for transvaginal clinical trials. On February 28, 2007, a patient with elective surgical indication for diagnostic cancer staging was submitted to transvaginal NOTES procedure, and intra- and postoperative parameters were documented. In a 50-year-old female patient presenting with ascitis, diffuse abdominal pain, and weight loss for 2 months, diagnosis of peritoneal carcinomatosis was suspected, which was also found when a CT scan was performed. Transvaginal NOTES was used for diagnostic staging of the patient, using a colonoscope introduced into the abdomen through a small incision in the vagina. Biopsies of liver, diaphragm, ovaries, and peritoneum were successfully performed. Operative time was 105 min, vaginal access and closure was obtained in 15 min. Abdominal inventory was reliable, and all 16 biopsies taken were positive for ovarian adenocarcinoma. The patient was dismissed 48 hours after the procedure without complications. Recent literature and experience of the study group suggest possibilities for preliminary clinical applications by transvaginal natural orifice surgery for diagnostic purposes.
Walking and Bicycling to School: A Review
Authors: Sirard John R. , Slater Megan E.
Published: July 2008

Walking and bicycling (active commuting) to school has been proposed as a strategy for increasing youth physical activity and decreasing the prevalence of overweight. Citations for this review were retrieved through PubMed, Transport, ERIC, and ISI database searches using relevant keywords (1975 to March 2007), government and organization Web sites, and bibliographic citations. This review presents (1) prevalence estimates for active commuting to school; (2) the correlates of active commuting to school, presented using a new conceptual framework; (3) the associations between active commuting to school and health (ie, physical activity, weight status, environmental); and (4) a summary of the findings and recommendations for further research. Considerable heterogeneity exists among the reviewed studies for sample size and demographics, the methods used to measure active commuting, and the definition used to identify a positive case (active commuter). In general, active commuting to school is much less prevalent in the United States compared with European countries. A wide range of correlates of active commuting to school have been studied (individual to policy level). Active commuters tend to be more active than nonactive commuters, although no difference in weight status was observed in most studies. More research is needed to corroborate these findings and build on the knowledge base so that effective walk-to-school interventions can be implemented independently or as part of other health promotion efforts, including physician counseling for physical activity.
A study of adsorption and absorption mechanisms of copper in palygorskite
Authors: Cai Y. F. , Xue J. Y.
Published: July 2008

Desorption experiments performed on four Cu-adsorbed palygorskites suggest that the leached Cu2+ ion originates at the surface and/or net-like interstice of the palygorskite fibres. The leached fraction, calculated from the quantities of adsorbed Cu2+ before and after desorption, is <1%. This may indicate that the majority of Cu is in inaccessible structural sites. X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared (FTIR) spectroscopy and electron spin resonance (ESR) were used to determine the mineralogical character of the Cu-adsorbed palygorskite. Two photoelectron lines at 932.5 and/or 933.7 eV in the narrow scan Cu 2p3/2 spectra show that Cu adsorbed on the surface of palygorskite is in the Cu+ and Cu2+ state. The stretching vibrations of the octahedral cation shift ~3–5 cm–1 towards a greater wavenumber in the FTIR spectra of Cu-adsorbed palygorskite. It can be deduced that the Cu2+ is trapped in the channel of the palygorskite structure. The ESR spectra of the palygorskite give g values of 2.34, 2.12, 2.08 and 2.05, suggesting that some Cu ions cannot be reached by H+. These results confirm that Cu is adsorbed by palygorskite via three possible mechanisms: (1) the Cu is adsorbed onto the surface or in a net-like interstice, and its oxidation states are +1 and +2; (2) Cu forms a complex ion – [Cu(H2O)4]2+ or [Cu(H2O)6]2+, and is trapped in the channel; or (3) Cu enters into the hexagonal channel of the tetrahedral sites or the unoccupied octahedral sites of palygorskite.
Dickite in shallow oil reservoirs from Recôncavo Basin, Brazil: diagenetic implications for basin evolution
Authors: De Bona J. , Dani N. , Ketzer J. M. , De Ros L. F.
Published: July 2008

Fluvial and aeolian sandstones of the Sergi Formation are the most important reservoirs of the Recôncavo Basin, Brazil. Optical and scanning electron microscopy, X-ray diffraction and infrared spectroscopy revealed the occurrence of dickite, a clay mineral indicative of deep burial conditions (T >100ºC), in the shallow Buracica (630–870 m) and Água Grande (1300–1530 m) oilfields. Vermicular dickite replaces K-feldspar and plagioclase grains, and fills intra- and inter-granular pores. Its vermicular habit is a product of pseudomorphic kaolinite transformation during burial. The presence of dickite is in accordance with the intensity of compaction, post-compactional quartz cementation and δ18O values of calcite cements (T up to 109ºC). These petrological features of deep burial, as well as apatite fission-track analyses, indicate that uplift and erosion of at least 1 km, and probably >1500 m, affected the central part of the Recôncavo Basin and possibly the entire region. This uplift has not been detected previously by conventional structural and stratigraphic models.
Contrasting alteration processes in hydrothermally altered dolerites from the Betic Cordillera, Spain
Authors: Jiménez-Millán J. , Abad I. , Nieto F.
Published: July 2008

Dolerites from the Sierra de San Pedro (Betic Cordillera, southern Spain) develop three main types of microsystems during hydrothermal alteration: (1) centimetre-sized veins cross-cutting the dolerites; (2) microfractures in feldspar and diopside grains; and (3) alterations involving primary-igneous mafic phyllosilicate grains. The vein and microfracture sites developed alteration assemblages of randomly oriented smectites (saponite and beidellite) and halloysite. At these sites, the alteration mechanism was governed by complete dissolution of the parent material with subsequent crystallization of the products, with no parent-mineral crystallographic control. Pseudomorphed mafic phyllosilicate sites are characterized by oriented complex mineral assemblages made of chlorite, chlorite/smectite mixed layers, corrensite, saponite and relicts of biotite. These assemblages formed during the initial high-temperature stage of the hydrothermal process. In these microsites, the alteration sequence was controlled by the parent-mineral structure and chemistry, with products determined by structural relations with the parent phyllosilicate. Alteration of one phyllosilicate to the next most stable proceeds via interstratification of the parent and product phyllosilicates.
Physicochemical properties of talc ore from Pout-Kelle and Memel deposits (central Cameroon)
Authors: Nkoumbou C. , Villieras F. , Barres O. , Bihannic I. , Pelletier M. , Razafitianamaharavo A. , Metang V. , Yonta Ngoune C. , Njopwouo D. , Yvon J.
Published: July 2008

Physicochemical properties of representative samples from talc deposits discovered at Pout-Kelle and Memel in Cameroon have been investigated using a variety of techniques. The data allow the study of the mineral crystal-chemistry, chemical and modal compositions, grain size distribution, textures and surface heterogeneity, and morphometric characteristics. As a result, we found that talc (platy or round, Fe-rich) prevails (65–90%) over Cr-chlorite (7–26%), halloysite, chromite, rutile, brucite and magnesite. Chemically, talc ores are made up of SiO2, MgO, Fe2O3 and minor Al2O3. Mode values range from 50 to 55 μm at Memel and from 30 to 90 μm at Pout-Kelle. Specific surface areas measured by BET and t-plot methods range from 1.3 to 2.5 m2/g. The large values of morphometric characteristics are indicative of high crystallinity and platiness. Potential uses of these talc ores in the rubber, plastics and paper industries require beneficiation processes. Interestingly, the Memel deposit and most zones of the Pout-Kelle deposit are free of needle-shaped crystals, an advantage for environmental safety.
TLR agonists regulate alloresponses and uncover a critical role for donor APCs in allogeneic bone marrow rejection
Authors: Taylor Patricia A. , Ehrhardt Michael J. , Lees Christopher J. , Panoskaltsis-Mortari Angela , Krieg Arthur M. , Sharpe Arlene H. , Murphy William J. , Serody Jonathan S. , Hemmi Hiroaki , Akira Shizuo , Levy Robert B. , Blazar Bruce R.
Published: July 2008

Cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODNs) are synthetic ODNs with unmethylated DNA sequences that mimic viral and bacterial DNA and protect against infectious agents and tumor challenge. We show that CpG ODNs markedly accelerated graft-versus-host disease (GVHD) lethality by Toll-like receptor 9 (TLR9) ligation of host antigen-presenting cells (APCs), dependent upon host IFNγ but independent of host IL-12, IL-6, or natural killer (NK) cells. Imaging studies showed significantly more green fluorescent protein–positive (GFP+) effector T cells in lymphoid and nonlymphoid organs. In engraftment studies, CpG ODNs promoted allogeneic donor bone marrow (BM) rejection independent of host IFNγ, IL-12, or IL-6. During the course of these studies, we uncovered a previously unknown and critical role of donor BM APCs in modulating the rejection response. CpG ODNs promoted BM rejection by ligation of donor BM, but not host, TLR9. CpG ODNs did not impair engraftment of TLR9−/− BM unless wild-type myeloid (CD11b+) but not B-lineage (CD19+) BM cells were added to the donor inoculum. The importance of donor BM APCs in modulating the strength of the host antidonor rejection response was underscored by the finding that B7-1/B7-2−/− BM was less likely than wild-type BM to be rejected. Collectively, these data offer new insight into the mechanism of alloresponses regulating GVHD and BM rejection.
The Mll partial tandem duplication: differential, tissue-specific activity in the presence or absence of the wild-type allele
Authors: Dorrance Adrienne M. , Liu Shujun , Chong Anita , Pulley Benjamin , Nemer David , Guimond Martin , Yuan Weifeng , Chang Dennis , Whitman Susan P. , Marcucci Guido , Caligiuri Michael A.
Published: July 2008

The partial tandem duplication of MLL (MLL-PTD) is found in 5% to 10% of patients with acute myeloid leukemia (AML) and normal cytogenetics. Its expression in leukemic blasts is coincident with a silenced wild-type (WT) MLL allele. We therefore generated mice expressing the Mll-PTD in the absence of Mll-WT. These MllPTD/− mice die at birth unlike the normal life expectancy of MllPTD/WT, MllWT/−, and MllWT/WT mice. Using MllWT/WT fetal liver cells (FLC) as baseline, we compared MllPTD/− with MllPTD/WT FLC and found both had increased HoxA gene expression and granulocyte-macrophage colony-forming progenitor cells (CFU-GM); in contrast, only MllPTD/WT FLC had increased pluripotent hemopoietic progenitors (CFU-GEMM). The similarities between MllPTD/WT and MllPTD/− mice suggest that the Mll-PTD mutation can up-regulate target genes in a dominant, gain-of-function fashion. The differences between these 2 genotypes suggest that in select tissues the Mll-PTD requires cooperation with the Mll-WT in the genesis of the observed abnormality.
High-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE)
Authors: Chamberlain Alanna M. , Folsom Aaron R. , Heckbert Susan R. , Rosamond Wayne D. , Cushman Mary
Published: July 2008

We determined prospectively the risk of venous thromboembolism (VTE) in relation to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC) study and 4559 participants of the Cardiovascular Health Study (CHS). In addition, we determined the risk of VTE in relation to baseline subfractions of HDL (HDL2 and HDL3) and apolipoprotein A-I (apoA-I) in 14 488 participants of the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from 1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years in women; however, there was no apparent trend of VTE incidence across HDL-c quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c quartiles (with quartile 4 as the reference) were nonsignificant for both sexes and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC study, there was no trend of VTE hazard ratios across quartiles of HDL2, HDL3, or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.
Properties of a store-operated nonselective cation channel in airway smooth muscle
Authors: Helli P. B. , Janssen L. J.
Published: July 2008

Passive depletion of internal Ca2+stores in airway smooth muscle (ASM) activates nonselective cation channels (NSCCs) that mediate capacitative Ca2+entry. However, the single channel properties of these cation channels have yet to be resolved and their regulation by cytosolic Ca2+levels ([Ca2+]i) still remains unclear.

NSCC currents and changes in [Ca2+]iduring passive depletion of internal Ca2+stores were monitored in isolated bovine tracheal myocytes.

Loading cells with 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetracetic acid acetyl methyl ester (BAPTA-AM) to reduce [Ca2+]iand thereby deplete the store augmented a basal Gd3+- and La3+-sensitive, Ca2+-permeable NSCC current. This current mimics that which is evoked by store depletion using the sarcoplasmic reticulum Ca2+pump inhibitor cyclopiazonic acid (which concurrently and transiently elevates [Ca2+]i). Both interventions activated an ∼25-pS NSCC with properties identical to both spontaneous (basal) and BAPTA-AM-evoked single channel currents.

In summary, the present study provides novel evidence that a lanthanide-sensitive, 25-pS nonselective cation channel underlies both basal and store depletion-evoked membrane currents in airway smooth muscle and that this conductance likely contributes to the regulation of resting [Ca2+]iand capacitative Ca2+entry.
Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in COPD
Authors: Chappell S. , Daly L. , Morgan K. , Guetta-Baranes T. , Roca J. , Rabinovich R. , Lotya J. , Millar A. B. , Donnelly S. C. , Keatings V. , MacNee W. , Stolk J. , Hiemstra P. S. , Miniati M. , Monti S. , O’Connor C. M. , Kalsheker N.
Published: July 2008

The genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are poorly understood. Many candidate genes have been proposed, including enzymes that protect the lung against oxidative stress, such as microsomal epoxide hydrolase (EPHX1) and glutamate-cysteine ligase (GCL). To date, most reported findings have been for EPHX1, particularly in relation to functional variants associated with fast and slow metabolism of epoxide intermediates. The present study aimed to identify any association of variation in these genes with COPD susceptibility or severity.

In total, 1,017 white COPD patients and 912 nondiseased age and sex matched smoking controls were genotyped for six single nucleotide polymorphisms (SNPs) in EPHX1 (including the fast and slow variants and associated haplotypes), and eight SNPs in the two genes encoding GCL. GCL is a rate-limiting enzyme in the synthesis of glutathione, a major contributor to anti-oxidant protection in the lung.

No association of variation was found in EPHX1 or GCL with susceptibility to COPD or disease severity.

This is the largest reported study to date and is well powered to detect associations that have been previously suggested. The current data indicate that these genetic variants are unlikely to be related to susceptibility or disease severity in white chronic obstructive pulmonary disease patients.
Happiness to be gained in paediatric asthma care
Authors: Flapper B. C. T. , Duiverman E. J. , Gerritsen J. , Postema K. , van der Schans C. P.
Published: July 2008

The aim of the present study was to establish the efficacy in terms of morbidity and health-related quality of life (HRQoL) of a group asthma education-exercise programme to children with low (below 10th percentile value) quality-of-life scores.

A controlled, randomised, open, clinical trial was conducted. In total, 36 out of 53 unhappy children, among 204 (68%) respondents, treated in four paediatric practices, enrolled (mean age 10 yrs; range: 8–12 yrs), after random allocation in control and intervention groups (child, parent, teacher). Measurements were taken at baseline (T0) and after 3, 6 (T6) and 9 months (T9; intervention group only at 9 months). All but four controls completed the study.

From T0–T6, changes (Δ) in HRQoL were clinically important and significantly greater in the intervention group than in the control group, both for generic HRQoL (effect size (ES) 0.95; Δ 16%±12%versus-1±4%) and for asthma-specific HRQoL (ES 0.58; Δ 15%±17%versus1.5±14%). T9 measurements were consistent with T6 findings. Changes in sick days (ES 0.78), oral prednisone courses (ES 0.71) and doctor visits (ES 0.74) over a 6-month period were greater in the intervention group than in the control group. Changes could not be ascribed to change in lung function or medication.

In unhappy children, quality of life and morbidity may improve with a low intensity asthma education-exercise programme, even without gains in pulmonary function or exercise tolerance.
Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice
Authors: Tajima S. , Bando M. , Ishii Y. , Hosono T. , Yamasawa H. , Ohno S. , Takada T. , Suzuki E. , Gejyo F. , Sugiyama Y.
Published: July 2008

Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress.

Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg·kg−1of BLM. Edaravone (300 mg·kg−1) was administered by intraperitoneal administration 1 h before BLM challenge.

Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E2concentration in BALF on day 2.

In summary, edaravone was shown to inhibit lung injury and fibrosisviathe repression of lipid hydroperoxide production and the elevation of prostaglandin E2production in the present experimental murine system.
Phylogeny and biogeography of African Murinae based on mitochondrial and nuclear gene sequences, with a new tribal classification of the subfamily
Authors: Lecompte Emilie , Aplin Ken , Denys Christiane , Catzeflis François , Chades Marion , Chevret Pascale
Published: July 2008

Background

Within the subfamily Murinae, African murines represent 25% of species biodiversity, making this group ideal for detailed studies of the patterns and timing of diversification of the African endemic fauna and its relationships with Asia. Here we report the results of phylogenetic analyses of the endemic African murines through a broad sampling of murine diversity from all their distribution area, based on the mitochondrial cytochrome b gene and the two nuclear gene fragments (IRBP exon 1 and GHR).

Results

A combined analysis of one mitochondrial and two nuclear gene sequences consistently identified and robustly supported ten primary lineages within Murinae. We propose to formalize a new tribal arrangement within the Murinae that reflects this phylogeny. The diverse African murine assemblage includes members of five of the ten tribes and clearly derives from multiple faunal exchanges between Africa and Eurasia. Molecular dating analyses using a relaxed Bayesian molecular clock put the first colonization of Africa around 11 Mya, which is consistent with the fossil record. The main period of African murine diversification occurred later following disruption of the migration route between Africa and Asia about 7–9 Mya. A second period of interchange, dating to around 5–6.5 Mya, saw the arrival in Africa ofMus(leading to the speciose endemicNannomys), and explains the appearance of several distinctive African lineages in the late Miocene and Pliocene fossil record of Eurasia.

Conclusion

Our molecular survey of Murinae, which includes the most complete sampling so far of African taxa, indicates that there were at least four separate radiations within the African region, as well as several phases of dispersal between Asia and Africa during the last 12 My. We also reconstruct the phylogenetic structure of the Murinae, and propose a new classification at tribal level for this traditionally problematic group.
A method for visualizing surface-exposed and internal PfEMP1 adhesion antigens in Plasmodium falciparum infected erythrocytes
Authors: Bengtsson Dominique , Sowa Kordai M , Salanti Ali , Jensen Anja TR , Joergensen Louise , Turner Louise , Theander Thor G , Arnot David E
Published: July 2008

Background

The insertion of parasite antigens into the host erythrocyte membrane and the structure and distribution ofPlasmodium falciparumadhesion receptors on that membrane are poorly understood. Laser scanning confocal microscopy (LSCM) and a novel labelling and fixation method have been used to obtain high resolution immuno-fluorescent images of erythrocyte surface PfEMP1 and internal antigens which allow analysis of the accumulation of PfEMP1 on the erythrocyte membrane during asexual development.

Methods

A novel staining technique has been developed which permits distinction between erythrocyte surface PfEMP1 and intracellular PfEMP1, in parasites whose nuclear material is exceptionally well resolved. Primary antibody detection by fluorescence is carried out on the live parasitized erythrocyte. The surface labelled cells are then fixed using paraformaldehyde and permeabilized with a non-ionic detergent to permit access of antibodies to internal parasite antigens. Differentiation between surface and internal antigens is achieved using antibodies labelled with different fluorochromes and confocal microscopy

Results

Surface exposed PfEMP1 is first detectable by antibodies at the trophozoite stage of intracellular parasite development although the improved detection method indicates that there are differences between different laboratory isolates in the kinetics of accumulation of surface-exposed PfEMP1.

Conclusion

A sensitive method for labelling surface and internal PfEMP1 with up to three different fluorochromes has been developed for laser scanning confocal optical microscopy and the analysis of the developmental expression of malaria adhesion antigens.
Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer
Authors: Anglim Paul P , Galler Janice S , Koss Michael N , Hagen Jeffrey A , Turla Sally , Campan Mihaela , Weisenberger Daniel J , Laird Peter W , Siegmund Kimberly D , Laird-Offringa Ite A
Published: July 2008

Background

Lung cancer is the leading cause of cancer death in men and women in the United States and Western Europe. Over 160,000 Americans die of this disease every year. The five-year survival rate is 15% – significantly lower than that of other major cancers. Early detection is a key factor in increasing lung cancer patient survival. DNA hypermethylation is recognized as an important mechanism for tumor suppressor gene inactivation in cancer and could yield powerful biomarkers for early detection of lung cancer. Here we focused on developing DNA methylation markers for squamous cell carcinoma of the lung. Using the sensitive, high-throughput DNA methylation analysis technique MethyLight, we examined the methylation profile of 42 loci in a collection of 45 squamous cell lung cancer samples and adjacent non-tumor lung tissues from the same patients.

Results

We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25, TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection, this eight-locus panel showed 95.6% sensitivity and specificity.

Conclusion

We have identified 22 DNA methylation markers for squamous cell lung cancer, several of which have not previously been reported to be methylated in any type of human cancer. The top eight markers show great promise as a sensitive and specific DNA methylation marker panel for squamous cell lung cancer.
Examining warfarin underutilization rates in patients with atrial fibrillation: Detailed chart review essential to capture contraindications to warfarin therapy
Authors: Srivastava Ajay , Hudson Michael , Hamoud Ihab , Cavalcante Joao , Pai Chetan , Kaatz Scott
Published: July 2008

Introduction

Atrial fibrillation affects an estimated 2.5 million Americans and incurs an average annual stroke risk of 4.5% per year. Despite warfarin reducing stroke risk by approximately 66%, prior studies show warfarin usage rates to be about 50%. However, the methods that define warfarin as "inappropriate underutilization" might not be sensitive enough to pick up relative contraindications. We assessed the inappropriate underutilization of warfarin in atrial fibrillation patients at our hospital by abstracting individual patient charts.

Methods

Medical records were reviewed to determine stroke risk factors, warfarin use, and documented contraindications to warfarin use in 364 consecutive patients with atrial fibrillation.

Results

Amongst 364 atrial fibrillation patients, 54.6% received warfarin anticoagulation. Overall, 29.5 % of patients had documented reasons for not prescribing warfarin. Primary reasons listed by treating physicians included: gastrointestinal bleed 10.7%, secondary/transient atrial fibrillation 8.2%, and fall risk 6.3%. Only 7.1% of the patients had no documented reasons for the lack of warfarin use.

Conclusion

Consistent with previous reports, 45.4% of patients in this atrial fibrillation cohort were not prescribed warfarin. However, after reviewing medical charts for documented reasons why warfarin was not used, the inappropriate underutilization rate was only 7.1%. These findings suggest that studies utilizing administrative database and ICD-9 CM coding might overestimate warfarin underutilization.
Altered behavior and digestive outcomes in adult male rats primed with minimal colon pain as neonates
Authors: Wang Jing , Gu Chunping , Al-Chaer Elie D
Published: July 2008

Background

Neonatal colon irritation (CI; pain or inflammation) given for 2 weeks prior to postnatal day 22 (PND22), causes long-lasting functional disorders in rats that can be seen 6 months after the initial insult. This study looked at the effect of varying the frequency and duration of neonatal CI on the rate of growth, digestive outcomes, exploratory activity, and colon and skin sensitivity in adult rats.

Methods

Male Sprague-Dawley rats were given CI using repeated colorectal distension (CRD) at different time intervals and for varying durations starting at PND 8, 10 or 14. Control rats were handled by the investigator without any intracolonic insertion. Further experiments were done on adult rats. Digestive outcomes (food and water consumption, fecal and urinary outputs) were measured using metabolic cages. Exploratory behavior was measured using digital video tracking in an open field. Cutaneous sensitivity was assessed by measuring the responses to mechanical and heat stimuli applied to the shaved abdomen or hind paws. Visceral sensitivity was measured by recording electromyographic responses, under light isoflurane anesthesia, from the external oblique muscles in response to CRD.

Results

No significant weight differences were observed between CI and control rats. Exploratory behavior was reduced in rats with neonatal CI compared to control. Digestive outputs and somatic and visceral sensitivity changed between different treatment groups with earlier and more frequent insults yielding a higher deviation from normal.

Conclusion

The diversity of behavioral and digestive symptoms in these rats parallels the diversity of symptoms in patients with functional gastrointestinal disorders and is consistent with global plastic changes affecting more than one system in the organism.
A retrospective evaluation of patients switched from buprenorphine (subutex) to the buprenorphine/naloxone combination (suboxone)
Authors: Simojoki Kaarlo , Vorma Helena , Alho Hannu
Published: July 2008

Background

In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred ("forced transfer") their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003.

Methods

Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer.

Results

Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting "nothing" with any euphoria, or that it was a bad experience.

Conclusion

We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone.
A monoclonal antibody marker for the exclusion-zone filaments of Trypanosoma brucei
Authors: Bonhivers Mélanie , Landrein Nicolas , Decossas Marion , Robinson Derrick R
Published: July 2008

Background

Trypanosoma brucei is a haemoflagellate pathogen of man, wild animals and domesticated livestock in central and southern Africa. In all life cycle stages this parasite has a single mitochondrion that contains a uniquely organised genome that is condensed into a flat disk-like structure called the kinetoplast. The kinetoplast is essential for insect form procyclic cells and therefore is a potential drug target. The kinetoplast is unique in nature because it consists of novel structural proteins and thousands of circular, interlocking, DNA molecules (kDNA). Secondly, kDNA replication is critically timed to coincide with nuclear S phase and new flagellum biogenesis. Thirdly, the kinetoplast is physically attached to the flagellum basal bodies via a structure called the tripartite attachment complex (TAC). The TAC consists of unilateral filaments (within the mitochondrion matrix), differentiated mitochondrial membranes and exclusion-zone filaments that extend from the distal end of the basal bodies. To date only one protein, p166, has been identified to be a component of the TAC.

Results

In the work presented here we provide data based on a novel EM technique developed to label and characterise cytoskeleton structures in permeabilised cells without extraction of mitochondrion membranes. We use this protocol to provide data on a new monoclonal antibody reagent (Mab 22) and illustrate the precise localisation of basal body-mitochondrial linker proteins. Mab 22 binds to these linker proteins (exclusion-zone filaments) and provides a new tool for the characterisation of cytoskeleton mediated kinetoplast segregation.

Conclusion

The antigen(s) recognised by Mab 22 are cytoskeletal, insensitive to extraction by high concentrations of non-ionic detergent, extend from the proximal region of basal bodies and bind to the outer mitochondrial membrane. This protein(s) is the first component of the TAC exclusion-zone fibres to be identified. Mab 22 will therefore be important in characterising TAC biogenesis.
Comparative analysis reveals signatures of differentiation amid genomic polymorphism in Lake Malawi cichlids
Authors: Loh Yong-Hwee E , Katz Lee S , Mims Meryl C , Kocher Thomas D , Yi Soojin V , Streelman J Todd
Published: July 2008

Background

Cichlid fish from East Africa are remarkable for phenotypic and behavioral diversity on a backdrop of genomic similarity. In 2006, the Joint Genome Institute completed low coverage survey sequencing of the genomes of five phenotypically and ecologically diverse Lake Malawi species. We report a computational and comparative analysis of these data that provides insight into the mechanisms that make closely related species different from one another.

Results

We produced assemblies for the five species ranging in aggregate length from 68 to 79 megabase pairs, identified putative orthologs for more than 12,000 human genes, and predicted more than 32,000 cross-species single nucleotide polymorphisms (SNPs). Nucleotide diversity was lower than that found among laboratory strains of the zebrafish. We collected around 36,000 genotypes to validate a subset of SNPs within and among populations and across multiple individuals of about 75 Lake Malawi species. Notably, there were no fixed differences observed between focal species nor between major lineages. Roughly 3% to 5% of loci surveyed are statistical outliers for genetic differentiation (FST) within species, between species, and between major lineages. Outliers for FST are candidate genes that may have experienced a history of natural selection in the Malawi lineage.

Conclusion

We present a novel genome sequencing strategy, which is useful when evolutionary diversity is the question of interest. Lake Malawi cichlids are phenotypically and behaviorally diverse, but they appear genetically like a subdivided population. The unique structure of Lake Malawl cichlid genomes should facilitate conceptually new experiments, employing SNPs to identity genotype-phenotype association, using the entire species flock as a mapping panel.
Drift and Ductility Estimates in Regular Steel MRF Subjected to Ordinary Ground Motions: A Design-Oriented Approach
Authors: Karavasilis Theodore L. , Bazeos Nikitas , Beskos Dimitri E.
Published: July 2008

A simple procedure to estimate drift and ductility demands of regular steel frame buildings subjected to ordinary (i.e., without near fault effects) ground motions is described. Given the strength reduction (or behavior) factor, the procedure provides reliable estimates of the maximum roof displacement, the maximum interstorey drift ratio and the maximum rotation ductility along the height of the structure. The strength reduction factor refers to the point of the development of the first plastic hinge in the building and thus, pushover analysis and estimation of the overstrength factor are not required. This important feature enables both the rapid seismic assessment of existing structures and the direct deformation-controlled seismic design of new ones. The derivation of the proposed relations is based on regression analysis of the results of thousands of nonlinear time history analyses of steel frames. A comparison of the proposed method with the procedures adopted in current seismic design codes reveals the efficiency of the former.
Seismic Response of 2-D Semi-Sine Shaped Hills to Vertically Propagating Incident Waves: Amplification Patterns and Engineering Applications
Authors: Kamalian Mohsen , Jafari Mohammad Kazem , Sohrabi-Bidar Abdollah , Razmkhah Arash
Published: July 2008

This paper presents the most important results of an extensive numerical parametric study on seismic behavior of two-dimensional semi-sine shaped hills subjected to vertically propagating incident SV and P waves. The medium is assumed to have a linear elastic constitutive behavior. All calculations are executed in time-domain using the direct boundary element method. Clear perspectives of the amplification patterns of the hill are presented by investigation of the frequency-domain responses. It is shown that wave length, site geometry and in a less order of importance, wave type and material parameters, are the independent key parameters governing the hill's amplification pattern. Some preliminary simple equations and tables are presented which could be used as useful starting estimates to account for topography in seismic microzonation studies as well as seismic design of structures located on the hill.
Effect of Elastomeric Snubber Properties on Seismic Response of Vibration-Isolated Mechanical Equipment: An Experimental Study
Authors: Fathali Saeed , Filiatrault André
Published: July 2008

Earthquake-simulator experiments were conducted on a liquid centrifugal chiller supported by four isolation/restraint systems with built-in elastomeric snubbers. The test plan incorporated variations of input motion amplitudes and snubber properties to investigate their effect on three response quantities: peak dynamic forces induced into the snubbers, peak acceleration, and peak relative displacement response of the equipment. The elastomeric snubbers limited the displacement responses of the vibration-isolated equipment at the expense of excessive dynamic forces and amplification of the equipment acceleration response. The snubber gap size was the most influential property on the response quantities. For high-amplitude input motions, all the response quantities increased with an increase of the gap size. Due to the compressibility of the snubber elastomeric contact-surface, the actual gap size was always larger than the nominal gap size. Even with a nominal gap size less than 0.25 in., the seismic response of the equipment was substantially different from the seismic response of rigidly mounted equipment. Compared to snubbers with constant contact-surface, snubbers with expanding contact-surface resulted in lower dynamic forces. The thicker and softer contact-surface could lower the dynamic forces induced into the snubbers but resulted in larger relative displacement response of the equipment.
The Role of Remote Sensing in Earthquake Science and Engineering: Opportunities and Challenges
Authors: Rathje Ellen M. , Adams Beverley J.
Published: July 2008

Earthquake science and engineering are experience-driven fields in which lessons are learned after each significant earthquake. Remote sensing represents a suite of technologies that can play a significant role in documenting the effects of earthquakes and lead to important developments in our understanding of earthquakes. This paper describes current remote sensing technologies and the experience to date in using them in earthquake studies. The most promising activities that may benefit from remote sensing data products are identified, as well as the challenges that may impede the widespread use of remote sensing in earthquake studies. A comprehensive review of the use of remote sensing to document the effects of the 2003 Bam, Iran earthquake is presented, and recommendations for future developments in remote sensing in the context of earthquake science and engineering are provided.
Earthquake-induced Transient Ground Strains from Dense Seismic Networks
Authors: Paolucci Roberto , Smerzini Chiara
Published: July 2008

Earthquake-induced transient ground strains are evaluated based on the records obtained by two dense seismic networks, namely the Parkway Valley, New Zealand, and the UPSAR, California, arrays. The calculations are based on the spatial interpolation of the recorded displacements and a numerical differentiation to obtain the strain tensor at ground surface. The computed peak ground strains show an important dependence on azimuth, by a factor of about two. Furthermore, the relationship of the peak ground strains as a function of the most common measures of ground motion severity, such as peak ground acceleration, velocity and displacement, is explored. Our results are in reasonable agreement with other published relationships and with some of the few available direct records of strain. However, they point out the limitations of the simplified evaluations used in the engineering practice, which uniquely consider the wave passage effect on the ground strain evaluation, and tend to significantly underestimate the observations.
Two-Dimensional Nonlinear Earthquake Response Analysis of a Bridge-Foundation-Ground System
Authors: Zhang Yuyi , Conte Joel P. , Yang Zhaohui , Elgamal Ahmed , Bielak Jacobo , Acero Gabriel
Published: July 2008

This paper presents a two-dimensional advanced nonlinear FE model of an actual bridge, the Humboldt Bay Middle Channel (HBMC) Bridge, and its response to seismic input motions. This computational model is developed in the new structural analysis software framework OpenSees. The foundation soil is included to incorporate soil-foundation-structure interaction effects. Realistic nonlinear constitutive models for cyclic loading are used for the structural (concrete and reinforcing steel) and soil materials. The materials in the various soil layers are modeled using multi-yield-surface plasticity models incorporating liquefaction effects. Lysmer-type absorbing/transmitting boundaries are employed to avoid spurious wave reflections along the boundaries of the computational soil domain. Both procedures and results of earthquake response analysis are presented. The simulation results indicate that the earthquake response of the bridge is significantly affected by inelastic deformations of the supporting soil medium due to lateral spreading induced by soil liquefaction.
Health Economists' Views of Health Policy
Authors: Morrisey Michael A. , Cawley John
Published: July 2008

This article reports the views of a national survey of U.S. health economists on a series of questions ranging from mergers among health care providers to the profits of pharmaceutical manufacturers to fundamental health care reform. We find a high degree of agreement on issues of fact but considerable disagreement on issues that depend on values. Additional research may help to resolve some remaining disagreement about issues of fact but may do little to resolve disagreement over values. Results from this fall 2005 survey are compared with those from surveys conducted in 1989 and 1995.
Administrative “Health Courts” For Medical Injury Claims: The Federal Constitutional Issues
Authors: Elliott E. Donald , Narayan Sanjay A. , Nasmith Moneen S.
Published: July 2008

Our article analyzes whether the federal government may constitutionally supplant a traditional system of common-law trials before state judges and juries with new federal institutions designed by statute for compensating victims of medical injuries. Specifically, this article examines the federal constitutional issues raised by various proposals to replace traditional medical malpractice litigation in state courts with a federal system of administrative “health courts.” In doing so, we address the following constitutional issues:

Is there federal authority to preempt state law (the commerce clause and spending clause issues)? May jurisdiction be created in non - article 3 tribunals, and may claims be decided without trial by jury (the separation of powers and Seventh Amendment issues)? Would pilot programs that require some claims to be pursued in a federal administrative forum while other claimants are left to pursue traditional state tort law remedies be constitutional (the equal protection issue)?

The article concludes that a federal compensation system through administrative health courts should be constitutional provided the statute is appropriately drafted and that appropriate factual findings are made concerning the benefits to patients and the public as well as to doctors and their insurers.
Federal Administrative Health Courts Are Unconstitutional: A Reply to Elliott, Narayan, and Nasmith
Authors: Widman Amy , Hochberg Francine A.
Published: July 2008

This commentary responds to the essay by Elliott, Narayan, and Nasmith wherein they propose that the federal government may preclude plaintiffs with medically inflicted injuries from bringing state common-law tort claims against those whose negligence caused their injury. The administrative system championed by Elliott and other proponents is a radical departure from the current civil justice system. Specifically, we argue that the administrative health courts, as proposed, violate the commerce clause, the spending clause, the Seventh Amendment, and separation of powers principles. The commentary concludes that such a system is fatally flawed and cannot withstand constitutional scrutiny. Moreover, we are not persuaded that Congress will be able to ground such a radical constitutional restructuring in any sound public policy, as the majority of studies do not evidence Elliott, Narayan, and Nasmith's presumption that the civil justice system has failed in the medical malpractice context.