bluuebunny/crossref_metadata_2025 huggingface dataset:
The Inflammatory Response in Acyl-CoA Oxidase 1 Deficiency (Pseudoneonatal Adrenoleukodystrophy)
Authors: El Hajj H. I. , Vluggens A. , Andreoletti P. , Ragot K. , Mandard S. , Kersten S. , Waterham H. R. , Lizard G. , Wanders R. J. A. , Reddy J. K. , Cherkaoui-Malki Mustapha
Published: April 2012

Among several peroxisomal neurodegenerative disorders, the pseudoneonatal adrenoleukodystrophy (P-NALD) is characterized by the acyl-coenzyme A oxidase 1 (ACOX1) deficiency, which leads to the accumulation of very-long-chain fatty acids (VLCFA) and inflammatory demyelination. However, the components of this inflammatory process in P-NALD remain elusive. In this study, we used transcriptomic profiling and PCR array analyses to explore inflammatory gene expression in patient fibroblasts. Our results show the activation of IL-1 inflammatory pathway accompanied by the increased secretion of two IL-1 target genes, IL-6 and IL-8 cytokines. Human fibroblasts exposed to very-long-chain fatty acids exhibited increased mRNA expression of IL-1α and IL-1β cytokines. Furthermore, expression of IL-6 and IL-8 cytokines in patient fibroblasts was down-regulated by MAPK, p38MAPK, and Jun N-terminal kinase inhibitors. Thus, the absence of acyl-coenzyme A oxidase 1 activity in P-NALD fibroblasts triggers an inflammatory process, in which the IL-1 pathway seems to be central. The use of specific kinase inhibitors may permit the modulation of the enhanced inflammatory status.
A High Percentage of BRAFV600E Alleles in Papillary Thyroid Carcinoma Predicts a Poorer Outcome
Authors: Guerra Anna , Fugazzola Laura , Marotta Vincenzo , Cirillo Massimo , Rossi Stefania , Cirello Valentina , Forno Irene , Moccia Tania , Budillon Alfredo , Vitale Mario
Published: April 2012

Context:

BRAFV600E is considered a negative prognostic marker in papillary thyroid carcinoma (PTC), but unexplained conflicting results are present in the literature. In light of the new finding that most PTC consist of a mixture of tumor cells with wild-type and mutant BRAF, we examined the associations between the percentage of BRAFV600E alleles and both the clinicopathological parameters at time of diagnosis and the disease outcome in a large series of PTCs.

Study Design:

Tumors from 168 patients with PTC were genotyped for BRAFV600E using BigDye Terminator sequencing and pyrosequencing, and the clinical parameters were analyzed. The associations between clinicopathological characteristics, including disease recurrence at follow-up (median 5.1 yr) and the percentage of mutant BRAF alleles were assessed.

Results:

The observed prevalence of BRAFV600E was higher when using pyrosequencing then when using BigDye Terminator sequencing (53.6 vs. 36.9%). In the PTC positive for BRAFV600E, the percentage of mutant alleles ranged from 5.1 to 44.7% of the total BRAF alleles, with a median of 20.6%. The presence or the percentage of BRAFV600E alleles did not correlate significantly with sex, multicentricity, lymph node metastasis, or tumor stage. The percentage of BRAFV600E alleles directly correlated with age at diagnosis and tumor volume (R2 = 0.223, P = 0.039, and R2 = 0.166, P < 0.001, respectively). The percentage of BRAFV600E alleles (P = 0.014), tumor volume (P = 0.012), and lymph node metastasis (P = 0.008) predicted the disease outcome. The odds ratio of recurrence for PTC with BRAFV600E alleles of 30% or greater, compared with that for PTC with BRAFV600E alleles of less than 30%, was 5.31 (P = 0.002).

Conclusions:

A high percentage of BRAFV600E alleles defines a PTC molecular subtype and predicts a poorer disease outcome. The analysis of BRAF mutations by pyrosequencing is useful to refine the risk stratification of patients with PTC.
Words Spoken and Written: Divergent Meanings of Honor among Elites in Nineteenth-Century Rio Grande Do Sul
Authors: Monsma Karl
Published: April 2012

The article concerns differences in the nature and signs of honor among nineteenth-century Brazilian elites. Based primarily on the court records of a dispute between a frontier rancher and a wealthy urban merchant in Rio Grande do Sul, as well as the correspondence of the merchant with a wide variety of commercial and political contacts, it argues that honor symbolized the value and reliability of exchange partners among all elite groups, but differences in the nature of exchanges led to different means of gauging honor. Landowners involved mainly in local face-to-face exchanges evaluated male honor primarily by the observance of spoken agreements and promises, whereas merchants involved in long-distance trade emphasized careful accounting and the fulfillment of written obligations. In a vast country with severely limited educational opportunities for the great majority of the population, fluency in written communication and accounting skills became important means to accumulate wealth and power, allowing individuals with these skills to occupy central positions in long-distance trade and patronage networks. Differences in the nature of honor also fueled disdain and hatred in the civil wars of nineteenth-century Rio Grande do Sul, which tended to pit frontier ranchers against urban commercial and political elites.
The novel intestinal filament organizer IFO-1 contributes to epithelial integrity in concert with ERM-1 and DLG-1
Authors: Carberry Katrin , Wiesenfahrt Tobias , Geisler Florian , Stöcker Stephanie , Gerhardus Harald , Überbach Daniel , Davis Wayne , Jorgensen Erik , Leube Rudolf E. , Bossinger Olaf
Published: April 2012

The nematode Caenorhabditis elegans is an excellent model system in which to study in vivo organization and function of the intermediate filament (IF) system for epithelial development and function. Using a transgenic ifb-2::cfp reporter strain, a mutagenesis screen was performed to identify mutants with aberrant expression patterns of the IF protein IFB-2, which is expressed in a dense network at the subapical endotube just below the microvillar brush border of intestinal cells. Two of the isolated alleles (kc2 and kc3) were mapped to the same gene, which we refer to as ifo-1 (intestinal filament organizer). The encoded polypeptide colocalizes with IF proteins and F-actin in the intestine. The apical localization of IFO-1 does not rely on IFB-2 but is dependent on LET-413, a basolateral protein involved in apical junction assembly and maintenance of cell polarity. In mutant worms, IFB-2 and IFC-2 are mislocalized in cytoplasmic granules and accumulate in large aggregates at the C. elegans apical junction (CeAJ) in a DLG-1-dependent fashion. Electron microscopy reveals loss of the prominent endotube and disordered but still intact microvilli. Semiquantitative fluorescence microscopy revealed a significant decrease of F-actin, suggesting a general role of IFO-1 in cytoskeletal organization. Furthermore, downregulation of the cytoskeletal organizer ERM-1 and the adherens junction component DLG-1, each of which leads to F-actin reduction on its own, induces a novel synthetic phenotype in ifo-1 mutants resulting in disruption of the lumen. We conclude that IFO-1 is a multipurpose linker between different cytoskeletal components of the C. elegans intestinal terminal web and contributes to proper epithelial tube formation.
Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila
Authors: Benmimoun Billel , Polesello Cédric , Waltzer Lucas , Haenlin Marc
Published: April 2012

The interconnected Insulin/IGF signaling (IlS) and Target of Rapamycin (TOR) signaling pathways constitute the main branches of the nutrient-sensing system that couples growth to nutritional conditions in Drosophila. Here, we addressed the influence of these pathways and of diet restriction on the balance between the maintenance of multipotent hematopoietic progenitors and their differentiation in the Drosophila lymph gland. In this larval hematopoietic organ, a pool of stem-like progenitor blood cells (prohemocytes) is kept undifferentiated in response to signaling from a specialized group of cells forming the posterior signaling center (PSC), which serves as a stem cell niche. We show that, reminiscent of the situation in human, loss of the negative regulator of IIS Pten results in lymph gland hyperplasia, aberrant blood cell differentiation and hematopoietic progenitor exhaustion. Using site-directed loss- and gain-of-function analysis, we demonstrate that components of the IIS/TOR pathways control lymph gland homeostasis at two levels. First, they cell-autonomously regulate the size and activity of the hematopoietic niche. Second, they are required within the prohemocytes to control their growth and maintenance. Moreover, we show that diet restriction or genetic alteration mimicking amino acid deprivation triggers progenitor cell differentiation. Hence, our study highlights the role of the IIS/TOR pathways in orchestrating hematopoietic progenitor fate and links blood cell fate to nutritional status.
Behavioral Foundations of Microcredit: Experimental and Survey Evidence from Rural India
Authors: Bauer Michal , Chytilová Julie , Morduch Jonathan
Published: April 2012

We use experimental measures of time discounting and risk aversion for villagers in south India to highlight behavioral features of microcredit, a financial tool designed to reduce poverty and fix credit market imperfections. The evidence suggests that microcredit contracts may do more than reduce moral hazard and adverse selection by imposing new forms of discipline on borrowers. We find that, conditional on borrowing from any source, women with present-biased preferences are more likely than others to borrow through microcredit institutions. Another particular contribution of microcredit may thus be to provide helpful structure for borrowers seeking self-discipline. JEL: G21, I38, O15, O16, O18
Search, Design, and Market Structure
Authors: Bar-Isaac Heski , Caruana Guillermo , Cuñat Vicente
Published: April 2012

The Internet has made consumer search easier, with consequences for prices, industry structure, and the kinds of products offered. We provide an industry model with strategic design choices that explores these issues. A polarized market structure results: some firms choose designs aimed at broad-based audiences, while others target narrow niches. We analyze the effect of reduced search costs, finding results consistent with the reported prevalence of niche goods and long-tail and superstar phenomena. In particular, the model suggests that long-tail effects arise when there is a wide range of potential designs, relative to vertical heterogeneity among firms. JEL: D11, D21, D83, L11, L86, M31
Paying a Premium on Your Premium? Consolidation in the US Health Insurance Industry
Authors: Dafny Leemore , Duggan Mark , Ramanarayanan Subramaniam
Published: April 2012

We examine whether and to what extent consolidation in the US health insurance industry has contributed to higher employer-sponsored insurance premiums. We exploit the differential impact across local markets of a national merger of two insurers to identify the causal effect of concentration on premiums. Using data for large groups, we estimate premiums in average markets were approximately seven percentage points higher by 2007 due to increases in local concentration from 1998–2006. We also find evidence consolidation facilitates the exercise of monopsonistic power vis-à-vis physicians, leading to reductions in their absolute employment and earnings relative to other healthcare workers. JEL: G22, I13
Comparing Real Wage Rates
Authors: Ashenfelter Orley
Published: April 2012

A real wage rate is a nominal wage rate divided by the price of a good and is a transparent measure of how much of the good an hour of work buys. It provides an important indicator of the living standards of workers, and also of the productivity of workers. In this paper I set out the conceptual basis for such measures, provide some historical examples, and then provide my own preliminary analysis of a decade long project designed to measure the wages of workers doing the same job in over 60 countries—workers at McDonald's restaurants. The results demonstrate that the wage rates of workers using the same skills and doing the same jobs differ by as much as 10 to 1, and that these gaps declined over the period 2000–2007, but with much less progress since the Great Recession. (JEL C81, C82, D24, J31, N30, O57)
The Welfare Effects of Bundling in Multichannel Television Markets
Authors: Crawford Gregory S , Yurukoglu Ali
Published: April 2012

We measure how the bundling of television channels affects short-run welfare. We estimate an industry model of viewership, demand, pricing, bundling, and input-market bargaining using data on ratings, purchases, prices, bundles, and input costs. We conduct simulations of à la carte policies that require distributors to offer individual channels for sale to consumers. We estimate that negotiated input costs rise by 103.0 percent under à la carte. These higher input costs offset consumer benefits from purchasing individual channels. Mean consumer and total surplus change by an estimated —5.4 to 0.2 percent and —1.7 to 6.0 percent, respectively. (JEL D12, L11, L51, L82, M31)
The Use of Full-Line Forcing Contracts in the Video Rental Industry
Authors: Ho Katherine , Ho Justin , Mortimer Julie Holland
Published: April 2012

Bundling is at the forefront of many policy debates as new technologies allow firms to implement more complex bundling arrangements. Realistic analyses of bundling—particularly between suppliers and retailers—require detailed data on both supply arrangements and consumer demand. We analyze firms' use of bundling as a vertical restraint (known as full-line forcing) using extensive supply and demand data from the video rental industry. Our model captures key details of the market that determine firms' contractual choices, and sheds light on the implications of these decisions. The empirical approach provides a model for how to analyze bundling when detailed data are available. (JEL D86, L14, L81, L82)
Slow to Anger and Fast to Forgive: Cooperation in an Uncertain World
Authors: Fudenberg Drew , Rand David G , Dreber Anna
Published: April 2012

We study the experimental play of the repeated prisoner's dilemma when intended actions are implemented with noise. In treatments where cooperation is an equilibrium, subjects cooperate substantially more than in treatments without cooperative equilibria. In all settings there was considerable strategic diversity, indicating that subjects had not fully learned the distribution of play. Furthermore, cooperative strategies yielded higher payoffs than uncooperative strategies in the treatments with cooperative equilibria. In these treatments successful strategies were “lenient” in not retaliating for the first defection, and many were “forgiving” in trying to return to cooperation after inflicting a punishment. (JEL C72, C73, D81)
Relational Contracts and the Value of Relationships
Authors: Halac Marina
Published: April 2012

This article studies optimal relational contracts when the value of the relationship between contracting parties is not commonly known. I consider a principal-agent setting where the principal has persistent private information about her outside option. I show that if the principal has the bargaining power, she wants to understate her outside option to provide strong incentives and then renege on promised payments, while if the uninformed agent has the bargaining power, the principal wants to overstate her outside option to capture more surplus. I characterize how information is revealed, how the relationship evolves, and how this depends on bargaining power. (JEL C78, D82, D83, D86)
Violent Conflict and Behavior: A Field Experiment in Burundi
Authors: Voors Maarten J , Nillesen Eleonora E. M , Verwimp Philip , Bulte Erwin H , Lensink Robert , Soest Daan P. Van
Published: April 2012

We use a series of field experiments in rural Burundi to examine the impact of exposure to conflict on social, risk, and time preferences. We find that conflict affects behavior: individuals exposed to violence display more altruistic behavior towards their neighbors, are more risk-seeking, and have higher discount rates. Large adverse shocks can thus alter savings and investments decisions, and potentially have long-run consequences—even if the shocks themselves are temporary. (JEL C93, D12, D74, 012, 017, 018)
What Do Emissions Markets Deliver and to Whom? Evidence from Southern California's NOx Trading Program
Authors: Fowlie Meredith , Holland Stephen P , Mansur Erin T
Published: April 2012

An advantage of cap-and-trade programs over more prescriptive environmental regulation is that compliance flexibility and cost effectiveness can make more stringent emissions reductions politically feasible. However, when markets (versus regulators) determine where emissions occur, it becomes more difficult to assure that mandated emissions reductions are equitably achieved. We investigate these issues in the context of Southern California's RECLAIM program by matching facilities in RECLAIM with similar California facilities also in nonattainment areas. Our results indicate that average emissions fell 20 percent at RECLAIM facilities relative to our counterfactual. Furthermore, observed changes in emissions do not vary significantly with neighborhood demographic characteristics. (JEL H23, L51, Q53, Q58)
Measuring Economic Growth from Outer Space
Authors: Henderson J. Vernon , Storeygard Adam , Weil David N
Published: April 2012

We develop a statistical framework to use satellite data on night lights to augment official income growth measures. For countries with poor national income accounts, the optimal estimate of growth is a composite with roughly equal weights on conventionally measured growth and growth predicted from lights. Our estimates differ from official data by up to three percentage points annually. Using lights, empirical analyses of growth need no longer use countries as the unit of analysis; we can measure growth for sub- and supranational regions. We show, for example, that coastal areas in sub-Saharan Africa are growing slower than the hinterland. (JEL E01, E23, O11, 047, 057)
The conceptual bases of metaphors of dirt and cleanliness in moral and non-moral reasoning
Authors: Lizardo, Omar
Published: April 2012

In this paper I propose a new understanding of the often-noted phenomenon that much of our conceptualization and reasoning about moral propriety is framed by a set of metaphors that originate from a conceptual structure generated from our experiences with dirt and cleanliness. I argue that reliance on the dirty-clean dichotomy to conceptualize moral propriety or impropriety emerges from metaphorical extensions into various realms of experience (e.g., sports, governance, introspection) grounded in an idealized cognitive model in which dirt is conceptualized as matter out of place and clean is conceptualized as ordered arrangement. The analysis provides a unified framework with which to understand the use of dirty and clean as metaphors to categorize objects, events and actions in the moral domain. Finally, I suggest that the dirty-clean distinction is useful for understanding broader cultural issues (such as moral panics regarding media, immigration and disease), and I show that the conceptualization of certain non-moral properties can be understood using the same framework (e.g., the quality of being exceptional) of objects and actions.
Cutting and breaking in Äiwoo: Event integration and the complexity of lexical expressions
Authors: Næss, Åshild
Published: April 2012

This paper examines the lexical encoding of events of “cutting and breaking” in the Oceanic language Äiwoo. It shows that this language differs from previously described languages in this domain in several ways: in having complex “cut and break” forms consisting of two bound elements referring to distinct aspects of the cut and break event; in integrating these forms into a cline of lexicalisation vs. serialisation, arguably reflecting a conceptual-semantic continuum of event integration; and in violating previously suggested generalisations concerning the behaviour of verbs of cutting and breaking in inchoative alternations. It shows that lexicalisation may clearly be a matter of degree, and that the degree to which an event is construed as being constituted by independent subevents vs. subevents which cannot occur independently may be directly reflected in the type of formal expression a language provides to describe it. Furthermore, it suggests that the distinction between “cut” and “break” expressions, assumed in some of the literature to be a fairly straightforward bipartition, may in fact be more of a cline. The paper thus demonstrates the complexity of the cognitive domain of cutting and breaking events and the range of strategies that may be employed by a language in describing them.
Expression of thyroid-stimulating hormone receptor, octamer-binding transcription factor 4, and intracisternal A particle-promoted polypeptide in human breast cancer tissues
Authors: Govindaraj Vijayakumar , Yaduvanshi Nirmala Singh , Krishnamachar Harish , Rao A. Jagannadha
Published: April 2012

Background: Thyroid-stimulating hormone receptor (TSHR) is one of the members of glycoprotein hormone receptor family; activation of TSHR by thyroid-stimulating hormone (TSH) regulates thyroid function, proliferation, and differentiation. The other family members of glycoprotein hormone receptors, such as leutinizing hormone receptor (LHR), human chorionic gonadotropin (hCG), and follicle-stimulating hormone (FSH) are known to be expressed in nonendocrine tissues including human breast cancer and regulate proliferation and differentiation. The involvement of thyroid hormones in the growth and differentiation of normal breast tissue is well documented. However, the presence of TSHR in breast cancer has not been demonstrated. The aim of the present study was to establish the expression pattern of TSHR along with transcription factors, such as octamer 4 (OCT4) and intracisternal A particle-promoted polypeptide (IPP) in human breast tumor.

Materials and methods: For this study, patients with stages I–III breast cancers and adjacent noncancerous tissues were prospectively accrued and analyzed. We employed semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis to determine the expression levels of TSHR in normal and human breast cancer tissues.

Results: The results indicated that a significant increase in TSHR expression was observed in tumor tissues compared to normal breast tissues. RT-PCR analysis of OCT4 and IPP also revealed a significant increase in breast tumor tissues over the controls.

Conclusions: To our knowledge, this is the first report demonstrating expression of TSHR and IPP in normal breast and breast tumors. The expression of TSHR, IPP, and OCT4 increased in the human breast tumor samples over the noncancer tissues. However, further studies are needed to establish an unequivocal role for TSHR in breast tumor progression.
Pregnancy hormonal environment and mother’s breast cancer risk
Authors: Hilakivi-Clarke Leena , de Assis Sonia , Warri Anni , Luoto Riitta
Published: April 2012

Pregnancy can both reduce and increase lifetime breast cancer risk, and it also induces a short-term, transient increase in risk. Several biological mechanisms have been proposed to explain the protective effect, including pregnancy-induced increase in circulating estrogen levels leading to reduced estrogen receptor (ER) expression and activity. Persistent changes in ER-regulated gene expression may then alter the response of the breast to postpregnancy hormonal exposures originating, for example, from food. Understanding how pregnancy increases breast cancer risk has received less attention. Human studies indicate that those women who were exposed to an elevated pregnancy estrogenic environment, such as women who took the synthetic estrogen diethylstilbestrol or who had the highest circulating estrogen levels at the beginning or end of pregnancy, are at increased risk of developing breast cancer. There is also evidence that elevated leptin levels, for example, in pregnant women who gained excessive amount of weight, increase later breast cancer risk. This may reflect a close interaction between estradiol (E2), ER, and leptin. Our preclinical study suggests that an exposure to excess pregnancy E2 and leptin levels reverses the protective changes in genomic signaling pathways seen in the breast/mammary gland of parous women and rodents. Recent findings indicate that involution – the period after lactation when the breast regresses back to prepregnancy stage – may be related to some pregnancy-associated breast cancers. Importantly, in a preclinical model, the increase can be reversed by anti-inflammatory treatment, offering hope that the increase in lifelong breast cancer risk induced by late first pregnancy or by an exposure of pregnant women to an excessive hormonal environment may be reversible.
Grundfälle zur Staatshaftung im Baurecht
Authors: Greim Jeanine , Michl Fabian
Published: April 2012

Nach der grundlegenden Entscheidung des BGH vom 16. 9. 2010 zur Haftung der Gemeinde bei rechtswidrig verweigertem Einvernehmen sind verstärkt baurechtliche Prüfungsaufgaben mit staatshaftungsrechtlichem Bezug zu erwarten. Studenten, Examenskandidaten und Referendare sind daher gut beraten, sich Kenntnisse in diesem prüfungsrelevanten Rechtsgebiet anzueignen. Dieser Beitrag stellt anhand von Grundfällen die wesentlichen Argumentationslinien dar, die auch in einer Klausur erwartet werden können.
Die aktuelle Entscheidung Trianel – die Entfesselung des Umweltrechtsbehelfs durch den EuGH
Authors: Groß Thomas
Published: April 2012

In der Entscheidung vom 12. 5. 2011 hat der EuGH eine zentrale
Einschränkung der umweltrechtlichen Verbandsklage fär unionsrechtswidrig erklärt. Weder in der Zulässigkeit
noch in der Begründetheit eines Umweltrechtsbehelfs darf die Prüfung auf Normen beschränkt werden, die Rechte Einzelner
begründen. Damit ist die Debatte über den Umfang des
Rechtsschutzes im Umweltrecht wieder eröffnet.
Increased prevalence of subclinical cardiac valve fibrosis in patients with prolactinomas on long-term bromocriptine and cabergoline treatment
Authors: Elenkova Atanaska , Shabani Rabhat , Kalinov Krassimir , Zacharieva Sabina
Published: April 2012

Background

In contrast to cabergoline, evidence-based information about a possible profibrotic effect of bromocriptine in prolactinoma patients is extremely limited.

Objective

To assess the prevalence of valvular lesions among patients on long-term bromocriptine or cabergoline therapy.

Design

Case–control study.

Methods

A transthoracic echocardiographic evaluation was performed in 334 subjects divided into four groups: 103 cabergoline treated, 55 bromocriptine treated, 74 naïve patients, and 102 controls.

Results

Clinically relevant valve regurgitations were equally prevalent in all investigated groups whereas subclinical valve fibrosis was significantly more frequent in both bromocriptine- and cabergoline-treated patients (40 vs 43.6 vs 21.6 vs 23.5%; P=0.004). The odds ratio (OR) for developing valvular fibrosis was 2.27 (95% CI 1.17–4.41; P=0.016) for cabergoline and 2.66 (95% CI 1.22–5.78; P=0.014) for bromocriptine groups compared with subjects not exposed to dopamine agonists (DAs). A significantly higher pulmonary arterial pressure corresponding to the longer treatment duration was observed among patients taking bromocriptine compared with cabergoline-treated subjects.

Conclusions

Long-term treatment with cabergoline and bromocriptine seems not to be associated with an increased risk of clinically significant valve disease but possible subclinical lesions should be expected. An echocardiographic examination is recommended at the beginning and periodically during therapy with DAs acting as full or partial agonists of 5-hydroxytrytamine 2B receptors (cabergoline and bromocriptine). Bromocriptine seems not to be a safe alternative for patients receiving cabergoline treatment who have preexisting or diagnosed abnormalities suggesting valvular, interstitial myocardial, or pulmonary fibrosis. Further studies are needed to investigate the possible impact of DA treatment on pulmonary arterial pressure.
Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets
Authors: Tenhagen M , van Diest P J , Ivanova I A , van der Wall E , van der Groep P
Published: April 2012

Cancer treatments are increasingly focusing on the molecular mechanisms underlying the oncogenic processes present in tumors of individual patients. Fibroblast growth factor receptors (FGFRs) are among the many molecules that are involved in oncogenesis and are currently under investigation for their potential as drug targets in breast cancer patients. These receptor tyrosine kinases play a role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. Among breast cancer patients, several subgroups have been shown to harbor genetic aberrations in FGFRs, including amplifications ofFGFR1,FGFR2, andFGFR4and mutations inFGFR2andFGFR4. Here, we reviewin vitroandin vivomodels that have partly elucidated the molecular implications of these different genetic aberrations, the resulting tumor characteristics, and the potential of FGFRs as therapeutic targets for breast cancer treatment.
Neonatal Sweet Syndrome: A Potential Marker of Serious Systemic Illness
Authors: Gray Paul E. A. , Bock Vanessa , Ziegler David S. , Wargon Orli
Published: April 2012

Sweet syndrome is an inflammatory disease characterized by fever and painful erythematous plaques with a dermal neutrophilic infiltrate. It is most common in adults, where it is often parainflammatory or paraneoplastic, but is rare in children. We describe 3 cases of neonatal Sweet syndrome, including 1 patient who had myelodysplastic syndrome and immunodeficiency, the first report of a premalignancy underlying infantile Sweet syndrome. We reviewed the literature on patients presenting with neutrophilic dermatosis in the first 6 months of life. Of 20 cases, 6 had a probable viral etiology, 4 primary immunodeficiencies, 3 neonatal lupus syndrome, 1 gastrointestinal involvement, 1 HIV, and 5 probable genetic cases. Three of these had chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome, caused by mutations in the PSMB8 gene. Most children who presented within the first 6 weeks of life had either a serious underlying condition, such as primary immunodeficiency, or a genetic Sweet syndrome, with 2 fatalities among this latter group. The outcome of postinfective cases was good. Extracutaneous involvement was unusual, whereas postinflammatory scarring and cutis laxa occurred in a minority of patients. In conclusion, Sweet syndrome in the neonatal period often heralds a serious underlying disorder and requires thorough investigation.
Cumulative Social Risk and Obesity in Early Childhood
Authors: Suglia Shakira F. , Duarte Cristiane S. , Chambers Earle C. , Boynton-Jarrett Renée
Published: April 2012

OBJECTIVES:

The goal of this study was to examine the relationship between cumulative social adversity and childhood obesity among preschool-aged children (N = 1605) in the Fragile Families and Child Wellbeing Study.

METHODS:

Maternal reports of intimate partner violence, food insecurity, housing insecurity, maternal depressive symptoms, maternal substance use, and father’s incarceration were obtained when the child was 1 and 3 years of age. Two cumulative social risk scores were created by summing the 6 factors assessed at ages 1 and 3 years. Child height and weight were measured at 5 years of age. Logistic regression models stratified according to gender were used to estimate the association between cumulative social risk and obesity, adjusting for sociodemographic factors.

RESULTS:

Seventeen percent of children were obese at age 5 years, and 57% had at least 1 social risk factor. Adjusting for sociodemographic factors, girls experiencing high cumulative social risk (≥2 factors) at age 1 year only (odds ratio [OR]: 2.1 [95% confidence interval [CI]: 1.1–4.1]) or at 3 years only (OR: 2.2 [95% CI: 1.2–4.2]) were at increased odds of being obese compared with girls with no risk factors at either time point. Those experiencing high cumulative risk at age 1 and 3 years were not at statistically significant odds of being obese (OR: 1.9 [95% CI: 0.9–4.0]). No significant associations were noted among boys.

CONCLUSIONS:

There seems to be gender differences in the effects of cumulative social risk factors on the prevalence of obesity at 5 years of age. Understanding the social context of families could make for more effective preventive efforts to combat childhood obesity.
Health Risks of Oregon Eighth-Grade Participants in the “Choking Game”: Results From a Population-Based Survey
Authors: Ramowski Sarah K. , Nystrom Robert J. , Rosenberg Kenneth D. , Gilchrist Julie , Chaumeton Nigel R.
Published: April 2012

OBJECTIVE:

To examine the risk behaviors associated with participation in the “choking game” by eighth-graders in Oregon.

METHODS:

We obtained data from the 2009 Oregon Healthy Teens survey, a cross-sectional weighted survey of 5348 eighth-graders that questioned lifetime prevalence and frequency of choking game participation. The survey also included questions about physical and mental health, gambling, sexual activity, nutrition, physical activity/body image, exposure to violence, and substance use.

RESULTS:

Lifetime prevalence of choking game participation was 6.1% for Oregon eighth-graders, with no differences between males and females. Of the eighth-grade choking game participants, 64% had engaged in the activity more than once and 26.6% >5 times. Among males, black youth were more likely to participate than white youth. Among both females and males, Pacific Islander youth were much more likely to participate than white youth. Multivariate logistic regression revealed that sexual activity and substance use were significantly associated with choking game participation for both males and females.

CONCLUSIONS:

At >6%, the prevalence of choking game participation among Oregon youth is consistent with previous findings. However, we found that most of those who participate will put themselves at risk more than once. Participants also have other associated health risk behaviors. The comprehensive adolescent well visit, as recommended by the American Academy of Pediatrics, is a good opportunity for providers to conduct a health behavior risk assessment and, if appropriate, discuss the dangers of engaging in this activity.
Reference Ranges for Lymphocyte Counts of Neonates: Associations Between Abnormal Counts and Outcomes
Authors: Christensen Robert D. , Baer Vickie L. , Gordon Philip V. , Henry Erick , Whitaker Cody , Andres Robert L. , Bennett Sterling T.
Published: April 2012

BACKGROUND AND OBJECTIVE:

Both high and low lymphocyte counts at birth have been associated with adverse outcomes. However, the validity of defining a lymphocyte count as “abnormal” depends on having an accurate reference range. We established a reference range for neonatal lymphocyte counts by using multihospital data and used this to assess previously reported relationships between abnormal counts and early onset sepsis (EOS), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), periventricular leukomalacia, and birth asphyxia.

METHODS:

We first created a data set that excluded counts from neonates with diagnoses previously associated with abnormal lymphocyte counts. Then the complete data (counts excluded plus included in the reference range) were used to test associations between abnormal counts and EOS, IVH, ROP, periventricular leukomalacia, and outcomes after birth asphyxia.

RESULTS:

Lymphocyte counts were retrieved from 40 487 neonates, 10 860 of which were excluded from the reference range. A count >95th percentile was associated with EOS (2.07; 95% confidence interval [CI]: 1.80–2.38) and IVH ≥grade 3 (2.93; 95% CI: 1.83–4.71). A count <5th percentile was associated with EOS (odds ratio:1.24; 95% CI: 1.04–1.48), IVH ≥grade 3 (3.23; 95% CI: 1.95–5.36), and ROP ≥stage 3 (4.80: 95% CI: 2.38–9.66). Among 120 meeting criteria for birth asphyxia, those with a low count and a high nucleated red cell count had higher mortality (37% vs 11%, P = .001), more transfusions (P = .000), and more neurology referrals (P < .01).

CONCLUSIONS:

A reference range for lymphocytes can identify neonates with abnormal counts, which can be useful because these neonates are at higher risk for certain adverse outcomes.
Factors Related to Voluntary Parental Decision-Making in Pediatric Oncology
Authors: Miller Victoria A. , Nelson Robert M.
Published: April 2012

OBJECTIVE:

The aim of the current study was to examine demographic and contextual correlates of voluntariness in parents making research or treatment decisions for their children with cancer.

METHODS:

Participants included 184 parents of children with cancer who made a decision about enrolling the child in a research or treatment protocol within the previous 10 days. Parents completed questionnaires that assessed voluntariness, external influence by others, concern that the child’s care would be negatively affected if the parent did not agree, time pressure, information adequacy, and demographics.

RESULTS:

Lower perceived voluntariness was associated with lower education, male gender, minority status, and not having previous experience with a similar decision. Parents who reported lower voluntariness also perceived more external influence and time pressure, had more concern about the child’s care being negatively affected if they declined, and perceived that they had either too much or not enough information about the decision. In a multivariate regression, education, minority status, gender, external influence, and too little information remained significantly associated with voluntariness.

CONCLUSIONS:

Several groups of parents appear to be at risk for decreased voluntariness when making research or treatment decisions for their seriously ill children, including fathers, nonwhite parents, and those with less education. Parental voluntariness may be enhanced by helping parents to mitigate the effects of unhelpful or unwanted influences by others and ensuring that their information needs are met.
Diagnostic Imaging and Negative Appendectomy Rates in Children: Effects of Age and Gender
Authors: Bachur Richard G. , Hennelly Kara , Callahan Michael J. , Chen Catherine , Monuteaux Michael C.
Published: April 2012

BACKGROUND AND OBJECTIVES:

Diagnostic imaging is often used in the evaluation of children with possible appendicitis. The utility of imaging may vary according to a patient’s age and gender. The objectives of this study were (1) to examine the use of computed tomography (CT) and ultrasound for age and gender subgroups of children undergoing an appendectomy; and (2) to study the association between imaging and negative appendectomy rates (NARs) among these subgroups.

METHODS:

Retrospective review of children presenting to 40 US pediatric emergency departments from 2005 to 2009 (Pediatric Health Information Systems database). Children undergoing an appendectomy were stratified by age and gender for measuring the association between ultrasound and CT use and the outcome of negative appendectomy.

RESULTS:

A total of 8 959 155 visits at 40 pediatric emergency departments were investigated; 55 227 children had appendicitis. The NAR was 3.6%. NARs were highest for children younger than 5 years (boys 16.8%, girls 14.6%) and girls older than 10 years (4.8%). At the institutional level, increased rates of diagnostic imaging (ultrasound and/or CT) were associated with lower NARs for all age and gender subgroups other than children younger than 5 years, The NAR was 1.2% for boys older than 5 years without any diagnostic imaging.

CONCLUSIONS:

The impact of diagnostic imaging on negative appendectomy rate varies by age and gender. Diagnostic imaging for boys older than 5 years with suspected appendicitis has no meaningful impact on NAR. Diagnostic strategies for possible appendicitis should incorporate the risk of negative appendectomy by age and gender.
Effect of the Temperature of Annealing on the Performance of Fluorene and Bithiophene Copolymer in Bilayer Solar Cells
Authors: Yamamoto Natasha A. D. , Silva Daniel C. , Grova Isabel L. , Macedo Andreia G. , Marchiori Cleber F. N. , Koehler Marlus , Akcelrud Leni , Roman Lucimara S.
Published: April 2012

We have investigated the effect of temperature annealing on bilayer heterojunction solar cells based on poly[9,9’-hexyl-fluorene-alt-bithiophene] as active layer. Film morphology for different temperature annealing was probed by atomic force microscopy (AFM) and the values of roughness range from 0.59 up to 2.15 nm. The best photovoltaic performance was found for devices with active layer annealed at 200°C with power conversion efficiency (η) of 2.8 % while devices without annealing presented only 0.4%. This performance enhancement is attributed to the reduction of traps and increased hole mobility after the thermal annealing.
On the Existence of Ordered Phases of Encapsulated Diamondoids into Carbon Nanotubes
Authors: Legoas S. B. , dos Santos R. P. B. , Troche K. S. , Coluci V. R. , Galvao Douglas S.
Published: April 2012

We have investigated some diamondoids encapsulation into single walled carbon nanotubes (with diameters ranging from1.0 up to 2.2 nm) using fully atomistic molecular dynamics simulations. Diamondoids are the smallest hydrogen-terminated nanosized diamond-like molecules. Diamondois have been investigated for a large class of applications, ranging from oil industry to pharmaceuticals. Molecular ordered phases were observed for the encapsulation of adamantane, diamantane, and dihydroxy diamantanes. Chiral ordered phases, such as; double, triple, 4- and 5-stranded helices were also observed for those diamondoids. Our results also indicate that the modification of diamondoids through chemical functionalization with hydroxyl groups can lead to an enhancement of the molecular packing inside the carbon nanotubes in comparison to non-functionalized molecules. For larger diamondoids (such as, adamantane tetramers), we have not observed long-range ordering, but only a tendency of incomplete helical structural formation.
Engineering of Graphene Band Structure by Haptic Functionalization
Authors: Plachinda Paul , Solanki Raj , Evans David
Published: April 2012

We have employed first-principles density-functional calculations to study the electronic characteristics of graphene functionalized by metal-bis-arene and metal-carbonyl molecules. It is shown that functionalization with M-bis-arene (M(C6H6)@gr, M=Ti, V, Cr, Mn, Fe) molecules leads to an opening in the band gap of graphene (up to 0.81eV for the Cr derivative), and functionalization with M-carbonyl (M(CX)3@gr, X=O,N; M= Cr, Mn, Fe, Co) up to one 1eV for M=Cr and X=O, and therefore transforms graphene from a semi-metal to a semiconductor. The band gap induced by attachment of a metal atom topped by a functionalizing group is attributed to modification of π-conjugation and depends on the concentration of functionalizing molecules, metal’s and moiety’s electronic structure. This approach offers a means of tailoring the band structure of graphene and potentially its applications for future electronic devices.
Large-scale Solution Processable Graphene-based Thin Film Devices
Authors: Pesonen Markus , Majumdar Himadri S. , Kauppila Jussi , Lukkari Jukka , Österbacka Ronald
Published: April 2012

The purpose of this work is to fabricate large-scale solution processable graphene-based films from graphene oxide (GO) solution and to characterize the transport properties of these films. The graphene like film is produced by annealing of the GO film to form reduced graphene oxide (rGO) thin films. The conductive rGO thin films are useable as spacer layers in spin valves and as organic electrodes. Atomic Force Microscope (AFM) characterizations on the film thickness and morphology have been carried out and simple electrical transport studies performed on spin coated rGO thin films. We have fabricated rGO thin films ranging from few to tens of nanometers in thickness with conductivities in the order of 1-100 S/m. We also show that the morphology of the films play an important role in facilitating higher conductivities for rGO thin films.
Soft soil foundation improved by vacuum and surcharge loading
Authors: Indraratna Buddhima , Rujikiatkamjorn Cholachat , Kelly Richard , Buys Henk
Published: April 2012

The Pacific Highway has been upgraded to support the high transportation demand between Sydney and Brisbane, along the north-east coast of Australia. To avoid the traffic through the busy town of Ballina, a bypass route was designed to traverse on a floodplain consisting of very soft, highly compressible, saturated marine clays up to 30 m deep in certain locations. A vacuum-assisted surcharge load scheme in conjunction with prefabricated vertical drains was selected to reduce the required time to consolidate the deep subsoil layers. The design of the combined vacuum and surcharge fill system and the construction of the embankment are described, and a comparison of the performance between the combined vacuum and surcharge loading system with the conventional surcharge only system is highlighted. Field data are presented and interpreted to demonstrate how the embankments performed during construction in both vacuum and non-vacuum areas. Suitable design charts for vertical drains are presented and discussed with a worked example, considering both vertical and radial drainage.
Ground improvement: principles and applications in Asia
Authors: Raju Venu R. , Daramalinggam Jonathan
Published: April 2012

This paper presents an overview of various types of soils needing improvement and the various ground improvement techniques available. Factors influencing the choice of technique are discussed and this is followed by some applications of these techniques to different types of structure and soil conditions. Structures and facilities that have utilised ground improvement include roads and highways, railways, ports and airports, land reclamations, storage tanks, chemical plants, tunnels and residential buildings. The basis for choosing a particular technique for the project is explored, be it time, cost, technical performance or environmental considerations. It is shown that ground improvement is often the ideal foundation solution for such structures.
Pore pressure during stone column installation
Authors: Castro Jorge , Sagaseta César
Published: April 2012

During stone column installation, mainly by the vibro-displacement method, the vibrator displaces the native soil laterally as it is advancing into the ground. As a result, the surrounding soil and its properties are altered. The study of these installation effects, whether they are positive, negative or negligible, is nowadays one of the major concerns for an accurate design of ground improvement techniques. As a part of a wider research, a field test was set up to have a better understanding of the installation effects of stone columns. The site characterisation, the layout of the instrumentation and its results are presented here. Pore pressure was recorded by six piezometers in a quasi-continuum way during the installation of the nearby columns. The peaks of pore pressure during the vibrator penetration are analysed and compared with the analytical solution of the cavity expansion theory. In this case the dissipation of the pore pressure in the radial direction is very fast, and there is no remaining excess pore pressure after a few hours. Laboratory tests on soil samples were carried out before and after the column installation.