bluuebunny/crossref_metadata_2025 huggingface dataset:
ZD7288 Enhances Long-Term Depression at Early Postnatal Medial Perforant Path-Granule Cell Synapses
Authors: Guli Xiati , Tokay Tursonjan , Rohde Marco , Bender Roland A. , Köhling Rüdiger , Kirschstein Timo
Published: June 2012

Hyperpolarization-activated, cyclic nucleotide-gated nonselective (HCN) channels modulate both membrane potential and resistance and play a significant role in synaptic plasticity. We compared the influence of HCN channels on long-term depression (LTD) at the medial perforant path-granule cell synapse in early postnatal (P9–15) and adult (P30–60) rats. LTD was elicited in P9–15 slices using low-frequency stimulation (LFS, 900 pulses, 1 Hz;80±4% of baseline). Application of the specific HCN channel blocker ZD7288 (10 μM) before LFS significantly enhanced LTD (62±4%;P<0.01), showing HCN channels restrain LTD induction. However, when ZD7288 was applied after LFS, LTD was similar to control values and significantly different from the values obtained with ZD7288 application before LFS (81±5%;P<0.01), indicating that HCN channels do not modulate LTD expression. LTD in slices from adult rats were only marginally lower compared to those in P9–15 slices (85±6%), but bath application of ZD7288 prior to LFS resulted in the same amount of LTD (85±5%). HCN channels in adult tissue hence lose their modulatory effect. In conclusion, we found that HCN channels at the medial perforant path-granule cell synapse compromise LFS-associated induction, but not expression of LTD in early postnatal, but not in adult, rats.
HIV Mother-to-Child Transmission, Mode of Delivery, and Duration of Rupture of Membranes: Experience in the Current Era
Authors: Mark Siobhan , Murphy Kellie E. , Read Stanley , Bitnun Ari , Yudin Mark H.
Published: June 2012

Objective. To evaluate whether the length of time of rupture of membranes (ROM) in optimally managed HIV-positive women on highly active antiretroviral therapy (HAART) with low viral loads (VL) is predictive of the risk of mother to child transmission (MTCT) of the human immunodeficiency virus (HIV).Study Methods. A retrospective case series of all HIV-positive women who delivered at two academic tertiary centers in Toronto, Canada from January 2000 to November 2010 was completed.Results. Two hundred and ten HIV-positive women with viral loads <1,000 copies/ml delivered during the study period. VL was undetectable (<50 copies/mL) for the majority of the women (167, 80%), and <1,000 copies/mL for all women. Mode of delivery was vaginal in 107 (51%) and cesarean in 103 (49%). The median length of time of ROM was 0.63 hours (range 0 to 77.87 hours) for the entire group and 2.56 hours (range 0 to 53.90 hours) for those who had a vaginal birth. Among women with undetectable VL, 90 (54%) had a vaginal birth and 77 (46%) had a cesarean birth. Among the women in this cohort there were no cases of MTCT of HIV.Conclusions. There was no association between duration of ROM or mode of delivery and MTCT in this cohort of 210 virally suppressed HIV-positive pregnant women.
Consequences of Inhibiting Amyloid Precursor Protein Processing Enzymes on Synaptic Function and Plasticity
Authors: Wang Hui , Megill Andrea , He Kaiwen , Kirkwood Alfredo , Lee Hey-Kyoung
Published: June 2012

Alzheimer's disease (AD) is a neurodegenerative disease, one of whose major pathological hallmarks is the accumulation of amyloid plaques comprised of aggregatedβ-amyloid (Aβ) peptides. It is now recognized that soluble Aβoligomers may lead to synaptic dysfunctions early in AD pathology preceding plaque deposition. Aβis produced by a sequential cleavage of amyloid precursor protein (APP) by the activity ofβ- andγ-secretases, which have been identified as major candidate therapeutic targets of AD. This paper focuses on how Aβalters synaptic function and the functional consequences of inhibiting the activity of the two secretases responsible for Aβgeneration. Abnormalities in synaptic function resulting from the absence or inhibition of the Aβ-producing enzymes suggest that Aβitself may have normal physiological functions which are disrupted by abnormal accumulation of Aβduring AD pathology. This interpretation suggests that AD therapeutics targeting theβ- andγ-secretases should be developed to restore normal levels of Aβor combined with measures to circumvent the associated synaptic dysfunction(s) in order to have minimal impact on normal synaptic function.
Carrier Formation Dynamics of Organic Photovoltaics as Investigated by Time-Resolved Spectroscopy
Authors: Yonezawa Kouhei , Ito Minato , Kamioka Hayato , Yasuda Takeshi , Han Liyuan , Moritomo Yutaka
Published: June 2012

Bulk heterojunction (BHJ) based on a donor (D) polymer and an acceptor (A) fullerene derivative is a promising organic photovoltaics (OPV). In order to improve the incident photon-to-current efficiency (IPCE) of the BHJ solar cell, a comprehensive understanding of the ultrafast dynamics of excited species, such as singlet exciton (D*), interfacial charge-transfer (CT) state, and carrier (D+), is indispensable. Here, we performed femtosecond time-resolved spectroscopy of two prototypical BHJ blend films: poly(3-hexylthiophene) (P3HT)/[6,6]-phenyl C61-butyric acid methyl ester (PCBM) blend film and poly(9,9′-dioctylfluorene-co-bithiophene) (F8T2)/[6,6]-phenyl C71-butyric acid methyl ester (PC70BM) blend film. We decomposed differential absorption spectra into fast, slow, and constant components via two-exponential fitting at respective probe photon energies. The decomposition procedure clearly distinguished photoinduced absorptions (PIAs) due to D*, CT, and D+. Based on these assignments, we will compare the charge dynamics between the F8T2/PC70BM and P3HT/PCBM blend films.
CpG Island Methylation, Microsatellite Instability, and BRAF Mutations and Their Clinical Application in the Treatment of Colon Cancer
Authors: Wu Christina , Bekaii-Saab Tanios
Published: June 2012

There have been significant developments in colon cancer research over the last few years, enabling us to better characterize tumors individually and classifying them according to certain molecular or genetic features. Currently, we are able to use KRAS mutational status as a guide to therapy with anti-epidermal growth factor receptor antibodies. Other molecular features under research include BRAF mutation, microsatellite instability, and CpG island methylation. These three molecular features are often associated with tumors that have overlapping phenotypes and can be present simultaneously in the same tumor. However, they carry different prognostic and predictive qualities, making analysis of their interaction relatively complex. Much research thus far has examined the clinical relevance of microsatellite instability in helping determine prognosis and the predictive value of adjuvant 5-fluorouracil chemotherapy in stages II and III colon cancers. BRAF mutation appears to be a biomarker for poor prognosis. CpG island methylation is tightly associated with microsatellite instable tumors and BRAF mutation, but its clinical utility remains uncertain. Hereby, we examine preclinical and clinical data that supports the utilization of all three phenotypes in future research applied to clinical practice.
Physician Cross-Cultural Nonverbal Communication Skills, Patient Satisfaction and Health Outcomes in the Physician-Patient Relationship
Authors: Coelho Ken Russell , Galan Chardee
Published: June 2012

Recent empirical findings document the role of nonverbal communication in cross-cultural interactions. As ethnic minority health disparities in the United States continue to persist, physician competence in this area is important. We examine physicians' abilities to decode nonverbal emotions across cultures, our hypothesis being that there is a relationship between physicians' skill in this area and their patients' satisfaction and outcomes. First part tested Caucasian and South Asian physicians' cross-cultural emotional recognition ability. Physicians completed a fully balanced forced multiple-choice test of decoding accuracy judging emotions based on facial expressions and vocal tones. In the second part, patients reported on satisfaction and health outcomes with their physicians using a survey. Scores from the patient survey were correlated with scores from the physician decoding accuracy test. Physicians, regardless of their ethnicity, were more accurate at rating Caucasian faces and vocal tones. South Asian physicians were no better at decoding the facial expressions or vocal tones of South Asian patients, who were also less likely to be satisfied with the quality of care provided by their physicians and to adhere to their physicians' recommendations. Implications include the development of cultural sensitivity training programs in medical schools, continuing medical education and public health programs.
An Unusual Occurrence of Multiple Dental Anomalies in a Single Nonsyndromic Patient: A Case Report
Authors: Nagaveni N. B.
Published: June 2012

Dental anomalies are the formative defects caused by genetic disturbances or environmental factors during tooth morphogenesis. Simultaneous occurrence of various multiple anomalies has been reported previously, particularly in cases of chromosomal abnormalities that often manifest with multisystem involvement. Very few cases of multiple anomalies have been documented in patients with no known generalized abnormalities. The present paper shows an unusual occurrence of a combination of dental anomalies like mandibular canine transmigration, taurodontism in permanent mandibular molars, congenital agenesis of 14 numbers of permanent teeth excluding third molars, canine impaction, primary molars with pyramidal roots, midline diastema and generalized microdontia in an apparently normal 13-year-old Indian girl.
Simultaneous Sinus Lifting and Alveolar Distraction of a Severely Atrophic Posterior Maxilla for Oral Rehabilitation with Dental Implants
Authors: Kanno Takahiro , Mitsugi Masaharu , Paeng Jun-Young , Sukegawa Shintaro , Furuki Yoshihiko , Ohwada Hiroyuki , Nariai Yoshiki , Ishibashi Hiroaki , Katsuyama Hideaki , Sekine Joji
Published: June 2012

We retrospectively reviewed a new preimplantation regenerative augmentation technique for a severely atrophic posterior maxilla using sinus lifting with simultaneous alveolar distraction, together with long-term oral rehabilitation with implants. We also analyzed the regenerated bone histomorphologically. This study included 25 maxillary sinus sites in 17 patients. The technique consisted of alveolar osteotomy combined with simultaneous sinus lifting. After sufficient sinus lifting, a track-type vertical alveolar distractor was placed. Following a latent period, patient self-distraction was started. After the required augmentation was achieved, the distractor was left in place to allow consolidation. The distractor was then removed, and osseointegrated implants (average of 3.2 implants per sinus site, 80 implants) were placed. Bone for histomorphometric analysis was sampled from six patients and compared with samples collected after sinus lifting alone as controls (n=4). A sufficient alveolus was regenerated, and all patients achieved stable oral rehabilitation. The implant survival rate was 96.3% (77/80) after an average postloading followup of 47.5 months. Good bone regeneration was observed in a morphological study, with no significant difference in the rate of bone formation compared with control samples. This new regenerative technique could be a useful option for a severely atrophic maxilla requiring implant rehabilitation.
Stability Analysis for Stochastic Markovian JumpReaction‐Diffusion Neural Networks with Partially Known TransitionProbabilities and Mixed Time Delays
Authors: Zhang Weiyuan , Li Junmin , Shi Naizheng
Published: June 2012

The stability problem is proposed for a new class of stochastic Markovian jump reaction‐diffusion neural networks with partial information on transition probability and mixed time delays. The new stability conditions are established in terms of linear matrix inequalities (LMIs). To reduce the conservatism of the stability conditions, an improved Lyapunov‐Krasovskii functional and free‐connection weighting matrices are introduced. The obtained results are dependent on delays and the measure of the space AND, therefore, have less conservativeness than delay‐independent and space‐independent ones. An example is given to show the effectiveness of the obtained results.
Evaluation of Serodiagnostic Assays forMycobacterium bovisInfection in Elk, White-Tailed Deer, and Reindeer in the United States
Authors: Nelson Jeffrey T. , Orloski Kathleen A. , Lloyd Audra L. , Camacho Mark , Schoenbaum Mark A. , Robbe-Austerman Suelee , Thomsen Bruce V. , Hall S. Mark
Published: June 2012

In 2011, the United States Department of Agriculture conducted a project in which elk (Cervus elaphusspp.), white-tailed deer (WTD) (Odocoileus virginianus), and reindeer (Rangifer tarandus) were evaluated by the single cervical tuberculin test (SCT), comparative cervical tuberculin test (CCT), and serologic tests. The rapid antibody detection tests evaluated were the CervidTB Stat-Pak (Stat-Pak), and the Dual Path Platform VetTB (DPP). Blood was collected from presumably uninfected animals prior to tuberculin injection for the SCT. A total of 1,783 animals were enrolled in the project. Of these, 1,752 (98.3%) were classified as presumably uninfected, based on originating from a captive cervid herd with no history of exposure to TB. Stat-Pak specificity estimates were 92.4% in reindeer, 96.7% in WTD, and 98.3% in elk and were not significantly different from SCT specificity estimates. Using the DPP in series on Stat-Pak antibody-positive samples improved specificity in the three species. Thirty one animals were classified as confirmed infected, based on necropsy and laboratory results, and 27/31 were antibody positive on Stat-Pak for an estimated sensitivity of 87.1%. The study findings indicate that rapid serologic tests used in series are comparable to the SCT and CCT and may have a greater ability to detect TB-infected cervids.
Developing a Multidisciplinary Team for Disorders of Sex Development: Planning, Implementation, and Operation Tools for Care Providers
Authors: Moran Mary Elizabeth , Karkazis Katrina
Published: June 2012

In the treatment of patients with disorders of sex development (DSD), multidisciplinary teams (MDTs) represent a new standard of care. While DSDs are too complex for care to be delivered effectively without specialized team management, these conditions are often considered to be too rare for their medical management to be a hospital priority. Many specialists involved in DSD care want to create a clinic or team, but there is no available guidance that bridges the gap between a group of like-minded DSD providers who want to improve care and the formation of a functional MDT. This is an important dilemma, and one with serious implications for the future of DSD care. If a network of multidisciplinary DSD teams is to be a reality, those directly involved in DSD care must be given the necessary program planning and team implementation tools. This paper offers a protocol and set of tools to meet this need. We present a 6-step process to team formation, and a sample set of tools that can be used to guide, develop, and evaluate a team throughout the course of its operation.
Iron Deficiency Anaemia in Pregnancy and Postpartum: Pathophysiology and Effect of Oral versus Intravenous Iron Therapy
Authors: Khalafallah Alhossain A. , Dennis Amanda E.
Published: June 2012

Nutritional iron-deficiency anaemia (IDA) is the most common disorder in the world, affecting more than two billion people. The World Health Organization’s global database on anaemia has estimated a prevalence of 14% based on a regression-based analysis. Recent data show that the prevalence of IDA in pregnant women in industrialized countries is 17.4% while the incidence of IDA in developing countries increases significantly up to 56%. Although oral iron supplementation is widely used for the treatment of IDA, not all patients respond adequately to oral iron therapy. This is due to several factors including the side effects of oral iron which lead to poor compliance and lack of efficacy. The side effects, predominantly gastrointestinal discomfort, occur in a large cohort of patients taking oral iron preparations. Previously, the use of intravenous iron had been associated with undesirable and sometimes serious side effects and therefore was underutilised. However, in recent years, new type II and III iron complexes have been developed, which offer better compliance and toleration as well as high efficacy with a good safety profile. In summary, intravenous iron can be used safely for a rapid repletion of iron stores and correction of anaemia during and after pregnancy.
Spacetime Junctions and the Collapse to Black Holes in Higher Dimensions
Authors: Mena Filipe C.
Published: June 2012

We review recent results about the modelling of gravitational collapse to black holes in higher dimensions. The models are constructed through the junction of two exact solutions of the Einstein field equations: an interior collapsing fluid solution and a vacuum exterior solution. The vacuum exterior solutions are either static or containing gravitational waves. We then review the global geometrical properties of the matched solutions which, besides black holes, may include the existence of naked singularities and wormholes. In the case of radiating exteriors, we show that the data at the boundary can be chosen to be, in some sense, arbitrarily close to the data for the Schwarzschild-Tangherlini solution.
Assessing the Therapeutic Effect of 630 nm Light-Emitting Diodes Irradiation on the Recovery of Exercise-Induced Hand Muscle Fatigue with Surface Electromyogram
Authors: Yang Dandan , Wu Xiaoying , Hou Wensheng , Zheng Xiaolin , Zheng Jun , Jiang Yingtao
Published: June 2012

This paper aims to investigate the effect of light emitting diode therapy (LEDT) on exercise-induced hand muscle fatigue by measuring the surface electromyography (sEMG) of flexor digitorum superficialis. Ten healthy volunteers were randomly placed in the equal sized LEDT group and control group. All subjects performed a sustained fatiguing isometric contraction with the combination of four fingertips except thumb at 30% of maximal voluntary contraction (MVC) until exhaustion. The active LEDT or an identical passive rest therapy was then applied to flexor digitorum superficialis. Each subject was required to perform a re-fatigue task immediately after therapy which was the same as the pre-fatigue task. Average rectified value (ARV) and fractal dimension (FD) of sEMG were calculated. ARV and FD were significantly different between active LEDT and passive rest groups at 20%–50%, 70%–80%, and 100% of normalized contraction time (P<0.05). Compared to passive rest, active LEDT induced significantly smaller increase in ARV values and decrease in FD values, which shows that LEDT is effective on the recovery of muscle fatigue. Our preliminary results also suggest that ARV and FD are potential replacements of biochemical markers to assess the effects of LEDT on muscle fatigue.
Characterizing Cognitive Deficits and Dementia in an Aging Urban Population in India
Authors: Nair G. , Van Dyk K. , Shah U. , Purohit D. P. , Pinto C. , Shah A. B. , Grossman H. , Perl D. , Ganwir V. , Shanker S. , Sano M.
Published: June 2012

Rapid rise in the population of older adults in India will lead to the need for increased health care services related to diagnosis, management, and long-term care for those with dementia and cognitive impairment. A direct approach for service provision through memory clinics can be an effective, successful, and sustaining means of delivering specialized health care services. We have established a memory clinic in Mumbai, India by employing the diverse clinical skills available in Indian academic institutions, diagnostic and research expertise of clinicians and psychologists, and the support of the U.S. National Institutes of Health. Our project involved recruitment of patients, clinical and neuropsychological assessment, and standardized diagnostic procedures, demonstrating the feasibility of using research methods to develop a memory clinic. In this paper, we describe the development of a community-based memory clinic in urban India, including linguistic and cultural factors and present detailed results, including diagnostic characterization, on 194 subjects with various stages of cognitive deficits. Our findings support the feasibility of developing a memory clinic in a public hospital and successful use of research diagnostic criteria to categorize cognitive deficits observed in this population, which may be used to inform the development of other such clinics.
Structural and Optical Properties of Nanocrystalline 3,4,9,10-Perylene-Tetracarboxylic-Diimide Thin Film
Authors: El-Nahhas M. M. , Abdel-Khalek H. , Salem E.
Published: June 2012

Thin films of nanocrystalline 3,4,9,10-perylene-tetracarboxylic-diimide (PTCDI) were prepared on quartz substrates by thermal evaporation technique. The structural properties were identified by transmission electron microscopy (TEM) and the X-ray diffraction (XRD). The optical properties for the films were investigated using spectrophotometric measurements of the transmittance and reflectance at normal incidence of light in the wavelength range from 200 to 2500 nm. The optical constants (refractive indexnand absorption indexk) were calculated and found to be independent on the film thickness in the measured film thickness range 117–163 nm. The dispersion energy (Ed), the oscillator energy (Eo), and the high-frequency dielectric constantε∞were obtained. The energy band model was applied, and the types of the optical transitions responsible for optical absorption were found to be indirect allowed transition. The onset and optical energy gaps were calculated, and the obtained results were also discussed.
Behavioral Predictors of Colonization withLactobacillus crispatusorLactobacillus jenseniiafter Treatment for Bacterial Vaginosis: A Cohort Study
Authors: Mitchell Caroline , Manhart Lisa E. , Thomas Kathy , Fiedler Tina , Fredricks David N. , Marrazzo Jeanne
Published: June 2012

Objective: Evaluate predictors of vaginal colonization with lactobacilli after treatment for bacterial vaginosis (BV).Methods. Vaginal fluid specimens from women with BV underwent qPCR forLactobacillus crispatus,L. jensenii, andL. inerspre- and posttreatment.Results. Few women with BV were colonized withL. crispatus(4/44, 9%) orL. jensenii(1/44, 2%), though all hadL. iners.One month posttreatment 12/44 (27%) hadL. crispatus, 12/44 (27%)L. jensenii, and 43/44 (98%)L. iners.Presence ofL. jenseniiposttreatment was associated with cure (Risk Ratio (RR) 1.67; 95% CI 1.09–2.56);L. crispatusshowed a similar trend (RR 1.41; 95% CI 0.89–2.24,P=0.14). Receptive oral sex was associated with 2.2-log10lower concentration ofL. crispatus(95% CI −4.38, −.02), and digital-vaginal sex with 2.6-log10lower concentration (95% CI −4.87, −.33).Conclusion. One month after BV treatment, few women established colonization withL. crispatusorL. jensenii. Few behaviors were associated with colonization.
Assessment of Antiobesity Potential ofAchyranthes asperaLinn. Seed
Authors: Rani Neerja , Sharma Surendra Kumar , Vasudeva Neeru
Published: June 2012

The present study was designed to evaluate the quality control parameters, quantitative phytochemical analysis (total phenols, total flavonoids, and total saponin content), and the antiobesity effect of ethanol extract ofAchyranthes asperaLinn. seed (EAA) by employingin vitroandin vivomodels. Inin vitrostudy, the inhibitory activity of EAA on pancreatic amylase and lipase was measured. Thein vivopancreatic lipase activity was evaluated by measurement of plasma triacylglycerol levels after oral administration of EAA along with lipid emulsion to Swiss albino mice. The EAA inhibited pancreatic amylase and lipase activity in vitro and elevations of plasma triacylglycerol level in mice. Furthermore, the antiobesity effect of EAA (900 mg/kg) was assessed in mice fed a high-fat diet with or without EAA for 6 weeks. EAA significantly suppressed the increase in body,retroperitoneal adiposetissue, liver weights, and serum parameters, namely; total cholesterol, total triglyceride, and LDL-cholesterol level. The anti obesity effects of EAA in high-fat-diet-treated mice may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic amylase and lipase activity. Histopathological effects of EAA on the liver of mice were also assessed.
Angle of Arrival Estimation Using Cholesky Decomposition
Authors: Al-Jazzar Saleh O.
Published: June 2012

An angle of arrival (AOA) estimator is presented. Many applications require accurate AOA estimates such as wireless positioning and signal enhancement using space-processing techniques. The proposed AOA estimator depends on the Cholesky decomposition of the received signal autocorrelation matrix. The resultant decomposed matrices are used to modify the crosscorrelation matrix of the received signals at the antenna array doublets. The proposed method is named the Cholesky-decomposition-based-AOA (CDBA) estimator. In comparison with the TLS-ESPRIT algorithm which utilizes the eigenvalue decomposition (EVD) of the received signal autocorrelation and crosscorrelation matrices, the CDBA method has better performance than the TLS-ESPRIT algorithm especially in low signal-to-noise-ratio (SNR) cases. Simulations for the proposed CDBA method are shown to assess its performance.
Convergence Theorems for Maximal Monotone Operators, Weak Relatively Nonexpansive Mappings and Equilibrium Problems
Authors: Nammanee Kamonrat , Suantai Suthep , Cholamjiak Prasit
Published: June 2012

We introduce hybrid‐iterative schemes for solving a system of the zero‐finding problems of maximal monotone operators, the equilibrium problem, and the fixed point problem of weak relatively nonexpansive mappings. We then prove, in a uniformly smooth and uniformly convex Banach space, strong convergence theorems by using a shrinking projection method. We finally apply the obtained results to a system of convex minimization problems.
Nursing Leadership in a Rapidly Aging Society: Implications of “The Future of Nursing” Report in Japan
Authors: Masaki Harue , Nagae Hiroko , Teshima Megumi , Izumi Shigeko
Published: June 2012

The recent US Institute of Medicine (IOM) report about the future of nursing highlights the areas where nurses can serve, contribute, and move forward to improve health care in the United States. Japanese nursing scholars examined the IOM report for its implications in the Japanese context and explored the future of nursing in Japan. The purpose of this paper is to provide support for the premise that the report’s recommendations could have implications for the future of nursing outside of the United States, especially in Japan. Particular areas and activities by nurses in Japan will be presented as examples of nurses taking leadership in designing care for the rapidly aging society of Japan.
Improved Bounds for Restricted Isometry Constants
Authors: Ji Jiabing , Peng Jigen
Published: June 2012

The purpose of this paper is to establish improved bounds for restricted
isometry constants δk. Our results, to some extent, improve and extend the well‐known bound (δk < 0.307) in (Cai et al., 2010) to δk < 0.308.
Nonlinear Dynamic Model-Based Adaptive Control of a Solenoid-Valve System
Authors: Lee DongBin , Naseradinmousavi Peiman , Nataraj C.
Published: June 2012

In this paper, a nonlinear model-based adaptive control approach is proposed for a solenoid-valve system. The challenge is that solenoids and butterfly valves have uncertainties in multiple parameters in the nonlinear model; various kinds of physical appearance such as size and stroke, dynamic parameters including inertia, damping, and torque coefficients, and operational parameters especially, pipe diameters and flow velocities. These uncertainties are making the system not only difficult to adjust to the environment, but also further complicated to develop the appropriate control approach for meeting the system objectives. The main contribution of this research is the application of adaptive control theory and Lyapunov-type stability approach to design a controller for a dynamic model of the solenoid-valve system in the presence of those uncertainties. The control objectives such as set-point regulation, parameter compensation, and stability are supposed to be simultaneously accomplished. The error signals are first formulated based on the nonlinear dynamic models and then the control input is developed using the Lyapunov stability-type analysis to obtain the error bounded while overcoming the uncertainties. The parameter groups are updated by adaptation laws using a projection algorithm. Numerical simulation results are shown to demonstrate good performance of the proposed nonlinear model-based adaptive approach and to compare the performance of the same solenoid-valve system with a non-adaptive method as well.
The Changing Face of HIV in Pregnancy in Rhode Island 2004–2009
Authors: Firth Jacqueline , Wang Chia-Ching , Gillani Fizza , Alexander Nicole , Dufort Elizabeth , Rana Aadia , Cu-Uvin Susan
Published: June 2012

Meeting the needs of HIV-infected pregnant women requires understanding their backgrounds and potential barriers to care and safe pregnancy. Foreign-born women are more likely to have language, educational, and economic barriers to care, but may be even more likely to choose to keep a pregnancy. Data from HIV-infected pregnant women and their children in Rhode Island were analyzed to identify trends in demographics, viral control, terminations, miscarriages, timing of diagnosis, and adherence to followup. Between January 2004 and December 2009, 76 HIV-infected women became pregnant, with a total of 95 pregnancies. Seventy-nine percent of the women knew their HIV status prior to becoming pregnant. Fifty-four percent of the women were foreign-born and 38 percent of the 16 women who chose to terminate their pregnancies were foreign-born. While the number of HIV-infected women becoming pregnant has increased only slightly, the proportion that are foreign-born has been rising, from 41 percent between 2004 and 2005 to 57.5 percent between 2006 and 2009. A growing number of women are having multiple pregnancies after their HIV diagnosis, due to the strength of their desire for childbearing and the perception that HIV is a controllable illness that does not preclude the creation of a family.
Intestinal Schistosomiasis as Unusual Aetiology for Acute Appendicitis, Nowadays a Rising Disease in Western Countries
Authors: López de Cenarruzabeitia I. , Landolfi S. , Armengol Carrasco M.
Published: June 2012

Intestinal schistosomiasis as unusual aetiology for acute appendicitis, nowadays a rising disease in western countries. Recent changes in global migration has led to an immigration growth in our scenario, upsurging people coming from endemic areas of schistosomiasis. Schistosomal appendicitis, seldom reported in developed countries, is now an expected incrising entity in our hospitals during the near future. Due to this circumstances, we believe that schistosomiasis should be consider as a rising source for acute appendicitis in western countries. In order to illustrate this point, we present a case of a 45-years-old black man, from Africa, was admitted via A&E because of acute abdominal pain, located in right lower quadrant. Acute appendicitis was suspected, and he underwent laparotomy and appendectomy. Pathological study by microscope revealed a gangrenous appendix with abscesses and parasitic ova into the submucosal layer of the appendix, suggesting Schistosomiasis.
Development and Validation of HLPC Method for the Estimation of Lamotrigine in Bulk and Pharmaceutical Formulations
Authors: Reddy T. Vijaya Bhaskara , Ramu G. , Biksham Babu A. , Rambabu C.
Published: June 2012

A simple, precise, accurate, and rapid HPLC method was developed to estimate the amount of lamotrigine in bulk and its pharmaceutical formulations. Waters Alliance HPLC system equipped with autosampler, ultraviolet detector, and Symmetry C8 (4.6 mm ID × 150 mm, 3.5 μm, Make: XTerra) column were used for the quantification of the drug. Separation was carried out at a flow rate of 0.7 mL/min. of mobile phase (acetonitrile and potassium dihydrogen phosphate buffer of pH = 7.0 in the ratio 60 : 40 v/v), and the detection was carried out at a wavelength of 215 nm. The retention time of lamotrigine was found to be 2.797 min. The linearity was obeyed in the range of concentration 5–25 μg/mL. The developed method was found to be repeatable and reproducible; hence, it can be used as an alternative method in assay of the lamotrigine in any pharmaceutical industries.
OT1-03-01: A Randomized Phase III Clinical Trial of Standard Adjuvant Endocrine Therapy +/− Chemotherapy in Patients (pts) with 1–3 Positive Nodes, Hormone Receptor (HR)-Positive and HER2−Negative Breast Cancer with Recurrence Score (RS) of 25 or Less: SWOG S1007.
Authors: Gonzalez-Angulo AM , Barlow WE , Gralow JR , Meric-Bernstam F , Hayes DF , Moinpour CM , Ramsey SD , Schott AF , Sparks DB , Albain KS , Hortobagyi GN
Published: June 2012

Background

Multi-gene tumor assays have provided clinically useful prognostic information for pts with HR receptor and node-positive breast cancer. The 21-gene RS was shown to be prognostic for pts treated with tamoxifen alone, and exploratory studies suggested that it may be predictive of benefit from chemotherapy. In retrospective analyses from SWOG S8814, pts with low RS appeared to get no benefit from adjuvant CAF chemotherapy, while those with higher RS did. These retrospective data require validation, especially since more modern chemotherapy might be more effective than the regimen used in S8814.

Specific Aims/Trial Design: In January 2011, SWOG activated a phase III randomized clinical trial (registration number NCT01272037) to test the efficacy of using modern chemotherapy regimens in node positive pts with low RS, whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value. The trial is similar to the Tailor RX study, but focuses on a node-positive population with low and intermediate RS.

Eligibility Criteria: Pts with 1 to 3 positive lymph nodes, HR-positive and HER2−negative invasive breast cancer with RS ≤ 25 are eligible for randomization. Pts will be informed of their RS.

Target and Present Accrual: Approximately 9400 patients will be screened to randomize 4000, stratified by RS (0-13 vs. 14–25), menopausal status, and axillary surgery (sentinel node vs. complete dissection); 46 are presently registered.

Statistical Methods: The trial is powered to find a significant interaction of treatment assignment and the continuous RS value and, subsequently, derive a cut point for using the assay to guide treatment decisions. Pts who consent to screening are required to consent to banking of the tumor tissue and blood for further studies. Patient Reported Outcomes will be collected pre, post-screening and post-randomization. The study also has a cost-effectiveness analysis.

Funding: Supported in part by National Cancer Institute grants CA32102 & CA38926, and in part by the Susan G. Komen for the Cure® Research Program, and the Breast Cancer Research Foundation.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-03-01.
OT3-01-05: PARP Inhibition after Preoperative Chemotherapy in Patients with Triple-Negative Breast Cancer (TNBC) or Known BRCA 1/2 Mutations: Hoosier Oncology Group BRE09-146.
Authors: Miller KD , Perkins SM , Badve SS , Sledge GW , Schneider BP
Published: June 2012

Background

Based on recently reported I-SPY trial, TNBC patients who had residual disease category II or III had 2-year disease free survival (DFS) of only ∼40% (J Clin Oncol 2009;27:18s). Currently, no standard systemic therapy exists for this high-risk group. It represents a real opportunity to explore the potential impact of novel therapies. Recent laboratory and early clinical studies (Nature 2005;434:913) identified a unique sensitivity to DNA-damaging chemotherapy and PARP inhibition. We initiated a randomized phase II trial of DNA-damaging chemotherapy (cisplatin) or PARP-inhibition + cisplatin in TNBC patients with substantial residual invasive disease after standard anthracycline and/or taxane containing neoadjuvant chemotherapy.

Methods: To ensure a high-risk population, patients must have residual disease category 0–2 based on the Miller-Payne classification system, residual cancer burden classification II or III, residual lymph node involvement, or at least 2 cm of residual invasive disease in the breast. After completion of standard radiation therapy (when indicated), patients are randomized 1:1 to cisplatin (75 mg/M2 IV Day 1 every 3 weeks x 4 cycles) alone or in combination with PARP inhibition (PF-01367338 — 24 mg IV D1, 2, 3 of each 3 week cycle with a single dose escalation to 30 mg in the absence of significant toxicity in cycle 1 followed by maintenance PARP inhibition weekly x 24 weeks). The primary objective is 2-year DFS. To detect an improvement in 2-year DFS from 40% with cisplatin alone to 63.2% in the cisplatin + PF-01367338 arm (corresponding to HR=0.5), with 80% power using a one-side log-rank test with 0.10 level of significance, 102 patients are required in the primary analysis. Secondary objectives include safety, 1-year DFS, overall survival, and biomarkers of tumor recurrence, resistance to chemotherapy and/or PARP inhibition. Two dose escalation safety cohorts (N=13) were completed without dose limiting toxicity; the randomized portion began enrolment in 11/2010 has enrolled 20 patients as of 05/2011.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-05.
P1-01-06: Mechanisms of Tumor Immune Escape in Triplenegative Breast Cancers (TNBC) with and without Mutated BRCA 1.
Authors: Segerer SE , Kapp M , Hahne JC , Dietl J , Engel JB
Published: June 2012

Background

Triplenegative breast cancer (TNBC) is associated with a dismal prognosis, although these tumors are chemosensitive. This phenomenon could be at least in part due to tumor immune escape. The current study investigates the host's immune response to TNBC cells and explores the presence of immunesuppressive factors, such as pAKT-expression and infiltration with FoxP3 positive regulatory T-cells (Tregs), in human TNBC samples.

Material and Methods: NK-cell induced lysis of tumor cells was evaluated in human breast cancer cell lines MCF-7 (ER/PR pos.), HCC 1937 (triplenegative, BRCA 1 mutated) and HCC 1806 (triplenegative). Expression of pAKT and infiltration with Tregs was determined by immunehistochemistry and evaluated semiquantatitavely (0 no expression- 3 strong expression). Control groups consisted of: Fibroadenoma (N=6), prohpyhlactic mastectomy (BRCA 1 mutated, N=3), ER/PR + breast cancer (N=13). They were compared with triplenegative breast cancers: N = 9 BRCA wildtype and N = 6 BRCA 1 mutated.

Results: At an effector target/target-ratio of 10/1 NK-cell induced lysis in HCC 1937 and HCC 1806 was 2.27 and 4.45 increased, respectively, as compared to MCF 7 cells. No infiltration with Tregs was detected in fibroadenoma and prophylactic mastectomy samples. Infiltration with FoxP3-positive Tregs was 0.92 +/− 0.75 in ER/PR+ breast cancers and 2.66 +/−0.5 (p<0.05) in TNBC and 2.16 +/−0.98 (p<0.05) in TNBC with BRCA mutation, respectively. Expression of pAKT was 1.45 +/− 1.29 in ER/PR + breast cancers and 1.77 +/−1.20 in TNBC and 2.66 +/−0.51 (p<0.05) TNBC/with BRCA mutation.

Discussion: TNBC cells stimulated the NK-cell response to a stronger extent than did ER-positive MCF 7 cells mirrored by a more pronounced NK-cell- induced lysis. Thus, the observed stronger infiltration with FoxP3-positive Tregs in TNBC tumor samples could reflect a compensatory mechanism to suppress the host's immune response. In other tumor entities, such as ovarian cancer infiltration with Tregs is associated with a worse overall survival (1). Thus, the significantly increased infiltration with Tregs, could suggest that the worse prognosis of TNBC is due to tumor immune escape and further investigation of immunemodulatory therapeutic strategies in TNBC could prove fruitful.

(1) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.

Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W.

Nat Med. 2004 Sep;10(9):942–9.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-06.
P2-12-31: Moderate Immunohistochemical Expression of HER2 (2+) without HER2 Gene-Amplification Is a Negative Prognostic Factor in Early Breast Cancer.
Authors: Rossi V , Sarotto I , Maggiorotto F , Tomasi Cont N , Redana S , Aglietta M , Ponzone R , Montemurro F
Published: June 2012

Purpose: We sought to evaluate whether moderate HER2 immunohistochemical (IHC) expression (2+ and no HER2/amplification) identifies early breast cancer (EBC) with a distinct prognostic profile.

Methods: A total of 1295 women (median age 58, range 22–94) undergoing surgery for EBC from Jan 1995 to Sept 2009 were retrospectively reviewed. All patients had undergone HER2 testing by the HercepTest and, when needed, by fluorescence in-situ hybridization (FISH). All tests were carried on at our Institutional Surgical Pathology laboratory. The impact of HER2 status on disease-free survival (DFS) was corrected for other clinical and pathological potential covariates by Cox Proportional Regression Analysis.

Results: A total of 494 (38%), 486 (38%), 119 (9%) and 196 (15%) of the patients had HER2 0+, 1+ 2+ and positive (3+ or FISH+) tumors, respectively. Sixty-one of 196 patients with HER2−positive EBC received adjuvant trastuzumab. A total of 298 DFS events occurred at median follow-up of 59 months (4-137 months). By using HER2 0+ status as reference, multivariate analysis revealed that HER2 2+ expression was associated with a significant increase in the risk of a DFS event (HR 2.303, 95% C.I. 1.501−3.533, p<0.001), whereas HER2 1+ was not (HR 0.976, 95% C.I. 0.698−1.365, p=0.889). We performed exploratory two-group comparisons by further classifying tumors according to hormone-receptor status (cutoff for ER and PgR positivity ≥10% of stained cells). Results are summarized in the table. HER2 2+ expression was associated with worse prognosis in both ER and/or PgR positive and ER/PgR negative tumors. In the latter group, HER2 2+ expression was associated with a particularly high rate of DFS events, with a 60-month projected DFS of 20%. Furthermore, while DFS curves plateaued at 60 months for HER2−positive tumors (with and without adjuvant trastuzumab) and for ER/PgR negative tumors with HER2 0/1+ expression, hormone receptor positive/HER2 2+ tumors displayed a particularly high rate of late relapses (beyond 60 months). Results did not change using a 1% cutoff to define ER and PgR positivity.

Conclusion: Moderate HER2 positivity (IHC 2+/FISH negative) identifies EBC patients at increased risk of a DFS event, regardless of hormone receptor status. Due to suggestions from large randomized trials that the benefits of trastuzumab may not be limited to HER2−positive tumors, patients with HER2 2+ EBC are ideal candidates for studies testing this hypothesis.

Multivariate Hazard Ratios, corrected by age, lymph-node status, tumor diameter, tumor grade, proliferation (Ki 67 index) and receipt of adjuvant chemotherapy

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-31.
P2-18-05: Cardiotoxicity Risks of Adjuvant Trastuzumab in Asian Breast Cancer Patients.
Authors: Shih V , Chan A , Sim MH , Teo C , Chen W , Wong ZW
Published: June 2012

Background: Adjuvant trastuzumab (T)-based chemotherapy reduces relapse and improves overall survival in early breast cancer. However, T-associated cardiotoxicity potentially limits its use. Our study aims to report the incidence, severity and reversibility of cardiotoxicity amongst Asian breast cancer patients.

Methods: This is a retrospective review of patients who have received adjuvant T from June 2005 to March 2011 at our centre. CT was defined as a drop in left ventricular ejection fraction (LVEF) to less than 50% and / or reduction of ≥ 10% of baseline. Cardiovascular (CVS) risk factors were defined as having at least one of the following factors: family or previous history of CAD, hypertension, diabetes mellitus, hyperlipidemia and smoking. One-way repeated measures ANOVA was used to evaluate the mean LVEF change and Chi-square test to evaluate the association of demographics and CT.

Results: A total of 314 female patients were reviewed. CT was reported in 124 (39.5%), of whom 96 had asymptomatic decline in LVEF and 28 were symptomatic. T was withheld (n=53) due to asymptomatic decline in LVEF (n=40), symptomatic heart failure (n=3) and both (n=10). Forty-three patients with resolution of CHF (n=11) or LVEF recovery (n=32) were rechallenged. Cardiotoxicity recurred in 14 - asymptomatic decline in LVEF (n=10), recurrent CHF (n=1) and both (n=3). Overall, there were no cardiac-related deaths. Factors that predicted for CT included low normal pre-trastuzumab LVEF (<60%) (p=0.01), prior anthracyclines (p=0.011), decline in LVEF pre-anthracycline and before T (p=0.022) and BMI ≥ 23kg/m2 (p=0.018). Three-monthly LVEF showed statistically significant decline against baseline over the time points (p=0.005). As expected, the decline in LVEF demonstrated significant interaction with CT groups and non CT group (p<0.001).

Conclusions: A higher incidence of CT (39.5%) was observed among Asian breast cancer patients compared to previously reported in Caucasians (24%). Although 77.4% of patients presented with asymptomatic decline in LVEF, approximately one-third of patients experienced recurrent CT upon rechallenge.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-18-05.