bluuebunny/crossref_metadata_2025 huggingface dataset:
WE‐D‐204B‐05: Online Monitoring and Error Detection of Real‐Time Tumor Displacement Prediction Accuracy Using Statistical Process Control
Authors: Malinowski KT , Mc Avoy TJ , George R , Dieterich S , D'Souza WD
Published: August 2010

Purpose: To investigate two statistical process control (SPC) metrics, the Hotelling (T2) statistic and the input‐variable‐squared‐prediction‐error (Q(x)), for predicting degradation in real‐time tumor displacement accuracy without explicit measurement of tumor displacement. Method and Materials: Independently but concurrently localized tumor and external surrogate positions from a database of Cyberknife Synchrony™ cases (130 treatment fractions from 63 lung tumors, 10 fractions from 5 liver tumors, and 48 fractions from 23 pancreas tumors) were analyzed. Each fraction consisted of 40–112 measurements obtained at an average rate of 0.018 Hz. The first 10 measured internal/external samples in each fraction were used to create fraction‐specific models of tumor displacement using external surrogates. The regression coefficients relating the 3D positions of the 3 skin markers to the 3D tumor positions were calculated using partial‐least‐squares (PLS) regression. The PLS model was applied to all subsequent localizations in the fraction. The T2‐ and Q(x)‐statistics in the training data were used to develop 90th, 95th and 99th percentile ranges of expected T2 and Q(x) values. The sensitivities and specificities of T2, Q(x), T2̆Q(x), and T2̑Q(x) for predicting real‐time tumor displacement errors greater than 3mm and 5mm were determined. Results: The T2, Q(x), T2̆Q(x), and T2̑Q(x) statistics' sensitivities and specificities varied with error threshold and acceptable percentile ranges of values. In general, the Q(x) statistic was associated with high sensitivity and low specificity, while the T2 statistic was associated with moderate sensitivity and moderate specificity. For 90th percentile T2, 99th percentile Q(x) and 3 mm error, the sensitivities of T2, Q(x), T2̆Q(x), and T2̑Q(x) were 69%, 88%, 92%, and 64%, respectively, and the specificities were 62%, 37%, 28%, and 72%, respectively. Conclusion: This study illustrates the feasibility of SPC metrics for detecting breakdowns in tumor displacement prediction accuracy using external sensors.

Conflict of Interest: Funded by NIH grant CA 124766
WE‐D‐204B‐08: Tracking 3D Trajectory of Internal Markers Using Radiographic Sequential Stereo Imaging: Estimation of Breathing Motion
Authors: Mostafavi H , Sloutsky A , Jeung A
Published: August 2010

Purpose: To show that Sequential Stereo Algorithm can track internal markers that move with respiration using a single imager and to determine the accuracy and required number of images (dose) for typical breathing trajectories. Method and Materials: The Sequential Stereo Algorithm, developed at Varian Medical Systems, Palo Alto, CA (patent pending) uses images acquired at different times and from different directions to track point targets moving in 3D. It performs best for trajectories that are approximately repeating in space, but not necessarily periodic; no prior knowledge or additional surrogate signal is needed. One application is to track radio opaque markers moving by respiration in the lung or liver, using kV images acquired on a gantry‐based onboard imager while the gantry is rotating. We evaluated the algorithm using three different studies: 1) The Tracking concept was proven with projections from clinical CBCT scans (used retrospectively) exhibiting respiration motion. 2) Tracking accuracy was measured in a phantom experiment by kV imaging of a marker that moved on a known trajectory using a computer controlled 3‐axis stage. 3) The sensitivity of accuracy to imaging frequency was determined by simulation study involving a virtual moving marker. Actual patient trajectories that included irregular breathing were driving both the stage and the simulated virtual point. Results: Using 3.5fps imaging over 30 Sec and 180° gantry rotation the 3D tracking error at measurement points was 0.65mm RMS (1.83mm max) for the phantom imaging study, and 0.75mm RMS (1.64mm max) for the simulation. For an irregular breathing interval the error was 1.01mm RMS (3.64mm max). Simulation showed that error remains consistently under 1mm for imaging frequency greater than 3fps. Conclusion: Sequential Stereo can accurately track internal markers that move with respiration in 3D, and may potentially be useful in real‐time adaptive radiotherapy techniques.
WE‐E‐204B‐05: MR Relaxation Properties for Fe‐Containing MWCNTs and Potential for Combined MR Imaging and Tumor Ablation Therapy
Authors: Ding X , Bourland J , Singh R , Burke A , Hatcher H , Olson J , Carroll D , Kraft R , Torti S , Torti F
Published: August 2010

Purpose: Investigate MR relaxation and laser heating properties of Fe‐containing Multi‐Walled Carbon Nanotubes (MWCNTs), to determine their potential uses as Magnetic Resonance Imaging (MRI) Contrast Agents (CAs) and Laser Absorbing Agents (LAAs) for laser‐induced thermal therapy (LITT) for cancer. Methods and Materials: MRI relaxation properties of 3 different Fe‐containing MWCNT solution (600mg, 200mg 60mg Fe) were determined in a 1.5T MR scanner using a multi‐echo pulse sequence. To study in vivo MR properties for LITT of cancer, two breast tumor bearing mice were intratumorly injected with 600mg Fe MWCNTs and N‐Doped MWCNTs which contains very few iron articles as a comparison, followed by Near Infared (NIR) LITT (3W/cm2, 30seconds). 7T MR T2 maps of the mouse tumors with instilled MWCNTs were acquired at 5 time points during and after LITT. Additionally, LITT using 600mg Fe‐containing MWCNTs was evaluated using a larger group of mice (n=4). Results: MWCNT R2 (or 1/T2) measurements, shows that the 600mg Fe MWCNTs' R2 is about 5 times higher than R2 for a commercial MR CAs (Feridex I.V.® (ferumoxides)). Thus, Fe‐containing MWCNTs may perform very well as T2‐weighted MR CAs. Futhermore, the in vivo MR study shows that 600mg Fe MWCNTs CAs effectively change the tumor T2 relaxation from 61ms to 22ms and creates a void signal in the implanted target area, enabling tumor localization for MR‐guided LITT. After one week post‐LITT, Fe‐containing MWCNTs were still located in the implanted target region, indicating minimum migration/ diffusion, and T2 relaxation properties were stable. The in vivo study also showed that 600mg Fe‐containing MWCNTs + LITT show potential as a new cancer therapy. Conclusion: Fe‐containing MWCNTs have favorable MR relaxation values and biological stability, and show great potential as a dual‐modality agent for T2 MR Contrast imaging and NIR laser absorption for MR‐guided LITT.
TH‐C‐204B‐03: Monitoring the Response to Photodyamic Therapy in Murine Tumours with Contrast‐Enhanced Micro‐CT
Authors: Nasui O.C. , Bisland S. , Ford N.L.
Published: August 2010

Purpose: To identify if contrast‐enhanced micro‐computed tomography (micro‐CT) can be used as a non‐invasive imaging device to detect the vascular response of murine tumours following photodynamic therapy (PDT). Method and Materials: A solution of RIF‐1 cells (105) was injected subcutaneously in the posterior flank of C3H mice 3 weeks prior to the treatment. Two groups of treated mice and two control groups were used (n=5 per group). The two PDT‐groups were treated with fluences of 150 J/cm2 and 50 J/cm2. The photosensitizer dose was kept constant in both groups. One control group was exposed to light only (no photosensitizer was administered) while the other did not receive any type of treatment. The imaging procedure consisted of 10 eight‐second scans: 2 pre‐PDT (before and after contrast agent administration) and 8 post‐PDT (at various time‐points up to 24 hours). The tumours removed after the last scan were prepared for histology. The PDT response was quantified by finding the ratio of blood‐to‐tumour volume from the micro‐CT images. The ratios were compared at each time‐point among the four groups in order to identify the group and time‐point showing the strongest PDT response detectable with micro‐CT. Results: A significant vascular response was detected at 8 and 24 hours after treatment when using a light fluence of 150 J/cm2 (p < 0.01). Hematoxylin and eosin staining confirmed the treatment effects at the cellular level. Conclusion: Our results indicate that contrast‐enhanced micro‐CT can be used as a non‐invasive imaging tool to detect the vascular response of tumours following PDT.
TH‐C‐204B‐04: Assessing the Potential of Cerenkov Radiation for in Vivo Imaging of Tumor Hypoxia
Authors: Noll J , Ali R , Vilalta M , Graves E
Published: August 2010

Purpose: To assess whether in vivo optical imaging using Cerenkov radiation can (a) produce results that are comparable to those from microPET tumor imaging and (b) provide information that facilitates future dual‐tracer imaging experiments. Method and Materials: (a) Subcutaneous tumors were established by injecting HT‐29 human colon adenocarcinoma cells into the shoulders of 4 nude mice and were grown until they reached a volume of 1cm3. 200microCi of 18F‐EF5 was injected via intraperitoneal injection and 3 mice were imaged using microPET whilst the other was imaged in an IVIS Spectrum. Images were acquired immediately and 1 hour following injection on both machines using acquisition times of 10mins (PET) and 2mins (IVIS). (b) A mathematical model of the Cerenkov emission spectrum was developed and used to predict the ability of Cerenkov imaging to resolve signals from different tracers. Results: (a) In the initial PET and IVIS images the tracer signal was confined to the region of the gastrointestinal region and there was no accumulation in the tumor. After 1 hour both sets of images showed similar biodistribution throughout the body along with uptake in the tumor. (b) The model predicted that different radionuclides can be distinguished through an energy‐dependent red‐shift in their emission spectra leading to higher intensity signals in the optical spectrum. Conclusion: We have shown that 18F‐EF5 Cerenkov imaging of subcutaneous tumors can be performed optically. More specifically our results show that the biodistribution and tumor uptake observed using this technique is in agreement with the microPET data. Our modeling suggests that the spectral differences between radionuclides coupled with the differences in decay rates between tracers labeled with different radioisotopes could be used to develop techniques for separating signals from two tracers for surface‐level tumors thus potentially allowing multiple aspects of tumor biology to be imaged simultaneously.
TH‐C‐204B‐06: MR Guided High‐Intensity Focused Ultrasound for Cancer Therapy: A Feasibility Study Using an Animal Model
Authors: Ma C , Mu Z , Chen L
Published: August 2010

Purpose: Ultrasound is a non‐invasive agent that has high precision and deep penetration in tissues enabling increased doses to the tumor while sparing nearby normal tissues. MR guided focused ultrasound (MRgFUS) thermal ablation has been applied for cancer surgery and bone palliation clinically. The aim of this work is to explore the feasibility of MRgFUS for prostate cancer therapy. Method and Materials: An InSightec ExAblate 2000 with a 1.5T GE MR scanner was used in this study. Suitable ultrasound parameters were investigated to perform non‐thermal sonications keeping the temperature below 42°C as measured in real time by MR thermometry. LNCaP cells (106) were injected into the prostate of male mice (n=8). When tumors reached the volume of 49±3mm3 on MRI the tumor‐bearing mice were treated with MRgFUS once a week for two consecutive weeks. Animals were treated with pulsed ultrasound (1MHz; 5W acoustic power; 5Hz frequency; 0.5duty cycle: 0.1sec power on 0.1sec power off) for 60sec in each sonication. A total of 4–6 sonications were used to cover the entire tumor volume. The animals were allowed to survive for 4 weeks after the last treatment. The tumor growth was monitored on MRI and compared with the control group. Results: Significant tumor growth delay was observed in the mice treated with MRgFUS. The mean tumor volume for the MRgFUS treated mice was about 30% smaller than that of the control mice 1 week after the MRgFUS treatment and it was about 50% smaller 4 weeks after the MRgFUS treatment. Conclusions: Our results demonstrated that non‐thermal MRgFUS has a great potential for cancer therapy. Further experiments are needed to derive optimal ultrasound parameters and fractionation schemes to maximize the therapeutic effect. This work is supported by Focused Ultrasound Surgery Foundation DOD PC073127 and Varian Medical Systems. Technical support from InSightec is acknowledged.
TH‐C‐204C‐02: Advanced MR Spectroscopy Methods for Studying Metabolism and Radiation Treatment Response in Brain Tumors
Authors: Andronesi O , Seco J , Shih H , Sorensen G
Published: August 2010

Magnetic resonance spectroscopy imaging (MRSI) provides completely non‐invasively detailed metabolic information which correlates with physiological or pathological conditions. Hence it is becoming a valuable tool in image guided radio(proton)therapy where it can probe dose conformity (radiation delivered over the tumor volume and surrounding tissues) and could provide in‐vivo new insights about the biology of tumor response to radiation.

Traditionally in‐vivo MRSI faces several challenges that may limit its potential such as: 1) inaccuracy in signal localization (chemical shift displacement error and voxel bleeding); 2) low spatial resolution; and 3) long acquisition times for 3D volumetric scans. However recent advances in hardware and pulse sequence design can mitigate many of these problems. Use of adiabatic pulses can provide precise and uniform signal excitation and together with fast acquisition schemes of the k‐space such as spiral trajectories allows fast acquisition of high resolution 3D MRSI scans. In addition real‐time motion correction and shimming strategies can improve the reliability of MRSI scans. Moreover MRSI scans that have multiple frequency dimensions (such as 2D chemical shift correlation spectra) can now be performed in‐vivo to unambiguously identify overlapped metabolite signals.

This lecture will begin with an overview of the basic principles of in‐vivo MRS which will be followed by details of advanced MRSI methods such as adiabatic excitation fast spiral acquisition of 3D MRSI data and 2D chemical shift correlation spectra. Examples of in‐vivo MRSI data obtained on brain tumor patients treated with conventional radiotherapy and proton beam therapy will be shown in the end.

Learning Objectives:

1. Basic principles of MRSI.

2. Understand the critical artifacts that might confound MRS and the importance of improved methods for reliable MRSI.

3. Clinical applications of MRSI to monitor radiation therapy for brain tumors.
TH‐D‐204B‐03: IMRT and VMAT Inverse Planning with Compressed Sensing Techniques
Authors: Xing L , Zhu L , Meng B , Boyd S
Published: August 2010

The classical Shannon‐Nyquist sampling theorem specifies that to avoid losing information when capturing a signal one must sample at least two times faster than the signal bandwidth. In many medical applications the Nyquist rate may be either impractical or too expensive to be realized practically. Compressed sensing provides a practically valuable approach for finding optimal solutions with under‐ sampled data. In this talk I will summarize our recent work on using compressed sensing for IMRT and VMAT inverse planning. We show that effective utilization of prior knowledge of the systems through compressed sensing can greatly reduce the required number of measurement samples determined by the Shannon‐Nyquist theorem and leads to significantly improved IMRT/VMAT plans. Compressed sensing has significant interactions and bearings on fields of radiation oncology and medical imaging.

Learning Objectives:

1. Familiarize with the concept of compressed sensing.

2. Understand the fundamental limitations of currently available IMRT and VMAT inverse planning methods.

3. Appreciate the need for a compressed sensing based inverse planning.

4. Show the impact of the proposed new inverse planning algorithm.

5. Provide perspectives on future research topics.
Origin and Molecular Evolution of the Determinant of Methicillin Resistance in Staphylococci
Authors: Tsubakishita Sae , Kuwahara-Arai Kyoko , Sasaki Takashi , Hiramatsu Keiichi
Published: August 2010

Methicillin-resistant
Staphylococcus aureus
(MRSA) is one of the most important multidrug-resistant pathogens around the world. MRSA is generated when methicillin-susceptible
S. aureus
(MSSA) exogenously acquires a methicillin resistance gene,
mecA
, carried by a mobile genetic element, staphylococcal cassette chromosome
mec
(SCC
mec
), which is speculated to be transmissible across staphylococcal species. However, the origin/reservoir of the
mecA
gene has remained unclear. Finding the origin/reservoir of the
mecA
gene is important for understanding the evolution of MRSA. Moreover, it may contribute to more effective control measures for MRSA. Here we report on one of the animal-related
Staphylococcus
species,
S. fleurettii
, as the highly probable origin of the
mecA
gene. The
mecA
gene of
S. fleurettii
was found on the chromosome linked with the essential genes for the growth of staphylococci and was not associated with SCC
mec
. The
mecA
locus of the
S. fleurettii
chromosome has a sequence practically identical to that of the
mecA
-containing region (∼12 kbp long) of SCC
mec
. Furthermore, by analyzing the corresponding gene loci (over 20 kbp in size) of
S. sciuri
and
S. vitulinus
, which evolved from a common ancestor with that of
S. fleurettii
, the speciation-related
mecA
gene homologues were identified, indicating that
mecA
of
S. fleurettii
descended from its ancestor and was not recently acquired. It is speculated that SCC
mec
came into form by adopting the
S. fleurettii mecA
gene and its surrounding chromosomal region. Our finding suggests that SCC
mec
was generated in
Staphylococcus
cells living in animals by acquiring the intrinsic
mecA
region of
S. fleurettii
, which is a commensal bacterium of animals.
Membrane Efflux and Influx Modulate both Multidrug Resistance and Virulence of
Klebsiella pneumoniae
in a
Caenorhabditis elegans
Model
Authors: Bialek Suzanne , Lavigne Jean-Philippe , Chevalier Jacqueline , Marcon Estelle , Leflon-Guibout Véronique , Davin Anne , Moreau Richard , Pagès Jean-Marie , Nicolas-Chanoine Marie-Hélène
Published: August 2010

Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for
Klebsiella pneumoniae
. The potential impact of this multidrug resistance (MDR) on the virulence of
K. pneumoniae
was evaluated in the
Caenorhabditis elegans
model. For 2 of the 3 MDR clinical isolates studied, a significant increase in
acrB
transcription was found in comparison with their antibiotic-susceptible revertants. ATCC 138821 and MDR, revertant, and derivative strains with altered porin expression were studied. Strains proved or suspected to overexpress an efflux system were significantly more virulent than the ATCC and revertant strains (time to kill 50% of nematodes [LT
50
] in days: 3.4 to 3.8 ± 0.2 versus 4.1 to 4.4 ± 0.3,
P
< 0.001). Inversely, strains with altered porin expression were significantly less virulent, independently of the expression level of efflux system (LT
50
= 5.4 to 5.6 ± 0.2,
P
< 0.001). Altered porin expression did not change MICs of CMP and NAL but did those of FOX (4 to 16× MIC) and ertapenem (16 to 64× MIC). The strains with a normally or an overexpressed efflux system that received the β-lactamase CTX-M-15 became more widely resistant without modification of their virulence potential, suggesting that balance between resistance and virulence is dependent on the type of resistance mechanisms. In conclusion, this study shows that the expression of both efflux systems and porins is a key factor not only for antibiotic resistance but also virulence potential in
K. pneumoniae
.
BLIND SOURCE SEPARATION OF SPATIO-TEMPORAL MIXED SIGNALS USING PHASE INFORMATION OF ANALYTIC WAVELET TRANSFORM
Authors: ASHINO RYUICHI , MANDAI TAKESHI , MORIMOTO AKIRA
Published: August 2010

The cocktail party problem deals with the specialized human listening ability to focus one's listening attention on a single talker among a cacophony of conversations and background noises. The blind source separation problem is how to enable computers to solve the cocktail party problem in a satisfactory manner. The simplest version of spatio-temporal mixture problem, which is a type of blind source separation problem, has been solved by a generalized version of the quotient signal estimation method based on the analytic wavelet transform, under the assumption that the time delays are integer multiples of the sampling period. The analytic wavelet transform is used to represent time-frequency information of observed signals. Without the above assumption, improved algorithms, utilizing phase information of the analytic wavelet transforms of the observed signals, are proposed. A series of numerical simulations is presented.
ULTRASOUND ENHANCED SKIN OPTICAL CLEARING: MICROSTRUCTURAL CHANGES
Authors: XU XIANGQUN , SUN CHAOJIE
Published: August 2010

Our previous studies demonstrated the ultrasound-induced skin optical clearing enhancement with topical application of optical clearing agents on in vitro porcine skin and in vivohuman skin. The objective of this study was to investigate the possible mechanisms of the enhanced skin optical clearing by ultrasound medications. Optical clearing effects of ex vivo guinea pig abdomen skin topically applied with 60% glycerol or the combination of 60% glycerol and ultrasound were studied by optical coherence tomography (OCT). Microstructure of skin surface was examined by scanning electron microscopy (SEM). Ultrasound with a frequency of 1 MHz and a power of 0.75 W over a 3-cm probe was simultaneously applied with glycerol solution for 15 min. The combination of 60% glycerol and ultrasound results in a 19% increase in OCT 1/e light penetration depth after 30 min, which is much better than 60% glycerol alone. SEM images demonstrated that changes in skin microstructure due to the tight order of the lipid bilayers in the stratum corneum disrupted and the separation of keratinocytes by the application of ultrasound contribute to the ultrasound-enhanced intact skin optical clearing effects.
QUANTITATIVE CONTROL OF OPTICAL CLEARING EFFECTS STUDIED WITH TISSUE-LIKE PHANTOM
Authors: JIANG JINGYING , CHEN WEI , GONG QILIANG , XU KEXIN
Published: August 2010

Tissue optical clearing by use of optical clearing agents (OCAs) has been proven to have potential to reduce the highly scattering effect of biological tissues in optical techniques. However, the difference in tissue samples could lead to unreliable results, making it difficult to quantitatively control the dose of OCAs during the course of tissue optical clearing. In this work, in order to study the effects of optical clearing, we customized tissue-like phantoms with optical properties of some biological tissue. Diffuse reflectance and total transmittance of tissue-like phantoms with different OCAs (DMSO or glycerol) and porcine skin tissues were measured. Then optical property parameters were calculated by inverse adding-doubling (IAD) algorithm. Results showed that OCAs could lead to a reduction in scattering of tissue-like phantoms as it did to porcine skin tissue in vitro. Furthermore, a series of relational expressions could be fit to quantitatively describe the relationship between the doses of OCAs and the reduction of scattering effects. Therefore, proper tissue-like phantom could facilitate optical clearing to be used in quantitative control of tissue optical properties, and further promote the application potential of optical clearing to light-based noninvasive diagnostic and therapeutic techniques.
Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men
Authors: Veldhuis Johannes D. , Takahashi Paul Y. , Keenan Daniel M. , Liu Peter Y. , Mielke Kristi L. , Weist Suanne M.
Published: August 2010

Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH) unit, but the relative roles of the CNS and pituitary are not established. We postulated that relatively greater LH responses to flutamide (brain-permeant antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect greater feedback via CNS than pituitary/peripheral androgen receptor-dependent pathways. To this end, 24 healthy men ages 20–73 yr, BMI 21–32 kg/m2, participated in a prospective, placebo-controlled, randomized, double-blind crossover study of the effects of antiandrogen control of pulsatile, basal, and entropic (pattern regularity) measurements of LH secretion. Analysis of covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH secretion ( P = 0.003), 2) potentiated the age-related abbreviation of LH secretory bursts ( P = 0.025), 3) suppressed incremental GnRH-induced LH release ( P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release ( P = 0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1) raising mean LH ( P = 0.002) and T ( P = 0.017) concentrations, 2) accelerating LH pulse frequency ( P = 0.013), 3) amplifying total (basal plus pulsatile) LH ( P = 0.002) and T ( P < 0.001) secretion, 4) shortening LH secretory bursts ( P = 0.032), and 5) reducing LH secretory regularity ( P < 0.001). Both flutamide and bicalutamide elevated basal (nonpulsatile) LH secretion ( P < 0.001). These data suggest the hypothesis that topographically selective androgen receptor pathways mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy men.
Estrogen sulfotransferase regulates body fat and glucose homeostasis in female mice
Authors: Khor Victor K. , Dhir Ravindra , Yin Xiaoyan , Ahima Rexford S. , Song Wen-Chao
Published: August 2010

Estrogen regulates fat mass and distribution and glucose metabolism. We have previously found that estrogen sulfotransferase (EST), which inactivates estrogen through sulfoconjugation, was highly expressed in adipose tissue of male mice and induced by testosterone in female mice. To determine whether inhibition of estrogen in female adipose tissue affects adipose mass and metabolism, we generated transgenic mice expressing EST via the aP2 promoter. As expected, EST expression was increased in adipose tissue as well as macrophages. Parametrial and subcutaneous inguinal adipose mass and adipocyte size were significantly reduced in EST transgenic mice, but there was no change in retroperitoneal or brown adipose tissue. EST overexpression decreased the differentiation of primary adipocytes, and this was associated with reductions in the expression of peroxisome proliferator-activated receptor-γ, fatty acid synthase, hormone-sensitive lipase, lipoprotein lipase, and leptin. Serum leptin levels were significantly lower in EST transgenic mice, whereas total and high-molecular-weight adiponectin levels were not different in transgenic and wild-type mice. Glucose uptake was blunted in parametrial adipose tissue during hyperinsulinemic-euglycemic clamp in EST transgenic mice. In contrast, hepatic insulin sensitivity was improved but muscle insulin sensitivity did not change in EST transgenic mice. These results reveal novel effects of EST on adipose tissue and glucose homeostasis in female mice.
Age-Related Modifications of Muscle Synergies and Spinal Cord Activity During Locomotion
Authors: Monaco Vito , Ghionzoli Alessio , Micera Silvestro
Published: August 2010

Recent findings have shown that neural circuits located in the spinal cord drive muscular activations during locomotion while intermediating between descending signals and peripheral sensory information. This relationship could be modified by the natural aging process. To address this issue, the activity of 12 ipsilateral leg muscles was analyzed in young and elderly people (7 subjects per group) while walking at six different cadences (40–140 steps/min). These signals were used to extract synergies underlying muscle activation and to map the motoneuronal activity of the pools belonging to the lumbosacral enlargement (L2–S2). The comparison between the two groups showed that neither temporal patterning of motor primitives nor muscles loading synergies seemed to be significantly affected by aging. Conversely, as the cadence increased, spinal maps differ significantly between the groups, showing higher and scattered activity during the whole gait cycle in elders and well-defined bursts in young subjects. The results suggested that motor primitives lead the synchronization of muscle activation mainly depending on the biomechanical demand of the locomotion; hence they are not significantly affected by aging. Nevertheless, at the spinal cord level, biomechanical requirements, peripheral afference, and descending inputs are differently integrated between the two groups, probably reflecting age-related changes of both nervous system and motor control strategies during locomotion.
Disease and phenotype gene set analysis of disease-based gene expression in mouse and human
Authors: De Supriyo , Zhang Yongqing , Garner John R. , Wang S. Alex , Becker Kevin G.
Published: August 2010

The genetic contributions to common disease and complex disease phenotypes are pleiotropic, multifactorial, and combinatorial. Gene set analysis is a computational approach used in the analysis of microarray data to rapidly query gene combinations and multifactorial processes. Here we use novel gene sets based on population-based human genetic associations in common human disease or experimental genetic mouse models to analyze disease-related microarray studies. We developed a web-based analysis tool that uses these novel disease- and phenotype-related gene sets to analyze microarray-based gene expression data. These gene sets show disease and phenotype specificity in a species-specific and cross-species fashion. In this way, we integrate population-based common human disease genetics, mouse genetically determined phenotypes, and disease or phenotype structured ontologies, with gene expression studies relevant to human disease. This may aid in the translation of large-scale high-throughput datasets into the context of clinically relevant disease phenotypes.
Tyrosine Phosphatase Inhibitor-3 Sensitizes Melanoma and Colon Cancer to Biotherapeutics and Chemotherapeutics
Authors: Kundu Suman , Fan Keke , Cao Mingli , Lindner Daniel J. , Tuthill Ralph , Liu Lili , Gerson Stanton , Borden Ernest , Yi Taolin
Published: August 2010

Drug resistance is a major obstacle in cancer treatments and diminishes the clinical efficacy of biological, cytotoxic, or targeted therapeutics. Being an antiapoptotic mediator of chemoresistance in breast and lung cancer cells, MKP1 phosphatase might be targeted for overcoming chemoresistance and improving therapeutic efficacy. In this work, tyrosine phosphatase inhibitor-3 (TPI-3) was identified as a novel small molecule inhibitor of MKP1 and was capable of sensitizing tumors to bio- and chemotherapeutics in mice as a tolerated oral agent. Effective against recombinant MKP1, TPI-3 selectively increased MKP1 phosphosubstrates in Jurkat cells and induced cell death via apoptosis at nanomolar concentrations. TPI-3 also increased MKP1 phosphosubstrates in WM9 human melanoma cells and synergized with biotherapeutic IFNα2b in the growth inhibition of melanoma cells in vitro (combination index, <1). WM9 xenografts unresponsive to individual agents were significantly inhibited (62%, P = 0.001) in mice by a tolerated combination of oral TPI-3 (10 mg/kg, 5 d/wk) and IFNα2b. MKP1 expression was detected in human melanoma cell lines and tissue samples at levels up to six times higher than those in normal or nonmalignant melanocytes. TPI-3 also interacted positively with chemotherapeutics, 5-fluorouracil/leucovorin, against MC-26 colon cancer cells in vitro and in mice. Altogether, our data show the preclinical activities of TPI-3 in overcoming cancer resistance to bio- and chemotherapeutics, implicate MKP1 as a drug-resistant molecule in melanoma, and support the targeting of MKP1 for improving cancer therapeutic efficacy. Mol Cancer Ther; 9(8); 2287–96. ©2010 AACR.
Lessons from a Case of Oromandibular Mucormycosis Treated with Surgery and a Combination of Amphotericin B Lipid Formulation plus Caspofungin
Authors: Ojeda-Uribe Mario , Herbrecht Raoul , Kiefer Marie Hélène , Schultz Philippe , Chain Jorge , Chenard Marie-Pierre , Servant Jean Marie , Debry Christian
Published: August 2010

A rare case of oromandibular Rhizopus oryzae infection is described in a 55-year-old woman with acute myeloid leukaemia and decompensated diabetes mellitus. The infection developed during induction chemotherapy when the patient was neutropenic. She was treated with a combination of amphotericin B lipid formulation and caspofungin plus surgery. Debridement surgery included excision of the lower lip, chin, floor of the mouth, a portion of the tongue, as well as mandibular resection at the level of the horizontal branches. Eight weeks of combined antifungal therapy were followed by secondary prophylaxis with amphotericin B lipid formulation during consolidation chemotherapy after achieving complete response of both leukaemia and mucormycosis. Reconstructive surgery was carried out including insertion of a new biomaterial porous mandibular prosthesis, which showed excellent functionality after long-term follow-up, followed by several plastic surgery procedures once good tolerability and no adverse effects of the prosthesis were observed. This case shows that a well-coordinated multidisciplinary approach is critical to increase the chances of clinical success in this life-threatening infection.
Erythropoietin Protects Podocytes from Damage by Advanced Glycation End-Products
Authors: Ruester Christiane , Franke Sybille , Bondeva Tzvetanka , Wolf Gunter
Published: August 2010

Background: Podocyte damage and accumulation of advanced glycation end-products (AGEs) are implicated in the development and progression of diabetic nephropathy. We have previously shown that changes in podocyte pathophysiology, such as hypertrophy and reduced migration, are closely linked with the induction of the cell cycle inhibitor p27Kip1 and a decrease in neuropilin-1 (NRP1) expression. We investigated whether the erythropoietin receptor activators CERA and epoetin-β may prevent AGE-mediated changes in podocytes. Methods: Differentiated mouse podocytes in culture were challenged by AGE-modified bovine serum albumin (BSA) or control BSA in the presence or absence of CERA as well as epoetin-β. Cell cycle analysis and determination of apoptosis markers were performed. p27Kip1 and NRP1 expression was measured by RT-PCR and Western blots. Results: Differentiated mouse podocytes in culture expressed erythropoietin receptors which were phosphorylated after incubation with CERA or epoetin-β. CERA or epoetin-β prevented the p27Kip1-dependent cell cycle arrest and cellular hypertrophy induced by AGE-BSA incubation. Furthermore, the p27Kip1-dependent AGE-BSA-induced decrease in cell viability and decrease in cell proliferation was ameliorated in the presence of CERA or epoetin-β. Following erythropoietin treatment, AGE-BSA failed to further reduce NRP1 expression, resulting in improved podocyte migration. Conclusion: Treatment with the erythropoietin receptor activators epoetin-β or CERA protected podocytes from AGE-BSA-mediated damage via an effect on p27Kip1 and NRP1 expression. Consequently, early treatment with erythropoietin may help to prevent diabetic nephropathy.
Exercise Training Stimulates Ischemia-Induced Neovascularization via Phosphatidylinositol 3-Kinase/Akt-Dependent Hypoxia-Induced Factor-1α Reactivation in Mice of Advanced Age
Authors: Cheng Xian Wu , Kuzuya Masafumi , Kim Weon , Song Haizhen , Hu Lina , Inoue Aiko , Nakamura Kae , Di Qun , Sasaki Takeshi , Tsuzuki Michitaka , Shi Guo-Ping , Okumura Kenji , Murohara Toyoaki
Published: August 2010

Background—

Exercise stimulates the vascular response in pathological conditions, including ischemia; however, the molecular mechanisms by which exercise improves the impaired hypoxia-induced factor (HIF)-1α–mediated response to hypoxia associated with aging are poorly understood. Here, we report that swimming training (ST) modulates the vascular response to ischemia in aged (24-month-old) mice.

Methods and Results—

Aged wild-type mice (MMP-2
+/+
) that maintained ST (swimming 1 h/d) from day 1 after surgery were randomly assigned to 4 groups that were treated with either vehicle, LY294002, or deferoxamine for 14 days. Mice that were maintained in a sedentary condition served as controls. ST increased blood flow, capillary density, and levels of p-Akt, HIF-1α, vascular endothelial growth factor, Fit-1, and matrix metalloproteinase-2 (MMP-2) in MMP-2
+/+
mice. ST also increased the numbers of circulating endothelial progenitor cells and their function associated with activation of HIF-1α. All of these effects were diminished by LY294002, an inhibitor of phosphatidylinositol 3-kinase; enhanced by deferoxamine, an HIF-1α stabilizer; and impaired by knockout of MMP-2. Finally, bone marrow transplantation confirmed that ST enhanced endothelial progenitor cell homing to ischemic sites in aged mice.

Conclusions—

ST can improve neovascularization in response to hypoxia via a phosphatidylinositol 3-kinase–dependent mechanism that is mediated by the HIF-1α/vascular endothelial growth factor/MMP-2 pathway in advanced age.
Management of Transplant Renal Artery Stenosis
Authors: Seratnahaei Arash , Shah Amber , Bodiwala Kunal , Mukherjee Debabrata
Published: August 2010

End-stage renal disease (ESRD) was universally fatal until dialysis (peritoneal and hemodialysis) and renal transplantation were introduced. However, there are multiple complications associated with transplantation including transplant renal artery stenosis (TRAS). Transplant renal artery stenosis is an important cause of premature renal failure, uncontrolled hypertension, and allograft loss. There are 3 treatment modalities available for TRAS: optimal medical therapy alone, percutaneous intervention, and surgical revascularization both with optimal medical therapy. Percutaneous transluminal angioplasty (PTA) has now become the initial treatment of choice for TRAS. However, there are conflicting data regarding the efficacy of PTA, with growing evidence showing lack of significant benefit in blood pressure (BP) or renal function in patients undergoing PTA versus medical management. However, there have been no randomized control studies that have established the superiority of either method. We review the existing data and analyze management of TRAS as reported in multiple case series including findings from our center.
Does Oral N-Acetylcysteine Reduce Contrast-Induced Renal Injury in Patients With Peripheral Arterial Disease Undergoing Peripheral Angiography? A Randomized-Controlled Study
Authors: Sadat Umar , Walsh Stewart R. , Norden Anthony G. , Gillard Jonathan H. , Boyle Jonathan R.
Published: August 2010

The nephroprotective role of N-acetylcysteine (NAC) against contrast-induced nephropathy (CIN) in patients undergoing peripheral arterial angiography remains unclear. A total of 40 patients undergoing peripheral arterial angiography were randomized to receive intravenous (iv) hydration only (group 1) or oral NAC in addition to iv hydration (group 2; ISRCTN: 35882618). Primary outcome was reduction in the elevation of urinary retinol binding protein (RBP), albumin—creatinine ratio (ACR), and serum creatinine (serC). Groups 1 and 2 had equivocal percentage reduction in RBP and ACR levels from baseline (P = .80 and .30). A significant reduction in serC was, however, observed with NAC by third postprocedure day (P = .04). One patient in the treatment arm developed CIN compared with 3 patients in the control group (P = .33). Equivocal changes in RBP and ACR levels by both treatments seem to indicate that either is equally effective in affording renal protection.
Gear tooth diagnosis using wavelet multi-resolution analysis enhanced by Kaiser’s windowing
Authors: Omar Farag K. , Gaouda A.M.
Published: August 2010

Wavelet multi-resolution analysis shows promising results for gear tooth damage diagnostics. However, selecting an accurate mother wavelet, defining dynamic threshold value and identifying the resolution levels to be considered in gear fault detection and diagnosis are still challenging tasks. This paper proposes an enhanced wavelet-based technique for detecting, locating and estimating the severity of defects in gear tooth fracture. The proposed technique improves the wavelet multi-resolution analysis by decomposing the noisy data into different resolution levels with data sliding through Kaiser’s window. Only the maximum expansion coefficients at each resolution level are used in de-noising, detecting and measuring the severity of the defects. A small set of coefficients is used in the monitoring process without assigning threshold values or performing signal reconstruction. The proposed technique shows accurate results in detecting and localizing gear tooth fracture.
Thriving in the New: Implication of Exploration on Organizational Longevity
Authors: Piao Ming
Published: August 2010

This study investigates the longevity implication of exploration. An analysis of 1980-1999 data from the hard disk drive industry suggests that exploitation to the exclusion of exploration generally undermines firms’ long-term viability. However, this general pattern does not guarantee the long-term benefit of each individual exploration attempt. Depending on how long an exploration process overlaps an exploitation process, the longevity implication of exploration varies: If the temporal overlap is too long or too short, a firm tends to lose its longevity; however, if the temporal overlap remains at a moderate level, a firm can extend its longevity.
Protesting Mobile Phone Masts: Risk, Neoliberalism, and Governmentality
Authors: Drake Frances
Published: August 2010

Studies of protests against mobile phone masts typically concentrate on the potential health risks associated with mobile phones and their masts. Beck’s Risk Society has been particularly influential in informing this debate. This focus on health, however, has merely served to limit the discussion to those concerns legitimated by science conveniently ignoring other disputed issues. In contrast, this article contends that it is necessary to use a wider notion of risk to understand fully how the current political emphasis on active citizenship may have contributed to the protests. It examines how neoliberal governmentality and the move to empower people are in contention with one another. The study draws upon case material from a small village protest group in United Kingdom and argues that much of the tension arises from the encouragement of the public on one hand to become active citizens but on the other to be passive consumers.
Menopausal Symptoms Among Four Major Ethnic Groups in the United States
Authors: Im Eun-Ok , Lee Bokim , Chee Wonshik , Brown Adama , Dormire Sharon
Published: August 2010

The purpose of the study was to explore ethnic differences in symptoms experienced during the menopausal transition among four major ethnic groups in the United States. This study was done via a cross-sectional Internet survey among 512 midlife women recruited using a convenience sampling. The instruments included questions on background characteristics, ethnicity-related factors, health, and menopausal status and the Midlife Women’s Symptom Index. The data were analyzed using descriptive and inferential statistics. Significant ethnic differences were found in the total number and severity of the symptoms. The most frequently reported symptoms and predictors of the total number and severity of the symptoms differed by ethnic identity. More in-depth cultural studies are needed to understand the reasons for the ethnic differences in menopausal symptom experience.
Review of Outcomes of Cardiac Support Groups After Cardiac Events
Authors: Song Yeoungsuk , Lindquist Ruth , Windenburg Denise , Cairns Beth , Thakur Azra
Published: August 2010

Cardiac support groups may positively affect adjustment after cardiac events and quality of life (QoL). However, although participation in support groups is presumed to be beneficial, there were few studies regarding the potential benefit. The purpose of this review was to examine studies focused on the effects of cardiac support groups on health-related outcomes. Four studies met the inclusion criteria for review. Eight categories of support group outcomes were identified, including psychological outcomes, health behaviors, clinical health, health-related QoL, self-reported health conditions, social support, life situation, and knowledge. Most cardiac support group outcomes, though positive, were not statistically significantly different from those of control groups in studies reviewed. Psychosocial need of patients following cardiac events is indicated, including stress management and social support, and encouraging the establishment of realistic individual goals. More research is needed to establish cost-effective formats for support groups and to determine specific outcomes that can be achieved.
Police Presence, Isolation, and Sexual Assault Prosecution
Authors: Wood Darryl S. , Rosay André B. , Postle Greg , TePas Katherine
Published: August 2010

This article considers the effects of geographic isolation and local police presence on the processing of 239 sexual assault cases reported to the Alaska State Troopers. Geographic isolation is hypothesized to hinder case processing due to its impact on the celerity and thoroughness of investigations, whereas the presence of local police is hypothesized to facilitate case processing by legitimizing reported offenses and assisting with evidence collection. Controlling for a host of important legal and “extra legal” case characteristics, the authors find that geographic isolation and local police presence did significantly influence case processing. However, contrary to expectations, geographic isolation facilitates case processing in that sexual assault cases from isolated locations are actually more likely to be referred for prosecution. As expected, local police presence facilitates case processing by enhancing the likelihood that referred cases would be accepted for prosecution. Implications for rural policing are discussed.
Constructing Hot Spots Policing: Unexamined Consequences for Disadvantaged Populations and for Police Legitimacy
Authors: Rinehart Kochel Tammy
Published: August 2010

Police practitioners and academics alike have heralded hot spots policing as evidence-based practice. It has encountered few hurdles in its path to widespread implementation in the United States. Examining the social construction of its diffusion, including the empirical, theoretical, social-political, technological, and media contexts that converged to promote its diffusion, reveals a partial, positively skewed image perpetuated among the public, scholars, and policymakers. Through a different lens, hot spots policing might have led to concerns about legitimacy, discussion of bias, and lack of public support. Instead, the infectious popularity of this reform may thus far have buffered it from critical consideration of the potentially disproportionate impact of hot spots policing on disadvantaged community members and its consequences for police legitimacy—evidence that should be important to evidence-based practice. This article promotes a research agenda that extends beyond short term crime-reduction to investigate these important unstudied consequences.