bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of dual‐energy subtraction for converting CT numbers to electron density based on a single linear relationship
Authors: Saito Masatoshi
Published: March 2012

Purpose:

The conversion of the computed tomography (CT) number to electron density is one of the main processes that determine the accuracy of patient dose calculations in radiotherapy treatment planning. However, the CT number and electron density of tissues cannot be generally interrelated via a simple one‐to‐one correspondence because the CT number depends on the effective atomic number as well as the electron density. The purpose of this study is to present a simple conversion from the energy‐subtracted CT number (ΔHU) by means of dual‐energy CT (DECT) to the relative electron density (ρe) via a single linear relationship.

Methods:

The ΔHU–ρe conversion method was demonstrated by performing analytical DECT image simulations that were intended to imitate a second‐generation dual‐source CT (DSCT) scanner with an additional tin filtration for the high‐kV tube. The ΔHU–ρe calibration line was obtained from the image simulation with a 33 cm‐diameter electron density calibration phantom equipped with 16 inserts including polytetrafluoroethylene, polyvinyl chloride, and aluminum; the elemental compositions of these three inserts were quite different to those of body tissues. The ΔHU–ρe conversion method was also applied to previously published experimental CT data, which were measured using two different CT scanners, to validate the clinical feasibility of the present approach. In addition, the effect of object size on ρe‐calibrated images was investigated by image simulations using a 25 cm‐diameter virtual phantom for two different filtrations: with and without the tin filter for the high‐kV tube.

Results:

The simulated ΔHU–ρe plot exhibited a predictable linear relationship over a wide range of ρe from 0.00 (air) to 2.35 (aluminum). Resultant values of the coefficient of determination, slope, and intercept of the linear function fitted to the data were close to those of the ideal case. The maximum difference between the ideal and simulated ρe values was −0.7%. The satisfactory linearity of ΔHU–ρe was also confirmed from analyses of the experimental CT data. In the experimental cases, the maximum difference between the nominal and simulated ρe values was found to be 2.5% after two outliers were excluded. When compared with the case without the tin filter, the ΔHU–ρe conversion performed with the tin filter yielded a lower dose and more reliable ρe values that were less affected by the object‐size variation.

Conclusions:

The ΔHU–ρe calibration line with a simple one‐to‐one correspondence would facilitate the construction of a well‐calibrated ρe image from acquired dual‐kV images, and currently, second generation DSCT may be a feasible modality for the clinical use of the ΔHU–ρe conversion method.
Maternal depression and infant growth and development in British Pakistani women: a cohort study
Authors: Husain Nusrat , Cruickshank John Kennedy , Tomenson Barbara , Khan Sarah , Rahman Atif
Published: March 2012

Objectives

Perinatal depression has been found to be a strong and independent risk factor for poor child growth and development in low-income South Asian populations. The authors aimed to study if there was a similar association in first and second-generation British women of Pakistani origin.

Design

A prospective cohort study.

Setting

The study was conducted in the North-West of England, in areas with high density of Pakistani-origin population. The subjects were recruited from Central Manchester Hospital in the City of Manchester and East Lancashire Hospital in Lancashire.

Participants

704 physically healthy women were assessed in two phases (screening and detailed assessment of high scorers and a proportion of low scorers) during the third trimester of pregnancy to obtain at birth a cohort of 63 infants of depressed mothers and 173 infants of psychologically well mothers.

Primary and secondary outcome measures

All infants were weighed and measured at birth and 6 months, and their development was assessed using the Bayley Scales of Infant Development–Third Edition.

Results

There was no difference in the birth weight or weight and height at 6 months of infants of depressed mothers versus infants of psychologically well mothers. The only significant difference between the two groups was in the infants' adaptive behaviour; infants of depressed mothers scored significantly lower than those of psychologically well mothers (mean difference 4.6, t=2.81, df 195, p=0.006). The associations remained significant after adjustment for socio-demographic factors by multivariate analyses.

Conclusions

Prenatal depression is not associated with impaired growth in this sample of British Pakistani women. There is, however, an association of prenatal depression with parent-reported problems in the infants' adaptive behaviour. Further research is needed to understand various pathways through which maternal depression affects infant outcomes in low- and high-income settings.
Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa: a prospective cohort study
Authors: Olsen Birgitta , Månsson Fredrik , Camara Cidia , Monteiro Mario , Biai Ansu , Alves Alfredo , Andersson Sören , Norrgren Hans , Unemo Magnus
Published: March 2012

Background

Knowledge regarding characteristics and transmission ofNeisseria gonorrhoeae,Chlamydia trachomatisandMycoplasma genitaliumand antibiotic resistance inN gonorrhoeaein Guinea-Bissau, West Africa, is entirely lacking.

Objectives

To characteriseN gonorrhoeae,C trachomatisandM genitaliumsamples from Guinea-Bissau and to define bacterial populations, possible transmission chains and forN gonorrhoeaespread of antibiotic-resistant isolates.

Design

Prospective cohort study.

Setting

Two sexual health and family planning clinics, Bissau, Guinea-Bissau.

Participants

Positive samples from 711 women and 27 men.

Material and methods

Positive samples forN gonorrhoeae(n=31),C trachomatis(n=60) andM genitalium(n=30) were examined. The gonococcal isolates were characterised with antibiograms, serovar determination andN gonorrhoeaemultiantigen sequence typing (NG-MAST). TheC trachomatis ompAgene and theM genitalium mgpBgene were sequenced, and phylogenetic analyses were performed.

Results

ForN gonorrhoeae, the levels of resistance (intermediate susceptibility) to ciprofloxacin, erythromycin, rifampicin, ampicillin, tetracycline, penicillin G and cefuroxime were 10% (0%), 6% (10%), 13% (10%), 68% (0%), 74% (0%), 68% (16%) and 0% (84%), respectively. All isolates were susceptible to cefixime, ceftriaxone, spectinomycin and azithromycin, and the minimum inhibitory concentrations of kanamycin (range: 8–32 mg/l) and gentamicin (range: 0.75–6 mg/l) were low (no resistance breakpoints exist for these antimicrobials). 19 NG-MAST sequence types (STs) (84% novel STs) were identified. Phylogenetic analysis of theC trachomatis ompAgene revealed genovar G as most prevalent (37%), followed by genovar D (19%). 23mgpBSTs were found among theM genitaliumisolates, and 67% of isolates had unique STs.

Conclusions

The diversity among the sexually transmitted infection (STI) pathogens may be associated with suboptimal diagnostics, contact tracing, case reporting and epidemiological surveillance. In Guinea-Bissau, additional STI studies are vital to estimate the STI burden and form the basis for a national sexual health strategy for prevention, diagnosis and surveillance of STIs.
Decision-making by ambulance clinicians in London when managing patients with epilepsy: a qualitative study
Authors: Burrell Lisa , Noble Adam , Ridsdale Leone
Published: March 2012

Background

In the UK, epilepsy is the neurological condition with the highest rate of accident and emergency department re-attendance, with most arriving by ambulance. Ambulance clinicians triage patients and assess their need for attendance. This study examined the decision-making process of ambulance clinicians in these situations.

Methods

In-depth interviews with 15 ambulance clinicians working in South London.

Results

Interviewees identified that epileptic seizures that self-resolve present a triage challenge. They reported insufficient training and guidance available for these situations and substantial reliance on experience to direct their practice. Fears of litigation in the event of complications, pressures of public expectation and limited on-scene access to relevant patient information or appropriate alternative care pathways were reported to be significant factors influencing decisions for care for epilepsy seizures.

Discussion

Ambulance clinicians reported negotiating a balance between patient safety and patient choice, when deciding whether to transport a patient with epilepsy to hospital or not. Clinician fears and the pressures and limitations of practice may result in hospital conveyance being used as a safety precaution in some instances.

Conclusions

Decisions regarding conveyance of patients with epilepsy in this study were substantially guided by ambulance clinician experience rather than by robust training and guidelines. This study supports the need for improved guidance that addresses this common area of practice and the development of alternative care pathways that may be used by ambulance clinicians for patients with epilepsy.
Outcome and relapse risks of thrombotic thrombocytopaenic purpura: an Egyptian experience
Authors: El-Husseiny Noha M , Goubran Hady , Fahmy Hala M , Tawfik Nehad M , Moustafa Heba , Amin Sherif N , El-Ekiaby Magdy
Published: March 2012

Background

Thrombotic thrombocytopaenic purpura (TTP) is a rare life-threatening disease. Plasma exchange has significantly decreased the mortality from this disease, which still tends to recur in a substantial proportion of patients. This study describes the clinical spectrum and response to treatment and explores the risks of relapse in a cohort of patients.

Methods

Patients treated for TTP at the Clinical Haematology Unit, Cairo University, Egypt, between 2000 and 2008 were identified. Complete demographic, clinical history and full clinical examination, laboratory, treatment modalities and duration, and outcome data were collected and analysed. The follow-up duration was 24 months.

Results

30 patients; 13 men (43%) and 17 women (57%) with a median age of 42 years were treated for 46 episodes of TTP. The median duration of disease onset to diagnosis for the first episode was 7 days. Twenty-three patients (76.66%) were diagnosed as idiopathic primary and seven patients (23.33%) were secondary TTP. Four patients died during the first 24 h. Of the 26 patients, 22 (85.6%) achieved remission with an average of 7.55 plasma exchange sessions, Another nine patients had 25 relapses (mean 2.7). Splenectomy was performed in three patients (11.5%). The 24-month overall survival was 80%. The initial low platelet count and high LDH were the only two statistically significant relapse predictors.

Conclusions

The current results conform to the reported literature on the outcome of TTP. The very early mortality due to late referral highlights the need of education about the disease among primary healthcare providers.
IDEALS OF POLYNOMIAL SEMIRINGS IN TROPICAL MATHEMATICS
Authors: IZHAKIAN ZUR , ROWEN LOUIS
Published: March 2012

We describe the ideals, especially the prime ideals, of semirings of polynomials over layered domains, and in particular over supertropical domains. Since there are so many of them, special attention is paid to the ideals arising from layered varieties, for which we prove that every prime ideal is a consequence of finitely many binomials. We also obtain layered tropical versions of the classical Principal Ideal Theorem and Hilbert Basis Theorem.
ON δ-LOCAL MODULES AND AMPLY δ-SUPPLEMENTED MODULES
Authors: TRIBAK RACHID
Published: March 2012

The first part of this paper investigates the structure of δ-local modules. We prove that the following statements are equivalent for a module M:

(i) M is δ-local;

(ii) M is a coatomic module with either

(a) M is a semisimple module having a maximal submodule N such that N is projective and M/N is singular, or

(b) M has a unique essential maximal submodule K ≤ M such that for every maximal submodule L ≠ K, M/L is projective.

The second part establishes some properties of finitely generated amply δ-supplemented modules.
PROPERTIES OF SNYDER SPACE
Authors: STERN A.
Published: March 2012

We argue that Snyder's algebra has two distinct representations and they yield a lattice description of space. We also argue that particle dynamics can be defined on such a lattice in a manner which is consistent with Poincaré invariance.
Application of a homogenous membrane potential assay to assess mitochondrial function
Authors: Sakamuru Srilatha , Li Xiao , Attene-Ramos Matias S. , Huang Ruili , Lu Jianming , Shou Louie , Shen Min , Tice Raymond R. , Austin Christopher P. , Xia Menghang
Published: March 2012

Decreases in mitochondrial membrane potential (MMP) have been associated with mitochondrial dysfunction that could lead to cell death. The MMP is generated by an electrochemical gradient via the mitochondrial electron transport chain coupled to a series of redox reactions. Measuring the MMP in living cells is commonly used to assess the effect of chemicals on mitochondrial function; decreases in MMP can be detected using lipophilic cationic fluorescent dyes. To identify an optimal dye for use in a high-throughput screening (HTS) format, we compared the ability of mitochondrial membrane potential sensor (Mito-MPS), 5,5′,6,6′-tetrachloro-1,1′,3,3′ tetraethylbenzimidazolylcarbocyanine iodide, rhodamine 123, and tetramethylrhodamine to quantify a decrease in MMP in chemically exposed HepG2 cells cultured in 1,536-well plates. Under the conditions used, the optimal dye for this purpose is Mito-MPS. Next, we developed and optimized a homogenous cell-based Mito-MPS assay for use in 1,536-well plate format and demonstrated the utility of this assay by screening 1,280 compounds in the library of pharmacologically active compounds in HepG2 cells using a quantitative high-throughput screening platform. From the screening, we identified 14 compounds that disrupted the MMP, with half-maximal potencies ranging from 0.15 to 18 μM; among these, compound clusters that contained tyrphostin and 3′-substituted indolone analogs exhibited a structure-activity relationship. Our results demonstrate that this homogenous cell-based Mito-MPS assay can be used to evaluate the ability of large numbers of chemicals to decrease mitochondrial function.
Pendelluft in Chronic Obstructive Lung Disease Measured with Lung Sounds
Authors: Vyshedskiy Andrey , Murphy Raymond
Published: March 2012

Objective. The phenomenon of pendelluft was described over five decades ago. In patients with regional variations in resistance and elastance, gas moves at the beginning of inspiration out of some alveoli into others. Gas moves in the opposite direction at the end of inspiration. The objective of this study was to apply the method of lung sounds mapping, which is known to provide regional information about gas flow, to study pendelluft in COPD patients.Methods. A 16-channel lung sound analyzer was used to collect sounds from patients with COPD (n=90) and age-matched normals (n=90). Pendelluft at the beginning of inspiration is expected to result in vesicular sounds leading the tracheal sound by a few milliseconds. Pendelluft at the end of inspiration is expected to result in vesicular sounds lagging the tracheal sound. These lead and lag times were calculated for the 14 chest wall sites.Results. The lead time was significantly longer in COPD patients:123±107 ms versus48±59 ms in controls (P<0.0001). The lag time was also significantly longer in COPD patients:269±249 ms in COPD patients versus147±124 ms in controls (P<0.0001). When normalized by the duration of the inspiration at the trachea, the lead was14±13% for COPD versus4±5% for controls (P<0.0001). The lag was28±25% for COPD versus13±12% for controls (P<0.0001). Both lead and lag correlated moderately with the GOLD stage (correlation coefficient 0.43).Conclusion. Increased lead and lag times in COPD patients are consistent with the phenomenon of pendelluft as has been observed by other methods.
Antiproliferative Factor-Induced Changes in Phosphorylation and Palmitoylation of Cytoskeleton-Associated Protein-4 Regulate Its Nuclear Translocation and DNA Binding
Authors: Zacharias David A. , Mullen Matthew , Planey Sonia Lobo
Published: March 2012

Cytoskeleton-associated protein 4 (CKAP4) is a reversibly palmitoylated and phosphorylated transmembrane protein that functions as a high-affinity receptor for antiproliferative factor (APF)—a sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). Palmitoylation of CKAP4 by the palmitoyl acyltransferase, DHHC2, is required for its cell surface localization and subsequent APF signal transduction; however, the mechanism for APF signal transduction by CKAP4 is unknown. In this paper, we demonstrate that APF treatment induces serine phosphorylation of residues S3, S17, and S19 of CKAP4 and nuclear translocation of CKAP4. Additionally, we demonstrate that CKAP4 binds gDNA in a phosphorylation-dependent manner in response to APF treatment, and that a phosphomimicking, constitutively nonpalmitoylated form of CKAP4 localizes to the nucleus, binds DNA, and mimics the inhibitory effects of APF on cellular proliferation. These results reveal a novel role for CKAP4 as a downstream effecter for APF signal transduction.
The “Chimera”: An Off-The-Shelf CPU/GPGPU/FPGA Hybrid Computing Platform
Authors: Inta Ra , Bowman David J. , Scott Susan M.
Published: March 2012

The nature of modern astronomy means that a number of interesting problems exhibit a substantial computational bound and this situation is gradually worsening. Scientists, increasingly fighting for valuable resources on conventional high-performance computing (HPC) facilities—often with a limited customizable user environment—are increasingly looking to hardware acceleration solutions. We describe here a heterogeneous CPU/GPGPU/FPGA desktop computing system (the “Chimera”), built with commercial-off-the-shelf components. We show that this platform may be a viable alternative solution to many common computationally bound problems found in astronomy, however, not without significant challenges. The most significant bottleneck in pipelines involving real data is most likely to be the interconnect (in this case the PCI Express bus residing on the CPU motherboard). Finally, we speculate on the merits of our Chimera system on the entire landscape of parallel computing, through the analysis of representative problems from UC Berkeley’s “Thirteen Dwarves.”
Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease
Authors: Tikellis Chris , Thomas M. C.
Published: March 2012

Angiotensin-converting enzyme 2 (ACE2) shares some homology with angiotensin-converting enzyme (ACE) but is not inhibited by ACE inhibitors. The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1–7 (Ang 1–7) which opposes the actions of Ang II. Increased Ang II levels are thought to upregulate ACE2 activity, and in ACE2 deficient mice Ang II levels are approximately double that of wild-type mice, whilst Ang 1–7 levels are almost undetectable. Thus, ACE2 plays a crucial role in the RAS because it opposes the actions of Ang II. Consequently, it has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease where its expression is decreased. Not surprisingly, current therapeutic strategies for ACE2 involve augmenting its expression using ACE2 adenoviruses, recombinant ACE2 or compounds in these diseases thereby affording some organ protection.
Facile and One Pot Synthesis of Gold Nanoparticles Using Tetraphenylborate and Polyvinylpyrrolidone for Selective Colorimetric Detection of Mercury Ions in Aqueous Medium
Authors: Boopathi Sidhureddy , Senthilkumar Shanmugam , Phani Kanala Lakshminarasimha
Published: March 2012

In this work, we reported for the first time, a facile and one step synthesis of gold nanoparticles from HAuCl4, employing tetraphenylborate as the reducing agent. The synthesis is not only facile but also yields “dumb-bell-shaped”particles. This shape appears to arise from a possible emulsion of the products of oxidation/decomposition of tetraphenylborate by HAuCl4, surrounding the particle. The size and shape of the AuNPs were characterized by Transmission electron microscopy (TEM) and UV-visible Spectroscopy. Interestingly, the addition of polyvinylpyrrolidone (PVP) during the synthesis was found to enhance the stability of the nanoparticle dispersion. The particles synthesized under these conditions assume “spherical” shape with the appearance of only transverse surface plasmon resonance band. The highlight of the observations is that the gold nanoparticles synthesized using tetraphenylborate as reducing agent and PVP as stabilizer are highly stable in alkaline medium, in contrast to the synthesis wherein borohydride is used as reducing agent. The AuNPs synthesized using tetraphenylborate and PVP show their mercury sensing behavior only in the alkaline medium. The color of the nanoparticle dispersion undergoes distinct color change from pink to blue with the addition of mercury ions. They also show dramatic selectivity to mercury ions in presence of other interfering ions, Pb2+, Zn2+and Ca2+.
Asymptotic Stability of the Golden‐Section Control Law for Multi‐Input and Multi‐Output Linear Systems
Authors: Sun Duo-Qing , Sun Zhu-Mei
Published: March 2012

This paper is concerned with the problem of the asymptotic stability of the characteristic model‐based golden‐section control law for multi‐input and multi‐output linear systems. First, by choosing a set of polynomial matrices of the objective function of the generalized least‐square control, we prove that the control law of the generalized least square can become the characteristic model‐based golden‐section control law. Then, based on both the stability result of the generalized least‐square control system and the stability theory of matrix polynomial, the asymptotic stability of the closed loop system for the characteristic model under the control of the golden‐section control law is proved for minimum phase system.
A Microwave Holographic Procedure for Large Symmetric Reflector Antennas Using a Fresnel-Zone Field Data Processing
Authors: Mazzarella Giuseppe , Montisci Giorgio , Serra Giampaolo
Published: March 2012

In this paper we propose a new holographic procedure for the diagnostic of large reflector antennas, based on the direct use of the Fresnel-field pattern. The relation leading from the Fresnel field to the current on the reflector surface is formulated in the least-squares sense as a discrete data inverse problem and then regularized by using a singular value decomposition approach. A detailed theoretical analysis of the problem and full assessment of the presented technique are provided. Simulations are carried out by using the radiative near-field pattern generated with a commercial software. Results show good accuracy and robustness to noise for the retrieval of the panel-to-panel misalignment of a reflector antenna.
Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP
Authors: Jiao Liyan , Li Hanping , Li Lin , Zhuang Daomin , Liu Yongjian , Bao Zuoyi , Liu Siyang , Li Jingyun
Published: March 2012

Objective. To clarify the impact of H221Y mutation on drug resistance to NVP.Methods. 646 bp HIV-1polgene fragments (from 592 to 1237 nucleotide) with different NNRTIs mutation profiles from AIDS patients receiving antiretroviral therapy containing NVP regimens were introduced into pNL4-3 backbone plasmid. H221Y and (or) Y181C mutations were reverted to wild type amino acids by site-directed mutagenesis, then strains containing various mutation patterns were packaged. Phenotypic drug resistance was analyzed on TZM-bl cells.Results. 12 strains containing different drug-resistant mutation profiles were constructed, including the K101Q series (K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, and K101Q), the V179D series (V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, and V179D), and the K103N series (K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, K103N). For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by2.1±0.5to3.6±0.5fold. To the mutation profiles K101Q/H221Y, K101Q, V179D/H221Y, V179D, K103N/H221Y, and K103N, the presence of Y181C reduced NVP susceptibility by41.9±8.4to1297.0±289.1fold. For the strains containing K101Q, V179D, and K103N, the presence of Y181C/H221Y combination decreased NVP susceptibility by100.6±32.5to3444.6±834.5fold.Conclusion. On the bases of various NNRTIs mutation profiles, Y181C remarkably improved the IC50to NVP, although H221Ymutation alone just increases 2.1 ∼ 3.6-fold resistance to NVP, the mutation could improve 100.6 ∼ 3444.6-fold resistance to NVP when it copresent with Y181C, the phenotypic drug resistance fold was improved extremely. For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by2.1±0.5to3.6±0.5fold.
Enhanced Supercapacitance of Hydrous Ruthenium Oxide/Mesocarbon Microbeads Composites toward Electrochemical Capacitors
Authors: Yuan Changzhou , Hou Linrui , Li Diankai , Yang Long , Li Jiaoyang
Published: March 2012

A facile hydrothermal strategy was proposed to synthesize RuO2⋅nH2O/mesocarbon microbeads (MCMBs) composites. Further physical characterizations revealed that RuO2⋅nH2O nanoparticles (NPs) were well dispersed upon the surfaces of the MCMB pretreated in 6 M KOH solution. Electrochemical data indicated that the RuO2⋅nH2O/MCMB composites owned higher electrochemical utilization of RuO2species, better power property, and better electrochemical stability, compared with the single RuO2phase. The good dispersion of RuO2⋅nH2O NPs and enhanced electronic conductivity made the H+ions and electrons easily contact the RuO2⋅nH2O phase for efficient energy storage at high rates.
Association Analysis ofULK1with Crohn’s Disease in a New Zealand Population
Authors: Morgan Angharad R. , Lam Wen-Jiun , Han Dug-Yeo , Fraser Alan G. , Ferguson Lynnette R.
Published: March 2012

The geneULK1is an excellent candidate for Crohn’s disease (CD) due to its role in autophagy. A recent study provided evidence for the involvement ofULK1in the pathogenesis of CD (Henckaerts et al., 2011). We attempted to validate this association, using a candidate gene SNP study ofULK1in CD. We identified tagging SNPs and genotyped these SNPs using the Sequenom platform in a Caucasian New Zealand dataset consisting of 406 CD patients and 638 controls. In this sample, we were able to demonstrate an association between CD and several differentULK1SNPs and haplotypes. Phenotypic analysis showed an association with age of diagnosis 17–40 years and inflammatory behaviour. The findings of this study provide evidence to suggest that genetic variation inULK1may play a role in interindividual differences in CD susceptibility and clinical outcome.
Transcranial Magnetic Stimulation with the Maximum Voluntary Muscle Contraction Facilitates Motor Neuron Excitability and Muscle Force
Authors: Touge Tetsuo , Urai Yoshiteru , Ikeda Kazuyo , Kume Kodai , Deguchi Kazushi
Published: March 2012

Three trials of transcranial magnetic stimulation (TMS) during the maximum voluntary muscle contraction (MVC) were repeated at 15-minute intervals for 1 hour to examine the effects on motor evoked potentials (MEPs) in the digital muscles and pinching muscle force before and after 4 high-intensity TMSs (test 1 condition) or sham TMS (test 2 condition) with MVC. Under the placebo condition, real TMS with MVC was administered only before and 1 hour after the sham TMS with MVC. Magnetic stimulation at the foramen magnum level (FMS) with MVC was performed by the same protocol as that for the test 2 condition. As a result, MEP sizes in the digital muscles significantly increased after TMS with MVC under test conditions compared with the placebo conditions (P<0.05). Pinching muscle force was significantly larger 45 minutes and 1 hour after TMS with MVC under the test conditions than under the placebo condition (P<0.05). FMS significantly decreased MEP amplitudes 60 minutes after the sham TMS with MVC (P<0.005). The present results suggest that intermittently repeated TMS with MVC facilitates motor neuron excitabilities and muscle force. However, further studies are needed to confirm the effects of TMS with MVC and its mechanism.
An Apoptosis Methylation Prognostic Signature for Early Lung Cancer in the IFCT-0002 Trial
Authors: de Fraipont Florence , Levallet Guénaëlle , Creveuil Christian , Bergot Emmanuel , Beau-Faller Michèle , Mounawar Mounia , Richard Nicolas , Antoine Martine , Rouquette Isabelle , Favrot Marie-Christine , Debieuvre Didier , Braun Denis , Westeel Virginie , Quoix Elisabeth , Brambilla Elisabeth , Hainaut Pierre , Moro-Sibilot Denis , Morin Franck , Milleron Bernard , Zalcman Gérard
Published: March 2012

Purpose: To evaluate prognostic and predictive molecular biomarkers in early-stage non–small cell lung carcinoma (NSCLC) receiving neoadjuvant chemotherapy.

Experimental Design: The IFCT-0002 trial compared two neoadjuvant regimens in 528 stages I to II NSCLC patients. DNA extraction of snap-frozen surgical samples taken from 208 patients receiving gemcitabine-cisplatin or paclitaxel-carboplatin regimens allowed for the identification of 3p allelic imbalance, Ras association domain family 1A (RASSF1A) and death-associated protein kinase 1 (DAPK1) promoter methylation, and epidermal growth factor receptor, K-ras, and TP53 mutations. Multivariate analysis identified prognostic and predictive effects of molecular alterations. A Bootstrapping approach was used to assess stability of the prognostic models generating optimism corrected indexes.

Results: RASSF1A methylation correlated significantly with shorter disease-free survival (DFS; adjusted HR = 1.88, 95% CI: 1.25–2.82, P = 0.0048) and shorter median overall survival (OS; adjusted HR = 2.01, 95% CI: 1.26–3.20, P = 0.020). A computed bootstrap resampling strategy led to a prognostic model, including RASSF1A, DAPK1, and tumor stage, dividing patients into three prognostic groups, with median OS ranging from 34 months for high-risk patients (HR for death = 3.85, 95% CI: 1.79–6.40) to more than 84 months for moderate (HR = 1.85, 95% CI: 0.97–3.52) and low-risk patients (reference group; P = 0.00044). In addition, RASSF1A methylation predicted longer DFS in patients treated with paclitaxel-carboplatin compared with gemcitabine-cisplatin (adjusted HR = 0.47, 95% CI: 0.23–0.97, Pinteraction = 0.042).

Conclusions: Following neoadjuvant chemotherapy, RASSF1A methylation negatively impacted prognosis of early-stage NSCLC. Along with DAPK1 methylation and tumor stage, RASSF1A methylation allowed definition of three subgroups with strikingly different prognosis. Conversely, significantly longer DFS following paclitaxel-based neoadjuvant chemotherapy for patients whose tumors showed RASSF1A methylation suggested its predictive interest in stages I and II NSCLC. Clin Cancer Res; 18(10); 2976–86. ©2012 AACR.
Expression Levels of Vascular Cell Adhesion Molecule-1 in Young and Nonobese Women with Polycystic Ovary Syndrome
Authors: Seow Kok-Min , Juan Chi-Chang , Wang Peng-Hui , Ho Low-Tone , Hwang Jiann-Loung
Published: March 2012

Background/Aims: The objective of this study was to measure levels of mRNAs for inflammatory markers and resistin in human peripheral blood mononuclear cells (PBMCs) in young and nonobese women with polycystic ovary syndrome (PCOS). Methods: Fifteen young, nonobese women with PCOS and 10 age-matched controls were enrolled in this study. Levels of mRNAs for resistin and the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human PBMCs were measured using real-time PCR. Results: The mean age and BMI of the women with PCOS were 27.54 ± 6.3 years and 27.4 ± 5.7, respectively. The women with PCOS had significantly higher fasting and 2-hour insulin levels, homeostasis model assessment of insulin resistance index (HOMAIR) and total cholesterol levels than the controls. VCAM-1 and ICAM-1 mRNA levels were significantly higher in women with PCOS than in controls, whereas no differences in resistin, IL-6, TNF-α and MCP-1 mRNA levels were observed between the groups. After adjusting for the BMI, only VCAM-1 mRNA levels were significantly higher in women with PCOS than in controls and correlated with the HOMAIR and total cholesterol. Conclusion: Elevated VCAM-1 in human PBMCs in young, nonobese women with PCOS is associated with insulin resistance, independent of the BMI.
Quantitative High-Field Diffusion Tensor Imaging of Cerebral White Matter in Asymptomatic High-Grade Internal Carotid Artery Stenosis
Authors: Herweh C. , Attigah N. , Nagel S. , Demirel S. , Ringleb P.A. , Boeckler D. , Bendszus M.
Published: March 2012

Background: Recently, several studies using diffusion-sensitized MRI reported changes in patients with high-grade internal carotid artery stenosis (ICAS) suggestive of subtle brain tissue damage. We used diffusion tensor imaging (DTI) to investigate the microstructural cerebral white matter integrity in asymptomatic patients with high-grade ICAS. Methods: In 15 asymptomatic patients with unilateral high grade (>70%) ICAS, we used 3T MRI including DTI. We used a region-of-interest approach comparing quantitative DTI metrics between both hemispheres including the so-called border zones. MR images were also assessed for periventricular white matter lesions (PWML) as well as collaterals via the circle of Willis. Results: There was no significant intraindividual difference of fractional anisotropy or mean diffusivity values between the hemispheres for any region. PWML was graded 0° in 6 patients, I° in 9 and II° in 2. Conclusions: In clinically asymptomatic patients with high-grade unilateral ICAS, there was no difference between the DTI parameters of the affected and the unaffected hemisphere. These findings contrast with other studies in asymptomatic high-grade ICAS, which is likely due to patient selection. These findings argue against concomitant chronic tissue integrity changes and implicate the benignity of asymptomatic carotid artery disease in individual patients.
Nicotinic Acetylcholine Receptor Expression and Susceptibility to Cholinergic Immunomodulation in Human Monocytes of Smoking Individuals
Authors: van der Zanden Esmerij P. , Hilbers Francisca W. , Verseijden Caroline , van den Wijngaard Rene M. , Skynner Mike , Lee Kevin , Ulloa Luis , Boeckxstaens Guy E. , de Jonge Wouter J.
Published: March 2012

Objective: Smoking is generally accepted as a factor that affects the disease course in inflammatory bowel disease patients. Whether these effects can be contributed to the immunomodulatory effects of nicotine via nicotinic acetylcholine receptor (nAChR) activation is unclear. As previous data suggest that the α7 nicotinic acetylcholine receptor (CHRNA7) and its duplicated variant CHRFAM7A may specifically participate in the inflammatory response of monocytes, we evaluated whether repeated nicotine exposure or smoking affects monocyte CHRNA7 and CHRFAM7A expression and cholinergic immunomodulation. Methods: The human monocyte cell line THP-I was incubated with nicotine for different time points before endotoxin exposure. In a pilot volunteer study using smoking (n = 4) and nonsmoking (n = 7) individuals, vagal output was stimulated by olive oil administration after which monocytes were analyzed for nicotinic receptor expression. Serum tumor necrosis factor (TNF) levels were determined using ELISA and expression levels of the nAChR subunits CHRNA7, CHRNB2 or CHRFAM7A were analyzed using QPCR. Results: Repeated nicotine exposure upregulated CHRNA7 expression on THP-I monocytes and led to an enhanced potential of α7 nAChR agonist GSK1345038A to reduce TNF levels. Furthermore, CHRNA7 was only detectable in isolated blood monocytes of smokers. On the other hand, the expression of CHRFAM7A and CHRNB2 was not affected by nicotine exposure. Lipopolysaccharides-induced TNF secretion was inhibited by nicotinic receptor activation in THP-I monocytes, but this response was not consistently seen in blood monocytes from smoking individuals. Conclusions: We conclude that CHRNA7 expression on blood monocytes is upregulated in smoking individuals, which may contribute to cholinergic immunomodulation.
Macrophages and Systemic Iron Homeostasis
Authors: Ganz Tomas
Published: March 2012

As a principal aspect of their scavenging function, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recover iron, mainly for the production of hemoglobin in new erythrocytes but also for other carriers and enzymes requiring iron. Splenic red pulp macrophages are specialized for iron recycling with increased expression of proteins for the uptake of hemoglobin, breakdown of heme and the export of iron. In humans, recycling macrophages contribute the majority of the iron flux into extracellular fluid, exceeding the contribution of dietary iron absorption and release of stored iron from hepatocytes. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin. In addition to their homeostatic role, macrophages employ multiple mechanisms to contain microbial infections by depriving microbes of iron. This review discusses the iron-scavenging function of macrophages in the context of iron homeostasis and host defense.
Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer
Authors: Sterlacci William , Fiegl Michael , Tzankov Alexandar
Published: March 2012

Non-small-cell lung cancer (NSCLC) is among the most frequently diagnosed malignancy and a leading cause for cancer mortality worldwide. Despite various efforts, practical prognostic and predictive markers are still few. We review recent findings concerning the cell cycle in NSCLC and discuss prognostic and predictive aspects as well as the challenge of targeted therapeutic approaches. Deregulation of the cell cycle is a common event in NSCLC. Usually, several defects of cell cycle regulation are concomitant and have a cumulative adverse effect on prognosis. Therefore, analysis of a variety of interacting molecules is desirable for adequate deductions. Immunohistochemical interpretations should include the subcellular staining localization, since this can reflect the functional properties of a protein. Overexpression of cyclins, especially D-type cyclins, has repeatedly been associated with poor prognosis in NSCLC. Predictive data is less conclusive; however, loss of the expression of cyclin-dependent kinase inhibitors seems to correlate with sensitivity to antiproliferative drugs. Various inhibitors of Aurora kinases are currently being evaluated regarding their potential as targeted therapies in NSCLC. In conclusion, the cell cycle offers several prognostic, predictive and therapeutic possibilities in NSCLC, many still developmental. Progress in this field has the potential to improve the current scenario for NSCLC patients.
Effect of Moderate Elevation above Sea Level on Blood Oxygen Saturation in Healthy Young Adults
Authors: Goldberg Shmuel , Buhbut Eadit , Mimouni Francis B. , Joseph Leon , Picard Elie
Published: March 2012

Background: Arterial hemoglobin oxygen saturation (SaO2) decreases at an altitude of >1,500 m. There are no reports on normal SaO2 at altitudes between 0 and 1,500 m. The clinical significance of decreased SaO2 at such altitudes is unclear. Objective: To test the hypothesis that in healthy volunteers normal SaO2 at moderate altitude (MA; 725 m) is lower than that at almost sea level (SL; 43 m). Methods: SaO2 was measured by transcutaneous pulse oximetry in young healthy volunteers at MA and was compared to equivalent measurements at SL. In addition, a 6-min walk test was performed and SaO2 at the end of the walk was compared between the two locations. Results: 111 males were checked at MA and 101 at SL. At rest, nadir SaO2 was 95% at MA compared to 97% at SL. Mean SaO2 at rest was slightly higher at SL (98.53 ± 0.52) compared to MA (98.11 ± 0.8; p < 0.01). In subjects who completed the 6-min walk test, SaO2 slightly decreased after the test in both locations, by 0.38 ± 0.65% in the SL group and by 0.37 ± 1.12% in the MA group. This difference is not statistically significant by univariate analysis; however, a multiple regression analysis indicated that the drop in SaO2 was higher at MA than at low altitude. Conclusions: We found a low but significant difference in SaO2 between near-SL and at an altitude of 725 m. The clinical significance of this difference, in terms of human health, is probably minimal.
β-Defensins: Multifunctional Modulators of Infection, Inflammation and More?
Authors: Semple Fiona , Dorin Julia R.
Published: March 2012

Defensins comprise one of the largest groups of host defence peptides, present throughout evolution, in fungi and flowering plants as well as in invertebrates and vertebrates. These cysteine-rich, cationic peptides have a common ability to kill a broad range of microorganisms including bacteria, yeast and viruses. As such, they are a strong component of the arsenal that is an organism’s innate immunity. It is becoming increasingly clear, however, that antimicrobial action is only one of the numerous roles of these multifunctional peptides. In recent years, the functions of defensins in immunomodulation have been widely investigated, and their involvement in other processes (such as fertility) is becoming evident. This review addresses recent advances in the immunomodulatory activity of β-defensins as well as the involvement of β-defensins in fertility, development, wound healing and cancer.
Prediction of Optimal Deployment Projection for Transcatheter Aortic Valve Replacement
Authors: Binder Ronald K. , Leipsic Jonathon , Wood David , Moore Teri , Toggweiler Stefan , Willson Alex , Gurvitch Ronen , Freeman Melanie , Webb John G.
Published: March 2012

Background—

Identifying the optimal fluoroscopic projection of the aortic valve is important for successful transcatheter aortic valve replacement (TAVR). Various imaging modalities, including multidetector computed tomography (MDCT), have been proposed for prediction of the optimal deployment projection. We evaluated a method that provides 3-dimensional angiographic reconstructions (3DA) of the aortic root for prediction of the optimal deployment angle and compared it with MDCT.

Methods and Results—

Forty patients undergoing transfemoral TAVR at St Paul's Hospital, Vancouver, Canada, were evaluated. All underwent preimplant 3DA and 68% underwent preimplant MDCT. Three-dimensional angiographic reconstructions were generated from images of a C-arm rotational aortic root angiogram during breath-hold, rapid ventricular pacing, and injection of 32 mL contrast medium at 8 mL/s. Two independent operators prospectively predicted perpendicular valve projections. The implant angle was chosen at the discretion of the physician performing TAVR. The angles from 3DA, from MDCT, the implant angle, and the postdeployment perpendicular prosthesis view were compared. The shortest distance from the postdeployment perpendicular prosthesis projection to the regression line of predicted perpendicular projections was calculated. All but 1 patient had adequate image quality for reproducible angle predictions. There was a significant correlation between 3DA and MDCT for prediction of perpendicular valve projections (
r
=0.682,
P
<0.001). Deviation from the regression line of predicted angles to the postdeployment prosthesis view was 5.1±4.6° for 3DA and 7.9±4.9° for MDCT (
P
=0.01).

Conclusions—

Three-dimensional angiographic reconstructions and MDCT are safe, practical, and accurate imaging modalities for identifying the optimal perpendicular valve deployment projection during TAVR.
Most Important Papers in Health Costs, Cost-Effectiveness, and Resource Utilization
Authors: Dharmarajan Kumar , Lampropulos Julianna , Bikdeli Behnood , Mody Purav , Gupta Aakriti ,   for The Editor
Published: March 2012

The following are highlights from the new series,
Circulation: Cardiovascular Quality and Outcomes Topic Review
. This series will summarize the most important manuscripts (as selected by the Editor) that have published in the
Circulation
portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes, and general cardiology audience. The studies included in this article represent the most significant research in the area of health costs, cost-effectiveness, and resource utilization.
The Psychological Profile of White-collar Offenders
Authors: Ragatz Laurie L. , Fremouw William , Baker Edward
Published: March 2012

The authors replicated Walters and Geyer (2004) by examining how white-collar offenders differ from non-white-collar offenders on criminal thinking and lifestyle criminality. To extend Walters and Geyer’s work, they explored psychopathic characteristics and psychopathology of white-collar offenders compared with non-white-collar offenders. The study sample included 39 white-collar only offenders (offenders who had committed only white-collar crime), 88 white-collar versatile offenders (offenders who previously had committed non-white-collar crime), and 86 non-white-collar offenders incarcerated in a federal prison. Groups were matched on age and ethnicity. Offenders completed self-report measures of criminal thinking, psychopathic traits, and psychopathology. Lifestyle criminality was gathered via file review. Results demonstrated white-collar offenders had lower scores on lifestyle criminality but scored higher on some measures of psychopathology and psychopathic traits compared with non-white-collar offenders. White-collar versatile offenders were highest in criminal thinking. Logistic regression findings demonstrated that white-collar offenders could be distinguished from non-white-collar offenders by substance use.
The Graduate School Application Process
Authors: Sanders Cheryl E. , Landrum R. Eric
Published: March 2012

One hundred and thirty-four undergraduate psychology majors completed a survey assessing their evaluative ratings of importance of factors related to the graduate school application process. Results revealed that students rated issues with research experience, letters of recommendation, and GPA as strongly important. These results support efforts to enhance the preparation of undergraduate psychology students who aspire to attend graduate school.
Why Do People Move Their Eyes When They Think?
Authors: Ehrlichman Howard , Micic Dragana
Published: March 2012

The saccadic eye movements that people make when thinking have been largely ignored in the eye-movement literature. Nevertheless, there is evidence that such eye movements are systematically related to internal thought processes. On average, people move their eyes about twice as often when searching through long-term memory as they do when engaged in tasks that do not require such search. This pattern occurs when people are in face-to-face situations, when they are in the dark, and when they have their eyes closed. Because these eye movements do not appear to serve visual processing, we refer to them as “nonvisual” eye movements and discuss why the eyes move during thinking that does not involve vision.