bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of connexins in metastatic breast cancer and melanoma brain colonization
Authors: Stoletov Konstantin , Strnadel Jan , Zardouzian Erin , Momiyama Masashi , Park Frederick D. , Kelber Jonathan A. , Pizzo Donald P. , Hoffman Robert , VandenBerg Scott R. , Klemke Richard L.
Published: January 2013

Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain specifically in close contact with the existing brain vasculature. However, it is not known how contact with the vascular niche promotes microtumor formation. Here, we investigate the role of connexins in mediating early events in brain colonization using transparent zebrafish and chicken embryo models of brain metastasis. We provide evidence that breast cancer and melanoma cells utilize connexin gap junction proteins (Cx43, Cx26) to initiate brain metastatic lesion formation in association with the vasculature. RNAi depletion of connexins or pharmacological blocking of connexin-mediated cell-cell communication with carbenoxolone inhibited brain colonization by blocking tumor cell extravasation and blood vessel co-option. Activation of the metastatic gene twist in breast cancer cells increased Cx43 protein expression and gap junction communication leading to increased extravasation, blood vessel co-option, and brain colonization. Conversely, inhibiting twist activity reduced Cx43-mediated gap junction coupling and brain colonization. Database analyses of patient histories revealed increased expression of connexins 26 and 43 in primary melanoma and breast cancer tumors, respectively, which correlated with increased cancer recurrence and metastasis. Together our data indicate that connexins 43 and 26 mediate cancer cell metastasis to the brain and suggests that connexins might be exploited therapeutically to benefit cancer patients with metastatic disease.
High Impact of FDG-PET/ct in Diagnostic Strategies for Ovarian Cancer
Authors: Zytoon Ashraf Anas , Murakami Koji , Eid Hazem , El-Gammal Mahmoud
Published: January 2013

Background

Ovarian cancer has the highest mortality of all gynecologic malignancies. FDG-PET/CT was proven to be accurate for identification of primary ovarian tumors, regional lymph nodes, and distant metastases.

Purpose

To evaluate ovarian masses at FDG-PET/CT in correlation with histopathologic findings.

Material and Methods

Ninety-eight patients underwent whole body FDG-PET/CT examination. Eighty-six patients with primary ovarian cancer and 12 patients with metastatic disease to the ovaries were included.

Results

PET/CT imaging was true-positive in 87/94 patients with malignant tumors. In 4/4 patients with benign tumors, PET/CT results were true-negative, with sensitivity of 92.6%, specificity 100%, total test accuracy 92.9%. Fifty-seven patients were diagnosed as stage IV ovarian cancer with distant metastasis.

Conclusion

The anatomical/functional examination by FDG-PET/CT was proven to be valuable in increasing the diagnostic accuracy that can help improve patient management.
Investor Sentiment, Disagreement, and the Breadth–Return Relationship
Authors: Cen Ling , Lu Hai , Yang Liyan
Published: January 2013

We study the cross-sectional breadth–return relation by assuming that investors subject to market sentiment hold a biased belief in the aggregate. With a dynamic multiasset model, we predict that the breadth–return relationship can be either positive or negative depending on the relative strength of two offsetting forces—disagreement and sentiment. We find evidence consistent with our predictions. The breadth–return relationship is positive when the sentiment effect is small. However, the relationship becomes negative when (i) the time-series variation of market-wide sentiment is high and (ii) the cross-sectional dispersion of firm-specific exposure to market-wide sentiment variation is large. Our unified framework reconciles a few seemingly inconsistent empirical studies in this literature and explains puzzling cross-sectional return patterns observed during the Internet bubble and the subprime crisis periods.

This paper was accepted by Brad Barber, finance.
High-Definition Infrared Spectroscopic Imaging
Authors: Reddy Rohith K. , Walsh Michael J. , Schulmerich Matthew V. , Carney P. Scott , Bhargava Rohit
Published: January 2013

The quality of images from an infrared (IR) microscope has traditionally been limited by considerations of throughput and signal-to-noise ratio (SNR). An understanding of the achievable quality as a function of instrument parameters, from first principals is needed for improved instrument design. Here, we first present a model for light propagation through an IR spectroscopic imaging system based on scalar wave theory. The model analytically describes the propagation of light along the entire beam path from the source to the detector. The effect of various optical elements and the sample in the microscope is understood in terms of the accessible spatial frequencies by using a Fourier optics approach and simulations are conducted to gain insights into spectroscopic image formation. The optimal pixel size at the sample plane is calculated and shown much smaller than that in current mid-IR microscopy systems. A commercial imaging system is modified, and experimental data are presented to demonstrate the validity of the developed model. Building on this validated theoretical foundation, an optimal sampling configuration is set up. Acquired data were of high spatial quality but, as expected, of poorer SNR. Signal processing approaches were implemented to improve the spectral SNR. The resulting data demonstrated the ability to perform high-definition IR imaging in the laboratory by using minimally-modified commercial instruments.
Novel Technique for Improvement in Calibration of the Photoelastic Modulator in Circular and Linear Dichroism Spectroscopy
Authors: DiNitto Julie M. , Kenney John M.
Published: January 2013

Both the voltage-induced and the inherent (static) birefringence of a photoelastic modulator (PEM) affect the phase difference between orthogonal components of light passing through the PEM. This phase difference determines the polarization state of the light and is essential for determining true circular and linear dichroism (CD and LD, respectively) spectroscopy. Presented here are a more complete theoretical model of CD and LD and a new technique to determine the phase difference and static birefringence of a PEM in CD and LD. The intensity of the light for various configurations of the analyzer is interpreted (by using Mueller matrices and Stokes parameters) to calibrate the voltage-induced phase difference and to characterize the static birefringence in the photoelastic modulator. The effects of the static birefringence as well as intermediate polarization states (between left- and right-circularly polarized light) on LD and CD are characterized. Appropriate adjustments to the voltage applied to the PEM in order to mitigate these effects are discussed. It is expected that the techniques presented here will have a broad impact on the calibration of CD and LD spectrometers.
A Novel Method of Terahertz Spectroscopy and Imaging in Reflection Geometry
Authors: Lai Wei-En , Zhang Huai-Wu , Zhu Yao-Hua , Wen Qi-Ye
Published: January 2013

In reflection geometry of terahertz spectroscopy, the biological sample is usually placed on a sample window. This paper presents a novel method for eliminating the effect of the ringing, i.e., the interference between reflections of the reference and the sample, and from the air–window and sample–window interfaces, respectively. In the proposed method, a special thickness of substrate is designed to acquire an accurate reference reflection. The reflections of the samples of deionized water and ethanol were examined, and the calculation of optical properties of the samples by using our proposed method agrees with standard data. The main advantages of this method are simplicity, accuracy, and ease of application for reflection systems with different incident angles.
Atmospheric Pressure Acetylene Detection by UV Photo-Fragmentation and Induced C2 Emission
Authors: Miles Paul C. , Li Bo , Li Zhongshan , Aldén Marcus
Published: January 2013

Detection of C2H2 via UV photo-fragmentation, followed by monitoring the C2 d3Πg– a3Πu fluorescence, is explored at atmospheric pressure and at temperatures of 295 K, 600 K, and 800 K, for excitation wavelengths 210 to 240 nm using a broadband laser source (~3 cm−1 fwhm). At the lower temperature, C2 emissions correlate closely with C2H2 Ã←X absorption bands, and the excitation spectra suggest a higher-transition probability for the v″ 4 = 2 and 3 states than for the v″ 4 = 0 and 1 states. As temperature increases, the excitation spectra exhibit a higher nonresonant background.
Application of Spectroscopic Ellipsometry and Mueller Ellipsometry to Optical Characterization
Authors: Garcia-Caurel Enric , De Martino Antonello , Gaston Jean-Paul , Yan Li
Published: January 2013

This article provides a brief overview of both established and novel ellipsometry techniques, as well as their applications. Ellipsometry is an indirect optical technique, in that information about the physical properties of a sample is obtained through modeling analysis. Standard ellipsometry is typically used to characterize optically isotropic bulk and/or layered materials. More advanced techniques such as Mueller ellipsometry, also known as polarimetry in the literature, are necessary for the complete and accurate characterization of anisotropic and/or depolarizing samples that occur in many instances, both in research and in real-life activities. In this article, we cover three main subject areas: Basic theory of polarization, standard ellipsometry, and Mueller ellipsometry. The first section is devoted to a short, pedagogical introduction of the formalisms used to describe light polarization. The second section is devoted to standard ellipsometry. The focus is on the experimental aspects, including both pros and cons of commercially available instruments. The third section is devoted to recent advances in Mueller ellipsometry. Application examples are provided in the second and third sections to illustrate how each technique works.
Hypersurfaces of revolution with proportional principal curvatures
Authors: Coll Vincent , Harrison Michael
Published: January 2013

We classify hypersurfaces of revolution for which the principal curvatures are proportional. These hypersurfaces form a one-parameter family indexed by the reals. The subsequent classification unites at least two important families of hypersurfaces of revolution: the generalized catenoids and the equizonal ovaloids.
The conjugacy classes of finite nonsolvable subgroups in the plane Cremona group
Authors: Tsygankov Vladimir Igorevich
Published: January 2013

The aim of this paper is to give a finer geometric description of the algebraic varieties parametrizing conjugacy classes of nonsolvable subgroups in the plane Cremona group
On the counting of holomorphic discs in toric Fano manifolds
Authors: Cho Cheol-Hyun
Published: January 2013

Open Gromov-Witten invariants in general are not well-defined. We discuss in detail the enumerative numbers of the Clifford torus T2 in ℂP2. For cyclic A∞-algebras, we show that a certain generalized way of counting may be defined up to Hochschild or cyclic boundary elements. In particular we obtain a well-defined function on Hochschild or cyclic homology of a cyclic A∞-algebra, which is invariant under cyclic A∞ homomorphisms. We discuss the example of the Clifford torus T2 and compute the invariant for a specific cyclic cohomology class.
Microstructure and corrosion properties of 5A06 aluminum matrix surface composite fabricated by friction stir processing
Authors: Liu Peng , Sun Qing-zhou , Liu Yan , Sun Qi-lei
Published: January 2013

A novel aluminum matrix surface composite added with an Al-based amorphous was fabricated by friction stir processing (FSP). The surface composite region shows the obvious sandwich structure. It is considered to be a combination of the base metal and the amorphous strip via FSP. A large number of ultrafine-grained structures, which were composed of the α-Al and α-Al amorphous structures can be observed in the surface composite. The average hardness of the surface composite is about HV97, higher than the base metal, which is about HV80. The as-received sample has the highest resistance to corrosion in a salt solution. The surface composite added with the amorphous strip had lower icorr, corrosion current density, and higher passivation current than the surface composite not added with the amorphous strip.
Cortical Control of Affective Networks
Authors: Kumar Sunil , Black Sherilynn J. , Hultman Rainbo , Szabo Steven T. , DeMaio Kristine D. , Du Jeanette , Katz Brittany M. , Feng Guoping , Covington Herbert E. , Dzirasa Kafui
Published: January 2013

Transcranial magnetic stimulation and deep brain stimulation have emerged as therapeutic modalities for treatment refractory depression; however, little remains known regarding the circuitry that mediates the therapeutic effect of these approaches. Here we show that direct optogenetic stimulation of prefrontal cortex (PFC) descending projection neurons in mice engineered to express Chr2 in layer V pyramidal neurons (Thy1–Chr2 mice) models an antidepressant-like effect in mice subjected to a forced-swim test. Furthermore, we show that this PFC stimulation induces a long-lasting suppression of anxiety-like behavior (but not conditioned social avoidance) in socially stressed Thy1–Chr2 mice: an effect that is observed >10 d after the last stimulation. Finally, we use optogenetic stimulation and multicircuit recording techniques concurrently in Thy1–Chr2 mice to demonstrate that activation of cortical projection neurons entrains neural oscillatory activity and drives synchrony across limbic brain areas that regulate affect. Importantly, these neural oscillatory changes directly correlate with the temporally precise activation and suppression of limbic unit activity. Together, our findings show that the direct activation of cortical projection systems is sufficient to modulate activity across networks underlying affective regulation. They also suggest that optogenetic stimulation of cortical projection systems may serve as a viable therapeutic strategy for treating affective disorders.
The Rod Pathway of the Microbat Retina Has Bistratified Rod Bipolar Cells and Tristratified AII Amacrine Cells
Authors: Müller Brigitte , Butz Elisabeth , Peichl Leo , Haverkamp Silke
Published: January 2013

We studied the retinal rod pathway ofCarollia perspicillataandGlossophaga soricina, frugivorous microbats of the phyllostomid family. Protein kinase Cα (PKCα) immunolabeling revealed abundant rod bipolar cells (RBCs) with axon terminals in the innermost sublamina of the inner plexiform layer (IPL), which is typical for mammals. Extraordinarily, the RBC axons showed additional synaptic contacts in a second sublamina further out in the IPL. Dye injections of PKCα-prelabeled RBCs ofC. perspicillataconfirmed the bistratified axon morphology. The functional partition of the IPL into ON and OFF sublayers was shown by using antibodies against vesicular glutamate transporter 1 [labeling all ON and OFF bipolar cell (BC) axon terminals] and G-protein γ13 (labeling all ON BCs). The ON sublayer occupied 75% of the IPL thickness, including both strata of the RBC axons. RBC output onto putative AII amacrine cells (ACs), the crucial interneurons of the rod pathway, was identified by calretinin, PKCα, and CtBP2 triple immunolabeling. Dye injections of calretinin-prelabeled ACs revealed tristratification of the AII ACs corresponding to the bistratified RBCs. Triple immunolabeling for PKCα, nitric oxide synthetase (NOS), and either GABACor CtBP2 indicated GABAergic feedback onto RBCs via NOS-immunoreactive ACs. AII output analysis showed glycineric synapses with glycine receptor α1 expression between AII cells and OFF cone BCs and connexin 36-labeled gap junctions between AII cells and ON cone BCs. We conclude that microbats have a well developed rod pathway with great similarities to that of other mammals, but with an unusual IPL stratification pattern of RBCs and AIIs.
Two Novel DEG/ENaC Channel Subunits Expressed in Glia Are Needed for Nose-Touch Sensitivity inCaenorhabditis elegans
Authors: Han Lu , Wang Ying , Sangaletti Rachele , D'Urso Giulia , Lu Yun , Shaham Shai , Bianchi Laura
Published: January 2013

Neuronal DEG/ENaC (degenerin and epithelial Na+channel) Na+channels have been implicated in touch sensation. For example, MEC-4 is expressed in touch neurons inCaenorhabditis elegansand mediates gentle-touch response. Similarly, homologous mammalian ASIC2 and ASIC3 are expressed in sensory neurons and produce touch phenotypes when knocked out in mice. Here, we show that novel DEG/ENaC subunits DELM-1 and DELM-2 (degenerin-like channel mechanosensory linked-1 and degenerin-like channel mechanosensory linked-2) are expressed in glia associated with touch neurons inC. elegansand that their knock-out causes defects in mechanosensory behaviors related to nose touch and foraging, which are mediated by OLQ and IL1 sensory neurons. Cell-specific rescue supports that DELM-1 and DELM-2 are required cell-autonomously in glia to orchestrate mechanosensory behaviors. Electron microscopy reveals that indelm-1knock-outs, OLQ and IL1 sensory neurons and associated glia are structurally normal. Furthermore, we show that knock-out of DELM-1 and DELM-2 does not disrupt the expression or cellular localization of TRPA-1, a TRP channel needed in OLQ and IL1 neurons for touch behaviors. Rather, rescue of thedelm-1nose-touch-insensitive phenotype by expression of a K+channel in socket glia and of a cationic channel in OLQ neurons suggests that DELM channels set basal neuronal excitability. Together, our data show that DELM-1 and DELM-2 are expressed in glia associated with touch neurons where they are not needed for neuronal structural integrity or cellular distribution of neuronal sensory channels, but rather for their function.
Different Roles of BDNF in Nucleus Accumbens Core versus Shell during the Incubation of Cue-Induced Cocaine Craving and Its Long-Term Maintenance
Authors: Li Xuan , DeJoseph M.R. , Urban Janice H. , Bahi Amine , Dreyer Jean-Luc , Meredith Gloria E. , Ford Kerstin A. , Ferrario Carrie R. , Loweth Jessica A. , Wolf Marina E.
Published: January 2013

Brain-derived neurotrophic factor (BDNF) contributes to diverse types of plasticity, including cocaine addiction. We investigated the role of BDNF in the rat nucleus accumbens (NAc) in the incubation of cocaine craving over 3 months of withdrawal from extended access cocaine self-administration. First, we confirmed by immunoblotting that BDNF levels are elevated after this cocaine regimen on withdrawal day 45 (WD45) and showed that BDNF mRNA levels are not altered. Next, we explored the time course of elevated BDNF expression using immunohistochemistry. Elevation of BDNF in the NAc core was detected on WD45 and further increased on WD90, whereas elevation in shell was not detected until WD90. Surface expression of activated tropomyosin receptor kinase B (TrkB) was also enhanced on WD90. Next, we used viral vectors to attenuate BDNF-TrkB signaling. Virus injection into the NAc core enhanced cue-induced cocaine seeking on WD1 compared with controls, whereas no effect was observed on WD30 or WD90. Attenuating BDNF-TrkB signaling in shell did not affect cocaine seeking on WD1 or WD45 but significantly decreased cocaine seeking on WD90. These results suggest that basal levels of BDNF transmission in the NAc core exert a suppressive effect on cocaine seeking in early withdrawal (WD1), whereas the late elevation of BDNF protein in NAc shell contributes to incubation in late withdrawal (WD90). Finally, BDNF protein levels in the NAc were significantly increased after ampakine treatment, supporting the novel hypothesis that the gradual increase of BDNF levels in NAc accompanying incubation could be caused by increased AMPAR transmission during withdrawal.
Spatial and Object-Based Attention Modulates Broadband High-Frequency Responses across the Human Visual Cortical Hierarchy
Authors: Davidesco Ido , Harel Michal , Ramot Michal , Kramer Uri , Kipervasser Svetlana , Andelman Fani , Neufeld Miri Y. , Goelman Gadi , Fried Itzhak , Malach Rafael
Published: January 2013

One of the puzzling aspects in the visual attention literature is the discrepancy between electrophysiological and fMRI findings: whereas fMRI studies reveal strong attentional modulation in the earliest visual areas, single-unit and local field potential studies yielded mixed results. In addition, it is not clear to what extent spatial attention effects extend from early to high-order visual areas. Here we addressed these issues using electrocorticography recordings in epileptic patients. The patients performed a task that allowed simultaneous manipulation of both spatial and object-based attention. They were presented with composite stimuli, consisting of a small object (face or house) superimposed on a large one, and in separate blocks, were instructed to attend one of the objects. We found a consistent increase in broadband high-frequency (30–90 Hz) power, but not in visual evoked potentials, associated with spatial attention starting with V1/V2 and continuing throughout the visual hierarchy. The magnitude of the attentional modulation was correlated with the spatial selectivity of each electrode and its distance from the occipital pole. Interestingly, the latency of the attentional modulation showed a significant decrease along the visual hierarchy. In addition, electrodes placed over high-order visual areas (e.g., fusiform gyrus) showed both effects of spatial and object-based attention. Overall, our results help to reconcile previous observations of discrepancy between fMRI and electrophysiology. They also imply that spatial attention effects can be found both in early and high-order visual cortical areas, in parallel with their stimulus tuning properties.
Neurobiological Dissociation of Retrieval and Reconsolidation of Cocaine-Associated Memory
Authors: Otis James M. , Dashew Kidane B. , Mueller Devin
Published: January 2013

Drug use is provoked by the presentation of drug-associated cues, even following long periods of abstinence. Disruption of these learned associations would therefore limit relapse susceptibility. Drug-associated memories are susceptible to long-term disruption during retrieval and shortly after, during memory reconsolidation. Recent evidence reveals that retrieval and reconsolidation are dependent on β-adrenergic receptor (β-AR) activation. Despite this, whether retrieval and reconsolidation are dependent on identical or distinct neural mechanisms is unknown. The prelimbic medial prefrontal cortex (PL-mPFC) and basolateral amygdala (BLA) have been implicated in the expression and reconsolidation of associative memories. Therefore, we investigated the necessity of β-AR activation within the PL-mPFC and BLA for cocaine-associated memory retrieval and reconsolidation in rats. Before or immediately after a cocaine-induced conditioned place preference (CPP) retrieval trial, β-AR antagonists were infused into the PL-mPFC or BLA, followed by daily testing. PL-mPFC infusions before, but not after, a CPP trial disrupted CPP memory retrieval and induced a persistent deficit in retrieval during subsequent trials. In contrast, BLA β-AR blockade had no effect on initial CPP memory retrieval, but prevented CPP expression during subsequent trials indicative of reconsolidation disruption. Our results reveal a distinct dissociation between the neural mechanisms required for cocaine-associated memory retrieval and reconsolidation. Using patch-clamp electrophysiology, we also show that application of a β-AR antagonist prevents norepinephrine-induced potentiation of PL-mPFC pyramidal cell and γ-aminobutyric-acid (GABA) interneuron excitability. Thus, targeted β-AR blockade could induce long-term deficits in drug-associated memory retrieval by reducing neuronal excitability, providing a novel method of preventing cue-elicited drug seeking and relapse.
Common Rules Guide Comparisons of Speed and Direction of Motion in the Dorsolateral Prefrontal Cortex
Authors: Hussar Cory R. , Pasternak Tatiana
Published: January 2013

When a monkey needs to decide whether motion direction of one stimulus is the same or different as that of another held in working memory, neurons in dorsolateral prefrontal cortex (DLPFC) faithfully represent the motion directions being evaluated and contribute to their comparison. Here, we examined whether DLPFC neurons are more generally involved in other types of sensory comparisons. Such involvement would support the existence of generalized sensory comparison mechanisms within DLPFC, shedding light on top-down influences this region is likely to provide to the upstream sensory neurons during comparison tasks. We recorded activity of individual neurons in the DLPFC while monkeys performed a memory-guided decision task in which the important dimension was the speed of two sequentially presented moving random-dot stimuli. We found that many neurons, both narrow-spiking putative local interneurons and broad-spiking putative pyramidal output cells, were speed-selective, with tuning reminiscent of that observed in the motion processing middle temporal (MT) cortical area. Throughout the delay, broad-spiking neurons were more active, showing anticipatory rate modulation and transient periods of speed selectivity. During the comparison stimulus, responses of both cell types were modulated by the speed of the first stimulus, and their activity was highly predictive of the animals' behavioral report. These results are similar to those found for comparisons of motion direction, suggesting the existence of generalized neural mechanisms in the DLPFC subserving the comparison of sensory signals.
Crystal structure of bis-aqua(μ4-pyridine-2,4,6-tricarboxylato-κ3N,O,O') cerium(III)-water(1:1), {[Ce(ptc)(H2O)2]·H2O}n, C8H8CeNO9
Authors: Zhao Cheng-Qiang , Ou Yang-Miao , Zhao Zhi-Yuan , Yin Xiu-Ju , Jiang Yi-Min
Published: January 2013

C8H8CeNO9, monoclinic, P21/c (no. 14), a = 6.8545(8) Å, b = 12.077(1) Å, c = 13.625(2) Å, β = 100.035(1)°, V = 1110.6 Å3, Z = 4, Rgt(F) = 0.0188, wRref(F2) = 0.0480, T = 291 K.
Crystal structure of catena-((μ2-4-amino-3,5-bis(4-pyridyl)-1,2,4-triazole) copper(I)chloride, C12H10ClCuN6
Authors: Xia Daocheng , Feng Feng
Published: January 2013

C12H10ClCuN6, monoclinic, P21/n (no. 14), a = 7.7819(4) Å, b = 12.9634(6) Å, c = 12.4449(6) Å, β = 91.456(4)°, V = 1255.0 Å3, Z = 4, Rgt(F) = 0.0474, wRref(F2) = 0.0938, T = 293 K.
Crystal structure of a transition metal Zn(II) complex with 1-phenyl-3- methyl-5-hydroxypyrazole-4-carbaldehyde-(8'-aminoquinoline)- hydrazone, C20H17N5O5Zn
Authors: Zhong Ai-Guo
Published: January 2013

C20H17N5O5Zn, monoclinic, P21/n (no. 14), a = 9.036(2) Å, b = 13.917(4) Å, c = 15.964(4) Å, β = 100.265(3)°, V = 1975.4 Å3, Z = 4, Rgt(F) = 0.0422, wRref(F2) = 0.0893, T = 296 K.
Factors Associated with Research Wrongdoing in Nigeria
Authors: Adeleye Omokhoa A. , Adebamowo Clement A.
Published: January 2013

Concerns about research wrong doing in biomedical research are growing in developing countries, where research ethics training and research regulatory systems are just emerging. In a first-time study in Africa, medical/dental researchers ( N = 132) in two states in Nigeria were interviewed on a wide range of research wrongdoings and potential predictors. Using multivariate logistic regression, significant predictors of research wrongdoing were identified. Some 22.0% admitted to at least one of fabrication, falsification, and plagiarism, the predictors of which were knowledge gaps in research ethics and pressure to publish enough papers for promotion. Acknowledging inadequate knowledge of research ethics was a predictor of admitting a wrongdoing. Systems that support ethical research, including skilled training and funding, are recommended.
Therapeutic Misdirection: An Analysis of Protocol Exception Requests in Clinical Trials
Authors: Green Jonathan M.
Published: January 2013

While many studies have examined the effects of therapeutic misconception on research participants, less is known about how the behavior of physician-investigators is affected. Requests for protocol exceptions submitted to the IRB at a major academic center over a three-year period were examined. These were classified into one of seven categories and analyzed based on the type of trial, the investigator, and the funding source. The results show that exceptions are frequent, are often motivated by therapeutic intent, and have the potential to adversely impact both participants and the validity of study data, leading to what we have termed therapeutic misdirection. Studies of exception requests may be an objective way to gauge the extent and impact of the physician-investigator conflict.
Improving Informed Consent with Minority Participants: Results from Researcher and Community Surveys
Authors: Quinn Sandra Crouse , Garza Mary A. , Butler James , Fryer Craig S. , Casper Erica T. , Thomas Stephen B. , Barnard David , Kim Kevin H.
Published: January 2013

Strengthening the informed consent process is one avenue for improving recruitment of minorities into research. This study examines that process from two different perspectives, that of researchers and that of African American and Latino community members. Through the use of two separate surveys, we compared strategies used by researchers with the preferences and attitudes of community members during the informed consent process. Our data suggest that researchers can improve the informed consent process by incorporating methods preferred by the community members along with methods shown in the literature for increasing comprehension. With this approach, the informed consent process may increase both participants' comprehension of the material and overall satisfaction, fostering greater trust in research and openness to future research opportunities.
Does the Requirement of Getting Active Consent from Parents in School-Based Research Result in a Biased Sample? An Empirical Study
Authors: Jelsma Jennifer , Burgess Theresa , Henley Lesley
Published: January 2013

Active parental consent is a requirement that may threaten the validity of including minors in research. This study investigated possible sources of bias between the responses of children whose parents actively consented to their participation in a school-based survey and those of children whose parents were nonresponders. Due to a serious administrative error in a study to examine health-related quality of life (HRQoL), all 514 eligible schoolchildren were tested, although only 177 parents signed consent. After deliberation, the relevant human research ethics committee gave permission to include all results in the analysis. The HRQoL was not different between the groups. Male children returned significantly fewer consent forms (p=.026). More of the nonresponding group reported that their parents “Never had enough time for them” (p=.023). The high nonresponse rate and associations between response and parental interest and gender indicate that some bias may be introduced through the need for active consent, but overall there were no differences in responses to the quality of life questionnaire.
Competition, Cultural Geography, and Tonal Space in the Book of Madrigals L’amorosa Ero (1588)
Authors: Bizzarini Marco , Privitera Massimo
Published: January 2013

Around 1587 the Brescian nobleman Count Marc’Antonio Martinengo di Villachiara, who was renowned for his political and military experience as well as competence in both music and poetry, wrote a madrigal text, set it to music, and sent it to seventeen composers in different parts of Italy. Published under the title of L’amorosa Ero (Brescia, 1588), the collection gives the opportunity to compare some of the most influential composers such as Marenzio, Luzzaschi, Ingegneri, Striggio, and many others. The first part of the article focuses on the historical background to this collection, with special attention given to the musical activities in Brescia and in other cities (Cremona, Verona, Parma, Turin, and Rome). Martinengo’s political and military career and the music patronage of his family are discussed in detail, followed by an in-depth survey of most of the composers of L’amorosa Ero (particularly Alfonso Ferabosco, Claudio Merulo, Marc’Antonio Ingegneri, and Antonio Morsolino) to unveil their personal relationships with Martinengo. The hierarchy of composers represented in the madrigal collection turns out to be quite elaborate and reflects their political relevance in their time. The second part of the article is dedicated to the musical content of the collection.  Given that L’amorosa Ero consists of the compositional responses of multiple composers to the same text—which, moreover, they all set in the same mode—the collection offers a unique opportunity to compare composers’ styles. Starting with a close examination of Martinengo’s poem, including its formal and emotional aspects, we follow with a comparative analysis, restricted to the first section of eight emblematic madrigals by Martinengo, Fiorino, Bertani, Ingegneri, Marenzio, Zoilo, Giovannelli, and Luzzaschi. The main analytical tool is the definition of tonal space, that is to say a dynamic articulation of mode that emerges through the interaction of such elements as melodic contour and cadences. Our analysis shows that, despite the limitations of mode and text, the music of the collection is strikingly diverse, ranging from traditional to more innovative styles.
IGF2 increases de novo steroidogenesis in prostate cancer cells
Authors: Lubik Amy A , Gunter Jennifer H , Hollier Brett G , Ettinger Susan , Fazli Ladan , Stylianou Nataly , Hendy Stephen C , Adomat Hans H , Gleave Martin E , Pollak Michael , Herington Adrian , Nelson Colleen C
Published: January 2013

IGF2 is a mitogenic foetal growth factor commonly over-expressed in cancers, including prostate cancer (PC). We recently demonstrated that insulin can activatede novosteroidogenesis in PC cells, a major pathway for reactivation of androgen pathways and PC progression. IGF2 can activate the IGF1 receptor (IGF1R) or insulin receptor (INSR) or hybrids of these two receptors. We therefore hypothesized that IGF2 may contribute to PC progression viade novosteroidogenesis.IGF2mRNA but not IGF2 receptor mRNA expression was increased in patient samples during progression to castrate-resistant PC as was immunoreactivity to INSR and IGF1R antibodies. Treatment of androgen receptor (AR)-positive PC cell lines LNCaP and 22RV1 with IGF2 for 48 h resulted in increased expression of steroidogenic enzyme mRNA and protein, including steroid acute regulatory protein (StAR), cytochrome p450 family member (CYP)17A1, aldo–keto reductase family member (AKR)1C3 and hydroxysteroid dehydrogenase (HSD)17B3. IGF2 treatment resulted in increased steady state steroid levels and increasedde novosteroidogenesis resulting in AR activation as demonstrated byPSAmRNA induction. Inhibition of the IGF1R/INSR signalling axis attenuated the effects of IGF2 on steroid hormone synthesis. We present a potential mechanism for prostatic IGF2 contributing to PC progression by inducing steroidogenesis and that IGF2 signalling and related pathways present attractive targets for PC therapy.
Association of Maltreatment With High-Risk Internet Behaviors and Offline Encounters
Authors: Noll Jennie G. , Shenk Chad E. , Barnes Jaclyn E. , Haralson Katherine J.
Published: January 2013

OBJECTIVE:

High-risk Internet behaviors, including viewing sexually explicit content, provocative social networking profiles, and entertaining online sexual solicitations, were examined in a sample of maltreated and nonmaltreated adolescent girls aged 14 to 17 years. The impact of Internet behaviors on subsequent offline meetings was observed over 12 to 16 months. This study tested 2 main hypotheses: (1) maltreatment would be a unique contributor to high-risk Internet behaviors and (2) high-quality parenting would dampen adolescents’ propensity to engage in high-risk Internet behaviors and to participate in offline meetings.

METHODS:

Online and offline behaviors and parenting quality were gleaned from 251 adolescent girls, 130 of whom experienced substantiated maltreatment and 121 of whom were demographically matched comparison girls. Parents reported on adolescent behaviors and on the level of Internet monitoring in the home. Social networking profiles were objectively coded for provocative self-presentations. Offline meetings with persons first met online were assessed 12 to 16 months later.

RESULTS:

Thirty percent of adolescents reported having offline meetings. Maltreatment, adolescent behavioral problems, and low cognitive ability were uniquely associated with high-risk Internet behaviors. Exposure to sexual content, creating high-risk social networking profiles, and receiving online sexual solicitations were independent predictors of subsequent offline meetings. High-quality parenting and parental monitoring moderated the associations between adolescent risk factors and Internet behaviors, whereas use of parental control software did not.

CONCLUSIONS:

Treatment modalities for maltreated adolescents should be enhanced to include Internet safety literacy. Adolescents and parents should be aware of how online self-presentations and other Internet behaviors can increase vulnerability for Internet-initiated victimization.
Utility of Hepatic Transaminases in Children With Concern for Abuse
Authors: Lindberg Daniel M. , Shapiro Robert A. , Blood Emily A. , Steiner R. Daryl , Berger Rachel P. ,   for the ExSTRA investigators
Published: January 2013

OBJECTIVE:

Routine testing of hepatic transaminases, amylase, and lipase has been recommended for all children evaluated for physical abuse, but rates of screening are widely variable, even among abuse specialists, and data for amylase and lipase testing are lacking. A previous study of screening in centers that endorsed routine transaminase screening suggested that using a transaminase threshold of 80 IU/L could improve injury detection. Our objectives were to prospectively validate the test characteristics of the 80-IU/L threshold and to determine the utility of amylase and lipase to detect occult abdominal injury.

METHODS:

This was a retrospective secondary analysis of the Examining Siblings To Recognize Abuse research network, a multicenter study in children younger than 10 years old who underwent subspecialty evaluation for physical abuse. We determined rates of identified abdominal injuries and results of transaminase, amylase, and lipase testing. Screening studies were compared by using basic test characteristics (sensitivity, specificity) and the area under the receiver operating characteristic curve.

RESULTS:

Abdominal injuries were identified in 82 of 2890 subjects (2.8%; 95% confidence interval: 2.3%–3.5%). Hepatic transaminases were obtained in 1538 (53%) subjects. Hepatic transaminases had an area under the receiver operating characteristic curve of 0.87. A threshold of 80 IU/L yielded sensitivity of 83.8% and specificity of 83.1%. The areas under the curve for amylase and lipase were 0.67 and 0.72, respectively.

CONCLUSIONS:

Children evaluated for physical abuse with transaminase levels >80 IU/L should undergo definitive testing for abdominal injury.
Parental Explicit Heuristics in Decision-making for Children With Life-threatening Illnesses
Authors: Renjilian Chris B. , Womer James W. , Carroll Karen W. , Kang Tammy I. , Feudtner Chris
Published: January 2013

OBJECTIVE:

To identify and illustrate common explicit heuristics (decision-making aids or shortcuts expressed verbally as terse rules of thumb, aphorisms, maxims, or mantras and intended to convey a compelling truth or guiding principle) used by parents of children with life-threatening illnesses when confronting and making medical decisions.

METHODS:

Prospective cross-sectional observational study of 69 parents of 46 children who participated in the Decision-making in Pediatric Palliative Care Study between 2006 and 2008 at the Children’s Hospital of Philadelphia. Parents were guided individually through a semistructured in-depth interview about their experiences and thoughts regarding making medical decisions on behalf of their ill children, and the transcribed interviews were qualitatively analyzed.

RESULTS:

All parents in our study employed explicit heuristics in interviews about decision-making for their children, with the number of identified explicit heuristics used by an individual parent ranging from tens to hundreds. The heuristics served 5 general functions: (1) to depict or facilitate understanding of a complex situation; (2) to clarify, organize, and focus pertinent information and values; (3) to serve as a decision-making compass; (4) to communicate with others about a complex topic; and (5) to justify a choice.

CONCLUSIONS:

Explicit heuristics played an important role in decision-making and communication about decision-making in our population of parents. Recognizing explicit heuristics in parent interactions and understanding their content and functions can aid clinicians in their efforts to partner with parents in the decision-making process.
Mutations of the thyroid peroxidase gene in Chinese siblings with congenital goitrous hypothyroidism
Authors: Ma Shao-Gang , Wu Xiao-Juan , Liu Hong , Xu Wei , He Le
Published: January 2013

OBJECTIVES: To investigate thyroid peroxidase gene (TPO) mutations in a Chinese siblings with congenital goitrous hypothyroidism (CGH). SUBJECTS AND METHODS: The proband, his sister, and their parents were enrolled. All subjects underwent clinical examination and laboratory tests. Mutation screening of the TPO gene was performed by sequencing fragments amplified from extracted genomic DNA. RESULTS: The siblings were diagnosed as CGH with neurodevelopmental deficits. Two compound heterozygous inactivating mutations were found in the two patients: a frameshift mutation between positions 2268 and 2269 (c.2268-2269 insT) and a missense mutation at c.2089 G>A (p.G667S) of the TPO gene. Their parents, with normal thyroid hormone levels, were heterozygous for mutations c.2268-2269 insT and c.2089 G>A, respectively. The polymorphisms of c.1207 G>T, c.1283 G>C, and c.2088 C>T were detected in the family. CONCLUSIONS: CGH of the Chinese siblings was due to the TPO gene mutations (c.2268-2269 insT and c.2089 G>A). Arq Bras Endocrinol Metab. 2012;56(9):614-7
Optimizing nucleic acid extraction from thyroid fine-needle aspiration cells in stained slides, formalin-fixed/paraffin-embedded tissues, and long-term stored blood samples
Authors: Kizys Marina M. L. , Cardoso Mirian G. , Lindsey Susan C. , Harada Michelle Y. , Soares Fernando A. , Melo Maria Clara C. , Montoya Marlyn Z. , Kasamatsu Teresa S. , Kunii Ilda S. , Giannocco Gisele , Martins João Roberto M. , Cerutti Janete M. , Maciel Rui M. B. , Dias-da-Silva Magnus R.
Published: January 2013

OBJECTIVE: Adequate isolation of nucleic acids from peripheral blood, fine-needle aspiration cells in stained slides, and fresh and formalin-fixed/paraffin-embedded tissues is crucial to ensure the success of molecular endocrinology techniques, especially when samples are stored for long periods, or when no other samples can be collected from patients who are lost to follow-up. Here, we evaluate several procedures to improve current methodologies for DNA (salting-out) and RNA isolation. MATERIALS AND METHODS: We used proteinase K treatment, heat shock, and other adaptations to increase the amount and quality of the material retrieved from the samples. RESULTS: We successfully isolated DNA and RNA from the samples described above, and this material was suitable for PCR, methylation profiling, real-time PCR and DNA sequencing. CONCLUSION: The techniques herein applied to isolate nucleic acids allowed further reliable molecular analyses. Arq Bras Endocrinol Metab. 2012;56(9):618-26
Clinical judgment to estimate pretest probability in the diagnosis of Cushing's syndrome under a Bayesian perspective
Authors: Cipoli Daniel E. , Martinez Edson Z. , Castro Margaret de , Moreira Ayrton C.
Published: January 2013

OBJECTIVE: To estimate the pretest probability of Cushing's syndrome (CS) diagnosis by a Bayesian approach using intuitive clinical judgment. MATERIALS AND METHODS: Physicians were requested, in seven endocrinology meetings, to answer three questions: "Based on your personal expertise, after obtaining clinical history and physical examination, without using laboratorial tests, what is your probability of diagnosing Cushing's Syndrome?"; "For how long have you been practicing Endocrinology?"; and "Where do you work?". A Bayesian beta regression, using the WinBugs software was employed. RESULTS: We obtained 294 questionnaires. The mean pretest probability of CS diagnosis was 51.6% (95%CI: 48.7-54.3). The probability was directly related to experience in endocrinology, but not with the place of work. CONCLUSION: Pretest probability of CS diagnosis was estimated using a Bayesian methodology. Although pretest likelihood can be context-dependent, experience based on years of practice may help the practitioner to diagnosis CS. Arq Bras Endocrinol Metab. 2012;56(9):633-7
Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders
Authors: Tusset Cintia , Noel Sekoni D. , Trarbach Ericka B. , Silveira Letícia F. G. , Jorge Alexander A. L. , Brito Vinicius N. , Cukier Priscila , Seminara Stephanie B. , Mendonça Berenice B. de , Kaiser Ursula B. , Latronico Ana Claudia
Published: January 2013

OBJECTIVE: To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. SUBJECTS AND METHODS: Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH), and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. RESULTS: We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C>T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L, and p.W275* variants were identified in three unrelated males with normosmic IHH. CONCLUSION: Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. Arq Bras Endocrinol Metab. 2012;56(9):646-52