bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between vehicle exterior design and perceived loudness of vehicle acceleration sound
Authors: Igata Takumi , Yoshida Junji
Published: April 2012

To increase cabin comfort, not only decreasing sound pressure level but also improving the sound quality is essential. In addition, when the sound quality of the vehicle matches with the exterior design, the sound is considered to be perceived more attractive. In this study, to investigate the relationship between the perceptions of the sound and the exterior design, the loudness of acceleration sounds were evaluated with vehicle exterior images. In the loudness evaluation test, 10 acceleration sounds and 10 exterior images were prepared and half of the images were luxury vehicle images and the others were sporty vehicle images. The experimental subject evaluated the loudness of presented sound with the luxury or sporty vehicle exterior image. Twenty one male subjects participated in the test. Eleven of them drove vehicles frequently and the others were infrequently. As a result, frequently driving subjects felt the acceleration sound louder by having luxury vehicle impression. In contrast, infrequently driving subjects felt the sound softer by having the same vehicle impression. Consequently, it was clarified that perceived loudness was influenced by vehicle exterior design, and the tendency was changed depending on the driving frequency.
How do driving sounds influence the subjective evaluation of longitudinal acceleration?
Authors: Skoda Sabrina , Steffens Jochen , Becker-Schweitzer Joerg
Published: April 2012

The evaluation of vehicle interior sounds in a listening study is always based on multiple sensory interactions. In a driving simulator several visual and somatosensory stimuli are presented to the test subjects in addition to the pure driving sounds. These multisensory stimuli are processed consciously and unconsciously by the human brain. Thus attention processes and also the evaluation behavior change in comparison to monosensory acoustical experiments. In the automotive industry electric powered vehicles currently are a hot topic. These vehicles have a very quiet noise behavior compared to vehicles with combustion engines. So the question arises how driving sounds comprise to the subjective evaluation of a vehicle's acceleration. Do we associate loud driving sounds with strong acceleration? Which part takes the spectral structure of a sound? In a comparative listening study different vehicle interior sounds and different accelerations were evaluated in two different driving simulators. Based on the results from the study the influence of driving sounds on the subjective evaluation of longitudinal acceleration is discussed.
Acoustical Society of America Honorary Fellowship
Authors: Maa Dah-You
Published: April 2012

An individual who has attained eminence in acoustics or who has rendered outstanding service to acoustics may be elected to Honorary Fellowship in the Acoustical Society of America.
Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model
Authors: Kannan Sujatha , Dai Hui , Navath Raghavendra S. , Balakrishnan Bindu , Jyoti Amar , Janisse James , Romero Roberto , Kannan Rangaramanujam M.
Published: April 2012

A dendrimer-drug conjugate attenuates neuroinflammation and improves motor function in a rabbit model of cerebral palsy.
Targeted Delivery of PLK1-siRNA by ScFv Suppresses Her2
+
Breast Cancer Growth and Metastasis
Authors: Yao Yan-dan , Sun Tian-meng , Huang Song-yin , Dou Shuang , Lin Ling , Chen Jia-ning , Ruan Jian-bin , Mao Cheng-qiong , Yu Feng-yan , Zeng Mu-sheng , Zang Jian-ye , Liu Qiang , Su Feng-xi , Zhang Peter , Lieberman Judy , Wang Jun , Song Erwei
Published: April 2012

Antibody-mediated delivery of anticancer siRNAs suppresses Her2
+
breast cancer growth and metastasis.
Engineering a Hyperthermophilic Archaeon for Temperature-Dependent Product Formation
Authors: Basen Mirko , Sun Junsong , Adams Michael W. W.
Published: April 2012

Microorganisms growing near the boiling point have enormous biotechnological potential but only recently have molecular engineering tools become available for them. We have engineered the hyperthermophilic archaeon
Pyrococcus furiosus
, which grows optimally at 100°C, to switch its end products of fermentation in a temperature-controlled fashion without the need for chemical inducers. The recombinant strain (LAC) expresses a gene (
ldh
) encoding lactate dehydrogenase from the moderately thermophilic
Caldicellulosiruptor bescii
(optimal growth temperature [
T
opt
] of 78°C) controlled by a “cold shock” promoter that is upregulated when cells are transferred from 98°C to 72°C. At 98°C, the LAC strain fermented sugar to produce acetate and hydrogen as end products, and lactate was not detected. When the LAC strain was grown at 72°C, up to 3 mM lactate was produced instead. Expression of a gene from a moderately thermophilic bacterium in a hyperthermophilic archaeon at temperatures at which the hyperthermophile has low metabolic activity provides a new perspective to engineering microorganisms for bioproduct and biofuel formation.

IMPORTANCE
Extremely thermostable enzymes from microorganisms that grow near or above the boiling point of water are already used in biotechnology. However, the use of hyperthermophilic microorganisms themselves for biotechnological applications has been limited by the lack of their genetic accessibility. Recently, a genetic system for
Pyrococcus furiosus
, which grows optimally near 100°C, was developed in our laboratory. In this study, we present the first heterologous protein expression system for a microorganism that grows optimally at 100°C, a first step towards the potential expression of genes involved in biomass degradation or biofuel production in hyperthermophiles. Moreover, we developed the first system for specific gene induction in
P. furiosus
. As the cold shock promoter for protein expression used in this study is activated at suboptimal growth temperatures of
P. furiosus
, it is a powerful genetic tool for protein expression with minimal interference of the host’s metabolism and without the need for chemical inducers.
De novo development of dural arteriovenous fistula after endovascular embolization of pial arteriovenous fistula
Authors: Paramasivam Srinivasan , Toma Naoki , Niimi Yasunari , Berenstein Alejandro
Published: April 2012

Background

The development of de novo dural arteriovenous fistula(s) following endovascular embolization of a prior high-flow pial arteriovenous fistula (PAVF) has not previously been reported and the natural history is unknown. The anatomic basis, pathophysiologic mechanism, management and outcome are discussed.

Methods

Treatment-completed congenital PAVFs treated at our center between January 2005 and August 2011 were analyzed retrospectively. Among 16 cases of PAVFs treated by endovascular embolization, four developed de novo dural arteriovenous fistulas during treatment or on follow-up that were not present before treatment. Information was collected from the clinical case records, imaging by MRI on presentation and during follow-up, all angiographic images and records during each of the procedures and during follow-up.

Results

The time interval between the last embolization and identification of a dural fistula ranged from 3 to 14 months. Ten fistulas were identified in four patients, seven of which were embolized, four with glue, two with Onyx18 and one with absolute alcohol. None recanalized, while one patient developed fistula in an adjacent location that was subsequently treated with radiosurgery. Not all fistulas need treatment; small fistulas with a minimal flow can safely be observed.

Conclusions

De novo dural fistulas following endovascular embolization of high-flow PAVFs is not an uncommon development. They are mostly asymptomatic and develop anywhere along the drainage of the fistula, maturing over time and diagnosed during follow-up studies, emphasizing the need for follow-up angiography. They can be effectively treated by endovascular embolization. Localized refractory dural fistulas can be dealt with by radiosurgery.
MRT RECTANGULAR LATTICE BOLTZMANN METHOD
Authors: ZHOU JIAN GUO
Published: April 2012

A multiple-relaxation-time (MRT) collision operator is introduced into the author's rectangular lattice Boltzmann method for simulating fluid flows. The model retains both the advantages and the standard procedure of using a constant transformation matrix in the conventional MRT scheme on a square lattice, leading to easy implementation in the algorithm. This allows flow problems characterized by dominant feature in one direction to be solved more efficiently. Two numerical tests have been carried out and shown that the proposed model is able to capture complex flow characteristics and generate an accurate solution if an appropriate lattice ratio is used. The model is found to be more stable compared to the original rectangular lattice Boltzmann method using the single relaxation time.
SUPERSYMMETRY PHENOMENOLOGY BEYOND THE MSSM AFTER 5/fb OF LHC DATA
Authors: LODONE PAOLO
Published: April 2012

We briefly review the status of motivated beyond-the-MSSM phenomenology in the light of the LHC searches to date. In particular, we discuss the conceptual consequences of the exclusion bounds, of the hint for a Higgs boson at about 125 GeV, and of interpreting the excess of direct CP violation in the charm sector as a signal of New Physics. We try to go into the various topics in a compact way while providing a relatively rich list of references, with particular attention to the most recent developments.
THEORETICAL STUDIES OF THE RECTIFYING PERFORMANCE IN DIBLOCK MOLECULAR JUNCTIONS: THE ROLE OF THE ANCHORING GROUPS
Authors: XIA CAI-JUAN , LIU DE-SHENG , ZHANG DE-HUA , LIU HAN-CHEN
Published: April 2012

By applying nonequilibrium Green's function formalism combined with first-principles density functional theory, we investigate the effect of different anchoring groups on the rectifying behavior in diblock molecular junctions. The spatial distributions of molecular orbitals and the influence of transmission coefficients under various external voltage biases on the electronic transport through the molecular device are discussed in detail. The results show that the anchoring groups play a significant role on the electronic transport properties. The rectifying performance in molecular junctions can be manipulated, enhanced, or suppressed by a careful consideration of the effects of the anchoring group and such modifications become crucial in optimizing the electronic transport properties of chemical structures.
TRIANGLES, SQUARES AND GEODESICS
Authors: LEVITT RENA , MCCAMMOND JON
Published: April 2012

In the early 1990s Steve Gersten and Hamish Short proved that compact nonpositively curved triangle complexes have biautomatic fundamental groups and that compact nonpositively curved square complexes have biautomatic fundamental groups. In this paper we report on the extent to which results such as these extend to nonpositively curved complexes built out a mixture of triangles and squares. Since both results by Gersten and Short have been generalized to higher dimensions, this can be viewed as a first step towards unifying Januszkiewicz and Świȧtkowski's theory of simplicial nonpositive curvature with the theory of nonpositively curved cube complexes.
PARALLEL COMPUTATION OF RESOLVENTS BY MULTIMODULAR TECHNIQUES AND DECOMPOSITION FORMULA
Authors: AUBRY PHILIPPE , VALIBOUZE ANNICK
Published: April 2012

In this paper we significantly extend the limits of existing algebraic algorithms for computing Lagrange resolvents. Such algorithms are fundamental in effective Galois theory. However, they usually are of high complexity. For the case of absolute resolvents, N. Rennert has shown the value of a multimodular approach to reduce the complexity in space and time. We improve and generalize his work to the computation of any resolvent. In addition, we introduce a decomposition formula which allows us to split modular resolvents into resolvents of smaller degrees, thus both speeding computations and making it possible to efficiently parallelize them.
GRAPHICAL CALCULI FOR THE DUBROVNIK POLYNOMIAL WITH APPLICATIONS
Authors: JIN XIAN'AN
Published: April 2012

We introduce a polynomial for plane graphs, which is proposed to equal the Dubrovnik polynomial of the corresponding alternating link diagrams via the medial construction. Then using this polynomial we define another polynomial for doubly edge-weighted plane graphs, which has a natural connection with Dubrovnik polynomial of links formed from plane graphs by edge-tangle replacements. In the final, via this connection we give an explanation for a result due to Lipson and compute the Dubrovnik polynomials of classical pretzel links.
SUITABLE EXTENDER MODELS II: BEYOND ω-HUGE
Authors: WOODIN W. HUGH
Published: April 2012

We investigate large cardinal axioms beyond the level of ω-huge in context of the universality of the suitable extender models of [Suitable Extender Models I, J. Math. Log.10 (2010) 101–339]. We show that there is an analog of ADℝ at the level of ω-huge, more precisely the construction of the minimum model of ADℝ generalizes to the level of Vλ+1. This allows us to formulate the indicated generalization of ADℝ and then to prove that if the axiom holds in V at a proper class of λ then in every suitable extender model, the axiom holds at a proper class of λ (provided the relevant ω-huge embeddings can be chosen to preserve the suitable extender model).
STUDY ON MODAL TOPOLOGY OPTIMIZATION METHOD OF CONTINUUM STRUCTURE BASED ON EFG METHOD
Authors: GONG SHUGUANG , CHEN MIN , ZHANG JIANPING , HE RONG
Published: April 2012

The modal topology optimization method of continuum structure based on element-free Galerkin (EFG) method is presented by integrating solid isotropic material with penalization (SIMP) method with the optimality criteria method, and the penalty method is used to impose essential boundary conditions. The density of Gauss point and nodal density are selected as the design variables respectively, and the maximum of the first-order natural frequency is specified as the objective function. The sensitivity analysis algorithm is derived by using direct differential method. The examples are finished by selecting the two types of design variables respectively. The results obtained show that the checkerboard phenomenon does not appear when nodal density is selected as the design variable, and also verify that topology optimization method presented is feasible.
SCALED BOUNDARY FINITE ELEMENT METHOD FOR SEMI-INFINITE RESERVOIR WITH UNIFORM CROSS SECTION
Authors: LI SHANGMING
Published: April 2012

A unified scaled boundary finite element method (SBFEM) in the frequency domain was proposed for a semi-infinite reservoir with uniform cross section subjected to horizontal and vertical ground excitations, and a methodology was presented to solve the unified SBFEM through decomposing the unified SBFEM into two parts; one part modeling the reservoir subjected to horizontal excitations and the other part modeling the whole reservoir subjected to vertical excitations. The accuracy of the unified SBFEM and its solving methodology was validated through analyzing numerical examples. The SBFEM solutions were in good agreement with analytical or other numerical method's solutions.
A NONSINGULAR BOUNDARY ELEMENT METHOD FOR THE TORSION PROBLEM OF THE ANISOTROPIC UNIFORM BAR
Authors: ZHANG YAOMING , LIU ZHAOYAN , QU WENZHEN
Published: April 2012

The presentation is mainly devoted to the research on the regularized boundary integral equations (BIEs) with indirect unknowns for torsion problem of the anisotropic uniform bar. Based on a new view and idea, a novel regularization technique is pursued, in which the nonsingular indirect BIE (IBIE) excluding the CPV and HFP integrals is established. Such torsion problems can be solved directly by using the presented technique without transforming them into isotropic ones, for this reason, no inverse transform is required. Moreover, a unique feature of the shear stress BIEs expressed by density functions is that they are independent of the warp BIEs and, as such, can be collocated at the same locations as the warp BIEs. This provides additional and concurrently useable equations for various purposes. Besides, in the numerical implementation, the boundary geometric is depicted by exact elements, while the distribution of the boundary quantity on each element is approximated by a discontinuous quadratic element. Some numerical examples will be applied to validate the current scheme. It is shown that a better precision and high-computational efficiency can be achieved by the presentation.
Body composition determines direct FFA storage pattern in overweight women
Authors: Søndergaard E. , Gormsen L. C. , Nellemann B. , Jensen M. D. , Nielsen S.
Published: April 2012

Direct FFA storage in adipose tissue is a recently appreciated pathway for postabsorptive lipid storage. We evaluated the effect of body fat distribution on direct FFA storage in women with different obesity phenotypes. Twenty-eight women [10 upper body overweight/obese (UBO; WHR >0.85, BMI >28 kg/m2), 11 lower body overweight/obese (LBO; WHR <0.80, BMI >28 kg/m2), and 7 lean (BMI <25 kg/m2)] received an intravenous bolus dose of [9,10-3H]palmitate- and [1-14C]triolein-labeled VLDL tracer followed by upper body subcutaneous (UBSQ) and lower body subcutaneous (LBSQ) fat biopsies. Regional fat mass was assessed by combining DEXA and CT scanning. We report greater fractional storage of FFA in UBSQ fat in UBO women compared with lean women ( P < 0.01). The LBO women had greater storage per 106fat cells in LBSQ adipocytes compared with UBSQ adipocytes ( P = 0.04), whereas the other groups had comparable storage in UBSQ and LBSQ adipocytes. Fractional FFA storage was significantly associated with fractional VLDL-TG storage in both UBSQ ( P < 0.01) and LBSQ ( P = 0.03) adipose tissue. In conclusion, UBO women store a greater proportion of FFA in the UBSQ depot compared with lean women. In addition, LBO women store FFA more efficiently in LBSQ fat cells compared with UBSQ fat cells, which may play a role in development of their LBO phenotype. Finally, direct FFA storage and VLDL-TG fatty acid storage are correlated, indicating they may share a common rate-limiting pathway for fatty acid storage in adipose tissue.
A Neovascularized Left Atrial Mass
Authors: Hammami Rania , Abid Leila , Mallek Souad , Kharrat Ilyes , Ellouz Mariem , Hentati Mourad , Frikha Imed , Kammoun Samir
Published: April 2012

Background. The discovery of a large left atrial mass through echocardiography obliges the clinician to perform a differential diagnosis to distinguish tumor from thrombus. The neovascularization of the mass could be helpful to predict the type of the malformation and whether it is in favour of a vacular tumour rather than a thrombus .Observation. A 43-years-old man who had no cardiac antecedent reported that he have had dyspnea and palpitation since 10 months. The cardiac auscultation, revealed an irregular rhythm with diastolic murmur at the apex. The electrocardiogram showed an atrial fibrillation. The transthoracic echocardiography revealed a severe mitral stenosis with a huge left atrial mass, confirmed through transesophageal echocardiography. After 4 weeks of an efficient anticoagulant treatment, the mass was still persistent in the echocardiography. So we decided to resect the mass and to achieve a mitral valve replacement. The preoperative coronarography showed neovascularization among the mass and fistula from the circumflex artery. Considering the characteristic of the mass (neovascularization and resistance to anticoagulant), we strongly suspected a vascular tumor especially myxoma, but the histological exam revealed an organized thrombus.Conclusion. Coronary neovascularization is a specific sign for left atrial thrombus in mitral stenosis, but surgery is the best way to confirm diagnosis.
Role of Diabetes in the Prognosis and Therapeutic Outcome of Tuberculosis
Authors: Syed Suleiman Syed Azhar , Ishaq Aweis Daud M. , Mohamed Ali Jimale , RazakMuttalif Abdul , Moussa Mohamed A. A.
Published: April 2012

Background. Increased susceptibility of diabetic mellitus (DM) patients to infection, including tuberculosis (TB), is well documented. The prevalence of DM in Malaysia is reaching epidemic proportions. In this study, we sought to assess risk factors for TB and the impact of DM on the outcome of TB treatment.Methods. TB patients, diabetic patients, and diabetic patients with TB were divided into three groups of 200 subjects each. Data were obtained from patients’ medical files at the beginning and end of the study period. Prevalence rates of DM and HIV among TB patients were assessed. Prognosis, TB-related complications, anatomical site of infection, and duration of infection and diabetes were also examined.Results. The prevalence rates of HIV and DM amongst TB patients were 7.7 and 30%, respectively. The diabetic TB patient group contained more males (72%) and smokers (45.5%) compared to the nondiabetic group (58.3% and 33.5%, resp.). Approximately 74% of diabetic patients were Mycobacterium sputum positive compared to only 51% of nondiabetic patients. Diabetic patients were also more likely to develop pulmonary TB (87%) compared to nondiabetic TB patients (59%). Diabetic TB patients had a higher mortality rate (7.5%) compared to the TB only and DM only groups (1 and 2%, resp.). The duration of TB symptoms was longer in nondiabetic TB patients compared to diabetic TB patients (4.5 versus 2.6 months, resp.). Diabetes antedated TB by a mean time of 4 years.Conclusions. We found a higher number of sputum-smear-positive cases and pulmonary TB cases as well as a greater number of males and higher mortality rate in diabetic patients compared to nondiabetic patients.
Disseminated Cryptococcosis in an Immunocompetent Patient: A Case Report
Authors: Suchitha S. , Sheeladevi C. S. , Sunila R. , Manjunath G. V.
Published: April 2012

Cryptococcus neoformansis ubiquitous encapsulated yeast found throughout the world. It predominantly causes significant infections in immunocompromised individuals, of which 80–90% occur in people with human immunodeficiency virus (HIV) infection. Disseminated cryptococcal infection is uncommon and almost always occurs in HIV-infected patients. Disseminated disease, especially noncutaneous cryptococcal abscess in immunocompetent hosts, is exceedingly rare. We report a case of disseminated cryptococcosis with soft tissue, pulmonary, and cerebral involvement in an otherwise healthy immunocompetent patient initially diagnosed by fine needle aspiration cytology (FNAC).
Association of Oxidative Stress Markers with Atherogenic Index of Plasma in Adult Sickle Cell Nephropathy
Authors: Emokpae M. A. , Uadia P. O.
Published: April 2012

This paper evaluates the association of oxidative stress and atherogenic index of plasma in order to assess the cardiovascular risk in Sickle cell nephropathy especially as lipoprotein levels are lower in SCD than non-SCD patients. Antioxidant enzymes, malondialdehyde(MDA), urea, creatinine, and glomerular filtration rate were evaluated in 110 confirmed sickle cell disease patients: 65 males in steady state, aged21.1±6.0years, 30 males with macroalbuminuria, aged24.5±7.0, years and 15 with chronic kidney disease (CKD), aged31.8±2.0years. The mean activity levels of glutathione peroxidase (GPx), superoxide dismutase (Cu/ZnSOD), and catalase (CAT) were significantly lower (P<0.001) in SCD with macroalbuminuria and CKD while MDA was higher (P<0.001) in SCD with macroalbuminuria and CKD compared with controls. There was negative correlation between GPx (P<0.001), Cu/ZnSOD (P<0.02), and Atherogenic index of plasma in SCD with CKD, while MDA shows a positive correlation (P<0.001) with AIP in SCD with CKD. There was however no correlation between CAT and AIP. Decreased activity levels of antioxidant enzymes and low HDL-cholesterol concentration were confirmed in adult SCD with CKD in Nigerians. The increase oxidative stress and high atherogenic index in CKD may accelerate the process of cardiovascular complications in adult SCD patients. Atherogenic index of plasma was negatively correlated with antioxidant enzymes and positively with MDA.
Thymoquinone, theNigella sativaBioactive Compound, Prevents Circulatory Oxidative Stress Caused by 1,2-Dimethylhydrazine in Erythrocyte during Colon Postinitiation Carcinogenesis
Authors: Jrah Harzallah Hanene , Grayaa Rahma , Kharoubi Wafa , Maaloul Aya , Hammami Mohamed , Mahjoub Touhami
Published: April 2012

We have performed this study to investigate the modulatory effect of thymoquinone (TQ), theNigella sativaactive compound, on erythrocyte lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine- (DMH-) induced colon carcinogenesis after initiation in male Wistar rats. Rats exposed to DMH showed an increase of malondialdehyde and conjugated diene levels, and an augmentation of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase activities was also noted. The TQ pretreatment restored the parameters cited above to near-normal values. However, the posttreatment shows an activity similar as that presented by DMH. Therefore, our investigation revealed that TQ was a useful compound preventing DMH-induced erythrocyte damages.
Adaptation of Differential Transform Method for the Numeric‐Analytic Solution of Fractional‐Order Rössler Chaotic and Hyperchaotic Systems
Authors: Freihat Asad , Momani Shaher
Published: April 2012

A new reliable algorithm based on an adaptation of the standard generalized differential transform method (GDTM) is presented. The GDTM is treated as an algorithm in a sequence of intervals (i.e., time step) for finding accurate approximate solutions of fractional‐order Rössler chaotic and hyperchaotic systems. A comparative study between the new algorithm and the classical Runge‐Kutta method is presented in the case of integer‐order derivatives. The algorithm described in this paper is expected to be further employed to solve similar nonlinear problems in fractional calculus.
LIGHT Delivery to Tumors by Mesenchymal Stem Cells Mobilizes an Effective Antitumor Immune Response
Authors: Zou Weibin , Zheng Huilin , He Tong-Chuan , Chang Jinjia , Fu Yang-Xin , Fan Weimin
Published: April 2012

Bone marrow–derived mesenchymal stem cells (MSC) have been shown to home into tumor tissues, where they promote tumor growth and suppress immune rejection. In this study, we tested whether MSCs engineered to express the immune stimulating factor LIGHT, a member of the TNF superfamily, could induce tumor regression. Using in vitro and in vivo migration assays, we found that LIGHT-expressing MSCs (MSC-L) displayed a strong tropism for tumor tissues. MSC-L treatment activated the LIGHT-signaling pathway, effectively organizing a potent antitumor immune response that stimulated an influx of T cells and inhibited tumor growth in vivo. CD4 T cells were found to play a role in the induction phase of the immune response, and CD8 T cells were shown to be essential for the effector phase. Together, our findings indicate that MSCs can effectively home into and deliver immune stimulating molecules to tumor tissues, thereby reversing the immune-suppressive environment, promoting antitumor immunity, and inhibiting tumor growth. Cancer Res; 72(12); 2980–9. ©2012 AACR.
A Phase I Clinical Trial of Ad5.SSTR/TK.RGD, a Novel Infectivity-Enhanced Bicistronic Adenovirus, in Patients with Recurrent Gynecologic Cancer
Authors: Kim Kenneth H. , Dmitriev Igor , O'Malley Janis P. , Wang Minghui , Saddekni Souheil , You Zhiying , Preuss Meredith A. , Harris Raymond D. , Aurigemma Rosemarie , Siegal Gene P. , Zinn Kurt R. , Curiel David T. , Alvarez Ronald D.
Published: April 2012

Purpose: Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer.

Experimental Design: Eligible patients were treated intraperitoneally for 3 days with 1 × 109 to 1 × 1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response.

Results: Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts.

Conclusions: This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted. Clin Cancer Res; 18(12); 3440–51. ©2012 AACR.
The Prognostic Value of FoxP3+ Tumor-Infiltrating Lymphocytes in Cancer: A Critical Review of the Literature
Authors: deLeeuw Ronald J. , Kost Sara E. , Kakal Juzer A. , Nelson Brad H.
Published: April 2012

CD8+ tumor-infiltrating lymphocytes (TIL) are associated with survival in a variety of cancers. A second subpopulation of TIL, defined by forkhead box protein P3 (FoxP3) expression, has been reported to inhibit tumor immunity, resulting in decreased patient survival. On the basis of this premise, several groups are attempting to deplete FoxP3+ T cells to enhance tumor immunity. However, recent studies have challenged this paradigm by showing that FoxP3+ T cells exhibit heterogeneous phenotypes and, in some cohorts, are associated with favorable prognosis. These discrepant results could arise from differences in study methodologies or the biologic properties of specific cancer types. Here, we conduct the first systematic review of the prognostic significance of FoxP3+ T cells across nonlymphoid cancers (58 studies from 16 cancers). We assessed antibody specificity, cell-scoring strategy, multivariate modeling, use of single compared with multiple markers, and tumor site. Two factors proved important. First, when FoxP3 was combined with one additional marker, double-positive T cells were generally associated with poor prognosis. Second, tumor site had a major influence. FoxP3+ T cells were associated with poor prognosis in hepatocellular cancer and generally good prognosis in colorectal cancer, whereas other cancer types were inconsistent or understudied. We conclude that FoxP3+ T cells have heterogeneous properties that can be discerned by the use of additional markers. Furthermore, the net biologic effects of FoxP3+ T cells seem to depend on the tumor site, perhaps reflecting microenvironmental differences. Thus, depletion of FoxP3+ T cells might enhance tumor immunity in some patient groups but be detrimental in others. Clin Cancer Res; 18(11); 3022–9. ©2012 AACR.
Sensitizing and Th2 Adjuvant Activity of Cysteine Protease Allergens
Authors: Cunningham Paula T. , Elliot Claire E. , Lenzo Jason C. , Jarnicki Andrew G. , Larcombe Alexander N. , Zosky Graeme R. , Holt Patrick G. , Thomas Wayne R.
Published: April 2012

Background: Innate properties that enhance immune responses might increase the propensity of certain allergens to induce allergic sensitization. Either a direct adjuvant effect or the increased immune response to the allergen could then increase allergic responses to bystander antigens. Here, we report on a model that does not use Th2-skewing adjuvants and yet achieves sensitization solely via the nasal mucosa. Methods: Animals were sensitized with either enzymatically active, inactive or non-activated cysteine proteases via the nasal mucosa. Following two sensitization phases, mice were challenged with a higher dose of allergen. For bystander sensitization, mice received recombinant Der p 2 at sensitization in conjunction with the cysteine protease and were challenged with rDer p 2 alone. Sensitization was determined by measuring allergen-specific antibody responses and cytokine and cellular infiltrates into the lungs following challenge. Results: Sensitization for Th2-type lung hypersensitivity for both the cysteine protease and bystander antigens was readily achieved and both were dependent on the proteolytic activity of the allergen. Bystander adjuvant activity was demonstrated for mice that were low IgE responders to the cysteine protease, showing a response independent from the immune response to the enhancing cysteine protease. Airway hyperreactivity was induced in the susceptible NOD strain of mouse, and mice subjected to prolonged administration of papain maintained the ability to produce lung hypersensitivity and Th2-type responses. Conclusions: These experiments demonstrate that cysteine protease activity at low doses can be an adjuvant for respiratory Th2 responses for themselves and bystander antigens in the absence of another adjuvant.
Inflammatory Biomarkers in Patients with Asymptomatic Primary Hyperparathyroidism
Authors: Emam Ahmed Alsayed , Mousa Sabela Gomaa , Ahmed Karema Yousif , Al-Azab Adel A.
Published: April 2012

Objective: To assess highly sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) as inflammatory biomarkers in patients with asymptomatic primary hyperparathyroidism (PHPT). Materials and Methods: A total of 26 patients with asymptomatic PHPT and 22 age- and sex-matched individuals as a control group were recruited for the study. Corrected serum calcium, phosphorus, alkaline phosphatase, serum 25-hydroxyvitamin D, intact parathyroid hormone (PTH), hs-CRP and IL-6 were measured for all subjects. Results: Serum hs-CRP and IL-6 were significantly higher in asymptomatic PHPT patients than in the control group (hs-CRP: 4.15 ± 0.54 vs. 2.24 ± 0.11 mg/l; IL-6: 4.50 ± 0.80 vs. 2.56± 0.29 pg/ml; p < 0.001). Moreover, in asymptomatic PHPT patients, serum PTH was significantly correlated with hs-CRP and IL-6 (r = 0.820, p < 0.001 and r = 0.787, p < 0.001, respectively). Conclusion: Inflammatory biomarkers were higher in patients with asymptomatic PHPT than in controls. Moreover, serum PTH was significantly correlated with inflammatory biomarkers which may suggest a subclinical inflammatory response in this group of patients.
Refined Staging for Chorioretinopathy in Long-Chain 3-Hydroxyacyl Coenzyme A Dehydrogenase Deficiency
Authors: Tyni Tiina , Immonen Tuuli , Lindahl Päivi , Majander Anna , Kivelä Tero
Published: April 2012

Objective: Neonatal screening and earlier diagnosis have improved the prognosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency, which causes a need to refine the staging of the pigmentary chorioretinopathy and thus improve monitoring and comparability of patients under dietary therapy. Methods: Seven children with LCHAD deficiency caused by homozygous G1528C mutation attended sequential fundus photography for stage 2 chorioretinopathy in 1997–2006. After arranging 21 pairs of fundus photographs according to the severity of the fundus changes, the images best representing 3 different grades of pigmentary deposits (P1–P3) and retinal pigment epithelial (RPE) atrophy (A1–A3) were chosen as reference photographs. To evaluate the substaging, 29 pairs of photographs were graded according to the reference photographs. Results: In the assessment of pigmentary deposits, the 3 ophthalmologists agreed in 41% and differed by a single substage in 45% of instances (combined weighted ĸ statistic was 0.38, indicating moderate agreement). In pairwise comparisons, the weighted ĸ statistic ranged from 0.31 to 0.56 (agreement, 71–81%). In the assessment of RPE atrophy, all 3 raters agreed in 17% and 2 raters in 70% of instances (combined ĸ statistic 0.018, indicating poor agreement). Discussion: Despite variation in imaging techniques and limitations in the visual assessment of fundus photographs, the agreement obtained in grading the pigmentary deposits was comparable to that reported for photographic grading of retinopathy of prematurity. We recommend photographic documentation and substaging based on reference photographs in the follow-up of LCHAD retinopathy. The refined staging allows a more detailed assessment on the progression of the retinopathy and optimization of the therapeutic protocols in individual patients and between centres using different therapeutic protocols.
Genetic Service Delivery: Infrastructure, Assessment and Information
Authors: Kaye C.I.
Published: April 2012

Identification of genomic determinants of complex disorders such as cancer, diabetes and cardiovascular disease has prompted public health systems to focus on genetic service delivery for prevention of these disorders, adding to their previous efforts in birth defects prevention and newborn screening. This focus is consistent with previously identified obligations of the public health system as well as the core functions of public health identified by the Institute of Medicine. Models of service delivery include provision of services by the primary care provider in conjunction with subspecialists, provision of services through the medical home with co-management by genetics providers, provision of services in conjunction with disorder-specific treatment centers, and provision of services through a network of genetics clinics linked to medical homes. Whatever the model for provision of genetic services, tools to assist providers include facilities for outreach and telemedicine, information technology, just-in-time management plans, and emergency management tools. Assessment tools to determine which care is best are critical for quality improvement and development of best practices. Because the workforce of genetics providers is not keeping pace with the need for services, an understanding of the factors contributing to this lag is important, as is the development of an improved knowledge base in genomics for primary care providers.
The Effect of Chronic Disease Family History on Healthcare Provider Practice and Patient Behavior among Oregonians
Authors: Zlot A.I. , Cox S.L. , Silvey K. , Leman R.
Published: April 2012

Family history is an independent risk factor for many chronic conditions. Therefore, efforts to prevent these diseases among asymptomatic people at high familial risk are justified to reduce the health burden of these chronic conditions. We analyzed 2006–2009 Oregon Behavioral Risk Factor Surveillance System data to examine associations between family history of diabetes, cardiovascular disease (CVD), colorectal cancer (CRC), breast cancer (BC), and: (1) patient-reported clinician recommendations, (2) adoption of preventive and screening behaviors, and (3) chronic disease risk factors among respondents without a personal history of the condition. A positive family history was associated with a higher likelihood of reported discussion by clinicians of CRC and BC screening and a greater likelihood of respondents having cholesterol and CRC screening. The combination of family history and clinician recommendations significantly increased the odds of CRC and BC screening compared to family history alone. A positive family history was also associated with respondents reporting lifestyle changes to prevent diabetes, CVD, and CRC, but not BC. Awareness of family history prompts clinicians to recommend screening and may motivate patients to be screened. Understanding positive family history may also motivate patients to adopt healthy lifestyles.
Epidemiological Study and Clinical Profile of Parkinson’s Disease in the Assiut Governorate, Egypt: A Community-Based Study
Authors: Khedr Eman M. , Al Attar Ghada S. , Kandil Mahmoud R. , Kamel Nageh F. , Abo Elfetoh Noha , Ahmed Mohamed A.
Published: April 2012

Background: Few comprehensive epidemiological studies of the prevalence of Parkinson’s disease (PD) have been undertaken in Arab countries, and none has been carried out in Egypt. A community-based survey was conducted in the Assiut Governorate to estimate the prevalence and clinical profile of PD. Methods: A community-based study was carried out, with random sampling of 7 districts, involving 6,498 inhabitants. Out of this sample, 578 subjects dropped out, leaving 3,066 males (51.8%) and 2,854 females (48.2%). There were 3,660 urban residents (61.8%) and 2,260 (38.2%) from the rural community. Patients were evaluated using a screening questionnaire, the Unified Parkinson Disease Rating Scale and the Non-Motor Symptoms Scale for PD. Results: Thirty-nine subjects were found to have parkinsonism, giving a crude prevalence rate of 659/100,000 inhabitants. Of these subjects, 33 were diagnosed with PD (21 males), with a mean age of 66.9 ± 8.4 years, a crude prevalence rate of 557/100,000 and an age-specific prevalence rate (≥50 years old) of 2,748/100,000. There were more males than females (3,395 vs. 1,989/100,000), but the difference was not significant. The highest age-specific prevalence rate was recorded among subjects 70–79 years old (7,263/100,000). There was a significantly higher prevalence among rural than urban inhabitants (973 vs. 301/100,000) and among illiterate than literate persons (1,103 vs. 280/100,000). The clinical profile of our patients was similar to that of other populations but was characterized by a high prevalence of mood/cognition dysfunction and gastrointestinal symptoms; there were few reported perceptual problems. Conclusion: The overall prevalence of PD was high, especially in older adults.
Auditory-Perceptual Voice Characteristics in Pre-Operative Patients Undergoing Thyroid or Parathyroid Surgery
Authors: Bone Sarah L. , Vertigan Anne E. , Eisenberg Robert L.
Published: April 2012

Objectives: To systematically evaluate auditory perceptual voice characteristics in people with thyroid disease prior to undergoing thyroid surgery. Patients and Methods: This study examined the auditory perceptual voice characteristics of 96 individuals with thyroid disease. Participants were categorised by type of thyroid disease (i.e. multinodular goitre, thyroid cancer, thyroid nodule, toxicity or parathyroidism) and by status of compression (i.e. compression versus no compression). Auditory perceptual voice ratings were made on samples of connected speech by using the Perceptual Voice Profile. Results: A high prevalence of participants had deviant auditory perceptual voice features; however, the majority of these abnormalities were slight to mild in severity and only 8% of participants had a clinically significant auditory perceptual abnormality. There was no significant difference in features between diagnostic categories, and only high pitch was rated as more significantly deviant in patients without compression versus those with compression. Conclusions: This study supports the need for auditory-perceptual ratings to be included as part of pre-operative multidimensional assessment of voice in patients with thyroid disease.
Gamma Knife Radiosurgery in the Treatment of Tumor-Related Facial Pain
Authors: Squire Sarah E. , Chan Michael D. , Furr R. Michael , Lowell Dorothy A. , Tatter Stephen B. , Ellis Thomas L. , Bourland J. Daniel , deGuzman Allan F. , Munley Michael T. , Ekstrand Kenneth E. , Shaw Edward G. , McMullen Kevin P.
Published: April 2012

Background: Intracranial neoplasms can cause pain similar to trigeminal neuralgia. Literature regarding radiosurgery for this is limited. We present a retrospective review of patients with tumor-related facial pain from benign lesions treated with gamma knife radiosurgery (GKRS) at Wake Forest University. Objectives: The primary objectives were to determine long-term pain relief and predictive factors for pain alleviation. Methods: We reviewed 515 patients treated with GKRS for benign meningioma, vestibular schwannoma or trigeminal schwannoma between August 1999 and August 2010. Twenty-one eligible patients had tumor-related facial pain prior to GKRS. The median marginal tumor dose was 12 Gy. Long-term pain relief data were obtained by chart review and telephone interview. Results: The median follow-up for symptom evaluation was 3.8 years. Seventeen of 21 patients (81%) experienced a Barrow Neurological Institute (BNI) score of I–III at 6 months following GKRS. Kaplan-Meier estimates of freedom from BNI IV–V relapse were 66% at 1 year and 53% at 2 years. No pain relapses occurred after 2 years. Conclusion: GKRS of benign lesions is a noninvasive option for patients with tumor-related facial pain. Pain relief is modest, with the majority of pain relapses occurring within 2 years and approximately one half of patients maintaining relief beyond 2 years.
Effect of Ischemia Duration on Autoantibody Response in Rats Undergoing Retinal Ischemia-Reperfusion
Authors: Joachim Stephanie C. , Jehle Thomas , Boehm Nils , Gramlich Oliver W. , Lagreze Wolf A. , Pfeiffer Norbert , Grus Franz H.
Published: April 2012

Both the innate and the adaptive immune systems are involved in the pathogenic processes following ischemia-reperfusion injury. We analyzed the possible correlation between the duration of ischemia and autoantibody diversification in a model of ocular ischemia. Rats were subjected to 30, 45, or 90 min of ischemia, and retinal ganglion cell (RGC) density and antibody reactivity were analyzed via customized protein microarray slides. After ocular ischemia, significant alterations in antibody response were observed, while increasing exposure caused more severe RGC damage. Distinct antibody responses after ischemia were detected; these alterations comprised decreased reactivities against cyclophilin A and glyceraldehyde-3-phosphate dehydrogenase, possibly due to increased binding of circulating antibodies to debris material. Other antibodies, like those against α5β1-integrin or β2-adrenergic receptor, were upregulated after ischemia.
Comparison of Lactulose and Glucose Breath Test for Diagnosis of Small Intestinal Bacterial Overgrowth in Patients with Irritable Bowel Syndrome
Authors: Rana S.V. , Sharma S. , Kaur J. , Sinha S.K. , Singh K.
Published: April 2012

Background and Aims: Validity of the lactulose breath test (LBT) to diagnose small intestinal bacterial overgrowth (SIBO) has been questioned. Therefore, a study was planned to compare LBT with glucose breath test (GBT) to diagnose SIBO in irritable bowel syndrome (IBS) patients and controls. Methods: 175 diarrhea-predominant IBS patients and 150 apparently healthy controls were enrolled. IBS was diagnosed according to Rome II criteria. Breath samples were collected every 10 min up to 180 min. Breath H2 and CH4 were measured using an SC MicroLyzer. SIBO was positive with a sustained increase in breath H2 or CH4 or both ≥10 ppm over a baseline value within <90 min in case of LBT and within <120 min in GBT. Results: SIBO was positive in 60/175 (34.3%) patients by lactulose and in 11/175 (6.2%) patients by GBT. In controls, LBT was positive for SIBO in 45/150 (30%) patients and in 1/150 (0.66%) patients by GBT. Positive LBT for SIBO was not significantly different in patients and controls; while using GBT, SIBO was significantly higher (p < 0.01) in patients as compared to controls. By using GBT as gold standard for SIBO, sensitivity, specificity, positive predictive value and negative predictive value of LBT in IBS patients was 63.6, 67.7, 11.7 and 96.6% respectively. Conclusion: LBT is not a good test to discriminate SIBO in IBS patients from controls.