bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model
Authors: Watts Ashlee E , Yeager Amy E , Kopyov Oleg V , Nixon Alan J
Published: February 2011

Introduction

Tendon injury is a common problem in athletes, with poor tissue regeneration and a high rate of re-injury. Stem cell therapy is an attractive treatment modality as it may induce tissue regeneration rather than tissue repair. Currently, there are no reports on the use of pluripotent cells in a large animal tendon model in vivo. We report the use of intra-lesional injection of male, fetal derived embryonic-like stem cells (fdESC) that express Oct-4, Nanog, SSEA4, Tra 1-60, Tra 1-81 and telomerase.

Methods

Tendon injury was induced using a collagenase gel-physical defect model in the mid-metacarpal region of the superficial digital flexor tendon (SDFT) of eight female adult Thoroughbred or Thoroughbred cross horses. Tendon lesions were treated one week later with intra-lesional injection of male derived fdESCs in media or media alone. Therapy was blinded and randomized. Serial ultrasound examinations were performed and final analysis at eight weeks included magnetic resonance imaging (MRI), biochemical assays (total DNA, glycosaminoglycan, collagen), gene expression (TNC, TNMD, SCX, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3, MMP13, 18S) and histology. Differences between groups were assessed with Wilcoxon's rank sum test.

Results

Cell survival was demonstrated via the presence of the SRY gene in fdESC treated, but not control treated, female SDFT at the end of the trial. There were no differences in tendon matrix specific gene expression or total proteoglycan, collagen or DNA of tendon lesions between groups. Tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern were significantly improved on histologic sections and ultrasound in the fdESC treated tendons.

Conclusions

Such profound structural effects lend further support to the notion that pluripotent stem cells can effect musculoskeletal regeneration, rather than repair, even without in vitro lineage specific differentiation. Further investigation into the safety of pluripotent cellular therapy as well as the mechanisms by which repair was improved seem warranted.
Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma
Authors: Kirschbaum Mark , Frankel Paul , Popplewell Leslie , Zain Jasmine , Delioukina Maria , Pullarkat Vinod , Matsuoka Deron , Pulone Bernadette , Rotter Arnold J. , Espinoza-Delgado Igor , Nademanee Auayporn , Forman Stephen J. , Gandara David , Newman Edward
Published: February 2011

Purpose

We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma.

Patients and Methods

In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability.

Results

All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue.

Conclusion

Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.
DHEA Suppresses Longitudinal Bone Growth by Acting Directly at Growth Plate through Estrogen Receptors
Authors: Sun Hongzhi , Zang Weijin , Zhou Bo , Xu Lin , Wu Shufang
Published: February 2011

Dehydroepiandrosterone (DHEA) is produced by the adrenal cortex and is the most abundant steroid in humans. Although in some physiological and pathological conditions the increased secretion of DHEA and its sulfated form is associated with accelerated growth rate and skeletal maturation, it is unclear whether DHEA can affect longitudinal bone growth and skeletal maturation by acting directly at the growth plate. In our study, DHEA suppressed metatarsal growth, growth plate chondrocyte proliferation, and hypertrophy/differentiation. In addition, DHEA increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, DHEA reduced chondrocyte proliferation and induced apoptosis. The DHEA-induced inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was nullified by culturing metatarsals with DHEA in the presence of ICI 182,780, an inhibitor of estrogen receptor, but not in the presence of Casodex, an inhibitor of androgen receptor. Lastly, nuclear factor-κB DNA binding activity was inhibited by the addition of DHEA in the medium of cultured chondrocyte. Our findings indicate that DHEA suppressed bone growth by acting directly at growth plate through estrogen receptor. Such growth inhibition is mediated by decreased chondrocyte proliferation and hypertrophy/differentiation and by increased chondrocyte apoptosis.
Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-Induced LH-Surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A
Authors: Bai Yinyang , Chang Fei , Zhou Rong , Jin Peng-Peng , Matsumoto Hirokazu , Sokabe Masahiro , Chen Ling
Published: February 2011

Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 μg BPA/kg·d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system.
Absence of Melatonin Induces Night-Time Hepatic Insulin Resistance and Increased Gluconeogenesis Due to Stimulation of Nocturnal Unfolded Protein Response
Authors: Nogueira Tatiane C. , Lellis-Santos Camilo , Jesus Daniel S. , Taneda Marco , Rodrigues Sandra C. , Amaral Fernanda G. , Lopes Ana Maria S. , Cipolla-Neto José , Bordin Silvana , Anhê Gabriel F.
Published: February 2011

It is known that the circadian rhythm in hepatic phosphoenolpyruvate carboxykinase expression (a limiting catalytic step of gluconeogenesis) and hepatic glucose production is maintained by both daily oscillation in autonomic inputs to the liver and night feeding behavior. However, increased glycemia and reduced melatonin (Mel) levels have been recently shown to coexist in diabetic patients at the end of the night period. In parallel, pinealectomy (PINX) is known to cause glucose intolerance with increased basal glycemia exclusively at the end of the night. The mechanisms that underlie this metabolic feature are not completely understood. Here, we demonstrate that PINX rats show night-time hepatic insulin resistance characterized by reduced insulin-stimulated RAC-α serine/threonine-protein kinase phosphorylation and increased phosphoenolpyruvate carboxykinase expression. In addition, PINX rats display increased conversion of pyruvate into glucose at the end of the night. The regulatory mechanism suggests the participation of unfolded protein response (UPR), because PINX induces night-time increase in activating transcription factor 6 expression and prompts a circadian fashion of immunoglobulin heavy chain-binding protein, activating transcription factor 4, and CCAAT/enhancer-binding protein-homologous protein expression with Zenith values at the dark period. PINX also caused a night-time increase in Tribble 3 and regulatory-associated protein of mammalian target of rapamycin; both were reduced in liver of PINX rats treated with Mel. Treatment of PINX rats with 4-phenyl butyric acid, an inhibitor of UPR, restored night-time hepatic insulin sensitivity and abrogated gluconeogenesis in PINX rats. Altogether, the present data show that a circadian oscillation of UPR occurs in the liver due to the absence of Mel. The nocturnal UPR activation is related with night-time hepatic insulin resistance and increased gluconeogenesis in PINX rats.
Essential Roles of Androgen Signaling in Wolffian Duct Stabilization and Epididymal Cell Differentiation
Authors: Murashima Aki , Miyagawa Shinichi , Ogino Yukiko , Nishida-Fukuda Hisayo , Araki Kimi , Matsumoto Takahiro , Kaneko Takehito , Yoshinaga Kazuya , Yamamura Ken-ichi , Kurita Takeshi , Kato Shigeaki , Moon Anne M. , Yamada Gen
Published: February 2011

The epididymis is a male accessory organ and functions for sperm maturation and storage under the control of androgen. The development of the epididymis is also androgen dependent. The Wolffian duct (WD), anlagen of the epididymis, is formed in both male and female embryos; however, it is stabilized only in male embryos by testicular androgen. Androgen drives subsequent differentiation of the WD into the epididymis. Although the essential roles of androgen in WD masculinization and epididymal function have been established, little is known about cellular events regulated precisely by androgen signaling during these processes. It is also unclear whether androgen signaling, especially in the epithelia, has further function for epididymal epithelial cell differentiation. In this study we examined the cellular death and proliferation controlled by androgen signaling via the androgen receptor (AR) in WD stabilization. Analyses using AR knockout mice revealed that androgen signaling inhibits epithelial cell death in this process. Analysis of AP2α-Cre;ARflox/Y mice, in which AR function is deleted in the WD epithelium, revealed that epithelial AR is not required for the WD stabilization but is required for epithelial cell differentiation in the epididymis. Specifically, loss of epithelial AR significantly reduced expression of p63 that is essential for differentiation of basal cells in the epididymal epithelium. We also interrogated the possibility of regulation of the p63 gene (Trp63) by AR in vitro and found that p63 is a likely direct target of AR regulation.
Wangechi Mutu: This You Call Civilization?
Authors: Frater Sally
Published: February 2011

Wangechi Mutu’s first solo exhibition in North America, This You Call Civilization? provides an overview of the artist’s oeuvre, focusing on several of her well-known collaged works, such as The Ark Collection and Histology of Fibroid Tumors of the Uterus, as well as more recent video works. The review examines how the exhibited works highlight Mutu’s ongoing interrogation of beauty, femininity, the environment, and the perceptions and depictions of Africa and “Africanness” in Western media.
History in Ousmane Sembène’s Guelwaar and Ceddo
Authors: Amkpa Awam , SenGupta Gunja
Published: February 2011

The legendary Senegalese filmmaker Ousmane Sembène, who once likened an African filmmaker to the “griot,” a sort of public historian cum social critic, engaged Africa’s precolonial past and its neocolonial present to visualize the possibility of a “transcendental subjectivity.” Departing from binary paradigms in which Africa is “traditional,” Europe “modern,” and imperialism “modernizing,” Sembène saw his society as a space imbued with plural modernities; his historical narratives not only contest the usual representations of colonial Africa but also demystify all fundamentalist historical narratives. Sembène’s films imagine alternatives to the recorded past and become a resource for continuous reinvention: Guelwaar inscribes a path out of divisive ethnoreligious essentialisms into a unified vox populi, and Ceddo uses the imagery and rhetoric of slavery to expose concentric layers of subordination, pointing to the instability of social identities and the possibility of subversion.
Mos limits the number of meiotic divisions in urochordate eggs
Authors: Dumollard Rémi , Levasseur Mark , Hebras Céline , Huitorel Philippe , Carroll Michael , Chambon Jean-Philippe , McDougall Alex
Published: February 2011

Mos kinase is a universal mediator of oocyte meiotic maturation and is produced during oogenesis and destroyed after fertilization. The hallmark of maternal meiosis is that two successive M phases (meiosis I and II) drive two rounds of asymmetric cell division (ACD). However, how the egg limits the number of meioses to just two, thereby preventing gross aneuploidy, is poorly characterized. Here, in urochordate eggs, we show that loss of Mos/MAPK activity is necessary to prevent entry into meiosis III. Remarkably, maintaining the Mos/MAPK pathway active after fertilization at near physiological levels induces additional rounds of meiotic M phase (meiosis III, IV and V). During these additional rounds of meiosis, the spindle is positioned asymmetrically resulting in further rounds of ACD. In addition, inhibiting meiotic exit with Mos prevents pronuclear formation, cyclin A accumulation and maintains sperm-triggered Ca2+ oscillations, all of which are hallmarks of the meiotic cell cycle in ascidians. It will be interesting to determine whether Mos availability in mammals can also control the number of meioses as it does in the urochordates. Our results demonstrate the power of urochordate eggs as a model to dissect the egg-to-embryo transition.
Characterization of a Dchs1 mutant mouse reveals requirements for Dchs1-Fat4 signaling during mammalian development
Authors: Mao Yaopan , Mulvaney Joanna , Zakaria Sana , Yu Tian , Morgan Katherine Malanga , Allen Steve , Basson M. Albert , Francis-West Philippa , Irvine Kenneth D.
Published: February 2011

The Drosophila Dachsous and Fat proteins function as ligand and receptor, respectively, for an intercellular signaling pathway that regulates Hippo signaling and planar cell polarity. Although gene-targeted mutations in two mammalian Fat genes have been described, whether mammals have a Fat signaling pathway equivalent to that in Drosophila, and what its biological functions might be, have remained unclear. Here, we describe a gene-targeted mutation in a murine Dachsous homolog, Dchs1. Analysis of the phenotypes of Dchs1 mutant mice and comparisons with Fat4 mutant mice identify requirements for these genes in multiple organs, including the ear, kidney, skeleton, intestine, heart and lung. Dchs1 and Fat4 single mutants and Dchs1 Fat4 double mutants have similar phenotypes throughout the body. In some cases, these phenotypes suggest that Dchs1-Fat4 signaling influences planar cell polarity. In addition to the appearance of cysts in newborn kidneys, we also identify and characterize a requirement for Dchs1 and Fat4 in growth, branching and cell survival during early kidney development. Dchs1 and Fat4 are predominantly expressed in mesenchymal cells in multiple organs, and mutation of either gene increases protein staining for the other. Our analysis implies that Dchs1 and Fat4 function as a ligand-receptor pair during murine development, and identifies novel requirements for Dchs1-Fat4 signaling in multiple organs.
Concentric zones, cell migration and neuronal circuits in theDrosophilavisual center
Authors: Hasegawa Eri , Kitada Yusuke , Kaido Masako , Takayama Rie , Awasaki Takeshi , Tabata Tetsuya , Sato Makoto
Published: February 2011

The Drosophila optic lobe comprises a wide variety of neurons, which form laminar neuropiles with columnar units and topographic projections from the retina. The Drosophila optic lobe shares many structural characteristics with mammalian visual systems. However, little is known about the developmental mechanisms that produce neuronal diversity and organize the circuits in the primary region of the optic lobe, the medulla. Here, we describe the key features of the developing medulla and report novel phenomena that could accelerate our understanding of the Drosophila visual system. The identities of medulla neurons are pre-determined in the larval medulla primordium, which is subdivided into concentric zones characterized by the expression of four transcription factors: Drifter, Runt, Homothorax and Brain-specific homeobox (Bsh). The expression pattern of these factors correlates with the order of neuron production. Once the concentric zones are specified, the distribution of medulla neurons changes rapidly. Each type of medulla neuron exhibits an extensive but defined pattern of migration during pupal development. The results of clonal analysis suggest homothorax is required to specify the neuronal type by regulating various targets including Bsh and cell-adhesion molecules such as N-cadherin, while drifter regulates a subset of morphological features of Drifter-positive neurons. Thus, genes that show the concentric zones may form a genetic hierarchy to establish neuronal circuits in the medulla.
Identification of PTPσ as an autophagic phosphatase
Authors: Martin Katie R. , Xu Yong , Looyenga Brendan D. , Davis Ryan J. , Wu Chia-Lun , Tremblay Michel L. , Xu H. Eric , MacKeigan Jeffrey P.
Published: February 2011

Macroautophagy is a dynamic process whereby portions of the cytosol are encapsulated in double-membrane vesicles and delivered to the lysosome for degradation. Phosphatidylinositol-3-phosphate (PtdIns3P) is concentrated on autophagic vesicles and recruits effector proteins that are crucial for this process. The production of PtdIns3P by the class III phosphatidylinositol 3-kinase Vps34, has been well established; however, protein phosphatases that antagonize this early step in autophagy remain to be identified. To identify such enzymes, we screened human phosphatase genes by RNA interference and found that loss of PTPσ, a dual-domain protein tyrosine phosphatase (PTP), increases levels of cellular PtdIns3P. The abundant PtdIns3P-positive vesicles conferred by loss of PTPσ strikingly phenocopied those observed in cells starved of amino acids. Accordingly, we discovered that loss of PTPσ hyperactivates both constitutive and induced autophagy. Finally, we found that PTPσ localizes to PtdIns3P-positive membranes in cells, and this vesicular localization is enhanced during autophagy. We therefore describe a novel role for PTPσ and provide insight into the regulation of autophagy. Mechanistic knowledge of this process is crucial for understanding and targeting therapies for several human diseases, including cancer and Alzheimer's disease, in which abnormal autophagy might be pathological.
Evidence of a central pattern generator regulating spermathecal muscle activity inLocusta migratoriaand its coordination with oviposition
Authors: da Silva Rosa , Lange Angela B.
Published: February 2011

Electrophysiological recordings were conducted to determine the control of spermathecal contractions during oviposition of interrupted egg-laying locusts, Locusta migratoria. Following transection of the central nervous system below the metathoracic ganglion, rhythmic patterned bursting was detected by extracellular recordings of the nerve N2B2 that innervates the muscles of the spermatheca. Subsequent transections at more posterior regions of the ventral nerve cord revealed more robust rhythmic bursting in N2B2. This rhythmic bursting pattern was found to be coordinated with bursting in the ventral opener nerve (N2B1) that innervates the ventral opener muscle. This muscle controls the ventral ovipositor valves. Electromyographic recordings from the spermathecal muscle and ventral opener muscle confirmed a rhythmic bursting pattern resulting in an increase in muscle activity. Taken together, the results indicate that there is probably a central pattern generator (CPG), which is regulated by descending inhibition, that controls the spermathecal muscle activity. This CPG appears to be located within the VIIth and VIIIth abdominal ganglia, and was found to integrate with the CPG that regulates oviposition digging in locusts. These results provide further insight into the intricate coordination and control of reproductive tissues underlying reproductive behaviours in locusts.
Trade Liberalization, Exports, and Technology Upgrading: Evidence on the Impact of MERCOSUR on Argentinian Firms
Authors: Bustos Paula
Published: February 2011

This paper studies the impact of a regional free trade agreement, MERCOSUR, on technology upgrading by Argentinean firms. To guide empirical work, I introduce technology choice in a model of trade with heterogeneous firms. The joint treatment of the technology and exporting choices shows that the increase in revenues produced by trade integration can induce exporters to upgrade technology. An empirical test of the model reveals that firms in industries facing higher reductions in Brazil's tariffs increase investment in technology faster. The effect of tariffs is highest in the upper-middle range of the firm-size distribution, as predicted by the model. (JEL F13, F15, O19, O24, O33).
Monetary Policy, Trend Inflation, and the Great Moderation: An Alternative Interpretation
Authors: Coibion Olivier , Gorodnichenko Yuriy
Published: February 2011

With positive trend inflation, the Taylor principle does not guarantee a determinate equilibrium. We provide new theoretical results on determinacy in New Keynesian models with positive trend inflation and new empirical findings on the Federal Reserve's reaction function before and after the Volcker disinflation to find that, (i) while the Fed likely satisfied the Taylor principle before Volcker, the US economy was still subject to self-fulfilling fluctuations in the 1970s, (ii) the US economy switched to determinacy during the Volcker disinflation, and (iii) the switch reflected changes in the Fed's response to macroeconomic variables and the decline in trend inflation. (JEL E12, E23, E31, E32, E52)
Resolving Conflicting Preferences in School Choice: The “Boston Mechanism” Reconsidered
Authors: Abdulkadiroğlu Atila , Che Yeon-Koo , Yasuda Yosuke
Published: February 2011

Despite its widespread use, the Boston mechanism has been criticized for its poor incentive and welfare performances compared to the Gale-Shapley deferred acceptance algorithm (DA). By contrast, when students have the same ordinal preferences and schools have no priorities, we find that the Boston mechanism Pareto dominates the DA in ex ante welfare, that it may not harm but rather benefit participants who may not strategize well, and that, in the presence of school priorities, the Boston mechanism also tends to facilitate greater access than the DA to good schools for those lacking priorities at those schools. (JEL D82, I21, I28)
The Problem of the Commons: Still Unsettled after 100 Years
Authors: Stavins Robert N
Published: February 2011

The problem of the commons is more important to our lives and thus more central to economics than a century ago when Katharine Coman led off the first issue of the American Economic Review. As the US and other economies have grown, the carrying capacity of the planet—in regard to natural resources and environmental quality—has become a greater concern, particularly for common-property and open-access resources. The focus of this article is on some important, unsettled problems of the commons. Within the realm of natural resources, there are special challenges associated with renewable resources, which are frequently characterized by open-access. An important example is the degradation of open-access fisheries. Critical commons problems are also associated with environmental quality. A key contribution of economics has been the development of market-based approaches to environmental protection. These instruments are key to addressing the ultimate commons problem of the twenty-first century—global climate change. (JEL Q15, Q21, Q22, Q25, Q54)
Learning from a Classroom Manufacturing Exercise
Authors: Gray Irwin
Published: February 2011

By performing a hands-on manufacture of a paper product along a fabrication line set up in a classroom, students experience the complexities of an actual production line—how to work with people to construct a smoothly flowing line and analyze and deal with technical changes. In particular, they learn how a change in one position on the line affects the manpower, methods, and machines of the entire line. The quantitative as well as qualitative problems of batch processing, work-in-progress inventory, misutilization of labor, and even elements of product liability become “live concepts” instead of dry exercises from a book. Students in an MBA program with no real-life experiences against which to reflect what they are learning in their classes are able to experience a working fabrication line in all its complexities. They are challenged by having to design their own products and the jigs and fixtures to make them—even when they have no engineering or specialized knowledge. One group, for example, manages to design a production jig for a folding step that other groups have been doing by hand; the jig enables a 57% improvement in production per labor minute. The exercises also demonstrate the costs of idle time: When a batch process is mishandled, worker idle time jumps to 19% of the total time needed to run the batch. This exercise prepares students for future job decisions involving production problems of in-house manufacturing or service operations, off-shore procurement, and quality control.
OR PRACTICE—Scheduling of Dynamic In-Game Advertising
Authors: Turner John , Scheller-Wolf Alan , Tayur Sridhar
Published: February 2011

Dynamic in-game advertising is a new form of advertising in which ads are served to video game consoles in real time over the Internet. We present a model for the in-game ad-scheduling problem faced by Massive Inc., a wholly owned subsidiary of Microsoft, and a leading global network provider of in-game ad space. Our model has two components: (1) a linear program (solved periodically) establishes target service rates, and (2) a real-time packing heuristic (run whenever a player enters a new level) tracks these service rates. We benchmark our model against Massive's legacy algorithm: When tested on historical data, we observe (1) an 80%–87% reduction in make-good costs (depending on forecast accuracy), and (2) a shift in the age distribution of served ad space, leaving more premium inventory open for future sales. As a result of our work, Massive has increased the number of unique individuals that see each campaign by, on average, 26% per week and achieved 33% smoother campaign delivery as measured by standard deviation of hourly impressions served.
Implementation of computerized add-on testing for hospitalized patients in a large academic medical center
Authors: Kim Ji Yeon , Kamis Irina K. , Singh Balaji , Batra Shalini , Dixon Roberta H. , Dighe Anand S.
Published: February 2011

Background: Physician requests for additional testing on an existing laboratory specimen (add-ons) are resource intensive and generally require a phone call to the laboratory. Verbal orders such as these have been noted to be associated with errors in accuracy. The aim of this study was to compare a novel computerized system for add-on requests to the prior verbal system.

Method: We compare the computerized add-on request system to the verbal system with respect to order completeness and workflow.

Results: We demonstrate that the computerized add-on system resulted in the complete in-laboratory documentation of the add-on request 100% of the time, compared to 58% with the verbal add-on system. In addition, we show that documentation of a verbal add-on request in the electronic medical record (EMR) occurred for 4% of requests, while in the computerized system EMR documentation occurred 100% of the time. We further demonstrate that the computerized add-on request process was well accepted by providers and did not significantly change the test mix of the add-on requests.

Conclusions: In computerized physician order entry (CPOE) implementations, add-on order functionality should be considered so these orders are documented in the EMR.
Control of Breathing by Raphe Obscurus Serotonergic Neurons in Mice
Authors: DePuy Seth D. , Kanbar Roy , Coates Melissa B. , Stornetta Ruth L. , Guyenet Patrice G.
Published: February 2011

We used optogenetics to determine the global respiratory effects produced by selectively stimulating raphe obscurus (RO) serotonergic neurons in anesthetized mice and to test whether these neurons detect changes in the partial pressure of CO2, and hence function as central respiratory chemoreceptors. Channelrhodopsin-2 (ChR2) was selectively (∼97%) incorporated into ∼50% of RO serotonergic neurons by injecting AAV2 DIOChR2-mCherry(adeno-associated viral vector double-floxed inverse open reading frame ofChR2-mCherry) into the RO of ePet-Cre mice. The transfected neurons heavily innervated lower brainstem and spinal cord regions involved in autonomic and somatic motor control plus breathing but eschewed sensory related regions. Pulsed laser photostimulation of ChR2-transfected serotonergic neurons increased respiratory frequency (fR) and diaphragmatic EMG (dEMG) amplitude in relation to the duration and frequency of the light pulses (half saturation, 1 ms; 5–10 Hz). dEMG amplitude and fR increased slowly (half saturation after 10–15 s) and relaxed monoexponentially (tau, 13–15 s). The breathing stimulation was reduced ∼55% by methysergide (broad spectrum serotonin antagonist) and potentiated (∼16%) at elevated levels of inspired CO2(8%). RO serotonergic neurons, identified by their entrainment to short light pulses (threshold, 0.1–1 ms) were silent (nine cells) or had a low and regular level of activity (2.1 ± 0.4 Hz; 11 cells) that was not synchronized with respiration. These and nine surrounding neurons with similar characteristics were unaffected by adding up to 10% CO2to the breathing mixture. In conclusion, RO serotonergic neurons activate breathing frequency and amplitude and potentiate the central respiratory chemoreflex but do not appear to have a central respiratory chemoreceptor function.
Long-term effects of radiotherapy on cardiovascular risk factors in acromegaly
Authors: Ronchi Cristina L , Verrua Elisa , Ferrante Emanuele , Bender Gwendolyn , Sala Elisa , Lania Andrea G , Fassnacht Martin , Beck-Peccoz Paolo , Allolio Bruno , Spada Anna , Arosio Maura
Published: February 2011

Objective

Radiation therapy (RT) is a useful adjuvant tool for acromegalic patients not cured by surgery and/or not responding to pharmacotherapy. However, its specific effects on cardio- and cerebrovascular morbidity are still on debate.

Design

Retrospective analysis of 42 acromegalic patients cured after conventional radiotherapy (CRT, n=31) or radiosurgery by gamma-knife (GKRS, n=11) followed for a median period of 16.5 years (range: 2–40). Totally, 56 patients cured by surgery alone, with similar GH/IGF1 levels and duration of disease remission, served as control group.

Methods

Changes in cardiovascular risk factors, such as body mass index, glucose metabolism, insulin resistance, blood pressure, and lipid profile (pre-defined primary end point) and occurrence of new major cardio- and cerebrovascular events (secondary end point) during follow-up.

Results

The number of obese, hypertensive, and dyslipidemic subjects increased over time only in patients cured with RT. In contrast, the glucose response to the oral glucose tolerance test and the percentage of subjects with glucose alterations improved only in controls. As expected, the percentage of patients with pituitary failure was deeply higher among RT patients than among controls (86 vs 30%, P<0.0005). Despite these findings, a similar number of RT patients and controls developed major cardio- or cerebrovascular events (4/42 vs 3/56, P: NS). No differences were found between CRT and GKRS subgroups.

Conclusions

Previous RT seems to be associated with a worse metabolic profile in acromegalic patients studied after a long-term follow-up. Nevertheless, a direct link between RT and cardiovascular events remains to be proven.
Maximally Efficient Modeling of DNA Sequence Motifs at All Levels of Complexity
Authors: Stormo Gary D
Published: February 2011

Identification of transcription factor binding sites is necessary for deciphering gene regulatory networks. Several new methods provide extensive data about the specificity of transcription factors but most methods for analyzing these data to obtain specificity models are limited in scope by, for example, assuming additive interactions or are inefficient in their exploration of more complex models. This article describes an approach—encoding of DNA sequences as the vertices of a regular simplex—that allows simultaneous direct comparison of simple and complex models, with higher-order parameters fit to the residuals of lower-order models. In addition to providing an efficient assessment of all model parameters, this approach can yield valuable insight into the mechanism of binding by highlighting features that are critical to accurate models.
Patterns of Comorbidity, Functioning, and Service Use for US Children With ADHD, 2007
Authors: Larson Kandyce , Russ Shirley A. , Kahn Robert S. , Halfon Neal
Published: February 2011

OBJECTIVE:

To determine patterns of comorbidity, functioning, and service use for US children with attention-deficit/hyperactivity disorder (ADHD).

METHODS:

Bivariate and multivariable cross-sectional analyses were conducted on data from the 2007 National Survey of Children's Health on 61 779 children ages 6 to 17 years, including 5028 with ADHD.

RESULTS:

Parent-reported diagnosed prevalence of ADHD was 8.2%. Children with ADHD were more likely to have other mental health and neurodevelopmental conditions. Parents reported that 46% of children with ADHD had a learning disability versus 5% without ADHD, 27% vs 2% had a conduct disorder, 18% vs 2% anxiety, 14% vs 1% depression, and 12% vs 3% speech problems (all P < .05). Most children with ADHD had at least 1 comorbid disorder: 33% had 1, 16% had 2, and 18% had 3 or more. The risk for having 3 or more comorbidities was 3.8 times higher for poor versus affluent children (30% vs 8%). Children with ADHD had higher odds of activity restriction (odds ratio: 4.14 [95% confidence interval: 3.34–5.15]), school problems (odds ratio: 5.18 [95% confidence interval: 4.47–6.01]), grade repetition, and poor parent-child communication, whereas social competence scores were lower and parent aggravation higher. Functioning declined in a stepwise fashion with increasing numbers of comorbidities, and use of health and educational services and need for care coordination increased.

CONCLUSIONS:

Clinical management of ADHD must address multiple comorbid conditions and manage a range of adverse functional outcomes. Therapeutic approaches should be responsive to each child's neurodevelopmental profile, tailored to their unique social and family circumstances, and integrated with educational, mental health and social support services.
Long-term Results of an Obesity Program in an Ethnically Diverse Pediatric Population
Authors: Savoye Mary , Nowicka Paulina , Shaw Melissa , Yu Sunkyung , Dziura James , Chavent Georgia , O'Malley Grace , Serrecchia John B. , Tamborlane William V. , Caprio Sonia
Published: February 2011

OBJECTIVE:

To determine if beneficial effects of a weight-management program could be sustained for up to 24 months in a randomized trial in an ethnically diverse obese population.

PATIENTS AND METHODS:

There were 209 obese children (BMI > 95th percentile), ages 8 to 16 of mixed ethnic backgrounds randomly assigned to the intensive lifestyle intervention or clinic control group. The control group received counseling every 6 months, and the intervention group received a family-based program, which included exercise, nutrition, and behavior modification. Lifestyle intervention sessions occurred twice weekly for the first 6 months, then twice monthly for the second 6 months; for the last 12 months there was no active intervention. There were 174 children who completed the 12 months of the randomized trial. Follow-up data were available for 76 of these children at 24 months. There were no statistical differences in dropout rates among ethnic groups or in any other aspects.

RESULTS:

Treatment effect was sustained at 24 months in the intervention versus control group for BMI z score (−0.16 [95% confidence interval: −0.23 to −0.09]), BMI (−2.8 kg/m2 [95% confidence interval: −4.0–1.6 kg/m2]), percent body fat (−4.2% [95% confidence interval: −6.4% to −2.0%]), total body fat mass (−5.8 kg [95% confidence interval: −9.1 kg to −2.6 kg]), total cholesterol (−13.0 mg/dL [95% confidence interval: −21.7 mg/dL to −4.2 mg/dL]), low-density lipoprotein cholesterol (−10.4 mg/dL [95% confidence interval: −18.3 mg/dL to −2.4 mg/dL]), and homeostasis model assessment of insulin resistance (−2.05 [95% confidence interval: −2.48 to −1.75]).

CONCLUSIONS:

This study, unprecedented because of the high degree of obesity and ethnically diverse backgrounds of children, reveals that benefits of an intensive lifestyle program can be sustained 12 months after completing the active intervention phase.
Extraction and determination of ascorbate and dehydroascorbate from apoplastic fluid of stem of rooted and non-rooted cuttings in relation to the rhizogenesis
Authors: Zuffellato-Ribas Katia Christina , Morini Stefano , Picciarelli Piero , Mignolli Francesco
Published: February 2011

Starting from semihardwood branches of peach and plum rootstocks (Prunus cerasifera E.) cv. MRS2/5, plum rootstocks (Prunus cerasifera × P. salicina) × (P. cerasifera × P. persica) cv. Ishtarà and olive tree (Olea europaea L.) cv. Frantoio, cuttings were collected and treated with 0 mg.L-1 and 2500 mg.L-1 of indolebutyric acid (IBA) by immersion in the base of the cuttings. After 60 days of planting, the cultivars MRS 2/5, Ishtarà and Frantoio presented a significative difference with relation to the rooting induction by application of the indolebutyric acid (27.5, 47.5 and 41.25 %, respectively), inducing a higher number of roots per cutting without at the same time significantly increasing the length of the roots themselves. The levels of ascorbate and dehydroascorbate in the rooted and non-rooted cuttings of the three cultivars were determined. These parameters varied in function of the consistency of the cuttings from each species, but showed a positive correlation between the increase of the rooting and the increase of the ascorbate in the reduced form.
Salinity-Based Pump-and-Dump Strategy for Drilling Salt With Supersaturated Fluids
Authors: Akers T.J.. J.
Published: February 2011

Riserless drilling with weighted-drilling-fluid systems, commonly referred to as a "pump-and-dump" drilling strategy, is an established drilling technique used on deepwater wells with shallow hazards. Large holes and high flow rates result in very large volumes of fluid being required to drill to total depth (TD), circulate the well clean, and cement the conductor-casing string. Fluids management becomes a major issue in the riserless hole section. In the Gulf of Mexico, mud is often densified in excess of well requirements and then blended with seawater in a "cut-back" operation to reach the desired density to pump downhole.

When performing riserless drilling into salt, a pump-and-dump strategy is often used. Dilution with seawater, however, results in an undersaturated fluid. This fluid leaches the salt, resulting in substantial hole enlargement. The hole enlargement can result in poor cementing jobs that require remediation or even an additional string of casing. A unique operation has been employed in the Santos basin of Brazil where a supersaturated-brine fluid was used to conduct a pump-and-dump operation with the goal of drilling with a saturated-brine fluid and minimizing hole enlargement. This paper details the planning of the operation, fluid design, and pilot testing. Fluids management, equipment rig up, and results are discussed in detail. The operation has been executed successfully twice, with both operations achieving the set objectives for the wells. Unforeseen complications that were encountered are discussed along with lessons learned that have been applied to subsequent operations.
The Challenges for Carbonate Petrophysics in Petroleum Resource Estimation
Authors: Bust Vivian K. , Oletu Joshua U. , Worthington Paul F.
Published: February 2011

An examination of the core and log analysis of carbonate reservoirs has confirmed that identified shortcomings are rooted in disparate pore character. Many of the interpretation methods were developed for clastic rocks, which typically show an intergranular porosity, sometimes augmented by fracture porosity. In carbonate reservoirs, the primary pore system comprises interparticle porosity that coexists with a highly variable secondary system of dissolution voids and/or fractures. As a consequence, carbonate reservoirs are markedly heterogeneous from pore to reservoir scales, and this variability poses significant challenges to data acquisition, petrophysical evaluation, and reservoir description. For example, the ranges of carbonate facies and their pore character often control the distributions of net pay, porosity, and hydrocarbon saturation. Putting these matters together, conventional petrophysical practices that exclusively use reservoir zonation based on lithology/mineralogy have limited application in carbonates. Instead, recourse is made to a zonal discrimination that draws upon the distribution of microporosity and its connectivity with macroporosity and fractures. The discrimination scheme uses downhole technologies such as high-resolution imaging and magnetic resonance logs, supported by advanced core analysis. On this basis, a value-adding workflow is proposed to increase confidence in those petrophysical deliverables that are used in static volumetric estimates of petroleum Resources.
Pore-Scale Modelling of the Effect of Viscous Pressure Gradients During Heavy Oil Depletion Experiments
Authors: Bondino Igor , McDougall Steven R. , Hamon Gerald
Published: February 2011

In this work, we implement a dynamic gas/oil interface tracking algorithm for the mobilization of bubbles under intense pressure gradients in order to improve the simulation of solution gas drive for heavy oil in the framework of a pre-existing pore-scale network simulator. The model is used to characterize both the stationary capillary controlled growth of bubbles characteristic of slow depletion rates (far-wellbore region) and the flow phenomena in the near-wellbore region: in this case, it is shown how viscous forces lead to an increased persistence of small bubbles for a longer time, creating an effect similar to what described as foamy oil.

The study has identified three different regimes of bubble growth, depending upon capillary number and depletion rate, and these regimes appear to cover the entire range of phenomena observed experimentally. These three regimes are (a) the conventional capillary-controlled growth pattern at low capillary numbers, (b) viscous biased growth at intermediate capillary numbers, and (c) bubble mobilization and breakup leading to foamy behaviour at the highest capillary numbers and depletion rates. A predictive methodology for the associated continuum-scale constitutive relationships, such as relative permeabilities, is also proposed for each of the three depressurization regimes.
Estimation of Reservoir Hydraulic Property From Surface Heave Monitoring During Subsurface Fluid Injection
Authors: Qiao Liping , Wong Ron C.K. , Aguilera Roberto
Published: February 2011

Subsurface fluid injections, such as wastewater disposal, waterflooding, and CO2 sequestration, cause reservoir dilation. The reservoir dilation induces displacements in the overburden extending up to the ground surface and resulting in surface heave. Previous studies have illustrated that it is possible to delineate the extent of the reservoir dilation from the surface heave measurement using an inverse technique. This paper proposes that the inverse technique can be extended to estimate the growth and propagation of the reservoir dilation during the fluid injection if the surface heave is monitored continually. Then, the reservoir pressure distribution and hydraulic properties could also possibly be determined from the fluid-flow equations. The results obtained from the proposed technique were compared with those obtained from a fully-coupled finite element (FE) simulation of a fluid injection problem. It was found that the numerical tool could be successfully adopted to estimate an approximate value of the reservoir permeability.
Large Sample Approximations of Probabilities of Correct Evolutionary Tree Estimation and Biases of Maximum Likelihood Estimation
Authors: Susko Edward
Published: February 2011

Simulation studies have been the main way in which properties of maximum likelihood estimation of evolutionary trees from aligned sequence data have been studied. Because trees are unusual parameters and because fitting is computationally intensive, such studies have a heavy computational cost. We develop an asymptotic framework that can be used to obtain probabilities of correct topological reconstruction and study other properties of likelihood methods when a single split is poorly resolved. Simulations suggest that while approximations to log likelihood differences are better for less well-resolved topologies, approximations to probabilities of correct reconstruction are generally good. We used the approximations to investigate biases in estimation and found that maximum likelihood estimation has a long-branch-repels bias. This differs from the long-branch-attracts bias often reported in the literature because it is a different form of bias. For maximum likelihood estimation, usually long-branch-attracts bias results arise in the presence of model misspecification and are a form of statistical inconsistency where the estimated tree converges upon an incorrect tree with long edges together. Here, by bias we mean a tendency to favour a particular topology when data are generated from a four-taxon star tree. While we find a tendency to favour the tree with long branches apart, with more extreme long edges, a strong small sequence-length long-branch-attracts bias overwhelms the long-branch-repels bias. The long-branch-repels bias generalizes to five and six taxa in the sense that subtrees containing taxa that are all distant from the poorly resolved split repel each other.