bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface observations of active normal fault propagation: implications for growth
Authors: MOREWOOD N. C. , ROBERTS G. P.
Published: October 2008

Abstract:
Geomorphological, sedimentological and structural observations demonstrate the rates of lateral propagation at both ends of the South Alkyonides Fault, a major active normal fault in the Gulf of Corinth, Greece. These data are used to study the temporal evolution of the displacement/length ratio of the fault. The South Alkyonides Fault has a surface trace of 38 km and a cumulative throw of 2.5–3.0 km. Palaeoseismology and geodesy show that the South Alkyonides Fault has a maximum displacement rate of 2.6–4.7 mm a
−1
. Lateral propagation of the South Alkyonides Fault has systematically beheaded drainage, forming footwall wind gaps and enclosed hanging-wall basins. Dated marine and terrestrial sediments allow estimation of the timing of wind gap formation and rates of lateral propagation of the South Alkyonides Fault. The western and eastern ends of the South Alkyonides Fault have been propagating at 12.1–16.7 mm a
−1
since
c.
0.33 Ma and <3.7 mm a
−1
since 1.36 Ma, respectively. The summed rate of lateral propagation is 15.8–20.4 mm a
−1
. The value for the ratio of displacement rate-to-lateral propagation rate (0.13–0.30) over the last several hundred thousand years is higher than the ratio of cumulative displacement/length (0.07–0.12). Lateral propagation may have slowed relative to the displacement rate through time.
Incipient continental collision and plate-boundary curvature: Late Pliocene–Holocene transtensional Hellenic forearc, Crete, Greece
Authors: ten Veen Johan H. , Kleinspehn Karen L.
Published: October 2008

Geodynamic controls on Late Pliocene–Holocene kinematics of the Hellenic forearc are assessed using the fan–deltaic basin fill of the Messaras forearc basin of south–central Crete. Previously unrecognized 070° sinistral faults developed in wrench-dominated transtension with strike-slip:normal-slip ratios of 10:1 to 100:1. Coeval folds developed in proximity to the 070° sinistral faults during deposition of the Galini Formation, making them candidates to have developed in transtension, and new chronostratigraphic and
87
Sr/
86
Sr data constrain the age of initial sinistral transtension and associated folding to
c
. 3.4 Ma. Sinistral fault activity continued through Late Holocene time based on the ages of displaced units with implications for seismic hazards in central Crete. The Messaras structural assemblages are symptomatic of the regional-scale Hellenic forearc with Plio-Pleistocene basins both offshore and onshore Crete controlled by sinistrally dominated 070° faults and secondary 020° extensional oversteps. Although the post-Miocene plate-convergence vectors became increasingly oblique, deformation in transtension, not transpression, has driven Hellenic forearc kinematics. Incipient collision with an African promontory blocked further outward expansion of the Aegean plate boundary along western Crete but induced forearc slivers to be displaced northeastward and sheared sinistrally off the free expanding edge of Aegea as the Cretan–Rhodes forearc was simultaneously stretched. Such a kinematic regime has probably operated since
c
. 3.4 Ma when the Messaras 070° wrench-dominated system became active and represents tectonic escape during incipient continental collision.
Structural styles in the Zagros Simple Folded Zone, Iran
Authors: Blanc E.J.-P. , Allen M.B. , Inger S. , Hassani H.
Published: October 2008

Arabia–Eurasia convergence is achieved in the NW Zagros by a combination of shortening on NW–SE-trending folds and thrusts, mainly in the Simple Folded Zone, and by right-lateral strike-slip on the NW–SE-trending Main Recent Fault. A balanced and restored cross-section across this part of the range indicates
c
. 49 km of shortening. This probably occurred since
c
. 5 Ma, providing an estimate of the long-term shortening rate across the Simple Folded Zone of
c
. 10 mm a
−1
. The geometries of exposed structures suggest both basement thrusts and thin-skinned décollement levels, with major folds possibly nucleated above basement faults. Fold geometries indicate several décollement horizons; shale units are candidates, as well as evaporites in the Neogene, Mesozoic, Lower Palaeozoic and upper Proterozoic successions. The SE part of the Simple Folded Zone deforms by north–south shortening on broadly east–west-trending folds and thrusts. The link between these regions occurs via a set of fault blocks
c
. 400 km wide in total, each bounded by north–south right-lateral faults. Incremental changes in the strike of some of the folds occur across these right-lateral faults, with more east–west orientations to the east.
Intrinsic Particle Properties from Vibrational Spectra of Aerosols
Authors: Sigurbjörnsson Ómar F. , Firanescu George , Signorell Ruth
Published: October 2008

The spectroscopy of aerosols is developing into an active and important field. It allows us to characterize aerosols in a nonintrusive way, in real time, and on site. Understanding the spectroscopic features of these highly complex systems requires the development of novel experimental as well as theoretical methods. This review focuses on infrared extinction spectra. The main goal is to summarize how information about intrinsic particle properties (such as size, shape, and architecture) can be gathered from observed spectroscopic patterns. We discuss the limitations of standard continuum approaches, which have been used for decades to analyze infrared spectra, and we demonstrate the importance of molecular models for the analysis of spectroscopic data.
Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat
Authors: Umstead Todd M. , Freeman Willard M. , Chinchilli Vernon M. , Phelps David S.
Published: October 2008

The incidence and severity of many lung diseases change with age. Some diseases, such as pneumonia, occur with increased frequency in children and the elderly. Proteins obtained by bronchoalveolar lavage (BAL) serve as the first line of defense against inhaled toxins and pathogens. Age-related changes in BAL protein expression and oxidative modification were examined in juvenile (1 mo), young adult (2 mo), and aged (18 mo) F344 rats using two-dimensional difference gel electrophoresis (2D-DIGE), matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-ToF/ToF) tandem mass spectrometry, and carbonyl immunoblotting. Using 2D-DIGE, we detected 563 protein spots, and MALDI-ToF/ToF identified 204 spots comprising 31 proteins; 21 changed significantly (17 increases) between juvenile and young adult or aged rats, but for 12 of these proteins, levels had a biphasic pattern, and levels in aged rats were less than in young adults. Relative carbonylation was determined by comparison of immunostaining with total protein staining on each oxidized protein blot. We found that aged rats had significantly increased oxidation in 13 proteins compared with juvenile rats. Many of the proteins altered in expression or oxidation level had functions in host defense, redox regulation, and protein metabolism. We speculate that low levels of expression of host defense proteins in juvenile rats and decreases in levels of these proteins between young adult and aged rats may predispose these groups to pneumonia. In addition, we have shown age-related increases in protein oxidation that may compromise host defense function in aged rats.
Poor Semen Quality and ROS-TAC Scores in Patients with Idiopathic Infertility
Authors: Pasqualotto Fábio F. , Sharma Rakesh K. , Pasqualotto Eleonora B. , Agarwal Ashok
Published: October 2008

Introduction: To compare the semen quality score and the seminal oxidative stress reactive oxygen species (ROS) and total antioxidant capacity (ROS-TAC score) in men with idiopathic infertility with normal donors and to a known group of fertile and infertile men. Material and Methods: Principal component analysis was applied to provide a standardized score in 36 men with idiopathic infertility and 19 controls attending our infertility clinic. A logistic regression analysis comparing the fertile and infertile men was used. Results: Compared to controls, patients with idiopathic infertility had significantly lower sperm concentration, sperm motility and normal morphology (p < 0.05) and lower semen quality scores (83.0 ± 14.5 vs. 100.0 ± 10.0; p < 0.001). Compared to controls, the ROS levels were higher in the idiopathic infertility group (2.3 ± 0.21 vs. 1.3 ± 0.3; p = 0.006), whereas the TAC levels were lower in the idiopathic infertility (1,014.75 ± 79.22 vs. 1,653 ± 115.29; p = 0.001). Idiopathic infertility patients had lower ROS-TAC scores (32.8 ± 14.2) than controls (50.0 ± 10.0) (p < 0.001). 64% of men with idiopathic infertility will remain infertile during 1-year follow-up. Conclusions: Patients with idiopathic infertility have lower scores of semen quality and ROS-TAC.
Urethral Reconstruction in Balanitis Xerotica Obliterans
Authors: Trivedi Sameer , Kumar Abhay , Goyal Neeraj K. , Dwivedi Udai S. , Singh Pratap B.
Published: October 2008

Objectives: To review the results of utilizing different grafts for substitution urethroplasty for anterior urethral stricture caused by balanitis xerotica obliterans (BXO). Methods: 153 patients who underwent substitution urethroplasty for anterior urethral strictures were included in this study. The stricture length varied from 3.8 to 16.4 cm (mean 10.2 cm). In 32% of the patients (49), local genital, penile (18), perineal (16) and scrotal (15) skin grafts were used. Over the 3 years our standard treatment policy has been to utilize a free mucosal graft from a non-genital area. Buccal mucosa was the most preferred, utilized in 74 (48.3%) patients and bladder mucosa in 12 (7.8%). Recently we have used lingual mucosal grafts in 18 (11.7%) patients for substitution urethroplasty. Results: The overall success rate for non-genital mucosal graft was 92.2%. The remaining 8 patients required more than one supplementary procedure postoperatively but none required a second urethroplasty. Of 49 patients who underwent substitution urethroplasty utilizing genital skin, the success rate was only 4%. 16.3% required one and 14.3% required multiple auxiliary procedures postoperatively. 34 patients (69.4%) required subsequent urethral reconstruction. Conclusions: A free graft urethroplasty using non-genital skin is recommended for anterior urethral stricture related to BXO.
Digital Image Analysis of Mean AgNOR Area Objectively Discriminates between Reactive Plasmacytosis and Multiple Myeloma in Cytologic Smears from Bone Marrow Aspirates
Authors: Gunia S. , Mai P.A. , Koch S.
Published: October 2008

Objective: To differentiate between reactive plasmacytosis (RP) and multiple myeloma (MM) in bone marrow aspirates by assessment of silver-stainable nucleolar organizer regions (AgNORs). Methods: Archival cytologic smears (n = 69) from bone marrow aspirates were retrospectively investigated. Twenty cases had RP and 49 cases MM (24 low-grade, 22 intermediate-grade and 3 high-grade MM). Diagnoses were confirmed by evaluation of the corresponding bone marrow trephine biopsies. Cytologic smears were subjected to AgNOR staining using a standardized silver-staining protocol and assessed by two independent clinical histopathologists using digital image analysis. AgNOR count and area were analyzed in 100 plasma cell nuclei per sample. Results: The mean AgNOR area was found to be significantly (p < 0.001) higher in low-grade MM (mean: 23.4 µm2; range: 19.2–26.7 µm2) than in RP cases (mean: 6.2 µm2; range: 3.8–8.4 µm2). In contrast, mean AgNOR count failed to disclose significant differences between low-grade MM (mean: 5.36; range: 1–7) and RP (mean: 3.68; range: 1–6). Conclusion: Digital image analysis of the mean AgNOR area might be used as a diagnostically useful adjunct to aid objectively in the challenging differentiation between RP and MM in bone marrow aspirates.
Single-Measurement Therapeutic Drug Monitoring of the HIV/AIDS Drugs Abacavir, Zidovudine, Lamivudine, Efavirenz, Nevirapine, Lopinavir and Nelfinavir
Authors: Donnerer Josef , Haas Bernhard J. , Kessler Harald H.
Published: October 2008

Background: There is currently no consensus about the significance of therapeutic drug monitoring (TDM) in the management of human immunodeficiency virus (HIV) infection. Objectives: In this study, single drug levels from routine clinical samples were determined in order to add further data on the therapeutic plasma level range and on drug levels under anti-HIV therapy in general. Materials and Methods: A total of 215 plasma samples obtained from patients with HIV infection for whom TDM was requested for the first time were evaluated. Plasma values were determined for abacavir and zidovudine between 1 and 3 h after drug intake. Lamivudine, efavirenz, nevirapine, lopinavir and nelfinavir plasma values were determined between 1 and 12 h after drug intake. Drug levels were determined with a home-brewed assay based on high-performance liquid chromatography. Results: Plasma concentrations of HIV drugs showed a large variability. Plasma concentrations of abacavir, zidovudine and lamivudine were found to be similar to those reported recently. For efavirenz and nevirapine, 37 and 61% of the samples did not meet the minimum trough levels suggested. For lopinavir and nelfinavir, the majority of the samples (78 and 80%) were found to be within the therapeutic plasma level range. Conclusion: Despite a large variation of anti-HIV drug plasma concentrations, single-measurement TDM may be sufficient in the routine management of the majority of patients.
Assessing Genuine Parents-Offspring Trios for Genetic Association Studies
Authors: Teo Yik Y. , Fry Andrew E. , Sanjoaquin Miguel A. , Pederson Bonnie , Small Kerrin S. , Rockett Kirk A. , Kwiatkowski Dominic P. , Clark Taane G.
Published: October 2008

Objectives: Family-based association tests such as the transmission disequilibrium test (TDT) are dependent on the successful ascertainment of true nuclear family trios. Relationship misspecification inevitably occurs in a proportion of trios collected for genotyping which undetected can lead to a loss of power and increased Type I error due to biases in over-transmission of common alleles. Here, we introduce a method for evaluating the authenticity of nuclear family trios. Methods: Operating in a Bayesian framework, our approach assesses the extent of pedigree inconsistent genotype configurations in the presence of genotyping errors. Unlike other approaches, our method: (i) utilizes information from three individuals collectively (the whole trio) rather than consider two independent pairwise relationships; (ii) down-weighs SNPs with poor performance; (iii) does not require the user to pre-define a rate of genotyping error, which is often unknown to the user and seldom fixed across the different SNPs considered which available methods unrealistically assumed. Results: Simulation studies and comparisons with a real set of data showed that our approach is more likely to correctly identify the presence of true and misspecified trios compared to available software, accurately infers the extent of relationship misspecification in a trio and accurately estimates the genotyping error rates. Conclusions: Assessing relationship misspecification depends on the fidelity of the genotype data used. Available algorithms are not optimised for genotyping technology with varying rates of errors across the markers. Through our comparison studies, our approach is shown to outperform available methods for assessing relationship misspecifications.
A Likelihood Model That Accounts for Censoring Due to Fetal Loss Can Accurately Test the Effects of Maternal and Fetal Genotype on the Probability of Miscarriage
Authors: O’Donnell Colin I. , Glueck Charles J. , Fingerlin Tasha E. , Glueck Deborah H.
Published: October 2008

Objective: Heritable maternal and fetal thrombophilia and/or hypofibrinolysis are important causes of miscarriage. Under the constraint that fetal genotype is observed only after a live birth, estimating risk is complicated. Censoring prevents use of published statistical methodology. We propose techniques to determine whether increases in miscarriage are due to the fetal genotype, maternal genotype, or both. Methods: We propose a study to estimate the risk of miscarriage contributed by an allele, expressed in either dominant or recessive fashion. Using a multinomial likelihood, we derive maximum likelihood estimates of risk for different genotype groups. We describe likelihood ratio tests and a planned hypothesis testing strategy. Results: Parameter estimation is accurate (bias <0.0011, root mean squared error <0.0780, n = 500). We used simulation to estimate power for studies of three gene mutations: the 4G hypofibrinolytic mutation in the plasminogen activator inhibitor gene (PAI-1), the prothrombin G20210A mutation, and the Factor V Leiden mutation. With 500 families, our methods have approximately 90% power to detect an increase in the miscarriage rate of 0.2, above a background rate of 0.2. Conclusion: Our statistical method can determine whether increases in miscarriage are due to fetal genotype, maternal genotype, or both despite censoring.
Population-Based Stroke Survey in Mumbai, India: Incidence and 28-Day Case Fatality
Authors: Dalal P.M. , Malik S. , Bhattacharjee M. , Trivedi N.D. , Vairale J. , Bhat P. , Deshmukh S. , Khandelwal K. , Mathur V.D.
Published: October 2008

Objectives: The aims of this study were (1) to establish a prospective community-based stroke registry in Mumbai of subjects having ‘first-ever stroke’ (FES) and (2) to collect standardized data on annual incidence, stroke subtypes, and case fatality rate at 28 days during the years 2005 and 2006. Background: An estimated 5.8 million people died from stroke (cerebrovascular disease) in 2005, two thirds of them were from low-/middle-income countries but reliable population-based studies are scarce. Methods: The manual on WHO STEPwise approach to stroke surveillance (STEPS Stroke; http://www.who.int/chp/steps/Manual pdf) was the operational protocol. We selected a well-defined community (H-district) having verifiable census data and being representative of the population structure of Mumbai (Bombay). Of 337,391 permanent residents, 156,861 persons between the age of 25 and 94+ years who were eligible for survey were screened. The responses to a predefined questionnaire (version 2.0) were entered in coded data sheets for analysis. Results: During the 2-year study period (January 2005 to December 2006), 456 (238 males and 218 females) had FES, indicating an annual incidence in subjects of 25 years and above of 145/100,000 persons (CI 95%: 120–170); for males it is 149/100,000 persons (CI 95%: 120–170) and for females it is 141/100,000 persons (CI 95%: 120–160). The age-standardized rate for study population (both sexes) by the direct method using Segi’s 1996 world population is 152/100,000/year (CI 95%: 132–172). Stroke diagnosis was supported by computed tomography in 407 (89.2%) of 456 FES cases: 366 (80.2%) had ischemic stroke, 81 (17.7%) had hemorrhagic stroke and 9 (1.9%) were in the unspecified category. The mean age was 66 ± (SD) 13.60 years, women were older as compared to men (mean age 68.9 ± 13.12 years vs. 63.4 ± 13.53 years). Case fatality: at 28 days, 320 (70%) of 456 FES cases were still alive and 136 (29.8%) had died. Of the 320 surviving patients 38.5% had moderate to severe disability by the modified Rankin scale. Conclusions: The results of Mumbai stroke study, using uniform definitions and methodologies, show that the annual standardized incidence rates, stroke subtypes and case fatality rate are very similar to those reported from developed nations. To plan effective intervention and prevention strategies, standardized data in representative samples of regional populations are urgently needed.
Comparison of Methods for Magnetic Resonance-Guided [18-F]Fluorodeoxyglucose Positron Emission Tomography in Human Carotid Arteries
Authors: Izquierdo-Garcia David , Davies John R. , Graves Martin J. , Rudd James H.F. , Gillard Jonathan H. , Weissberg Peter L. , Fryer Tim D. , Warburton Elizabeth A.
Published: October 2008

Background and Purpose—

Inflammation is a major risk factor for atherosclerotic plaque rupture and clinical events. Previous studies have shown that plaque [
18
F]fluorodeoxyglucose (FDG) uptake correlates with macrophage content. In this study we examined the reproducibility of 3 methods of quantifying plaque FDG uptake in the carotid arteries using positron emission tomography (PET). The correlation between 2 simplified uptake parameters (standardized uptake value [SUV], vessel wall-to-blood ratio [VBR]) and a gold standard technique (influx rate [K
i
]) was also determined. We used MRI to correct carotid plaque FDG uptake for partial volume error.

Methods—

Seven patients with a recent carotid territory transient ischemic attack underwent imaging twice within 8 days using MR and FDG-PET. MR coregistered to PET was used to delineate regions of interest, and to facilitate partial volume correction (PVC).

Results—

SUV was the most reproducible parameter irrespective of whether it was normalized by body surface area (BSA), lean body mass, or weight (intraclass correlation coefficient=0.85, 0.88, and 0.90, respectively). VBR correlated better to K
i
than SUV (
r
=0.58 VBR,
r
=0.46 SUV
BSA
). PVC improved these correlations to
r
=0.81 VBR and
r
=0.76 SUV
BSA
, and only slightly degraded the reproducibility of SUV (intraclass correlation coefficient=0.83–0.85).

Conclusions—

MR-guided FDG-PET is a highly reproducible technique in the carotid artery and the excellent anatomic detail provided by MR facilitates PVC. Of the methods examined, SUV
BSA
PVC
appears to represent the best compromise between reproducible and accurate determination of FDG metabolism in carotid artery vessel wall.
Metabolic Syndrome Clusters and the Risk of Incident Stroke
Authors: Rodriguez-Colon Sol M. , Mo Jingping , Duan Yinkang , Liu Jiahao , Caulfield Joanne E. , Jin Xuejuan , Liao Duanping
Published: October 2008

Background and Purpose—

Little is known about the metabolic syndrome (MetS) and the risk of incident stroke. This study is designed to identify particular clusters of MetS components that carry the highest risk of incident stroke.

Methods—

We analyzed the public use data from the population-based Atherosclerosis Risk in Communities study. At baseline, 14 993 stroke-free middle-aged individuals were followed-up over 9 years for incident stroke. MetS components were defined according to the National Heart, Lung, and Blood Institute/American Heart Association criteria. Incident stroke was identified using a standardized incident events identification and classification protocol. Proportional hazard models were used to assess the RRs and 95% CIs of ischemic stroke associated with MetS and its different clusters.

Results—

At baseline, the prevalence of MetS was 39%. The mean age was 54, with 26% blacks and 55% females. The hazard ratio of incident ischemic stroke associated with MetS among women (hazard ratio, 2.41; 95% CI, 1.69 to 3.49) and men (hazard ratio, 2.11; 95% CI, 1.56–2.85) was similar. There was a dose–response relationship between the numbers of MetS components and the risk of incidence stroke. Persons with either elevated blood pressure or elevated fasting glucose in the clusters to form a MetS had the highest risk for incident stroke (hazard ratio, 2.74–4.16 comparing to the reference group) than MetS without these 2 components (hazard ratio, ≤2.00 comparing to the reference group).

Conclusions—

The data support the need to target MetS, especially MetS, with these 2 highest risk components (elevated blood pressure or elevated fasting glucose) in the clusters.
Simvastatin Increases Notch Signaling Activity and Promotes Arteriogenesis After Stroke
Authors: Zacharek Alex , Chen Jieli , Cui Xu , Yang Yuping , Chopp Michael
Published: October 2008

Background and Purpose—

Notch signaling activity regulates arteriogenesis. Presenilin 1 (PS1) mediates Notch signaling activity via cleavage of Notch, liberating Notch intracellular domain (NICD). We tested the hypothesis that simvastatin enhances arteriogenesis after stroke by increasing PS1 activation of the Notch signaling pathway.

Methods—

Rats were subjected to middle cerebral artery occlusion (MCAo) and treated with or without simvastatin (1 mg/kg) starting 24 hours after stroke and daily for 7 days; they were euthanized 14 days after stroke. Immunostaining, Western blot, and real-time polymerase chain reaction assays were performed.

Results—

Simvastatin significantly increased arterial diameter, density, and vascular smooth muscle cell proliferation, and upregulated PS1, Notch1, and NICD expression in the ischemic border tissue and in the cerebral arteries compared with MCAo control rats, respectively. However, simvastatin did not increase arteriogenesis, PS1, and NICD expression in sham control animals. To investigate the mechanisms of simvastatin-induced arteriogenesis, primary cerebral artery cultures were used. Rats were subjected to MCAo and treated with or without simvastatin daily for 7 days. The cerebral arteries derived from these stroke rats were cultured in matrigel and treated with or without a γ40-secretase inhibitor II, which blocks Notch signaling activity, inhibiting NICD production. Arterial cell migration was measured. simvastatin treatment significantly increased arterial cell migration compared to control MCAo artery, whereas inhibition of Notch signaling activity by the γ40-secretase inhibitor II significantly attenuated simvastatin-induced arterial cell migration.

Conclusions—

These data indicate that simvastatin increases arteriogenesis after stroke, and that simvastatin upregulation of PS1 expression and Notch signaling activity may facilitate an increase in arteriogenesis.
Maximum Memory Capacity on Neural Networks with Short-Term Synaptic Depression and Facilitation
Authors: Mejias Jorge F. , Torres Joaquín J.
Published: October 2008

In this work, we study, analytically and employing Monte Carlo simulations, the influence of the competition between several activity-dependent synaptic processes, such as short-term synaptic facilitation and depression, on the maximum memory storage capacity in a neural network. In contrast to the case of synaptic depression, which drastically reduces the capacity of the network to store and retrieve “static” activity patterns, synaptic facilitation enhances the storage capacity in different contexts. In particular, we found optimal values of the relevant synaptic parameters (such as the neurotransmitter release probability or the characteristic facilitation time constant) for which the storage capacity can be maximal and similar to the one obtained with static synapses, that is, without activity-dependent processes. We conclude that depressing synapses with a certain level of facilitation allow recovering the good retrieval properties of networks with static synapses while maintaining the nonlinear characteristics of dynamic synapses, convenient for information processing and coding.
A Generalized Linear Integrate-and-Fire Neural Model Produces Diverse Spiking Behaviors
Authors: Mihalaş Ştefan , Niebur Ernst
Published: October 2008

For simulations of neural networks, there is a trade-off between the size of the network that can be simulated and the complexity of the model used for individual neurons. In this study, we describe a generalization of the leaky integrate-and-fire model that produces a wide variety of spiking behaviors while still being analytically solvable between firings. For different parameter values, the model produces spiking or bursting, tonic, phasic or adapting responses, depolarizing or hyperpolarizing after potentials and so forth. The model consists of a diagonalizable set of linear differential equations describing the time evolution of membrane potential, a variable threshold, and an arbitrary number of firing-induced currents. Each of these variables is modified by an update rule when the potential reaches threshold. The variables used are intuitive and have biological significance. The model's rich behavior does not come from the differential equations, which are linear, but rather from complex update rules. This single-neuron model can be implemented using algorithms similar to the standard integrate-and-fire model. It is a natural match with event-driven algorithms for which the firing times are obtained as a solution of a polynomial equation.
Must EU Borders have Doors for Refugees? On the Compatibility of Schengen Visas and Carriers' Sanctions with EU Member States' Obligations to Provide International Protection to Refugees
Authors: Lax Violeta Moreno
Published: October 2008

Whereas the EU is developing a highly protective Common European Asylum System in purported compliance with the Geneva Convention, it is also displaying growing reluctance to provide unhindered access to it to those in need. The question of physical access to protection is ambiguously dealt with within EU law. On the one hand, it appears that entry to the Schengen zone has been designed disregarding refugees' entitlement 'to special protection'. Prior to admission, refugees seem to have been assimilated to the broader class of (potentially illegal) immigrants and thus required to submit to general immigration conditions, including visa. On the other hand, some isolated EU law rules give the impression that refugees are to be exonerated from normal admittance requirements.This article intends to show how, 'in the light of present day conditions,' a contextual, dynamic and teleological interpretation of Articles 31 and 33 of the Geneva Convention as well as of Articles 3 ECHR and 2(2) of Protocol 4 ECHR require that the second set of EU rules be appropriately furthered.
Comments on Gouvernement de la Communauté française and Gouvernement wallon (Case C-212/06 of 1 April 2008) and Eind (Case C-291/05 of 11 December 2007)
Authors: Martin
Published: October 2008

In the Gouvernement de la Communauté française and Gouvernement wallon case, the Court of Justice was mainly faced with the question of the applicability of the Community law provisions governing free movement of persons in "internal situations" i.e., situations in which EU citizens who are nationals of the host Member States, may not invoke the protection of Community law due to the lack of a cross-border element. The Court resists the call of its AG, but its reply does not give a definitive answer to the situation of those nationals who have exercised, to some extent, their right to free movement. In the Eind case, the Court was confronted with the question whether the third country family member of a national of the host Member State, who has no right of residence in that State, nevertheless enjoys a right of family reunification there upon the return of that national from another Member State where he exercised his right to free movement. The Court answers that question positively, but its legal reasoning is questionable.
Survey Response Rates and Survey Administration in Counseling and Clinical Psychology
Authors: Van Horn Pamela S. , Green Kathy E. , Martinussen Monica
Published: October 2008

This article reports results of a meta-analysis of survey response rates in published research in counseling and clinical psychology over a 20-year span and describes reported survey administration procedures in those fields. Results of 308 survey administrations showed a weighted average response rate of 49.6%. Among possible moderators, response rates differed only by population sampled, journal in which articles were published, sampling source and method, and use of follow-up. Researchers whose studies were included in this meta-analysis used follow-up but rarely used incentives, prenotification, or other response-facilitation methods to maximize response rates. Although the future of survey research in general may rely more heavily on Internet data collection, mail surveys dominate in this field.
Tetrachoric Correlation
Authors: Long Michael A. , Berry Kenneth J. , Mielke Paul W.
Published: October 2008

An exact permutation test is provided for the tetrachoric correlation coefficient. Comparisons with the conventional test employing Student's t distribution demonstrate the necessity of using the permutation approach for small sample sizes and/or disproportionate marginal frequency totals.
Learning Disabilities and Risk-Taking Behavior in Adolescents
Authors: McNamara John , Vervaeke Sherri-Leigh , Willoughby Teena
Published: October 2008

Risk-taking behavior includes alcohol and drug use, delinquency, acts of aggression, sexual activity, and so on. Many studies have explored the relationship between adolescents and risk-taking behavior; however, only a few studies have examined this link in adolescents with learning disabilities (LD) or attention-deficit/hyperactivity disorder (ADHD). The purpose of the present study was to address that limitation by comparing the risk-taking behavior of adolescents with LD ( n = 230), with comorbid LD/ADHD ( n = 92), and without LD or ADHD ( n = 322) on their substance use, engagement in major and minor delinquency, acts of aggression, sexual activity, and gambling activities. The study also investigated whether psychosocial variables (e.g., well-being) may act as mediating variables that help explain between-group differences. Results suggest that it is a combination of the LD and the secondary psychosocial characteristics that explains why adolescents with LD and comorbid LD/ADHD more frequently engage in some risk-taking behavior.
Mechanisms of resistance to 5-aza-2′-deoxycytidine in human cancer cell lines
Authors: Qin Taichun , Jelinek Jaroslav , Si Jiali , Shu Jingmin , Issa Jean-Pierre J.
Published: October 2008

5-aza-2′-deoxycytidine (DAC) is approved for the treatment of myelodysplastic syndromes, but resistance to this agent is common. In search for mechanisms of resistance, we measured the half maximal (50%) inhibitory concentration (IC50) of DAC and found it differed 1000-fold among a panel of cancer cell lines. The IC50 was correlated with the doses of DAC that induced the most hypomethylation of long interspersed nuclear elements (LINE; R = 0.94, P < .001), but not with LINE methylation or DNA methyltransferase 1 (DNMT1), 3a, and 3b expression at baseline. Sensitivity to DAC showed a low correlation (R = 0.44, P = .11) to that of 5-azacytidine (AZA), but a good correlation to that of cytarabine (Ara-C; R = 0.89, P < .001). The 5 cell lines most resistant to DAC had a combination of low dCK, hENT1, and 2 transporters, and high cytosine deaminase. In an HL60 clone, resistance to DAC could be rapidly induced by drug exposure and was related to a switch from heterozygous to homozygous mutation of DCK. Transfection of wild-type DCK restored DAC sensitivity. DAC induced DNA breaks as evidenced by H2AX phosphorylation and increased homologous recombination rates by 7- to 10-fold. These results suggest that in vitro resistance to DAC can be explained by insufficient incorporation into DNA.
Critical role of class IA PI3K for c-Rel expression in B lymphocytes
Authors: Matsuda Satoshi , Mikami Yohei , Ohtani Masashi , Fujiwara Mari , Hirata Yasuko , Minowa Akiko , Terauchi Yasuo , Kadowaki Takashi , Koyasu Shigeo
Published: October 2008

The fact that the Xid mutation of Btk impairs the ability of pleckstrin homo-logy domain of Btk to bind phosphatidylinositol-(3,4,5)-trisphosphate, a product of class IA phosphoinositide-3 kinases (PI3Ks), has been considered strong evidence for the hypothesis that Btk functions downstream of PI3Ks. We demonstrate here that the Xid mutation renders the Btk protein unstable. Furthermore, class IA PI3K- and Btk-deficient mice show different phenotypes in B-cell development, collectively indicating that PI3Ks and Btk differentially function in BCR signal transduction. Nevertheless, both PI3K and Btk are required for the activation of NF-κB, a critical transcription factor family for B-cell development and function. We demonstrate that PI3Ks maintain the expression of NF-κB proteins, whereas Btk is known to be essential for IκB degradation and the translocation of NF-κB to the nucleus. The loss of PI3K activity results in marked reduction of c-Rel and to a lesser extent RelA expression. The lentivirus-mediated introduction of c-Rel corrects both developmental and proliferative defects in response to BCR stimulation in class IA PI3K-deficient B cells. These results show that the PI3K-mediated control of c-Rel expression is essential for B-cell functions.
TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements
Authors: Du Hong-Yan , Pumbo Elena , Ivanovich Jennifer , An Ping , Maziarz Richard T. , Reiss Ulrike M. , Chirnomas Deborah , Shimamura Akiko , Vlachos Adrianna , Lipton Jeffrey M. , Goyal Rakesh K. , Goldman Frederick , Wilson David B. , Mason Philip J. , Bessler Monica
Published: October 2008

Dyskeratosis congenita (DC) is a rare inherited form of bone marrow failure (BMF) caused by mutations in telomere maintaining genes including TERC and TERT. Here we studied the prevalence of TERC and TERT gene mutations and of telomere shortening in an unselected population of patients with BMF at our medical center and in a selected group of patients referred from outside institutions. Less than 5% of patients with BMF had pathogenic mutations in TERC or TERT. In patients with BMF, pathogenic TERC or TERT gene mutations were invariably associated with marked telomere shortening (≪ 1st percentile) in peripheral blood mononuclear cells (PBMCs). In asymptomatic family members, however, telomere length was not a reliable predictor for the presence or absence of a TERC or TERT gene mutation. Telomere shortening was not pathognomonic of DC, as approximately 30% of patients with BMF due to other causes had PBMC telomere lengths at the 1st percentile or lower. We conclude that in the setting of BMF, measurement of telomere length is a sensitive but nonspecific screening method for DC. In the absence of BMF, telomere length measurements should be interpreted with caution.
The evolution of prompt reaction to adverse ties
Authors: Van Segbroeck Sven , Santos Francisco C , Nowé Ann , Pacheco Jorge M , Lenaerts Tom
Published: October 2008

Background

In recent years it has been found that the combination of evolutionary game theory with population structures modelled in terms of dynamical graphs, in which individuals are allowed to sever unwanted social ties while keeping the good ones, provides a viable solution to the conundrum of cooperation. It is well known that in reality individuals respond differently to disadvantageous interactions. Yet, the evolutionary mechanism determining the individuals' willingness to sever unfavourable ties remains unclear.

Results

We introduce a novel way of thinking about the joint evolution of cooperation and social contacts. The struggle for survival between cooperators and defectors leads to an arms race for swiftness in adjusting social ties, based purely on a self-regarding, individual judgement. Since defectors are never able to establish social ties under mutual agreement, they break adverse ties more rapidly than cooperators, who tend to evolve stable and long-term relations. Ironically, defectors' constant search for partners to exploit leads to heterogeneous networks that improve the survivability of cooperators, compared to the traditional homogenous population assumption.

Conclusion

When communities face the prisoner's dilemma, swift reaction to adverse ties evolves when competition is fierce between cooperators and defectors, providing an evolutionary basis for the necessity of individuals to adjust their social ties. Our results show how our innate resilience to change relates to mutual agreement between cooperators and how "loyalty" or persistent social ties bring along an evolutionary disadvantage, both from an individual and group perspective.
Colonic diaphragm disease without significant non-steroidal anti-inflammatory drug use: a case report
Authors: Roche Jo C , Morris-Stiff Gareth , Champ Carrie , Williams Geraint T , Lewis Michael H
Published: October 2008

Introduction

Colonic diaphragm disease is an uncommon condition usually associated with the long-term use of non-steroidal anti-inflammatory drugs.

Case presentation

A 48-year-old woman presented as an emergency patient with abdominal pain and vomiting. Past medical history included inflammatory bowel disease of ulcerative colitis type for which she was taking azathioprine and prednisolone. On examination, she was shocked with signs of peritonism. Following resuscitation, she was taken for a laparotomy upon which a small amount of turbid fluid was identified but there was no direct evidence of an intra-abdominal perforation. A peritoneal lavage was performed and she was taken to the intensive care unit. A repeat laparotomy was performed on the sixth postoperative day, following a clinical deterioration and again no leak was identified. Given the history of ulcerative colitis, the perforation was presumed to be of colonic origin and a total colectomy and ileostomy was performed. Histopathological examination of the colectomy specimen revealed extensive colonic diaphragm disease with 30 thin-walled diaphragms, one of which reduced the lumen to a pin-hole. No perforation was identified.

Conclusion

To the best of the our knowledge, this is the first report of the development of colonic diaphragm disease in the absence of a history of non-steroidal anti-inflammatory drug ingestion. Given the history of ulcerative colitis we believe that the disease may have arisen as a result of the healing of the underlying inflamed colon rather than as a direct effect of non-steroidal anti-inflammatory drugs.
HIV prevention: What have we learned from community experiences in concentrated epidemics?
Authors: Spire Bruno , de Zoysa Isabelle , Himmich Hakima
Published: October 2008

Drawing on lessons learned from community experiences in concentrated epidemics, this paper explores three imperatives in the effort to reduce the sexual transmission of HIV: combat prevention fatigue, diversify HIV testing and combat stigma and discrimination. The paper argues for a non‐judgmental harm reduction approach to the prevention of sexual transmission of HIV that takes into account the interpretation of risk by diverse individuals and communities in the era of antiretroviral therapy. This approach requires greater attention to increasing access to opportunities to know one's serostatus, especially among key populations at greater risk. Novel approaches to diversifying HIV testing approaches at community level are needed. Finally, the paper makes a plea for bold measures to combat stigma and discrimination, which continues to represent a formidable barrier for access to services for affected populations and may contribute to HIV‐related risk behaviours. A “triple therapy” approach to address stigma and discrimination is discussed, which includes greater acceptance of people living with HIV and AIDS (PLWHA), improving relevant laws and policies, and involving prevention users‐ working with people rather than for people‐.

Note: this paper corresponds to the plenary talk of Bruno Spire at the XVIIth World AIDS Conference, August 8th, Mexico city: http://www.kaisernetwork.org/health_cast/player.cfm?id=4383
Inducible Nitric Oxide Synthase Is Involved in Endothelial Dysfunction of Mesenteric Small Arteries from Hypothyroid Rats
Authors: Virdis Agostino , Colucci Rocchina , Fornai Matteo , Polini Antonio , Daghini Elena , Duranti Emiliano , Ghisu Narcisa , Versari Daniele , Dardano Angela , Blandizzi Corrado , Taddei Stefano , Del Tacca Mario , Monzani Fabio
Published: October 2008

The time-dependent effects of mild hypothyroidism on endothelial function were assessed in rat mesenteric arteries. Male Wistar rats were treated with methimazole (MMI; 0.003%) or placebo up to 16 wk. Endothelial function of mesenteric small arteries was assessed by pressurized myograph. MMI-treated animals displayed a decrease in serum thyroid hormones, an increment of plasma TSH and inflammatory cytokines, and a blunted vascular relaxation to acetylcholine, as compared with controls. Endothelial dysfunction resulted from a reduced nitric oxide (NO) availability caused by oxidative excess. Vascular-inducible NO synthase (iNOS) expression was up-regulated. S-methylisothiourea (an iNOS inhibitor) normalized endothelium-dependent relaxations and restored NO availability in arteries from 8-wk MMI-animals and partly ameliorated these alterations in 16-wk MMI rats. Similar results were obtained when MMI-induced hypothyroidism was prevented by T4 replacement. Among controls, an impaired NO availability, secondary to oxidative excess, occurred at 16 wk, and it was less pronounced than in age-matched MMI animals. Both endothelial dysfunction and oxidant excess secondary to aging were prevented by apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor). Mesenteric superoxide production was reduced by S-methylisothiourea and T4 replacement in MMI animals and abolished by apocynin in controls (dihydroethidium staining). MMI-induced mild hypothyroidism is associated with endothelial dysfunction caused by a reduced NO availability, secondary to oxidative excess. It is suggested that in this animal model, characterized by TSH elevation and low-grade inflammation, an increased expression and function of iNOS, resulting in superoxide generation, accounts for an impaired NO availability.
Biomechanics of a convergently derived prey-processing mechanism in fishes: evidence from comparative tongue bite apparatus morphology and raking kinematics
Authors: Konow Nicolai , Sanford Christopher P. J.
Published: October 2008

A tongue-bite apparatus (TBA) governs raking behaviors in two major and unrelated teleost lineages, the osteoglossomorph and salmoniform fishes. We present data on comparative morphology and kinematics from two representative species, the rainbow trout (Oncorhynchus mykiss) and the Australian arowana (Scleropages jardinii), which suggest that both the TBA and raking are convergently derived in these lineages. Similar TBA morphologies were present, except for differences in TBA dentition and shape of the novel cleithrobranchial ligament (CBL), which is arc-shaped in O. mykissand straight in S. jardinii. Eight kinematic variables were used to quantify motion magnitude and maximum-timing in the kinematic input mechanisms of the TBA. Five variables differed inter-specifically (pectoral girdle retraction magnitude and timing, cranial and hyoid elevation and gape-distance timing), yet an incomplete taxon separation across multivariate kinematic space demonstrated an overall similarity in raking behavior. An outgroup analysis using bowfin (Amia calva) and pickerel (Esox americanus) to compare kinematics of raking with chewing and prey-capture provided robust quantitative evidence of raking being a convergently derived behavior. Support was also found for the notion that raking more likely evolved from the strike, a functionally distinct behavior, than from chewing,an alternative prey-processing behavior. Based on raking kinematic and muscle-activity data, we propose biomechanical models of the three input mechanisms that govern kinematics of the basihyal output mechanism during the raking power stroke: (1) cranial elevation protracts the upper TBA jaw from the lower (basihyal) TBA jaw; (2) basihyal retraction is caused directly by contraction of the sternohyoideus (SH); (3) hypaxial shortening, relayed via the pectoral girdle and SH–CBL complex, is an indirect basihyal retraction mechanism modeled as a four-bar linkage. These models will aid future analyses mapping structural and functional traits to the evolution of behaviors.
Perianal Hailey-Hailey disease: an unusual differential diagnosis of condylomata acuminata
Authors: Ewald K , Gross G
Published: October 2008

We describe a 25-year-old woman with multiple papules in the perianal and perineal area, clinically resembling condylomata acuminata. The histology revealed an acantholytic epidermis and focal parakeratosis. The lesions were diagnosed as Hailey-Hailey disease localized in the perianal areal and need to be distinguished from human papillomavirus-associated genital lesions.