bluuebunny/crossref_metadata_2025 huggingface dataset:
Network meta-analysis-highly attractive but more methodological research is needed
Authors: Li Tianjing , Puhan Milo A , Vedula Swaroop S , Singh Sonal , Dickersin Kay ,   The Ad Hoc Network Meta-analysis Methods Meeting Working Group
Published: August 2011

Network meta-analysis, in the context of a systematic review, is a meta-analysis in which multiple treatments (that is, three or more) are being compared using both direct comparisons of interventions within randomized controlled trials and indirect comparisons across trials based on a common comparator. To ensure validity of findings from network meta-analyses, the systematic review must be designed rigorously and conducted carefully. Aspects of designing and conducting a systematic review for network meta-analysis include defining the review question, specifying eligibility criteria, searching for and selecting studies, assessing risk of bias and quality of evidence, conducting a network meta-analysis, interpreting and reporting findings. This commentary summarizes the methodologic challenges and research opportunities for network meta-analysis relevant to each aspect of the systematic review process based on discussions at a network meta-analysis methodology meeting we hosted in May 2010 at the Johns Hopkins Bloomberg School of Public Health. Since this commentary reflects the discussion at that meeting, it is not intended to provide an overview of the field.
Biological interaction networks are conserved at the module level
Authors: Zinman Guy E , Zhong Shan , Bar-Joseph Ziv
Published: August 2011

Background

Orthologous genes are highly conserved between closely related species and biological systems often utilize the same genes across different organisms. However, while sequence similarity often implies functional similarity, interaction data is not well conserved even for proteins with high sequence similarity. Several recent studies comparing high throughput data including expression, protein-protein, protein-DNA, and genetic interactions between close species show conservation at a much lower rate than expected.

Results

In this work we collected comprehensive high-throughput interaction datasets for four model organisms (S. cerevisiae, S. pombe, C. elegans, and D. melanogaster) and carried out systematic analyses in order to explain the apparent lower conservation of interaction data when compared to the conservation of sequence data. We first showed that several previously proposed hypotheses only provide a limited explanation for such lower conservation rates. We combined all interaction evidences into an integrated network for each species and identified functional modules from these integrated networks. We then demonstrate that interactions that are part of functional modules are conserved at much higher rates than previous reports in the literature, while interactions that connect between distinct functional modules are conserved at lower rates.

Conclusions

We show that conservation is maintained between species, but mainly at the module level. Our results indicate that interactions within modules are much more likely to be conserved than interactions between proteins in different modules. This provides a network based explanation to the observed conservation rates that can also help explain why so many biological processes are well conserved despite the lower levels of conservation for the interactions of proteins participating in these processes.

Accompanying website: http://www.sb.cs.cmu.edu/CrossSP
Necrotizing sialometaplasia as a cause of a non-ulcerated nodule in the hard palate: a case report
Authors: Oliveira Alves Mônica Ghislaine , Kitakawa Dárcio , Carvalho Yasmin Rodarte , Guimarães Cabral Luiz Antonio , Almeida Janete Dias
Published: August 2011

Introduction

Necrotizing sialometaplasia is a benign, self-limiting and rare inflammatory disease which, on clinical and histological examination, mimics malignant neoplasms.

Case report

We report the case of a healthy 25-year-old Caucasian woman with a three-week history of a painless lump on her hard palate. Oral examination revealed a nodule consisting of two lobules on the right side that measured 2.5 cm. Her mucosa was normal in color and a fluctuant area was detected in the posterior region upon palpation. Our patient was submitted to incisional biopsy and histopathological examination. The histological diagnosis was necrotizing sialometaplasia. The lesion had healed spontaneously after 30 days, with observed signs of involution of the nodule.

Conclusion

Histopathological examination is necessary for the diagnosis of necrotizing sialometaplasia because the clinical features of this condition can mimic other diseases, particularly malignant neoplasms.
Development of Taenia pisiformis in golden hamster (Mesocricetus auratus)
Authors: Toral-Bastida Elizabeth , Garza-Rodriguez Adriana , Jimenez-Gonzalez Diego E , Garcia-Cortes Ramon , Avila-Ramirez Guillermina , Maravilla Pablo , Flisser Ana
Published: August 2011

The life cycle of Taenia pisiformis includes canines as definitive hosts and rabbits as intermediate hosts. Golden hamster (Mesocricetus auratus) is a rodent that has been successfully used as experimental model of Taenia solium taeniosis. In the present study we describe the course of T. pisiformis infection in experimentally infected golden hamsters. Ten females, treated with methyl-prednisolone acetate were infected with three T. pisiformis cysticerci each one excised from one rabbit. Proglottids released in faeces and adults recovered during necropsy showed that all animals were infected. Eggs obtained from the hamsters' tapeworms, were assessed for viability using trypan blue or propidium iodide stains. Afterwards, some rabbits were inoculated with eggs, necropsy was performed after seven weeks and viable cysticerci were obtained. Our results demonstrate that the experimental model of adult Taenia pisiformis in golden hamster can replace the use of canines in order to study this parasite and to provide eggs and adult tapeworms to be used in different types of experiments.
Randomized Phase III Trial of Sequential Adjuvant Chemoradiotherapy With or Without Erythropoietin Alfa in Patients With High-Risk Cervical Cancer: Results of the NOGGO-AGO Intergroup Study
Authors: Blohmer Jens-Uwe , Paepke Stefan , Sehouli Jalid , Boehmer Dirk , Kolben Martin , Würschmidt Florian , Petry Karl U. , Kimmig Rainer , Elling Dirk , Thomssen Christoph , von Minckwitz Gunter , Möbus Volker , Hinke Axel , Kümmel Sherko , Budach Volker , Lichtenegger Werner , Schmid Peter
Published: August 2011

Purpose

This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy.

Patients and Methods

Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events.

Results

The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups.

Conclusion

This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS.
Common Gene Rearrangements in Prostate Cancer
Authors: Rubin Mark A. , Maher Christopher A. , Chinnaiyan Arul M.
Published: August 2011

Prostate cancer is a common heterogeneous disease, and most patients diagnosed in the post prostate-specific antigen (PSA) era present with clinically localized disease, the majority of which do well regardless of treatment regimen undertaken. Overall, those with advanced prostate cancer at time of diagnosis do poorly after androgen withdrawal therapy. Understanding the biologic underpinning of prostate cancer is necessary to best determine the risk of disease progression and would be advantageous for the development of novel therapeutic approaches to impede or prevent disease. This review focuses on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a detailed understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease.
Androgen Receptor Rediscovered: The New Biology and Targeting the Androgen Receptor Therapeutically
Authors: Ryan Charles J. , Tindall Donald J.
Published: August 2011

Discoveries over the past decade suggest that castration-resistant prostate cancer (CRPC) is sensitive, but not resistant to, further manipulation of the androgen–androgen receptor (AR) axis. Several new therapies that target this axis have demonstrated clinical activity. In this article, preclinical and clinical findings occurring in the field of AR-targeted therapies are reviewed. Reviews of scientific and clinical development are divided into those occurring prereceptor (androgen production and conversion) and at the level of the receptor (AR aberrations and therapies targeting AR directly). Intracrine androgen production and AR amplification, among others, are among the principal aberrancies driving CRPC growth. Phase III data with abiraterone acetate and phase II data with MDV-3100, along with other similar therapies, confirm for the clinician that the scientific findings related to persistent AR signaling in a castrate milieu can be harnessed to produce significant clinical benefit for patients with the disease. Studies aimed at optimizing the timing of their use and exploring the mechanisms of resistance to these therapies are under way. The clinical success of therapies that directly target androgen synthesis as well as the most common aberrancies of the AR confirm that prostate cancer retains dependence on AR signaling, even in the castrate state.
End Points and Outcomes in Castration-Resistant Prostate Cancer: From Clinical Trials to Clinical Practice
Authors: Scher Howard I. , Morris Michael J. , Basch Ethan , Heller Glenn
Published: August 2011

New therapeutic approaches for castration-resistant prostate cancer (CRPC) introduce new treatment dilemmas: how best to sequence these options to maximally benefit patients, what tests to perform before and after treatment to assess disease status, and how to interpret the test results and use them to guide treatment. New and specific end points for different classes of drugs are needed to provide the information to guide these treatment decisions. In 2008, the Prostate Cancer Working Group 2 consensus criteria for early-phase clinical trials redefined clinical trial end points as first, to control, relieve, or eliminate disease manifestations present when treatment is started and second, to prevent or delay future disease manifestations. Disease manifestations include prostate-specific antigen (PSA), soft-tissue disease (nodes and/or viscera), bone disease (most common site of spread), and symptoms. Recent US Food and Drug Administration (FDA) approvals for CRPC therapies have been based on the prevent/delay end points that reflect unequivocal benefit to a patient: prolongation of life or reduction in skeletal-related events (SREs). For the practicing oncologist, the control/relieve/eliminate outcomes should serve primarily to inform the decision of whether to continue therapy. In this review, we consider individual end points such as PSA, imaging, and patient-reported outcomes in the context of the control/relieve/eliminate and prevent/delay framework. We address the time-to-event end points of metastasis prevention, SRE, time to progression, and overall survival in the context of regulatory approvals. We also discuss circulating tumor cells measured with the CellSearch assay, recently cleared by the FDA for monitoring CRPC.
Lifetime Risk and Sex Difference of Hepatocellular Carcinoma Among Patients With Chronic Hepatitis B and C
Authors: Huang Yen-Tsung , Jen Chin-Lan , Yang Hwai-I , Lee Mei-Hsuan , Su Jun , Lu Sheng-Nan , Iloeje Uchenna H. , Chen Chien-Jen
Published: August 2011

Purpose

Both hepatitis B (HBV) and C viruses (HCV) are causes of hepatocellular carcinoma (HCC), but lifetime risk and sex difference remain unclear. This study aimed to assess the lifetime risk and sex difference of HCC among patients with chronic HBV and/or HCV.

Methods

A prospective cohort of 23,820 residents of Taiwan age 30 to 65 years were enrolled from 1991 to 1992, with 477 instances of HCC occurring subsequently. Serum samples collected at enrollment were tested for seromarkers and viral load of HBV and HCV. Newly developed HCC was ascertained through computerized data linkage with national cancer registry and death certification systems.

Results

The cumulative lifetime (age 30 to 75 years) incidences of HCC for men and women positive for both HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV) were 38.35% and 27.40%; for those positive for HBsAg only, 27.38% and 7.99%; for those positive for anti-HCV only, 23.73% and 16.71%; and for those positive for neither, 1.55% and 1.03%, respectively. There was a significant male predominance in incidence of HCC for chronic HBV carriers but not for chronic carriers of HCV or both. Multivariate adjusted hazard ratio of developing HCC decreased with age in HBsAg-seropositive men but increased with age in anti-HCV–seropositive women. Among dual-infected participants, there was an inverse association between HBV and HCV viral load. Risk of HCC increased significantly with increasing viral load of HBV and HCV.

Conclusion

There exists a suppressive effect of HCV on HBV viral load. Individual and combined effects of the two viruses on HCC vary with sex and age.
Insulators form gene loops by interacting with promoters in Drosophila
Authors: Erokhin Maksim , Davydova Anna , Kyrchanova Olga , Parshikov Alexander , Georgiev Pavel , Chetverina Darya
Published: August 2011

Chromatin insulators are regulatory elements involved in the modulation of enhancer-promoter communication. The 1A2 and Wari insulators are located immediately downstream of the Drosophila yellow and white genes, respectively. Using an assay based on the yeast GAL4 activator, we have found that both insulators are able to interact with their target promoters in transgenic lines, forming gene loops. The existence of an insulator-promoter loop is confirmed by the fact that insulator proteins could be detected on the promoter only in the presence of an insulator in the transgene. The upstream promoter regions, which are required for long-distance stimulation by enhancers, are not essential for promoter-insulator interactions. Both insulators support basal activity of the yellow and white promoters in eyes. Thus, the ability of insulators to interact with promoters might play an important role in the regulation of basal gene transcription.
Non-redundant function of dystroglycan and β1 integrins in radial sorting of axons
Authors: Berti Caterina , Bartesaghi Luca , Ghidinelli Monica , Zambroni Desirée , Figlia Gianluca , Chen Zu-Lin , Quattrini Angelo , Wrabetz Lawrence , Feltri M. Laura
Published: August 2011

Radial sorting allows the segregation of axons by a single Schwann cell (SC) and is a prerequisite for myelination during peripheral nerve development. Radial sorting is impaired in models of human diseases, congenital muscular dystrophy (MDC) 1A, MDC1D and Fukuyama, owing to loss-of-function mutations in the genes coding for laminin α2, Large or fukutin glycosyltransferases, respectively. It is not clear which receptor(s) are activated by laminin 211, or glycosylated by Large and fukutin during sorting. Candidates are αβ1 integrins, because their absence phenocopies laminin and glycosyltransferase deficiency, but the topography of the phenotypes is different and β1 integrins are not substrates for Large and fukutin. By contrast, deletion of the Large and fukutin substrate dystroglycan does not result in radial sorting defects. Here, we show that absence of dystroglycan in a specific genetic background causes sorting defects with topography identical to that of laminin 211 mutants, and recapitulating the MDC1A, MDC1D and Fukuyama phenotypes. By epistasis studies in mice lacking one or both receptors in SCs, we show that only absence of β1 integrins impairs proliferation and survival, and arrests radial sorting at early stages, that β1 integrins and dystroglycan activate different pathways, and that the absence of both molecules is synergistic. Thus, the function of dystroglycan and β1 integrins is not redundant, but is sequential. These data identify dystroglycan as a functional laminin 211 receptor during axonal sorting and the key substrate relevant to the pathogenesis of glycosyltransferase congenital muscular dystrophies.
Biological and mathematical modeling of melanocyte development
Authors: Luciani Flavie , Champeval Delphine , Herbette Aurélie , Denat Laurence , Aylaj Bouchra , Martinozzi Silvia , Ballotti Robert , Kemler Rolf , Goding Colin R. , De Vuyst Florian , Larue Lionel , Delmas Véronique
Published: August 2011

We aim to evaluate environmental and genetic effects on the expansion/proliferation of committed single cells during embryonic development, using melanoblasts as a paradigm to model this phenomenon. Melanoblasts are a specific type of cell that display extensive cellular proliferation during development. However, the events controlling melanoblast expansion are still poorly understood due to insufficient knowledge concerning their number and distribution in the various skin compartments. We show that melanoblast expansion is tightly controlled both spatially and temporally, with little variation between embryos. We established a mathematical model reflecting the main cellular mechanisms involved in melanoblast expansion, including proliferation and migration from the dermis to epidermis. In association with biological information, the model allows the calculation of doubling times for melanoblasts, revealing that dermal and epidermal melanoblasts have short but different doubling times. Moreover, the number of trunk founder melanoblasts at E8.5 was estimated to be 16, a population impossible to count by classical biological approaches. We also assessed the importance of the genetic background by studying gain- and loss-of-function β-catenin mutants in the melanocyte lineage. We found that any alteration of β-catenin activity, whether positive or negative, reduced both dermal and epidermal melanoblast proliferation. Finally, we determined that the pool of dermal melanoblasts remains constant in wild-type and mutant embryos during development, implying that specific control mechanisms associated with cell division ensure half of the cells at each cell division to migrate from the dermis to the epidermis. Modeling melanoblast expansion revealed novel links between cell division, cell localization within the embryo and appropriate feedback control through β-catenin.
Helicobacter felis–Associated Gastric Disease in Microbiota-Restricted Mice
Authors: Schmitz Julia M. , Durham Carolyn G. , Schoeb Trenton R. , Soltau Thomas D. , Wolf Kyle J. , Tanner Scott M. , McCracken Vance J. , Lorenz Robin G.
Published: August 2011

Human Helicobacter pylori infection leads to multiple pathological consequences, including gastritis and adenocarcinoma. Although this association has led to the classification of H. pylori as a type 1 carcinogen, it is not clear if additional nonhelicobacter gastric microbiota play a role in these diseases. In this study, we utilized either specific pathogen-free C57BL/6 mice (B6.SPF) or mice colonized with altered Schaedler flora (B6.ASF) to evaluate the role of nonhelicobacter gastric microbiota in disease development after Helicobacter felis infection. Despite similar histological changes, H. felis persisted in B6.ASF stomachs, while H. felis could no longer be detected in the majority of B6.SPF mice. The B6.SPF mice also acquired multiple Lactobacillus spp. in their stomachs after H. felis infection. Our data indicate that potential mechanisms responsible for the ineffective H. felis clearance in the B6.ASF model include the absence of new gastric microbiota to compete for the gastric niche, the lack of expression of new gastric mucins, and a reduced ratio of H. felis–specific IgG2c:IgG1 serum antibodies. These data suggest that although H. felis is sufficient to initiate gastric inflammation and atrophy, bacterial eradication and the systemic immune response to infection are significantly influenced by pre-existing and acquired gastric microbiota.
Digital Microfluidic Platform for Multiplexing Enzyme Assays: Implications for Lysosomal Storage Disease Screening in Newborns
Authors: Sista Ramakrishna S , Eckhardt Allen E , Wang Tong , Graham Carrie , Rouse Jeremy L , Norton Scott M , Srinivasan Vijay , Pollack Michael G , Tolun Adviye A , Bali Deeksha , Millington David S , Pamula Vamsee K
Published: August 2011

BACKGROUND

Newborn screening for lysosomal storage diseases (LSDs) has been gaining considerable interest owing to the availability of enzyme replacement therapies. We present a digital microfluidic platform to perform rapid, multiplexed enzymatic analysis of acid α-glucosidase (GAA) and acid α-galactosidase to screen for Pompe and Fabry disorders. The results were compared with those obtained using standard fluorometric methods.

METHODS

We performed bench-based, fluorometric enzymatic analysis on 60 deidentified newborn dried blood spots (DBSs), plus 10 Pompe-affected and 11 Fabry-affected samples, at Duke Biochemical Genetics Laboratory using a 3-mm punch for each assay and an incubation time of 20 h. We used a digital microfluidic platform to automate fluorometric enzymatic assays at Advanced Liquid Logic Inc. using extract from a single punch for both assays, with an incubation time of 6 h. Assays were also performed with an incubation time of 1 h.

RESULTS

Assay results were generally comparable, although mean enzymatic activity for GAA using microfluidics was approximately 3 times higher than that obtained using bench-based methods, which could be attributed to higher substrate concentration. Clear separation was observed between the normal and affected samples at both 6- and 1-h incubation times using digital microfluidics.

CONCLUSIONS

A digital microfluidic platform compared favorably with a clinical reference laboratory to perform enzymatic analysis in DBSs for Pompe and Fabry disorders. This platform presents a new technology for a newborn screening laboratory to screen LSDs by fully automating all the liquid-handling operations in an inexpensive system, providing rapid results.
The Measurement of Platelet-Poor Plasma Serotonin: A Systematic Review of Prior Reports and Recommendations for Improved Analysis
Authors: Brand Theresa , Anderson George M
Published: August 2011

BACKGROUND

Recent reports of new and important roles for serotonin (5-hydroxytryptamine, 5-HT) in the periphery have substantially increased interest in measuring peripheral serotonin. Nearly all circulating serotonin is found within platelets and this pool has been assessed by measuring serotonin in whole blood or in platelet-rich plasma. Measurement of the much smaller but potentially critically important pool of human free plasma serotonin in platelet-poor plasma (PPP) has proven much more difficult, with a wide range of reference values reported.

CONTENT

To characterize the available data we carried out a systematic literature search of previous reports of PPP serotonin and attempted to determine the best estimate of true PPP serotonin concentration in humans. A total of 101 published reports that included PPP serotonin values in healthy controls were found and included in the summary statistical analyses. The distribution of PPP serotonin values demonstrated high skewness (+1.98), and the reported values ranged from 0.6 to 179 nmol/L, with a mean of 31.6 nmol/L, an SD of 38.9 nmol/L, and a median of 14.8 nmol/L.

Reported concentrations for human PPP or free plasma serotonin were highly discrepant, with most reports giving erroneously high values that should be disregarded. Inherent difficulties in selectively measuring the extremely low concentrations of serotonin present in PPP and in preparing PPP without contamination from platelet-derived serotonin contributed to the problem, as did the failure of researchers to compare their results with those from prior studies. There is a clear and pressing need for reference materials for the measurement of plasma (PPP) serotonin.
Les constructions attributives spécificationnelles portant sur les circonstances de l'action
Authors: Lauwers Peter
Published: August 2011

Cet article traite de deux types de phrases attributives spécificationnelles qui portent sur les circonstances de l'action, le premier étant construit avec un SN (L'heure de départ était3 heures), le second avec un constituant adverbial (L'heure de départ étaità 3 heures). Les deux types partagent bon nombre des propriétés des spécificationnelles, mais le second s'avàre le résultat d'un «crypto-clivage», c'est-à-dire de l'extraction d'un constituant sans marquage formel explicite. De ce fait, ce dernier constitue un cas intermédiaire entre les pseudo-clivées et les structures binominales, affichant différents degrés d'explicitation formelle et imposant des contraintes spécifiques.
I colori di Lucifero. Dante e il Pastore di Erma
Authors: Peri Massimo
Published: August 2011

I colori che contrassegnano le facce del Lucifero dantesco non sono tre ma quattro, poiché «tra bianca e gialla» designa aristotelicamente un colore composto che sembra ma non è. In realtà Dante usa un noto schema tetracromatico di origine pagana che informa tutta l'epistemologia del passato; è altresí altamente probabile, per non dire sicuro, che Dante conosca il Pastore di Erma, l'unico testo di tutta la tradizione europea che riferisce «i quattro colori» a un monstrum soprannaturale. Ciò getta qualche luce sui rapporti del Pastore con la cultura pagana, ma soprattutto pone inquietanti problemi teologici e psicologici che riguardano il trinitarismo di Dante e il dogma stesso della Trinità.
Effect of Antioxidants on Oxidative Stability and Quenching Performance of Soybean Oil and Palm Oil Quenchants
Authors: Belinato Gabriela , Canale Lauralice C. F. , Totten George E.
Published: August 2011

Although the quenching performance of various vegetable oils has been reported in the past, reports on the effect of antioxidants on the oxidative stability of these seed oils and on the initial quenching performance are less common. The objective of this work was to assess the effect of the relative oxidative stability of two readily available seed oils with significantly different degrees of saturation, soybean oil and palm oil, on quenching performance and to determine the ability of readily available antioxidants to stabilize these oils. In addition to the determination of relative oxidative stability, a further objective of this work was to assess the effect of antioxidants on the initial quenching performance of soybean oil and palm oil using a cooling curve analysis. The results of these studies are reported here.
From Cambridge to the Amazon in a Few Simple Steps
Authors: Janes Daniel E. , Swing Kelly , Cataldo Leah M.
Published: August 2011

Immersive experiences contribute to and enhance diverse curricula. Although more commonly applied to language curricula, student travel has much to offer science courses as well. Here, several options are described for secondary and college-level biology courses to participate in field-based study. The experience of one high school with one Amazonian field station is considered in detail, and several alternative opportunities for science-based student travel are provided as well. Traveling to the Amazon as an extension of classroom-based hypothesis generation and experimental design contextualized content for one high school biology course in a way that is powerful and repeatable.
The Case for Forensic Botany
Authors: Barratt Natalie M.
Published: August 2011

Would you rather solve a forensics puzzle or take a lab practical? An alternative to the traditional lab practical can be used to assess students' skills and knowledge in plant cell biology and anatomy. This forensics project challenges students to analyze evidence from crime scenarios. The instructor supplies the scenarios, evidence collected at the crime scene, and type specimens. The students prepare the evidence and type specimens for analysis by light and polarized light microscopy and then document and report their findings. Students enjoy this project and are able to demonstrate their skills as well as their knowledge.
Minimally Invasive Transaortic Repair of the Mitral Valve
Authors: Santana Orlando , Lamelas Joseph
Published: August 2011

Objective: We retrospectively evaluated the results of an edge-to-edge repair (Alfieri stitch) of the mitral valve performed via a transaortic approach in patients who were undergoing minimally invasive aortic valve replacement.

Methods: From January 2010 to September 2010, 6 patients underwent minimally invasive edge-to-edge repair of the mitral valve via a transaortic approach with concomitant aortic valve replacement. The patients were considered to be candidates for this procedure if they were deemed by the surgeon to be high-risk for a double valve procedure and if on preoperative transesophageal echocardiogram the mitral regurgitation jet originated from the middle portion (A2/P2 segments) of the mitral valve.

Results: There was no operative mortality. Mean cardiopulmonary bypass time was 137 minutes, and mean cross-clamp time was 111 minutes. There was a significant improvement in the mean mitral regurgitation grade, with a mean of 3.8 preoperatively and 0.8 postoperatively. The ejection fraction remained stable, with mean preoperative and postoperative ejection fractions of 43.3% and 47.5%, respectively. Follow-up transthoracic echocardiograms obtained at a mean of 33 days postoperatively (range, 8-108 days) showed no significant worsening of mitral regurgitation.

Conclusion: Transaortic repair of the mitral valve is feasible in patients undergoing minimally invasive aortic valve replacement.
Potential for Liver and Kidney Donation After Circulatory Death in Infants and Children
Authors: Shore Paul M. , Huang Rong , Roy Lonnie , Darnell Cindy , Grein Heather , Robertson Tammy , Thompson Lisa
Published: August 2011

OBJECTIVE:

To determine the potential effect of organ donation after circulatory death (DCD) on the number of kidney and liver donors in a PICU.

PATIENTS AND METHODS:

All deaths in the PICU of an academic, tertiary care children's hospital from May 1996 to April 2007 were retrospectively reviewed. Patient demographics, premortem physiology, and end-of-life circumstances were recorded and compared with basic criteria for potential organ donation. A sensitivity analysis was performed to examine the effect of more strict physiologic and time criteria as well as 3 different rates of consent for donation.

RESULTS:

There were 1389 deaths during 11 years; 634 children (46%) underwent withdrawal of life support, of whom 518 had complete data and were analyzed. There were 131 children (25% of those withdrawn, 9% of all deaths) who met basic physiologic and time criteria for organ donation (80 kidney; 107 liver). Consideration of consent rates in sensitivity analysis resulted in an estimated 24 to 85 organ donors, an increase of 28% to 99% over the 86 actual brain-dead donors during the same time period. Assuming historical rates of organ recovery, these DCD donors might have produced 30 to 88 additional kidneys and 8 to 56 additional livers, an increase of 21% to 60% in kidney donation and 13% to 80% in livers above the number of organs recovered from brain-dead donors.

CONCLUSIONS:

Although relatively few children may have been eligible for DCD, they might have increased the number of organ donors from our institution, depending greatly on consent rates. DCD merits additional discussion and exploration.
The Walking School Bus and Children's Physical Activity: A Pilot Cluster Randomized Controlled Trial
Authors: Mendoza Jason A. , Watson Kathy , Baranowski Tom , Nicklas Theresa A. , Uscanga Doris K. , Hanfling Marcus J.
Published: August 2011

OBJECTIVE:

To evaluate the impact of a “walking school bus” program on children's rates of active commuting to school and physical activity.

METHODS:

We conducted a pilot cluster randomized controlled trial among 4th-graders from 8 schools in Houston, Texas (N = 149). Random allocation to treatment or control conditions was at the school level. Study staff walked with children to and from school up to 5 days/week. Outcomes were measured the week before (time 1) and during weeks 4 and 5 of the intervention (time 2). The main outcome was the weekly rate of active commuting, and a secondary outcome was moderate-to-vigorous physical activity. Covariates included sociodemographics, distance from home to school, neighborhood safety, child BMI z score, parent self-efficacy/outcome expectations, and child self-efficacy for active commuting. A mixed-model repeated measures regression accounted for clustering by school, and stepwise procedures with backward elimination of nonsignificant covariates were used to identify significant predictors.

RESULTS:

Intervention children increased active commuting (mean ± SD) from 23.8% ± 9.2% (time 1) to 54% ± 9.2% (time 2), whereas control subjects decreased from 40.2% ± 8.9% (time 1) to 32.6% ± 8.9% (time 2) (P < .0001). Intervention children increased their minutes of daily moderate-to-vigorous physical activity from 46.6 ± 4.5 (time 1) to 48.8 ± 4.5 (time 2), whereas control children decreased from 46.1 ± 4.3 (time 1) to 41.3 ± 4.3 (time 2) (P = .029).

CONCLUSIONS:

The program improved children's active commuting to school and daily moderate-to-vigorous physical activity.
Parental Sedentary Restriction, Maternal Parenting Style, and Television Viewing Among 10- to 11-Year-Olds
Authors: Jago Russell , Davison Kirsten K. , Thompson Janice L. , Page Angie S. , Brockman Rowan , Fox Kenneth R.
Published: August 2011

OBJECTIVE:

To examine whether parenting styles or practices were associated with children's television (TV) viewing.

METHODS:

A total of 431 parent-child dyads (10- to 11-year-old children) from Bristol, United Kingdom, were included. Child and parent TV viewing were self-reported and categorized as <2, 2 to 4, or >4 hours/day. Children reported maternal parenting style (authoritarian, authoritative, or permissive). Child-reported maternal and paternal sedentary restriction scores were combined to create a family-level restriction score. Multinomial logistic regression was used to examine whether child TV viewing was predicted by parenting style or family restriction.

RESULTS:

A greater proportion of children with permissive mothers watched >4 hours of TV per day, compared with children with authoritarian or authoritative mothers (P = .033). A greater proportion of children for whom both parents demonstrated high restriction watched <2 hours of TV per day (P < .001). The risk of watching 2 to 4 hours (vs <2 hours) of TV per day was 2.2 times higher for children from low-restriction families (P = .010). The risk of watching >4 hours (vs <2 hours) of TV per day was 3.3 times higher for children from low-restriction families (P = .013). The risk of watching >4 hours of TV per day was 5.2 times higher for children with permissive (versus authoritative) mothers (P = .010).

CONCLUSIONS:

Clinicians need to talk directly with parents about the need to place limitations on children's screen time and to encourage both parents to reinforce restriction messages.
Clinical Prediction Rules for Children: A Systematic Review
Authors: Maguire Jonathon L. , Kulik Dina M. , Laupacis Andreas , Kuppermann Nathan , Uleryk Elizabeth M. , Parkin Patricia C.
Published: August 2011

CONTEXT:

The degree to which clinical prediction rules (CPRs) for children meet published standards is unclear.

OBJECTIVE:

To systematically review the quality, performance, and validation of published CPRs for children, compare them with adult CPRs, and suggest pediatric-specific changes to CPR methodology.

METHODS:

Medline was searched from 1950 to 2011. Studies were selected if they included the development of a CPR involving children younger than 18 years. Two investigators assessed study quality, rule performance, and rule validation as methodologic standards.

RESULTS:

Of 7298 titles and abstracts assessed, 137 eligible studies were identified. They describe the development of 101 CPRs addressing 36 pediatric conditions. Quality standards met in fewer than half of the studies were blind assessment of predictors (47%), reproducibility of predictors (18%), blind assessment of outcomes (42%), adequate follow-up of outcomes (36%), adequate power (43%), adequate reporting of results (49%), and 95% confidence intervals reported (36%). For rule performance, 48% had a sensitivity greater than 0.95, and 43% had a negative likelihood ratio less than 0.1. For rule validation, 76% had no validation, 17% had narrow validation, 8% had broad validation, and none had impact analysis performed. Compared with CPRs for adult health conditions, quality and rule validation seem to be lower.

CONCLUSIONS:

Many CPRs have been derived for children, but few have been validated. Relative to adult CPRs, several quality indicators demonstrated weaknesses. Existing performance standards may prove elusive for CPRs that involve children. CPRs for children that are more assistive and less directive and include patients' values and preferences in decision-making may be helpful.
Parent Involvement in Pain Management for NICU Infants: A Randomized Controlled Trial
Authors: Franck Linda S. , Oulton Kate , Nderitu Sue , Lim Magdalene , Fang Swee , Kaiser Anthony
Published: August 2011

OBJECTIVES:

To demonstrate feasibility and estimate the effect of an intervention to increase parental involvement in infant pain management in the NICU on parents' stress and postdischarge parenting competence and confidence.

METHODS:

The study involved a randomized controlled trial. Parents recruited from 4 NICUs were randomly assigned by site to receive (1) a pain information booklet and instruction on infant comforting techniques (n = 84 intervention) in addition to a generic NICU care booklet or (2) the generic NICU care booklet alone (n = 85 control). The primary outcome was postintervention Parent Stressor Scale: NICU (PSS:NICU) scores. Secondary outcomes included parent attitudes about infant pain, nursing pain assessment, and parenting competence and role attainment after discharge.

RESULTS:

No differences were found between groups in PSS:NICU scores. Significant differences favoring the intervention group were found for satisfaction with pain information, parents shown infant pain cues and comforting techniques, nursing pain assessment, and parent preference for involvement during painful procedures. Role attainment after discharge was higher for the intervention group than for the control group. Both the intervention and control groups highly valued attention to infant pain and wanted information and involvement.

CONCLUSIONS:

These results provide no evidence of a reduction in NICU-related stress for parents who receive an intervention to increase their understanding and involvement in infant pain management. However, parents in the intervention group were better prepared to take an active role in infant pain care and had more positive views about their role attainment in the postdischarge period.
Ethnic Variability in Persistent Asthma After In Utero Tobacco Exposure
Authors: Akuete Kwei , Oh Sam S. , Thyne Shannon , Rodriguez-Santana Jose R. , Chapela Rocio , Meade Kelley , Rodriguez-Cintron William , LeNoir Michael , Ford Jean G. , Williams L. Keoki , Avila Pedro C. , Burchard Esteban González , Tcheurekdjian Haig
Published: August 2011

BACKGROUND:

The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent.

OBJECTIVE:

To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children.

PATIENTS AND METHODS:

There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression.

RESULTS:

Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year.

CONCLUSIONS:

Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.
Simplified Prognostic Model in Patients with Oxaliplatin-Based or Irinotecan-Based First-Line Chemotherapy for Metastatic Colorectal Cancer: A GERCOR Study
Authors: Chibaudel Benoist , Bonnetain Franck , Tournigand Christophe , Bengrine-Lefevre Leila , Teixeira Luis , Artru Pascal , Desramé Jérôme , Larsen Annette K. , André Thierry , Louvet Christophe , Gramont Aimery
Published: August 2011

Learning Objectives

After completing this course, the reader will be able to: Describe prognostic factors in metastatic colorectal cancer.Estimate prognostic score with a simple model using only PS and LDH as parameters.

This article is available for continuing medical education credit at CME.TheOncologist.com

Background.

The present study was done to establish a prognostic model for patients and trials using an oxaliplatin-based or irinotecan-based first-line chemotherapy in metastatic colorectal cancer.

Patients and Methods.

Eight hundred three patients treated with FOLFOX or FOLFIRI in three prospective trials were randomly separated into learning (n = 535) and validation (n = 268) samples. Eleven baseline variables were evaluated in univariate and multivariate analysis as prognostic factors for overall survival, and a prognostic score was developed.

Results.

Independent prognostic factors identified in multivariate analysis for overall survival were performance status (PS) (p < .001), serum lactate dehydrogenase (LDH) (p < .001), and number of metastatic sites (p = .005). A prognostic score based on these three variables was found efficient (Harrell's C index 0.61). This new model was improved by selecting only PS and LDH (Harrell's C index 0.64). Three risk groups for death could be identified: a low-risk group (n = 184; median overall survival [OS] 29.8 months), an intermediate-risk group (n = 223; median OS 19.5 months), and a high-risk group (n = 128; median OS 13.9 months). Median survival for the low-, intermediate-, and high-risk groups were 26.8, 21.1, and 16.5 months, respectively, in the validation sample (Harrell's C index 0.63).

Conclusions.

Serum LDH level was the main prognostic factor in predicting survival, followed by WHO PS. We identified three risk groups for death depending on these two baseline parameters. This simple prognostic model can be useful for clinician's use and patient stratification in future clinical trials.
A simplified mechanically based model for predicting partially drained behaviour of penetrometers and shallow foundations
Authors: Houlsby G. T. , Cassidy M. J.
Published: August 2011

An analytical model is described for the behaviour of shallow foundations subjected to partially drained vertical penetration. The model is based on a simplified mechanical approach, allowing the calibration of model parameters for different foundation shape, size and soil conditions. As shown through simple examples, the resulting model exhibits (with some limitations) behaviour that closely resembles that obtained from geotechnical centrifuge experiments of a T-bar penetrometer and a circular spudcan footing installed at a variety of rates. An extension of the model to combined vertical and horizontal loading is also possible, although this would require further calibration with experimental data. The model retains a simplicity that may find application in the coupled analysis of offshore structures with foundations that are subjected to loading under different rates and drainage.
Factors driving mortality and growth at treeline: a 30‐year experiment of 92 000 conifers
Authors: Barbeito Ignacio , Dawes Melissa A. , Rixen Christian , Senn Josef , Bebi Peter
Published: August 2011

Understanding the interplay between environmental factors contributing to treeline formation and how these factors influence different life stages remains a major research challenge. We used an afforestation experiment including 92 000 trees to investigate the spatial and temporal dynamics of tree mortality and growth at treeline in the Swiss Alps. Seedlings of three high‐elevation conifer species (Larix decidua, Pinus mugo ssp. uncinata, and Pinus cembra) were systematically planted along an altitudinal gradient at and above the current treeline (2075 to 2230 m above sea level [a.s.l.]) in 1975 and closely monitored during the following 30 years. We used decision‐tree models and generalized additive models to identify patterns in mortality and growth along gradients in elevation, snow duration, wind speed, and solar radiation, and to quantify interactions between the different variables. For all three species, snowmelt date was always the most important environmental factor influencing mortality, and elevation was always the most important factor for growth over the entire period studied. Individuals of all species survived at the highest point of the afforestation for more than 30 years, although mortality was greater above 2160 m a.s.l., 50–100 m above the current treeline. Optimal conditions for height growth differed from those for survival in all three species: early snowmelt (ca. day of year 125–140 [where day 1 is 1 January]) yielded lowest mortality rates, but relatively later snowmelt (ca. day 145–150) yielded highest growth rates. Although snowmelt and elevation were important throughout all life stages of the trees, the importance of radiation decreased over time and that of wind speed increased. Our findings provide experimental evidence that tree survival and height growth require different environmental conditions and that even small changes in the duration of snow cover, in addition to changes in temperature, can strongly impact tree survival and growth patterns at treeline. Further, our results show that the relative importance of different environmental variables for tree seedlings changes during the juvenile phase as they grow taller.