bluuebunny/crossref_metadata_2025 huggingface dataset:
An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy
Authors: Rifkin Lucas H , Stojadinovic Strahinja , Stewart Collin H , Song Kwang H , Maxted Michael C , Bell Marcus H , Kashefi Natalie S , Speiser Michael P , Saint-Cyr Michel , Story Michael D , Rohrich Rod J , Brown Spencer A , Solberg Timothy D
Published: May 2012

Purpose

To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury.

Methods

A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software.

Results

No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.

Conclusions

We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.
Recent advances and novel agents for gastrointestinal stromal tumor (GIST)
Authors: Lamba Gurpreet , Ambrale Samir , Lee Byung , Gupta Ridhi , Rafiyath Shamudheen M , Liu Delong
Published: May 2012

The discovery of CD117 mutation in almost all gastrointestinal stromal tumors (GISTs) marked a milestone. Other spindle cell neoplasms arising from the GI tract including lipoma, schwannoma, hemangioma, leiomyoma, and leiomyosarcoma are typically CD117-negative. GIST research and clinical care now represent a paradigm of translating discoveries in the molecular pathogenesis of cancer into highly effective targeted therapies that selectively inhibit etiologic “driver” pathways, leading to dramatically improved clinical outcomes. A series of investigations and trials are underway to develop novel and effective ways to treat patients with GIST. In this review, we discuss the highlights of recent advances and novel agents for GIST therapy.
Characterization of inhibitory T cells induced by an analog of type II collagen in an HLA-DR1 humanized mouse model of autoimmune arthritis
Authors: Kimata Masaru , Cullins David L , Brown Monica L , Brand David D , Rosloniec Edward F , Myers Linda K , Stuart John M , Kang Andrew H
Published: May 2012

Introduction

We used DR1 transgenic mice and covalently linked DR1 multimers to characterize analog-specific inhibitory T cells in collagen-induced arthritis (CIA). Because of the low numbers of antigen-specific T cells in wild-type mice, functional T-cell studies in autoimmune arthritis have been challenging. The use of T-cell receptor (TCR) transgenic mice has provided useful information, but such T cells may not represent the heterogeneous T-cell response that occurs in natural settings. Our focus was to develop tools to identify and characterize the population of immunoregulatory T cells induced in wild-type mice by an analog peptide of CII259-273, which contains amino acid substitutions at positions 263 (N) and 266 (D) (analog peptide A12).

Methods

DR1 multimers, developed by loading empty class II molecules with exogenous peptide, provide a method for visualizing antigen-specific T cells with flow cytometry. However, the low binding avidity of A12 for the major histocompatibility complex (MHC) made this strategy untenable. To overcome this problem, we generated DR1 multimers in which the analog peptide A12 was covalently linked, hoping that the low-avidity analog would occupy enough binding clefts to allow detection of the responsive T cells.

Results

Staining with the tetramer revealed that A12-specific T cells were readily detectable at 10 days after immunization. These CD4(+) T cells are a highly selective subset of the TCR repertoire and have a limited clonality. Analysis of cytokine expression showed that cells detected by tetramer (A12) expressed primarily suppressive cytokines (interleukin-4 (IL-4) and IL-10) in response to collagen, compared with control cells. Although they did not express Fox-p3, they were extremely effective in preventing and suppressing inflammatory arthritis.

Conclusions

In summary, our studies showed that the use of covalently linked multimers allows characterization of analog-specific T cells that are otherwise difficult to detect. The suppressive character of the analog-specific T-cell response suggests that these cells attenuate autoimmunity and differ significantly in phenotype from the inflammatory T cells predominantly found in arthritic joints. Such reagents will become powerful tools to study T-cell responses in RA patients in upcoming clinical trials.
Obese trauma patients are at increased risk of early hypovolemic shock: a retrospective cohort analysis of 1,084 severely injured patients
Authors: Nelson Jana , Billeter Adrian T , Seifert Burkhardt , Neuhaus Valentin , Trentz Otmar , Hofer Christoph K , Turina Matthias
Published: May 2012

Introduction

Morbid obesity and its consequences are considered risk factors for adverse outcome in trauma, although the pathophysiologic mechanisms are incompletely understood. The aim of this study was to compare initial resuscitation, treatment, and short-term outcome of severely injured patients by body mass index (BMI).

Methods

A total of 1,084 severely injured patients with an injury severity score of 16 or greater were enrolled between 1996 and 2009 and grouped according to BMI. Their course of treatment and in-hospital outcome were analyzed by univariate and multivariate comparison.

Results

Of these patients, 603 (55.6%) were of normal weight with a BMI between 18.5 and 24.9, 361 (33.3%) had BMI values between 25 and 29.9, and 90 patients (8.3%) were obese (BMI ≥ 30). Thirty patients (2.8%) had BMI levels below 18.5. All groups were comparable with respect to injury severity, initial resuscitation, and time to ICU admission. There was a tendency towards higher mortality in obese patients (mortality 24.4%) and also overweight patients (mortality 18.8%) when compared with patients with a normal BMI (mortality 16.6%). Obese patients showed the highest mortality on day 0 (8.9% vs. 2.8% in the normal-weight group, P = 0.023), mostly due to persistent shock (6.7%). When corrected for BMI, obese patients are provided significantly lower volumes of intravenous fluids during the initial resuscitation period.

Conclusion

In contrast to the mostly American literature, only a low percentage of trauma patients at a European trauma center are obese. These patients are at risk of higher mortality from persistent hemorrhagic shock in the initial phase after trauma, which may potentially be related to relative hypovolemia during the resuscitation period. In the later course of treatment, no significant differences exist with respect to specific complications, hospital stay, or in-hospital mortality.
Effects of increasing compliance with minimal sedation on duration of mechanical ventilation: a quality improvement intervention
Authors: Amaral Andre CKB , Kure Lars , Jeffs Angie
Published: May 2012

Introduction

In the past two decades, healthcare adopted industrial strategies for process measurement and control. In the industry model, care is taken to avoid minimal deviations from a standard. In healthcare there is scarce data to support that a similar strategy can lead to better outcomes. Briefly, when compliance is high, further attempts to improve uptake of a process are seldom made. Our intensive care unit (ICU) improved the compliance with minimizing sedation from a high baseline of 80.4% (95% CI: 66.9 to 90.2) to 96.2% (95% CI: 95.2 to 97.0) 12 months after a quality improvement initiative. We sought to measure whether this minute improvement in compliance led to a reduction in duration of mechanical ventilation.

Methods

We collected data on compliance with the process during 12 months. A trained data collector abstracted data from charts every other day. Our database contains data for length of mechanical ventilation, mortality, type of admission, and acute physiology and chronic health evaluation (APACHE) II scores for the 12 months before and after the process improvement.

To control for secular trends we used an interrupted-time series with adjustment for auto-correlation. We calculated the expected length of mechanical ventilation on each month by the end of the intervention period, and calculated the fitted value for the post-intervention months.

Results

We included 1556 patients. There was an immediate effect of the intervention (regression coefficient = -0.129, P value < 0.001) and the secular trend was a determinant of length of mechanical ventilation (regression coefficient = 0.010, P value = 0.004). The trend post-intervention was not significant (regression coefficient = 0.004, P value = 0.380).

The relative change in the length of mechanical ventilation was 14.5% (IQR 13.8% to 15.8%) and the total expected decrease in mechanical ventilation days was 502.7 days (95% CI 300.9 to 729.1) over one year.

Conclusions

In a system already working at high levels of compliance, outcomes can still be improved. Our intervention was successful in reducing the length of mechanical ventilation. ICUs should have a process of quality assurance in place to provide constant monitoring of key quality of care processes and correct deviations from the proposed standard.
Nonadherence to Oral Mercaptopurine and Risk of Relapse in Hispanic and Non-Hispanic White Children With Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group
Authors: Bhatia Smita , Landier Wendy , Shangguan Muyun , Hageman Lindsey , Schaible Alexandra N. , Carter Andrea R. , Hanby Cara L. , Leisenring Wendy , Yasui Yutaka , Kornegay Nancy M. , Mascarenhas Leo , Ritchey A. Kim , Casillas Jacqueline N. , Dickens David S. , Meza Jane , Carroll William L. , Relling Mary V. , Wong F. Lennie
Published: May 2012

Purpose

Systemic exposure to mercaptopurine (MP) is critical for durable remissions in children with acute lymphoblastic leukemia (ALL). Nonadherence to oral MP could increase relapse risk and also contribute to inferior outcome in Hispanics. This study identified determinants of adherence and described impact of adherence on relapse, both overall and by ethnicity.

Patients and Methods

A total of 327 children with ALL (169 Hispanic; 158 non-Hispanic white) participated. Medication event-monitoring system caps recorded date and time of MP bottle openings. Adherence rate, calculated monthly, was defined as ratio of days of MP bottle opening to days when MP was prescribed.

Results

After 53,394 person-days of monitoring, adherence declined from 94.7% (month 1) to 90.2% (month 6; P < .001). Mean adherence over 6 months was significantly lower among Hispanics (88.4% v 94.8%; P < .001), patients age ≥ 12 years (85.8% v 93.1%; P < .001), and patients from single-mother households (80.6% v 93.1%; P = .001). A progressive increase in relapse was observed with decreasing adherence (reference: adherence ≥ 95%; 94.9% to 90%: hazard ratio [HR], 4.1; 95% CI,1.2 to 13.5; P = .02; 89.9% to 85%: HR, 4.0; 95% CI, 1.0 to 15.5; P = .04; < 85%: HR. 5.7; 95% CI, 1.9 to 16.8; P = .002). Cumulative incidence of relapse (± standard deviation) was higher among Hispanics (16.5% ± 4.0% v 6.3% ± 2.2%; P = .02). Association between Hispanic ethnicity and relapse (HR, 2.6; 95% CI, 1.1 to 6.1; P = .02) became nonsignificant (HR, 1.8; 95% CI, 0.6 to 5.2; P = .26) after adjusting for adherence and socioeconomic status. At adherence rates ≥ 90%, Hispanics continued to demonstrate higher relapse, whereas at rates < 90%, relapse risk was comparable to that of non-Hispanic whites.

Conclusion

Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence—an observation currently under investigation.
Dual Effect of Metformin on Breast Cancer Proliferation in a Randomized Presurgical Trial
Authors: Bonanni Bernardo , Puntoni Matteo , Cazzaniga Massimiliano , Pruneri Giancarlo , Serrano Davide , Guerrieri-Gonzaga Aliana , Gennari Alessandra , Trabacca Maria Stella , Galimberti Viviana , Veronesi Paolo , Johansson Harriet , Aristarco Valentina , Bassi Fabio , Luini Alberto , Lazzeroni Matteo , Varricchio Clara , Viale Giuseppe , Bruzzi Paolo , DeCensi Andrea
Published: May 2012

Purpose

Metformin is associated with reduced breast cancer risk in observational studies in patients with diabetes, but clinical evidence for antitumor activity is unclear. The change in Ki-67 between pretreatment biopsy and post-treatment surgical specimen has prognostic value and may predict antitumor activity in breast cancer.

Patients and Methods

After tumor biopsy, we randomly allocated 200 nondiabetic women with operable breast cancer to either metformin 850 mg/twice per day (n = 100) or placebo (n = 100). The primary outcome measure was the difference between arms in Ki-67 after 4 weeks adjusted for baseline values.

Results

Overall, the metformin effect on Ki-67 change relative to placebo was not statistically significant, with a mean proportional increase of 4.0% (95% CI, −5.6% to 14.4%) 4 weeks apart. However, there was a different drug effect depending on insulin resistance (homeostasis model assessment [HOMA] index > 2.8, fasting glucose [mmol/L] × insulin [mU/L]/22.5; Pinteraction = .045), with a nonsignificant mean proportional decrease in Ki-67 of 10.5% (95% CI, −26.1% to 8.4%) in women with HOMA more than 2.8 and a nonsignificant increase of 11.1% (95% CI, −0.6% to 24.2%) with HOMA less than or equal to 2.8. A different effect of metformin according to HOMA index was noted also in luminal B tumors (Pinteraction = .05). Similar trends to drug effect modifications were observed according to body mass index (P = .143), waist/hip girth-ratio (P = .058), moderate alcohol consumption (P = .005), and C-reactive protein (P = .080).

Conclusion

Metformin before surgery did not significantly affect Ki-67 overall, but showed significantly different effects according to insulin resistance, particularly in luminal B tumors. Our findings warrant further studies of metformin in breast cancer with careful consideration to the metabolic characteristics of the study population.
Comparative Analysis of the Value of Allogeneic Hematopoietic Stem-Cell Transplantation in Acute Myeloid Leukemia With Monosomal Karyotype Versus Other Cytogenetic Risk Categories
Authors: Cornelissen Jan J. , Breems Dimitri , van Putten Wim L.J. , Gratwohl Alois A. , Passweg Jakob R. , Pabst Thomas , Maertens Johan , Beverloo H. Berna , van Marwijk Kooy Marinus , Wijermans Pierre W. , Biemond Bart J. , Vellenga Edo , Verdonck Leo F. , Ossenkoppele Gert J. , Löwenberg Bob
Published: May 2012

Purpose

To determine to what extent allogeneic hematopoietic stem-cell transplantation (alloHSCT) quantitatively reduces relapse in acute myeloid leukemia with monosomal karyotype (MK-AML) compared with alternative postremission therapy and how it compares with other cytogenetic subcategories.

Patients and Methods

Of 2,560 patients (younger than age 61 years) without core-binding factor abnormalities including 305 patients with MK-AML receiving first-line induction treatment, 1,975 patients (77%) achieved remission, and 1,588 received consolidation in the first complete remission (CR1) after two induction cycles. Consolidation treatment of 107 patients with MK-AML consisted of alloHSCT (n = 45), chemotherapy (n = 48), or autologous HSCT (n = 14).

Results

The 5-year overall survival after start of consolidation was 19% for patients with MK-AML who received alloHSCT and 9% for those who received chemotherapy or autoHSCT (P = .02). Relapse-free survival (RFS) at 5 years was 17% versus 7% (P = .003). Cox regression analysis was performed with alloHSCT as a time-dependent covariate. Hazard ratios (HRs) associated with alloHSCT for relapse and RFS were 0.30 (95% CI, 0.24 to 0.37; P < .001), and 0.52 (95% CI, 0.43 to 0.62; P < .001), respectively. HRs were similar in MK-AML and the other cytogenetic subgroups.

Conclusion

AlloHSCT, applied as consolidation in CR1, is associated with a significant reduction of relapse and improvement of survival in MK-AML, with the same relative reduction of relapse or death as in other cytogenetic risk categories.
Molecular Mechanisms of Estrogen Receptors' Suppression of Lipogenesis in Pancreatic β-Cells
Authors: Tiano Joseph P. , Mauvais-Jarvis Franck
Published: May 2012

The gonadal steroid, 17β-estradiol (E2), suppresses pancreatic islet fatty acid and glycerolipid synthesis and prevents β-cell failure in rodent models of type 2 diabetes. β-Cell estrogen receptors (ER) mediate these actions by suppressing the expression and enzymatic activity of fatty acid synthase (FAS). Here, we explored the mechanism of FAS suppression. We show that E2, and pharmacological agonists for ERα, ERβ, and the G protein-coupled ER, suppress mRNA and protein expression of the transcriptional regulators of FAS, namely, sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate response element binding protein (ChREBP) in insulin-secreting INS-1 cells. ER suppress SREBP1c and ChREBP mRNA and protein expression via an extranuclear localization. Using two mouse lines with pancreas-specific null deletion of either ERα or the signal transducer and activator of transcription 3 (STAT3), we show that ERα activation in vivo reduces SREBP1c and ChREBP mRNA expression via a direct islet action involving STAT3 activation. The master regulators of lipogenesis, liver X receptor (LXR) α and β, transcriptionally up-regulate SREBP1c and ChREBP. We find that activation of ERα, ERβ, and G protein-coupled ER suppresses LXR's mRNA expression in INS-1 cells. We also observe that activation of ERα in mouse islets in vivo suppresses LXR mRNA in a STAT3-dependent manner. Finally, we show that E2 also activates and uses AMP-activated protein kinase in INS-1 cells to suppress SREBP1c protein expression. This study identifies extranuclear ER pathways involving STAT3 and AMP-activated protein kinase in the genetic control of lipogenesis with therapeutic implications to protect β-cells in type 2 diabetes.
Transgenerational Effects of Prenatal Synthetic Glucocorticoids on Hypothalamic-Pituitary-Adrenal Function
Authors: Iqbal Majid , Moisiadis Vasilis G. , Kostaki Alisa , Matthews Stephen G.
Published: May 2012

Approximately 10% of pregnant women are at risk of preterm delivery and receive synthetic glucocorticoids (sGC) to promote fetal lung development. Studies have indicated that prenatal sGC therapy modifies hypothalamic-pituitary-adrenal (HPA) function in first-generation (F1) offspring. The objective of this study was to determine whether differences in HPA function and behavior are evident in the subsequent (F2) generation. Pregnant guinea pigs (F0) received betamethasone (BETA; 1 mg/kg) or saline on gestational d 40/41, 50/51, and 60/61. F1 females were mated with control males to create F2 offspring. HPA function was assessed in juvenile and adult F2 offspring. Locomotor activity was assessed in juvenile offspring. Analysis of HPA-related gene expression was undertaken in adult hippocampi, hypothalami, and pituitaries. Locomotor activity was reduced in F2 BETA males (P < 0.05). F2 BETA offspring displayed blunted cortisol response to swim stress (P < 0.05). After dexamethasone challenge, F2 BETA males and females displayed increased and decreased negative feedback, respectively. F2 BETA females had reduced pituitary levels of proopiomelanocortin (and adrenocorticotropic hormone), and corticotropin-releasing hormone receptor mRNA and protein (P < 0.05). F2 BETA males displayed increased hippocampal glucocorticoid receptor (P < 0.001), whereas in BETA females, hippocampal glucocorticoid receptor and mineralocorticoid receptor mRNA were decreased (P < 0.05). In conclusion, prenatal BETA treatment affects HPA function and behavior in F2 offspring. In F2 BETA females, pituitary function appears to be primarily affected, whereas hippocampal glucocorticoid feedback systems appear altered in both F2 BETA males and females. These data have clinical implication given the widespread use of repeat course glucocorticoid therapy in the management of preterm labour.
Early Origins of the Metabolic Syndrome: Role of Small Size at Birth, Early Postnatal Weight Gain, and Adult IGF-I
Authors: Kerkhof Gerthe F. , Leunissen Ralph W. J. , Hokken-Koelega Anita C. S.
Published: May 2012

Background:

The relationship between low birth weight and increased risk for metabolic syndrome (MetS) in later life has been frequently described, but mechanisms underlying this association remain unknown.

Methods:

In 280 young adults of the PROGRAM study, aged 18–24 yr, we investigated associations of birth weight, gain in weight for length during early life, and adult IGF-I sd score (SDS), with number of MetS components (ordinal regression analyses), prevalence of MetS components and MetS (logistic regression analyses), and other metabolic parameters (linear regression analyses). Revised criteria of the National Cholesterol Educational Program (Adult Treatment Panel III) were used to determine components of MetS. The other metabolic parameters were C-reactive protein, insulin sensitivity, trunk fat mass, total cholesterol, and low-density lipoprotein cholesterol.

Results:

More gain in weight for length SDS in the first 3 months of life was significantly associated with an increased number of MetS components [odds ratio (OR) = 1.34], prevalence of low high-density lipoprotein cholesterol (OR = 1.49), prevalence of MetS (OR = 2.51), increased C-reactive protein levels, and lower insulin sensitivity (P = 0.007) at the age of 21 yr. Low birth weight SDS was associated with lower insulin sensitivity (P = 0.036), but low birth weight SDS and adult IGF-I SDS were not significantly associated with any of the MetS components or MetS prevalence at 21 yr.

Conclusion:

Our study demonstrates that higher gain in weight for length in the first 3 months of life is associated with a higher prevalence of MetS at 21 yr, whereas low birth weight and low adult IGF-I are not.
Histone recognition and nuclear receptor co-activator functions ofDrosophilaCara Mitad, a homolog of the N-terminal portion of mammalian MLL2 and MLL3
Authors: Chauhan Chhavi , Zraly Claudia B. , Parilla Megan , Diaz Manuel O. , Dingwall Andrew K.
Published: May 2012

MLL2 and MLL3 histone lysine methyltransferases are conserved components of COMPASS-like co-activator complexes. In vertebrates, the paralogous MLL2 and MLL3 contain multiple domains required for epigenetic reading and writing of the histone code involved in hormone-stimulated gene programming, including receptor-binding motifs, SET methyltransferase, HMG and PHD domains. The genes encoding MLL2 and MLL3 arose from a common ancestor. Phylogenetic analyses reveal that the ancestral gene underwent a fission event in some Brachycera dipterans, including Drosophila species, creating two independent genes corresponding to the N- and C-terminal portions. In Drosophila, the C-terminal SET domain is encoded by trithorax-related (trr), which is required for hormone-dependent gene activation. We identified the cara mitad (cmi) gene, which encodes the previously undiscovered N-terminal region consisting of PHD and HMG domains and receptor-binding motifs. The cmi gene is essential and its functions are dosage sensitive. CMI associates with TRR, as well as the EcR-USP receptor, and is required for hormone-dependent transcription. Unexpectedly, although the CMI and MLL2 PHDf3 domains could bind histone H3, neither showed preference for trimethylated lysine 4. Genetic tests reveal that cmi is required for proper global trimethylation of H3K4 and that hormone-stimulated transcription requires chromatin binding by CMI, methylation of H3K4 by TRR and demethylation of H3K27 by the demethylase UTX. The evolutionary split of MLL2 into two distinct genes in Drosophila provides important insight into distinct epigenetic functions of conserved readers and writers of the histone code.
Globalization and U.S. Wages: Modifying Classic Theory to Explain Recent Facts
Authors: Haskel Jonathan , Lawrence Robert Z , Leamer Edward E , Slaughter Matthew J
Published: May 2012

This paper seeks to review how globalization might explain the recent trends in real and relative wages in the United States. We begin with an overview of what is new during the last 10–15 years in globalization, productivity, and patterns of U.S. earnings. To preview our results, we then work through four main findings: First, there is only mixed evidence that trade in goods, intermediates, and services has been raising inequality between more- and less-skilled workers. Second, it is more possible, although far from proven, that globalization has been boosting the real and relative earnings of superstars. The usual trade-in-goods mechanisms probably have not done this. But other globalization channels—such as the combination of greater tradability of services and larger market sizes abroad—may be playing an important role. Third, seeing this possible role requires expanding standard Heckscher–Ohlin trade models, partly by adding insights of more recent research with heterogeneous firms and workers. Finally, our expanded trade framework offers new insights on the sobering fact of pervasive real-income declines for the large majority of Americans in the past decade.
Why is the Teen Birth Rate in the United States So High and Why Does It Matter?
Authors: Kearney Melissa S , Levine Phillip B
Published: May 2012

Why is the rate of teen childbearing is so unusually high in the United States as a whole, and in some U.S. states in particular? U.S. teens are two and a half times as likely to give birth as compared to teens in Canada, around four times as likely as teens in Germany or Norway, and almost ten times as likely as teens in Switzerland. A teenage girl in Mississippi is four times more likely to give birth than a teenage girl in New Hampshire—and 15 times more likely to give birth as a teen compared to a teenage girl in Switzerland. We examine teen birth rates alongside pregnancy, abortion, and “shotgun” marriage rates as well as the antecedent behaviors of sexual activity and contraceptive use. We demonstrate that variation in income inequality across U.S. states and developed countries can explain a sizable share of the geographic variation in teen childbearing. Our reading of the totality of evidence leads us to conclude that being on a low economic trajectory in life leads many teenage girls to have children while they are young and unmarried. Teen childbearing is explained by the low economic trajectory but is not an additional cause of later difficulties in life. Surprisingly, teen birth itself does not appear to have much direct economic consequence. Our view is that teen childbearing is so high in the United States because of underlying social and economic problems. It reflects a decision among a set of girls to “drop-out” of the economic mainstream; they choose nonmarital motherhood at a young age instead of investing in their own economic progress because they feel they have little chance of advancement.
Jonathan Levin: 2011 John Bates Clark Medalist
Authors: Einav Liran , Tadelis Steve
Published: May 2012

Jonathan Levin, the 2011 recipient of the American Economic Association's John Bates Clark Medal, has established himself as a leader in the fields of industrial organization and microeconomic theory. Jon has made important contributions in many areas: the economics of contracts and organizations; market design; markets with asymmetric information; and estimation methods for dynamic games. Jon's combination of breadth and depth is remarkable, ranging from important papers in very distinct areas such as economic theory and econometric methods to applied work that seamlessly integrates theory with data. In what follows, we will attempt to do justice not only to Jon's academic work, but also try to sketch a broader portrait of Jon's other contributions to economics as a gifted teacher, dedicated advisor, and selfless provider of public goods.
Retrospectives: The Introduction of the Cobb–Douglas Regression
Authors: Biddle Jeff
Published: May 2012

At the 1927 meetings of the American Economic Association, Paul Douglas presented a paper entitled “A Theory of Production,” which he had coauthored with Charles Cobb. The paper proposed the now familiar Cobb–Douglas function as a mathematical representation of the relationship between capital, labor, and output. The paper's innovation, however, was not the function itself, which had originally been proposed by Knut Wicksell, but the use of the function as the basis of a statistical procedure for estimating the relationship between inputs and output. The paper's least squares regression of the log of the output-to-capital ratio in manufacturing on the log of the labor-to-capital ratio—the first Cobb–Douglas regression—was a realization of Douglas's innovative vision that a stable relationship between empirical measures of inputs and outputs could be discovered through statistical analysis, and that this stable relationship could cast light on important questions of economic theory and policy. This essay provides an account of the introduction of the Cobb–Douglas regression: its roots in Douglas's own work and in trends in economics in the 1920s, its initial application to time series data in the 1927 paper and Douglas's 1934 book The Theory of Wages, and the early reactions of economists to this new empirical tool.
From the Desk of the Managing Editor
Authors: Taylor Timothy
Published: May 2012

Editing isn't “teaching” and it isn't “research,” so in the holy trinity of academic responsibilities it is apparently bunched with faculty committees, student advising, and talks to the local Kiwanis club as part of “service.” Yet for many economists, editing seems to loom larger in their professional lives. After all, EconLit indexes more than 750 academic journals of economics, which require an ever-shifting group of editors, co-editors, and advisory boards to function. Roughly one-third of the books in the annotated listings at the back of each issue of the Journal of Economic Literature are edited volumes. Here is one take on the enterprise of editing from someone who has been sitting in the Managing Editor's chair for all 100 issues of the Journal of Economic Perspectives since before the first issue of the journal mailed in Summer 1987.
Gains from Trade when Firms Matter
Authors: Melitz Marc J , Trefler Daniel
Published: May 2012

The rising prominence of intra-industry trade and huge multinationals has transformed the way economists think about the gains from trade. In the past, we focused on gains that stemmed either from endowment differences (wheat for iron ore) or inter-industry comparative advantage (David Ricardo's classic example of cloth for port). Today, we focus on three sources of gains from trade: 1) love-of-variety gains associated with intra-industry trade; 2) allocative efficiency gains associated with shifting labor and capital out of small, less-productive firms and into large, more-productive firms; and 3) productive efficiency gains associated with trade-induced innovation. This paper reviews these three sources of gains from trade both theoretically and empirically. Our empirical evidence will be centered on the experience of Canada following its closer economic integration in 1989 with the United States—the largest example of bilateral intra-industry trade in the world—but we will also describe evidence for other countries.
Hydroalcoholic extracts of Indian medicinal plants can help in amelioration from oxidative stress through antioxidant properties
Authors: Sarkar Rhitajit , Mandal Nripendranath
Published: May 2012

The in vitro study of the antioxidant properties of the hydroalcoholic extracts of various Indian medicinal plants can logically help to develop a better and safer way of amelioration from oxidative stress. As aimed, the present study has been done to estimate and thereby conclude regarding the antioxidant activities of a few Indian medicinal plants, viz., Terminalia chebula, Terminalia belerica, Emblica officinalis, Caesalpinia crista, Cajanus cajan, and Tinospora cordifolia. The extracts of the plants have been subjected to the evaluation of antioxidant properties through scavenging assays for reactive oxygen species like superoxide, nitric oxide, peroxynitrite, hypochlorous acid, singlet oxygen, etc. and measurement of TEAC values and other phytochemical parameters. The phenolic and flavonoid contents of each plant have been found to be correlated to their individual antioxidant activity. The results showed the hydroalcoholic extracts of the plants were efficient indicators of their antioxidant capacity thus concreting their basis to be used as natural antioxidant.
Vulnerability Assessment of Electric Power Systems Through Identification and Ranking of Vulnerable Areas
Authors: Cepeda Jaime C. , Colome Delia G.
Published: May 2012

Power systems usually support disturbances which may initiate a cascading event that could cause total or partial blackouts. Vulnerability assessment is made in order to establish mechanisms that reduce the risk of blackouts. This paper presents a novel approach for assessing vulnerability of an Electric Power System. For this purpose, several indices, that reflect the health of the system, are calculated and the grid is partitioned in electric areas depending on bus electric coherency. The indices allow assessing four different symptoms of system stress such as voltage instability, poorly-damped power oscillations, frequency deviations outside limits, and overloads. The combination of these indices yields a vulnerability index using a fuzzy inference system. The vulnerability index is an indicator of the health of each electric area. The methodology is tested in the 39 bus New England test system via time domain simulations. The results show that vulnerability begins to develop in a specific region of the system, so its assessment and ranking can be used to coordinate and focus control actions that mitigate the consequences of the disturbances and reduce the risk of cascading events and system blackouts.
UPQC for Power Quality Improvement in DG Integrated Smart Grid Network - A Review
Authors: Khadem Md. Shafiuzzaman K. , Basu Malabika , Conlon Michael F.
Published: May 2012

Quality of power supply has become an important issue with the increasing demand of Distributed Generation (DG) systems either connected to the grid through some power electronics grid-tie inverters or to work in isolated (microgrid) mode towards the development of a smart grid network. In this paper a technical review of Integration of Unified Power Quality Conditioner (UPQC) in Distributed Generation Network has been presented. Though the primary task of UPQC is to minimize the grid voltage and load current disturbance along with the reactive and harmonic power compensation, additional functionalities like compensation of voltage interruption and active power transfer to the load and grid have also been identified. Connection methodologies with their pros and cons are also described. Recent improvements in capacity expansion techniques and future trends for the application of UPQC to cope up with the expanding DG capacity are also reviewed.
Search for Optimum Operating Conditions for a Water Purification Process Integrated to a Heat Transformer with Energy Recycling using Artificial Neural Network Inverse Solved by Genetic and Particle Swarm Algorithms
Authors: El Hamzaoui Youness , Ali Bassam , Hernandez J. Alfredo , Aburto Obed Cortez , Oubram Outmane
Published: May 2012

The coefficient of performance (COP) for a water purification process integrated to an absorption heat transformer with energy recycling was optimized using the artificial intelligence. The objective of this paper is to develop an integrated approach using artificial neural network inverse (ANNi) coupling with optimization methods: genetic algorithms (GAs) and particle swarm algorithm (PSA). Therefore, ANNi was solved by these optimization methods to estimate the optimal input variables when a COP is required. The paper adopts two cases studies to accomplish the comparative study. The results illustrate that the GAs outperforms the PSA. Finally, the study shows that the GAs based on ANNi is a better optimization method for control on-line the performance of the system, and constitutes a very promising framework for finding a set of “good solutions”.
A Self-organized MIMO-OFDM-based Cellular Network
Authors: Grünheid Rainer , Fellenberg Christian
Published: May 2012

This paper presents a system proposal for a self-organized cellular network, which is based on the MIMO-OFDM transmission technique. Multicarrier transmission, combined with appropriate beamforming concepts, yields high bandwidth-efficiency and shows a robust behavior in multipath radio channels. Moreover, it provides a fine and tuneable granularity of space-time-frequency resources. Using a TDD approach and interference measurements in each cell, the Base Stations (BSs) decide autonomously which of the space-time-frequency resource blocks are allocated to the Mobile Terminals (MTs) in the cell, in order to fulfil certain Quality of Service (QoS) parameters. Since a synchronized Single Frequency Network (SFN), i.e., a re-use factor of one is applied, the resource blocks can be shared adaptively and flexibly among the cells, which is very advantageous in the case of a non-uniform MT distribution.
Multi-Objective Topology Design of Industrial Ethernet Networks
Authors: Zhang Lei , Lampe Mattias , Wang Zhi
Published: May 2012

The objective of this paper is to investigate methods to guarantee the network performance of industrial Ethernet networks by an optimized topology design. The proposed approach differs from former works on network design by taking into account the specific requirements of industrial applications, the Quality of Service (QoS) related features of industrial Ethernet protocols, and the increasing network complexity in the industrial field. A multi-objective variable neighbourhood search algorithm (MOVNS) is presented offering a co-design method of physical topology and logical topology to satisfy the requirements of real-time capability, high reliability, and fast recovery time. The result analysis on simulation test cases shows the proposed algorithm can greatly improve the performance of industrial Ethernet networks at a moderate computational complexity.
Ethical and Epistemological Insights: A Case Study of Participatory Action Research with Young People
Authors: Chabot Cathy , Shoveller Jean A. , Spencer Grace , Johnson Joy L.
Published: May 2012

Debates over how to determine age of consent for youth to participate in research feature prominently in the practice of researchers, research ethics boards (REBs), and community decision makers working with youth. In particular, tensions can arise over how the ethical principles of beneficence, autonomy, and justice are interpreted and applied in research involving young people. We discuss our experiences obtaining ethical approval to conduct a participatory action research project involving youth and the differences of opinion we encountered regarding underage youth's capability to make informed consent. We suggest that researchers, REBs, and community decision makers all share a responsibility to conduct proactive outreach to youth participants, so that they are adequately informed of their rights related to research.
Using Data to Improve Surrogate Consent for Clinical Research with Incapacitated Adults
Authors: Abdoler Emily , Wendler David
Published: May 2012

Current practice relies on surrogates to enroll incapacitated adults in research. Yet, it is unclear to what extent this practice protects adults who have lost the ability to consent for themselves. To address this question, we conducted two literature searches to identify articles which report empirical data on three issues central to protecting adults who have lost the ability to consent: (1) adults' willingness to participate in research should they lose the ability to consent; (2) adults' willingness to allow a surrogate to make research decisions for them; and (3) the extent to which surrogates' enrollment decisions are consistent with their charges' preferences and values. These searches identified 21 articles, representing 20 distinct datasets. The data indicate that many adults are willing to participate in research should they lose the ability to consent, and many are willing to allow their family members to make research decisions for them if they become incapacitated. The data also raise concern that surrogates may be making research enrollment decisions that, in some cases, are inconsistent with their charges' preferences and values. These findings suggest that modifications to current practice should be considered to better protect adults who have lost the ability to consent. One option would be to require, in addition to surrogate permission and subject assent, sufficient evidence that enrollment is consistent with the individual's preferences and values.
Including Individuals with Memory Impairment in the Research Process: The Importance of Scales and Response Categories Used in Surveys
Authors: Krestar Maura L. , Looman Wendy , Powers Sara , Dawson Nicole , Judge Katherine S.
Published: May 2012

Several ethical considerations emerge when conducting research with memory-impaired individuals, including the individuals' ability to comprehend and accurately respond to survey questions. However, little empirical research exists on how to format surveys to decrease cognitive demands, thereby allowing researchers to more accurately survey this population. The current study presents data from structured interviews with 125 community-residing, memory-impaired older adults about their illness experience. The interview contained 14 scales varying in subjectivity, directionality, and response choice content. While objectivity did not affect participants' ability to use the full range of responses, participants with greater cognitive impairment tended to use simpler, dichotomous response categories, especially when questions had bidirectional response choices. Results suggest that memory-impaired individuals can participate in survey research, that such surveys should contain unidirectional frequency/amount items when possible, and that not all memory-impaired individuals will have difficulty completing surveys.
Williams-Beuren Syndrome Hypercalcemia: Is TRPC3 a Novel Mediator in Calcium Homeostasis?
Authors: Letavernier Emmanuel , Rodenas Anita , Guerrot Dominique , Haymann Jean-Philippe
Published: May 2012

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder associated with hypercalcemia of unknown origin. This syndrome results from the deletion of contiguous genes on chromosome 7, including the general transcription factor IIi gene. The general transcription factor IIi gene encodes TFII-I, which suppresses cell-surface accumulation of transient receptor potential C3 (TRPC3) channels, involved in calcium transport in lymphocytes. We describe the case of a patient with WBS with hypercalcemia associated with abnormal TRPC3 expression. Analysis of peripheral lymphocytes revealed a sharp increase in TRPC3 expression, compared with control patients. To investigate the potential role of TRPC3 in calcium homeostasis, we performed specific immunostaining on the intestine and the kidney, major calcium-regulating tissues. We provide the first demonstration that TRPC3 is expressed in normal digestive epithelium and renal tubules in control patients, and overexpressed in the intestine in the patient with WBS. Taken together, these data suggest that calcium metabolism abnormalities observed in WBS may be attributable to TFII-I haploinsufficiency and subsequent TRPC3 overexpression, thereby increasing both digestive and renal calcium absorption. This original observation prompts further investigation of TRPC3 as a novel actor of calcium homeostasis.
Preliminary Development of a Rapid Assessment of Supervision Scale for Young Children
Authors: Anderst Jim , Dowd M. Denise , Schnitzer Patricia , Tryon Tom
Published: May 2012

OBJECTIVES:

Standardized evaluation tools have been shown to reduce variability in care. The objective of this study was to develop a clinically oriented evaluation tool for the rapid assessment of the adequacy of supervision of a young child.

METHODS:

The Rapid Assessment of Supervision Scale (RASS) was developed via a 3-step process: (1) a modified Delphi survey of child abuse experts identified the most important characteristics for use in the assessment of adequacy of supervision; (2) the RASS was designed by using standardized definitions and the results of the Delphi survey; and (3) a total of 4 medical professionals evaluated 139 real case scenarios by using the RASS. Reliability and feasibility were assessed.

RESULTS:

Sixty-seven child abuse experts participated in round 2 of the Delphi process and 50 participated in round 3. The RASS included 9 supervision characteristics identified from the Delphi process, standardized definitions, and a scoring system. The interclass correlation coefficients for interrater reliability of the mean RASS scores and overall supervision classification were 0.63 (95% confidence interval: 0.56–0.70; P = .000) and 0.59 (95% confidence interval: 0.51–0.67; P = .000), respectively, indicating moderate to strong agreement. For intrarater reliability, correlation coefficients for mean RASS scores indicated moderate to high correlation (0.50–0.83). Correlation for overall classification of supervision ranged from low to high (0.27–0.80).

CONCLUSIONS:

The RASS scale has been shown to be efficient and, in a small sample, to have moderate to substantial interrater agreement. Further development could result in a tool that aids clinicians and researchers in the evaluation of supervision.
The Impact of Genomics on Pediatric Research and Medicine
Authors: Connolly John J. , Hakonarson Hakon
Published: May 2012

In this review, we discuss some of the most recent developments in genomics research and their relevance to the field of pediatrics. In particular, we examine 3 major approaches that are being used to identify genetic correlates of disease: genome-wide association studies, copy number variation studies, and next-generation sequencing. In the past few years, these approaches have yielded major insights into the causes and pathophysiology of a wide range of diseases but are also constrained by certain limitations. This review provides an overview of the genomic landscape in complex pediatric disorders and sets the stage for translating new discoveries into clinical practice, the future of genomic medicine.