bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic position indicators and periodontitis: examining the evidence
Authors: Borrell Luisa N. , Crawford Natalie D.
Published: December 2011

Socioeconomic factors, such as education and income, are associated with disparities in the prevalence and severity of periodontal disease, and this has been recognized since the 1960s. Epidemiological reports have consistently shown that periodontal disease is inversely related to education and income after controlling for age and gender, and that differences in education and income explain most if not all of the observed disparities in periodontal disease between blacks and whites. Although race/ethnicity has been the main focus of studies on differences in periodontal diseases in the USA, periodontal disease disparities according to socioeconomic position (SEP) indicators (i.e. education, income, poverty–income ratio) remain pervasive in the USA. SEP indicators, as used in the epidemiological literature, involve use of socioeconomic measures as a proxy measure for an individual’s place, position and power in society. Thus, understanding disparities according to SEP indicators in periodontal health status may provide insight into why racial/ethnic disparities in periodontal health status persist. Here we review recent prevalence estimates of periodontitis according to SEP indicators, and critically assess the importance of SEP factors in periodontal epidemiolgy. The majority of the data available for review come from the USA. However, data from other countries are included where available. Specifically, we identify the advantages and disadvantages of the most commonly used SEP indicators in studying periodontal disease, summarize existing evidence on the association between SEP indicators and periodontitis, discuss the analytical issues associated with SEP indicators, and suggest future and alternative research directions for examining the association between SEP indicators and periodontitis.
Development of prognostic indicators using classification and regression trees for survival
Authors: Nunn Martha E. , Fan Juanjuan , Su Xiaogang , Levine Richard A. , Lee Hyo‐Jung , McGuire Michael K.
Published: December 2011

Development of an accurate prognosis is an integral component of treatment planning in the practice of periodontics. Prior work has evaluated the validity of using various clinical measured parameters for assigning periodontal prognosis as well as for predicting tooth survival and change in clinical conditions over time. We critically review the use of multivariate classification and regression trees (CART) for survival in developing evidence‐based periodontal prognostic indicators. We focus attention on two distinct methods for multivariate CART for survival: the marginal goodness‐of‐fit approach and the multivariate exponential approach. A number of common clinical measures have been found to be significantly associated with tooth loss from periodontal disease, including furcation involvement, probing depth, mobility, crown/root ratio and oral hygiene. However, the inter‐relationships among these measures, as well as the relevance of other clinical measures to tooth loss from periodontal disease (such as bruxism, family history of periodontal disease and overall bone loss), remain less clear. Although the inferences that can be drawn from any single study are necessarily limited, application of new approaches in epidemiological analyses to periodontal prognosis, such as CART for survival, should yield important insights into our understanding and treatment of periodontal diseases.
Delayed cutaneous wound healing in aged rats compared to younger ones
Authors: Soybir Onur C , Gürdal Sibel Ö , Oran Ebru Ş , Tülübaş Feti , Yüksel Meral , Akyıldız Ayşenur İ , Bilir Ayhan , Soybir Gürsel R
Published: December 2011

Delayed wound healing in elderly males is a complex process in which the factors responsible are not fully understood. This study investigated the hormonal, oxidative and angiogenic factors affecting wound healing in aged rats. Two groups consisting of eight healthy male Wistar Albino rats [young (30 ± 7 days) and aged (360 ± 30 days)], and a cutaneous incision wound healing model were used. Scar tissue samples from wounds on the 7th, 14th and 21st days of healing were evaluated for hydroxyproline and vascular endothelial growth factor content. Macrophage, lymphocyte, fibroblast and polymorphonuclear cell infiltration; collagen formation and vascularization were assessed by light and electron microscopy. The free oxygen radical content of the wounds was measured by a chemiluminescence method. Blood sample analysis showed that the hydroxyproline and total testosterone levels were significantly higher, and the oxygen radical content was significantly lower in young rats. Histopathological, immunohistochemical and ultrastructural evaluations revealed higher amounts of fibroblasts and collagen fibers, and more vascularization in young rats. These results are indicative of the delayed wound healing in aged rats. A combination of multiple factors including hormonal regulation, free oxygen radicals and impaired angiogenesis appears to be the cause of delayed cutaneous healing.
Evidence of aeolian sediment transport across an Ammophila arenaria‐dominated foredune, Mason Bay, Stewart Island
Authors: Petersen Philip S. , Hilton Michael J. , Wakes Sarah J.
Published: December 2011

Aeolian sedimentation across an Ammophila arenaria‐dominated foredune was assessed for eight months using sand traps. This research aimed to ascertain if such foredunes act as a barrier to transport between beaches and hinterland dune systems. At Mason Bay, sand was transported across the foredune at rates of up to 10 kg.hour−1per 100 m length of coast at wind velocities of 31 m.s−1. Results were compared with computational fluid dynamics modelled airflows and foredune volume changes. Saltation was important for up to 17 m past the stoss face. Rates of transport were well short of rates of volume gain. Approximately 2% or less of stoss face suspended sediment transport reached the hinterland. The foredune is primarily a sand sink.
Thirty years of primary immunodeficiencies in Turkey
Authors: Sanal Ozden , Tezcan Ilhan
Published: December 2011

Turkey, with its population of some 75 million, has a high rate of consanguineous marriages. Because the majority of the primary immunodeficiencies (PIDs) are inherited as autosomal recessive (AR) forms, the high consanguinity rate leads to a high prevalence of PID diseases in Turkey. The first pediatric immunology division was established in 1972, since then over 10 other immunology divisions have been established in different cities. Approximately 4,000 patients with possible PID are referred to these centers annually. The percentages of some of the major immunodeficiency groups and individual disease numbers among these patients differ somewhat in comparison with Western countries, likely because the relative incidences of PIDs with AR inheritance and of rare diseases are higher. These characteristics of the patient population, and our determination of differences in disease presentation and unusual features, have led us to undertake studies in collaboration with various centers in Western countries. These collaborations have contributed to the identification of the genes responsible for some rare immunodeficiencies, to the resolution of the genetic heterogeneity underlying conventional phenotypes, and to the description of new clinical phenotypes.
The creation and progress of the J Project in Eastern and Central Europe
Authors: Maródi László ,   the J Project Study Group
Published: December 2011

Primary immunodeficiencies (PIDs) have now become recognized as a worldwide health problem. Rapid development of immunological and genetic technologies has led to the discovery of more than 200 PIDs and more than 150 disease‐related genes. Progress in the field is expected to take a new turn after the introduction of new‐generation sequencing technologies that will enable searches for currently unknown PID‐related genes. By contrast, even with progress in molecular genetics, many patients remain ill and die early because of the lack of diagnostic or treatment facilities, or both. Thus, the gap between the knowledge accumulated and the appropriate management of patients with PIDs in everyday clinical practice has widened, necessitating PID awareness, particularly in countries with poor socioeconomic conditions. The J Project, established as a physician education and research collaboration program in Eastern and Central Europe, demonstrates how professional responsibility and long‐term joint efforts can make a beneficial difference for patients with inborn errors of immunity.
Hemoglobin A1c for the diagnosis of diabetes: To replace or to guide oral glucose tolerance tests?
Authors: Li Hung‐Yuan , Ma Wen‐Ya , Wei Jung‐Nan , Lin Mao‐Shin , Shih Shyang‐Rong , Hung Chi Sheng , Hua Cyue‐Huei , Chuang Lee‐Ming
Published: December 2011

Aims/Introduction:  To evaluate if hemoglobin A1c (A1C) can replace the use of the oral glucose tolerance test (OGTT) to diagnose diabetes in Chinese patients.

Materials and Methods:  Subjects without pre‐existing diabetes were included in this community‐based study. Each participant received a 75‐g OGTT and A1C tests.

Results:  A total of 1362 subjects, 512 men and 850 women, aged 18–88 years, were enrolled. The prevalence of diabetes was 7.4 and 7.3% by OGTT and by A1C ≥ 6.5% criteria, respectively. The optimal A1C cut‐off for diabetes defined by OGTT was 6.1%. The performance of A1C ≥ 6.1% to find diabetes by OGTT was poor, with a kappa 0.50, sensitivity 80% and specificity 91%. Using current criteria of fasting plasma glucose (FPG) < 5.56 mmol/L to exclude and ≥7 mmol/L to diagnose diabetes (FPG criterion), the sensitivity, specificity and OGTT required were 77.2, 100 and 13.5%, respectively. Using A1C < 5.9% to exclude and ≥7.0% to diagnose diabetes (A1C criterion), the sensitivity, specificity and OGTT required were 89.1, 99.8 and 26.5%, respectively. However, using FPG < 5.56 mmol/L and A1C < 6.1% to exclude, and A1C ≥ 7.0% to diagnose diabetes (A1C plus FPG criterion), the sensitivity, specificity and OGTT required were 85.2, 100 and 18.9%, respectively.

Conclusions:  To screen for diabetes, the A1C criterion is more sensitive than the FPG criterion, with more OGTT needed. The A1C plus FPG criterion reduced the number of OGTT needed with acceptable sensitivity. A1C can guide, but cannot replace, OGTT to diagnose diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00181.x, 2011)
Thiazolidinedione‐independent activation of peroxisome proliferator‐activated receptor γ is a potential target for diabetic macrovascular complications
Authors: Matsumura Takeshi , Taketa Kayo , Shimoda Seiya , Araki Eiichi
Published: December 2011

Macrovascular complications are responsible for the high morbidity and mortality in patients with diabetes. Peroxisome proliferator‐activated receptor γ (PPARγ) plays a central role in the process of adipocyte differentiation and insulin sensitization, and also possesses anti‐atherogenic effects. Recently, some statins, angiotensin II type 1 receptor blockers and calcium channel blockers have been reported to activate PPARγ. However, the impact of PPARγ activation on diabetic macrovascular complications is not fully understood. It has been reported that the activation of PPARγ by thiazolidinediones induces anti‐atherogenic effects in vascular cells, including monocytes/macrophages, endothelial cells and smooth muscle cells, in atherosclerotic animal models and in clinical studies. We have reported that hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which are used for treatment of hypercholesterolemia, activate PPARγ and mediate anti‐atherogenic effects through PPARγ activation in macrophages. Also, telmisartan, an angiotensin type I receptor blocker, has been reported to have anti‐atherogenic effects through PPARγ activation. Furthermore, we have reported that nifedipine, a dihydropyridine calcium channel blocker, can activate PPARγ, thereby mediating anti‐atherogenic effects in macrophages. Therefore, statin therapy and part of anti‐hypertensive therapy might produce beneficial effects through PPARγ activation in hypercholesterolemic and/or hypertensive patients with diabetes, and PPARγ might be a therapeutic target for diabetic macrovascular complications. In the present review, we focus on the anti‐atherogenic effects of PPARγ and suggest potential therapeutic approaches to prevent diabetic macrovascular complications. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00182.x, 2012)
RECONSTRUCTING WHAT ROMAN REPUBLIC?
Authors: CRAWFORD MICHAEL
Published: December 2011

The article, in discussing Karl Hoelkeskamp's Reconstructing the Roman Republic, argues that the relationship(s) between the role of theory and an analysis of the last generation of the Roman Republic is much more complex that H. allows, and that concentration on the elite, deriving ultimately from the approach of Christian Meier, is misguided; it also deals with other recent approaches to the functioning of Roman politics in the period in question, notably those of Millar and Mouritsen; and offers reflections on the role(s) of language and identity in modern historical writing.
ASSYRIA AT UCL: A RESEARCH PROJECT ON THE CORRESPONDENCE BETWEEN THE ASSYRIAN KING AND HIS MAGNATES IN THE 8TH CENTURY BC
Authors: RADNER KAREN
Published: December 2011

An introduction to the research project ‘Mechanisms of communication in an ancient empire: the correspondence between the king of Assyria and his magnates in the 8th century BC’ which, on the basis of a text corpus of 1,200 letters preserved in the original from the correspondence of king Sargon II of Assyria (r. 721–705 BC) with the highest state officials, investigates the administrative and practical setup of ancient empires.
Recombination adenovirus-mediated human lactoferrin cDNA inhibits the growth of human MCF-7 breast cancer cells
Authors: Wang Jianjie , Li Qingwang , Ou Yetao , Li Kun , Han Zengsheng , Wang Peijun , Zhou Shaobo
Published: December 2011

Objectives

Human lactoferrin, an 80 kDa iron-binding glycoprotein, has antitumour effects. We have explored the potential therapeutic role of re-expressing human lactoferrin gene product in human breast cancer.

Methods

A recombinant adenovirus expressing the human lactoferrin cDNA (ad-hLTF) was constructed and used to infect breast cancer cells.

Key findings

Seventy-two hours after infection, ad-hLTF had considerable cytotoxicity on MCF-7 cells. A time-course study showed that ad-hLTF infection of MCF-7 cells at 100 plaque-forming units per cell increased the number of cells in G0/G1 phase and appeared markedly at Sub-G1 apoptotic peak. The presence of apoptotic cells was confirmed using Annexin V-fluoresecein isothiocyanate apoptosis detection by flow cytometry. Ad-hLTF also resulted in a decrease of Bcl-2 protein and an increase in Bax protein.

Conclusions

Ad-hLTF plays an important role in the induction of cell cycle arrest and apoptosis in MCF-7 cells. The results demonstrated that ad-hLTF could have potential benefits in the treatment of breast cancer.
Deception dissociates from false belief reasoning in deaf children: Implications for the implicit versus explicit theory of mind distinction
Authors: de Villiers Peter A. , de Villiers Jill G.
Published: December 2011

Deception is a controversial aspect of theory of mind, and researchers disagree about whether it entails an understanding of the false beliefs of one's opponent. The present study asks whether children with delayed language and delayed explicit false belief reasoning can succeed on explicit deception tasks. Participants were 45 orally taught deaf children with varying language delays aged 4.5–8 years and 45 hearing children aged 3.5–6 years. Participants received a battery of language, executive function, deception, and both verbal and low‐verbal false belief tasks. The result reveal a dissociation of deception and false belief tasks: the deaf children are on par with their hearing peers on deception games, but show significant delays in false belief tasks even when the language demands are made minimal. Furthermore, different skills are predictors of success for the two types of task in the deaf children: language, and in particular complement syntax, is the best predictor of false belief reasoning; but executive function skills, especially inhibitory control, are the best predictors of deception. It is argued that deception at this level can be handled by behaviour rules without reference to mental states.
Overweight status and intrauterine exposure to gestational diabetes are associated with children's metabolic health
Authors: Chandler‐Laney P. C. , Bush N. C. , Granger W. M. , Rouse D. J. , Mancuso M. S. , Gower B. A.
Published: December 2011

Background

Offspring of women with gestational diabetes (OGD) have greater risk for obesity and impaired metabolic health. Whether impaired metabolic health occurs in the absence of obesity is not clear.

Objective

The purpose of this study was to investigate the independent and interactive effects of intrauterine exposure to gestational diabetes and of children's current weight status on their metabolic health.

Methods

Children aged 5–10 years (n = 51) with and without intrauterine exposure to gestational diabetes (OGD vs. offspring of non‐diabetic women [CTRL]) were grouped into normal weight (body mass index [BMI] < 85th %) and overweight (BMI > 85th %) according to Centers for Disease Control growth curves. Lipid profile was obtained by fasting blood draw, insulin sensitivity (SI) and secretion by liquid meal tolerance test, and body composition by dual‐energy X‐ray absorptiometry.

Results

Despite similar average BMI percentiles among normal weight OGD versus CTRL, and overweight OGD vs. CTRL, OGD had greater total %fat and trunk fat adjusted for leg fat compared with CTRL (P < 0.05). Overweight children had lower SI (P < 0.05) and greater basal, static, and total insulin secretion independent of SI (P < 0.05). OGD was independently associated with greater static insulin secretion (P < 0.05) and the interaction between OGD and overweight was associated with greater basal insulin secretion independent of SI (P < 0.01). OGD and overweight were each associated with lower high‐density lipoprotein‐cholesterol (HDL‐C) (P < 0.05).

Conclusion

Intrauterine exposure to gestational diabetes was associated with greater central adiposity and insulin secretion, and lower HDL‐C, irrespective of current weight status. Future research should examine respective contributions of the intrauterine environment and of underlying genotype on children's metabolic health.
Efficient nonlinear filtering of a singularly perturbed stochastic hybrid system
Authors: Park Jun H. , Rozovskii Boris , Sowers Richard B.
Published: December 2011

Our focus in this work is to investigate an efficient state estimation scheme for a singularly perturbed stochastic hybrid system. As stochastic hybrid systems have been used recently in diverse areas, the importance of correct and efficient estimation of such systems cannot be overemphasized. The framework of nonlinear filtering provides a suitable ground for on-line estimation. With the help of intrinsic multiscale properties of a system, we obtain an efficient estimation scheme for a stochastic hybrid system.
A Two-Dimensional Numerical Investigation of the Hysteresis Effect on Vortex Induced Vibration on an Elastically Mounted Rigid Cylinder
Authors: Wanderley Juan B. V. , Sphaier Sergio H. , Levi Carlos
Published: December 2011

The hysteresis effect on the vortex induced vibration (VIV) on a circular cylinder is investigated by the numerical solution of the two-dimensional Reynolds averaged Navier-Stokes equations. An upwind and total variation diminishing (TVD) conservative scheme is used to solve the governing equations written in curvilinear coordinates and the k-ɛ turbulence model is used to simulate the turbulent flow in the wake of the body. The cylinder is supported by a spring and a damper and free to vibrate in the transverse direction. In previous work, numerical results for the amplitude of oscillation and vortex shedding frequency were compared to experimental data obtained from the literature to validate the code for VIV simulations. In the present work, results of practical interest are presented for the power absorbed by the system, phase angle, amplitude, frequency, and lift coefficient. The numerical results indicate that the hysteresis effect is observed only when the frequency of vortex shedding gets closer to the natural frequency of the structure in air.
Shakedown of Thick Cylinders With Radial Openings Under Thermomechanical Loadings
Authors: Zheng X. T. , Xuan F. Z.
Published: December 2011

Shakedown and ratcheting behaviors of thick-walled cylindrical vessels with radial openings subjected to cyclic thermomechanical loadings are investigated by the inelastic finite element analysis. Different shakedown and ratcheting responses are described in the modified Bree diagram considering the influences of various opening radius ratios ri/Ri, thickness ratios Ro/Ri as well as different axial stress states. Then, two simplified shakedown assessment methods of perforated cylinders are discussed. The results indicate that elastic/plasticity shakedown boundary reduces significantly owing to the presence of a radial opening while varies slightly with the opening radius, which can be defined as 1.2 approximately in the modified Bree diagram for conservative elastic/plasticity shakedown evaluation. Moreover, shakedown/ratcheting boundary decreases significantly with increasing the opening radius or decreasing the axial stress. Finally, comparing with the calculated results, the two simplified methods are verified to be accurate and intuitive to estimate the shakedown behaviors of perforated cylinders under various thickness and opening radius conditions.
Delayed Reference Control Applied to Flexible Link Mechanisms: A Scheme for Effective and Stable Control
Authors: Boschetti Giovanni , Richiedei Dario , Trevisani Alberto
Published: December 2011

This paper extends the use of delayed reference controllers to the simultaneous motion and vibration control of flexible link mechanisms. Vibration damping is achieved by introducing an “equivalent damping force” into the system through the computation of a suitable delayed time. The delayed time, which is based on the measured vibrations, is then employed in the trajectory planner to set the reference input. The stability of the controller is discussed and its effectiveness is proved by applying it to a four-bar planar linkage with flexible links.
Dynamic Modeling of Damping Effects in Highly Damped Compliant Fingers for Applications Involving Contacts
Authors: Liu Chih-Hsing , Lee Kok-Meng
Published: December 2011

In many industries, it is often required to transfer objects using compliant fingers capable of accommodating a limited range of object shapes/sizes without causing damage to the products being handled. This paper presents a coupled computational and experimental method in time domain to characterize the damping coefficient of a continuum structure, particularly, its applications for analyzing the damping effect of a highly damped compliant finger on contact-induced forces and stresses. With the aid of Rayleigh damping and explicit dynamic finite element analysis (FEA), this method relaxes several limitations of commonly used damping identification methods (such as log-decrement and half-power methods) that are valid for systems with an oscillatory response and generally estimate the damping ratio for a lumped parameter model. This damping identification method implemented using off-the-shelf commercial FEA packages has been validated by comparing results against published data; both oscillatory and nonoscillatory responses are considered. Along with a detailed discussion on practical issues commonly encountered in explicit dynamic FEA for damping identification, the effects of damping coefficients on contact between a rotating compliant finger and an elliptical object has been numerically investigated and experimentally validated. The findings offer a better understanding for improving grasper designs for applications where joint-less compliant fingers are advantageous.
An Improved Delay-Dependent Stability Criterion for a Class of Lur’e Systems of Neutral Type
Authors: Ramakrishnan K. , Ray G.
Published: December 2011

In this paper, we consider the problem of delay-dependent stability of a class of Lur’e systems of neutral type with time-varying delays and sector-bounded nonlinearity using Lyapunov–Krasovskii (LK) functional approach. By using a candidate LK functional in the stability analysis, a less conservative absolute stability criterion is derived in terms of linear matrix inequalities (LMIs). In addition to the LK functional, conservatism in the proposed stability analysis is further reduced by imposing tighter bounding on the time-derivative of the functional without neglecting any useful terms using minimal number of slack matrix variables. The proposed analysis, subsequently, yields a stability criterion in convex LMI framework, and is solved nonconservatively at boundary conditions using standard LMI solvers. The effectiveness of the proposed criterion is demonstrated through a standard numerical example and Chua’s circuit.
Fully 3D list‐mode time‐of‐flight PET image reconstruction on GPUs using CUDA
Authors: Cui Jing‐yu , Pratx Guillem , Prevrhal Sven , Levin Craig S.
Published: December 2011

Purpose:

List‐mode processing is an efficient way of dealing with the sparse nature of positron emission tomography (PET) data sets and is the processing method of choice for time‐of‐flight (ToF) PET image reconstruction. However, the massive amount of computation involved in forward projection and backprojection limits the application of list‐mode reconstruction in practice, and makes it challenging to incorporate accurate system modeling.

Methods:

The authors present a novel formulation for computing line projection operations on graphics processing units (GPUs) using the compute unified device architecture (CUDA) framework, and apply the formulation to list‐mode ordered‐subsets expectation maximization (OSEM) image reconstruction. Our method overcomes well‐known GPU challenges such as divergence of compute threads, limited bandwidth of global memory, and limited size of shared memory, while exploiting GPU capabilities such as fast access to shared memory and efficient linear interpolation of texture memory. Execution time comparison and image quality analysis of the GPU‐CUDA method and the central processing unit (CPU) method are performed on several data sets acquired on a preclinical scanner and a clinical ToF scanner.

Results:

When applied to line projection operations for non‐ToF list‐mode PET, this new GPU‐CUDA method is >200 times faster than a single‐threaded reference CPU implementation. For ToF reconstruction, we exploit a ToF‐specific optimization to improve the efficiency of our parallel processing method, resulting in GPU reconstruction >300 times faster than the CPU counterpart. For a typical whole‐body scan with 75 × 75 × 26 image matrix, 40.7 million LORs, 33 subsets, and 3 iterations, the overall processing time is 7.7 s for GPU and 42 min for a single‐threaded CPU. Image quality and accuracy are preserved for multiple imaging configurations and reconstruction parameters, with normalized root mean squared (RMS) deviation less than 1% between CPU and GPU‐generated images for all cases.

Conclusions:

A list‐mode ToF OSEM library was developed on the GPU‐CUDA platform. Our studies show that the GPU reformulation is considerably faster than a single‐threaded reference CPU method especially for ToF processing, while producing virtually identical images. This new method can be easily adapted to enable more advanced algorithms for high resolution PET reconstruction based on additional information such as depth of interaction (DoI), photon energy, and point spread functions (PSFs).
The Role of Carbon Dioxide During the Onset of Antarctic Glaciation
Authors: Pagani Mark , Huber Matthew , Liu Zhonghui , Bohaty Steven M. , Henderiks Jorijntje , Sijp Willem , Krishnan Srinath , DeConto Robert M.
Published: December 2011

Antarctica glaciation began soon after a large decrease in the concentration of atmospheric carbon dioxide around 35 million years ago.
The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence
Authors: Alvarez Jorge Ivan , Dodelet-Devillers Aurore , Kebir Hania , Ifergan Igal , Fabre Pierre J. , Terouz Simone , Sabbagh Mike , Wosik Karolina , Bourbonnière Lyne , Bernard Monique , van Horssen Jack , de Vries Helga E. , Charron Frédéric , Prat Alexandre
Published: December 2011

Hedgehog signaling is required for maintaining the integrity of the blood-brain barrier.
Response to Comment on “Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State”
Authors: Boly Melanie , Garrido Marta Isabel , Gosseries Olivia , Bruno Marie-Aurélie , Boveroux Pierre , Schnakers Caroline , Massimini Marcello , Litvak Vladimir , Laureys Steven , Friston Karl
Published: December 2011

King
et al
. raise some technical issues about our recent study showing impaired top-down processes in the vegetative state. We welcome the opportunity to provide more details about our methods and results and to resolve their concerns. We substantiate our interpretation of the results and provide a point-by-point response to the issues raised.
The Pristine Universe
Authors: Kacprzak Glenn G.
Published: December 2011

Observations reveal two gaseous regions with a composition close to that of the universe before the first stars were formed.
Quantum Correlation Between Distant Diamonds
Authors: Duan L.-M.
Published: December 2011

Entanglement of spatially separated systems is not limited to atomic systems, but can be created between diamond crystals separated by several centimeters.
Personalized Cancer Diagnostics
Authors: Corless Christopher L.
Published: December 2011

A pilot study marshals sequencing resources and broad expertise to analyze patients' tumors in a cost-effective and clinically relevant time frame.
Where Does the Time Go?
Authors: Cho Adrian
Published: December 2011

One experiment saw neutrinos traveling faster than light. If the result can't be replicated, it may never be explained away.
Draft Genome Sequence of Penicillium marneffei Strain PM1
Authors: Woo Patrick C. Y. , Lau Susanna K. P. , Liu Bin , Cai James J. , Chong Ken T. K. , Tse Herman , Kao Richard Y. T. , Chan Che-Man , Chow Wang-Ngai , Yuen Kwok-Yung
Published: December 2011

Penicillium marneffei
is the most important thermal dimorphic, pathogenic fungus endemic in China and Southeast Asia and is particularly important in HIV-positive patients. We report the 28,887,485-bp draft genome sequence of
P. marneffei
, which contains its complete mitochondrial genome, sexual cycle genes, a high diversity of Mp1p homologues, and polyketide synthase genes.
Direct Analysis and Identification of Pathogenic Lichtheimia Species by Matrix-Assisted Laser Desorption Ionization–Time of Flight Analyzer-Mediated Mass Spectrometry
Authors: Schrödl Wieland , Heydel Tilo , Schwartze Volker U. , Hoffmann Kerstin , Große-Herrenthey Anke , Walther Grit , Alastruey-Izquierdo Ana , Rodriguez-Tudela Juan Luis , Olias Philipp , Jacobsen Ilse D. , de Hoog G. Sybren , Voigt Kerstin
Published: December 2011

Zygomycetes of the order Mucorales can cause life-threatening infections in humans. These mucormycoses are emerging and associated with a rapid tissue destruction and high mortality. The resistance of Mucorales to antimycotic substances varies between and within clinically important genera such as
Mucor
,
Rhizopus
, and
Lichtheimia
. Thus, an accurate diagnosis before onset of antimycotic therapy is recommended. Matrix-assisted laser desorption ionization (MALDI)–time of flight (TOF) mass spectrometry (MS) is a potentially powerful tool to rapidly identify infectious agents on the species level. We investigated the potential of MALDI-TOF MS to differentiate
Lichtheimia
species, one of the most important agents of mucormycoses. Using the Bruker Daltonics FlexAnalysis (version 3.0) software package, a spectral database library with
m/z
ratios of 2,000 to 20,000 Da was created for 19 type and reference strains of clinically relevant Zygomycetes of the order Mucorales (12 species in 7 genera). The database was tested for accuracy by use of 34 clinical and environmental isolates of
Lichtheimia
comprising a total of five species. Our data demonstrate that MALDI-TOF MS can be used to clearly discriminate
Lichtheimia
species from other pathogenic species of the Mucorales. Furthermore, the method is suitable to discriminate species within the genus. The reliability and robustness of the MALDI-TOF-based identification are evidenced by high score values (above 2.3) for the designation to a certain species and by moderate score values (below 2.0) for the discrimination between clinically relevant (
Lichtheimia corymbifera
,
L. ramosa
, and
L. ornata
) and irrelevant (
L. hyalospora
and
L. sphaerocystis
) species. In total, all 34 strains were unequivocally identified by MALDI-TOF MS with score values of >1.8 down to the generic level, 32 out of 34 of the
Lichtheimia
isolates (except CNM-CM 5399 and FSU 10566) were identified accurately with score values of >2 (probable species identification), and 25 of 34 isolates were identified to the species level with score values of >2.3 (highly probable species identification). The MALDI-TOF MS-based method reported here was found to be reproducible and accurate, with low consumable costs and minimal preparation time.
Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract
Authors: Mgode Georgies F. , Weetjens Bart J. , Nawrath Thorben , Cox Christophe , Jubitana Maureen , Machang'u Robert S. , Cohen-Bacrie Stéphan , Bedotto Marielle , Drancourt Michel , Schulz Stefan , Kaufmann Stefan H. E.
Published: December 2011

Trained African giant-pouched rats (
Cricetomys gambianus
) can detect
Mycobacterium tuberculosis
and show potential for the diagnosis of tuberculosis (TB). However, rats' ability to discriminate between clinical sputum containing other
Mycobacterium
spp. and nonmycobacterial species of the respiratory tract is unknown. It is also unknown whether nonmycobacterial species produce odor similar to
M. tuberculosis
and thereby cause the detection of smear-negative sputum. Sputum samples from 289 subjects were analyzed by smear microscopy, culture, and rats.
Mycobacterium
spp. were isolated on Lowenstein-Jensen medium, and nonmycobacterial species were isolated on four different media. The odor from nonmycobacterial species from smear- and
M. tuberculosis
culture-negative sputa detected by ≥2 rats (“rat positive”) was analyzed by gas chromatography-mass spectrometry and compared to the
M. tuberculosis
odor. Rats detected 45 of 56 confirmed cases of TB, 4 of 5 suspected cases of TB, and 63 of 228 TB-negative subjects (sensitivity, 80.4%; specificity, 72.4%; accuracy, 73.9%; positive predictive value, 41.7%; negative predictive value, 93.8%). A total of 37 (78.7%) of 47 mycobacterial isolates were
M. tuberculosis
complex, with 75.7% from rat-positive sputa. Ten isolates were nontuberculous mycobacteria, one was
M. intracellulare
, one was
M. avium
subsp.
hominissuis
, and eight were unidentified. Rat-positive sputa with
Moraxella catarrhalis
,
Streptococcus pneumoniae
,
Staphylococcus
spp., and
Enterococcus
spp. were associated with TB.
Rhodococcus
,
Nocardia
,
Streptomyces
,
Staphylococcus
, and
Candida
spp. from rat-positive sputa did not produce
M. tuberculosis
-specific volatiles (methyl nicotinate, methyl
para
-anisate, and
ortho
-phenylanisole). Prevalence of
Mycobacterium
-related
Nocardia
and
Rhodococcus
in smear-negative sputa did not equal that of smear-negative mycobacteria (44.7%), of which 28.6% were rat positive. These findings and the absence of
M. tuberculosis
-specific volatiles in nonmycobacterial species indicate that rats can be trained to specifically detect
M. tuberculosis
.
Prosthetic Joint Infection Caused by Helcococcus kunzii
Authors: Pérez-Jorge Conchita , Cordero José , Marin Mercedes , Esteban Jaime
Published: December 2011

Helcococcus kunziiwas isolated by sonication and conventional cultures obtained from a case of infection following total knee prosthesis in an immunocompetent patient. The patient recovered uneventfully. This is the first known case of anH. kunziiprosthetic joint infection.
Characterization of Ertapenem-Resistant Enterobacter cloacae in a Taiwanese University Hospital
Authors: Yang Fu-Chen , Yan Jing-Jou , Hung Kuei-Hsiang , Wu Jiunn-Jong
Published: December 2011

The emergence of carbapenem resistance in
Enterobacteriaceae
has become a great concern. The aim of this study was to characterize ertapenem-resistant
Enterobacter cloacae
isolates from a Taiwanese university hospital. A total of 355 nonduplicated
E. cloacae
isolates collected in 2007 were analyzed by antimicrobial susceptibility testing with and without an inhibitor of efflux pumps and AmpC β-lactamase. The phenotype of extended-spectrum β-lactamase (ESBL), profile of outer membrane proteins (OMPs), and clonal relatedness were investigated by the double-disk synergy test, urea/SDS-PAGE, and pulsed-field gel electrophoresis (PFGE), respectively. β-Lactamase genes were examined by PCR and sequencing, and the expression of efflux pump gene
acrB
was evaluated by reverse transcription-PCR. The contribution of porin deficiency to resistance was investigated by restoring functional porin genes on plasmids. We demonstrated that ertapenem resistance was prevalent (53/355; 14.9%) in
E. cloacae
. Among the strains, IMP-8, SHV-12, and TEM-1 β-lactamases were identified in 3 (5.7%), 40 (75.5%), and 46 (86.8%) isolates, respectively. PFGE showed clonal diversity among these isolates. Phenotypes of ESBL, AmpC β-lactamase overproduction, an active efflux pump, and change in the expression of OMPs were found in 18 (34%), 11 (20.8%), 51 (96.2%), and 23 (43.4%) of ertapenem-resistant strains, respectively. Ertapenem MICs were restored in strains with OmpC and OmpF expression plasmids. This study suggests that ESBL, AmpC β-lactamase overproduction, and decreased OMP expression combined with an active efflux pump contribute to the ertapenem resistance of
E. cloacae
. The presence of IMP-8 may also play a partial role in ertapenem resistance in Taiwan.
Preparation and Evaluation of Recombinant Severe Fever with Thrombocytopenia Syndrome Virus Nucleocapsid Protein for Detection of Total Antibodies in Human and Animal Sera by Double-Antigen Sandwich Enzyme-Linked Immunosorbent Assay
Authors: Jiao Yongjun , Zeng Xiaoyan , Guo Xiling , Qi Xian , Zhang Xiao , Shi Zhiyang , Zhou Minghao , Bao Changjun , Zhang Wenshuai , Xu Yan , Wang Hua
Published: December 2011

The recent emergence of the human infection confirmed to be caused by severe fever with thrombocytopenia syndrome virus (SFTSV) in China is of global concern. Safe diagnostic immunoreagents for determination of human and animal seroprevalence in epidemiological investigations are urgently needed. This paper describes the cloning and expression of the nucleocapsid (N) protein of SFTSV. An N-protein-based double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) system was set up to detect the total antibodies in human and animal sera. We reasoned that as the double-antigen sandwich ELISA detected total antibodies with a higher sensitivity than traditional indirect ELISA, it could be used to detect SFTSV-specific antibodies from different animal species. The serum neutralization test was used to validate the performance of this ELISA system. All human and animal sera that tested positive in the neutralization test were also positive in the sandwich ELISA, and there was a high correlation between serum neutralizing titers and ELISA readings. Cross-reactivity was evaluated, and the system was found to be highly specific to SFTSV; all hantavirus- and dengue virus-confirmed patient samples were negative. SFTSV-confirmed human and animal sera from both Anhui and Hubei Provinces in China reacted with N protein in this ELISA, suggesting no major antigenic variation between geographically disparate virus isolates and the suitability of this assay in nationwide application. ELISA results showed that 3.6% of the human serum samples and 47.7% of the animal field serum samples were positive for SFTSV antibodies, indicating that SFTSV has circulated widely in China. This assay, which is simple to operate, poses no biohazard risk, does not require sophisticated equipment, and can be used in disease surveillance programs, particularly in the screening of large numbers of samples from various animal species.
Liquid-Based Urine Cytology as a Tool for Detection of Human Papillomavirus, Mycoplasma spp., and Ureaplasma spp. in Men
Authors: Kawaguchi Shohei , Shigehara Kazuyoshi , Sasagawa Toshiyuki , Shimamura Masayoshi , Nakashima Takao , Sugimoto Kazuhiro , Nakashima Kazufumi , Furubayashi Keiichi , Namiki Mikio
Published: December 2011

Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV),
Mycoplasma
, and
Ureaplasma
. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of
Neisseria gonorrhoeae
and
Chlamydia trachomatis
. Papanicolaou tests were performed for cytological evaluation. HPV,
Mycoplasma
, and
Ureaplasma
genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by
in situ
hybridization (ISH). The β-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (
P
< 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples.
Mycoplasma genitalium
,
Mycoplasma hominis
,
Ureaplasma parvum
, and
Ureaplasma urealyticum
were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except
Ureaplasma parvum
) were significantly higher in urethritis cases than controls (
P
< 0.05). LB-URC is applicable for detection of HPV,
Mycoplasma
, and
Ureaplasma.
HPV infection occurs in urothelial cells, especially in gonococcal urethritis.
Evaluation of the VersaTREK System Compared to the Bactec MGIT 960 System for First-Line Drug Susceptibility Testing of Mycobacterium tuberculosis
Authors: Espasa M. , Salvadó M. , Vicente E. , Tudó G. , Alcaide F. , Coll P. , Martin-Casabona N. , Torra M. , Fontanals D. , González-Martín J.
Published: December 2011

The aim of this study was to evaluate the reliability of the VersaTREK system for
Mycobacterium tuberculosis
drug susceptibility testing compared with results obtained with the Bactec MGIT 960 system. A total of 67 strains were evaluated. Overall agreement was at 98.5%. Kappa indexes were 1.0 for isoniazid, rifampin, and ethambutol, 0.937 for pyrazinamide, and 0.907 for streptomycin. The VersaTREK system is validated for
M. tuberculosis
drug susceptibility testing.
A Non-Mouse-Adapted Enterovirus 71 (EV71) Strain Exhibits Neurotropism, Causing Neurological Manifestations in a Novel Mouse Model of EV71 Infection
Authors: Khong Wei Xin , Yan Benedict , Yeo Huimin , Tan Eng Lee , Lee Jia Jun , Ng Jowin K. W. , Chow Vincent T. , Alonso Sylvie
Published: December 2011

Enterovirus 71 (EV71) is a neurotropic pathogen that has been consistently associated with the severe neurological forms of hand, foot, and mouth disease. The lack of a relevant animal model has hampered our understanding of EV71 pathogenesis, in particular the route and mode of viral dissemination. It has also hindered the development of effective prophylactic and therapeutic approaches, making EV71 one of the most pressing public health concerns in Southeast Asia. Here we report a novel mouse model of EV71 infection. We demonstrate that 2-week-old and younger immunodeficient AG129 mice, which lack type I and II interferon receptors, are susceptible to infection with a non-mouse-adapted EV71 strain via both the intraperitoneal (i.p.) and oral routes of inoculation. The infected mice displayed progressive limb paralysis prior to death. The dissemination of the virus was dependent on the route of inoculation but eventually resulted in virus accumulation in the central nervous systems of both animal groups, indicating a clear neurotropism of the virus. Histopathological examination revealed massive damage in the limb muscles, brainstem, and anterior horn areas. However, the minute amount of infectious viral particles in the limbs from orally infected animals argues against a direct viral cytopathic effect in this tissue and suggests that limb paralysis is a consequence of EV71 neuroinvasion. Together, our observations support that young AG129 mice display polio-like neuropathogenesis upon infection with a non-mouse-adapted EV71 strain, making this mouse model relevant for EV71 pathogenesis studies and an attractive platform for EV71 vaccine and drug testing.
Sequencing of 21 Varicella-Zoster Virus Genomes Reveals Two Novel Genotypes and Evidence of Recombination
Authors: Zell Roland , Taudien Stefan , Pfaff Florian , Wutzler Peter , Platzer Matthias , Sauerbrei Andreas
Published: December 2011

Genotyping of 21 varicella-zoster virus (VZV) strains using a scattered single nucleotide polymorphism (SNP) method revealed ambiguous SNPs and two nontypeable isolates. For a further genetic characterization, the genomes of all strains were sequenced using the 454 technology. Almost-complete genome sequences were assembled, and most remaining gaps were closed with Sanger sequencing. Phylogenetic analysis of 42 genomes revealed five established and two novel VZV genotypes, provisionally termed VIII and IX. Genotypes VIII and IX are distinct from the previously reported provisional genotypes VI and VII as judged from the SNP pattern. The alignments showed evidence of ancient recombination events in the phylogeny of clade 4 and recent recombinations within single strains: 3/2005 (clade 1), 11 and 405/2007 (clade 3), 8 and DR (clade 4), CA123 and 413/2000 (clade 5), and strains of the novel genotypes VIII and IX. Bayesian tree inference of the thymidine kinase and the polymerase genes of the VZV clades and other varicelloviruses revealed that VZV radiation began some 110,000 years ago, which correlates with the out-of-Africa dispersal of modern humans. The split of ancestral clades 2/4 and 1/3/5/VIII/IX shows the greatest node height.