bluuebunny/crossref_metadata_2025 huggingface dataset:
What Is Hidden in My Data? Practical Strategies to Reveal Yule–Simpson’s Paradox and Strengthen Research Quality in Health Education Research
Authors: Smith Matthew Lee , Goltz Heather H.
Published: August 2012

Yule-Simpson’s paradox (YSP) often occurs when statistical data are aggregated from multiple groups, research sites, or time points. If YSP-type effects go unrecognized, health educators risk yielding erroneous and spurious findings or misinterpreting study data. These paradoxical effects may be avoided if health researchers carefully consider strategies to avoid YSP at the onset of and throughout research studies. This article presents strategies to reduce or avoid YSP-type effects across multiple stages of the research process. A practical checklist is also provided to minimize the likelihood YSP will go unnoticed in research studies.
Mechanical and visco-elastic analysis of viscose fiber based needle-punched nonwoven fabric mat reinforced polymer composites: Part I
Authors: Patnaik Amar , Tejyan Sachin
Published: August 2012

Composites were fabricated using viscose fiber-based needlepunched nonwoven fabric mat as a reinforcement material, with varying mass per unit area of fabric mat (VS200 gsm, VS400 gsm and VS600 gsm) and varying fabric mat weight percentage. The effect of varying mass per unit area of fabric mat and weight percentage loading of these different fabric mats were reported on mechanical, physical and visco-elastic properties of needlepunched nonwoven reinforced epoxy composites. The mechanical and physical characterization was analyzed experimentally, and thermo-mechanical stability studied via the dynamic mechanical analysis, to measure the storage modulus (E′), loss modulus (E″) and damping factor (tan δ) of nonwoven fabric mat-reinforced composites over a temperature range of 20℃ to 200℃ at 1 Hz frequency. The storage modulus (E′) diminish with increase in temperature, with a significant fall in the temperature range 50–80℃ for all the composites. Loss modulus (E″) shows the variation from 60 MPa to 150 MPa, whereas glass transient temperature ( Tg) from the tan δ peaks, varies from 70℃ to 85℃. The comparative analysis shows that with the incorporation of nonwoven fabric mat weight percentage in composites, all mechanical and physical properties of composites improve significantly. These mechanical and physical properties are also improving with raise in mass per unit area of fabric mats from VS200 gsm to VS600 gsm.
Learning to Lead, Unscripted
Authors: Gagnon Suzanne , Vough Heather C. , Nickerson Robert
Published: August 2012

We argue that improvisational theatre training creates a compelling experience of co-creation through interaction and, as such, can be used to build a distinctive kind of leadership skills. Theories of leadership as relational, collaborative or shared are in pointed contrast to traditional notions of an individual “hero leader” who possesses the required answers, and whom others follow. Corresponding thinking on how to develop these newer forms has, to date, been relatively rare. In this article, we draw on recent research to identify three core principles for learning affiliative leadership. We then apply literature on improvisational theatre and its main skill areas to build a model of developing affiliative leadership, and illustrate the model through an improvisation workshop in which participants learn the skills and principles that it sets out. The model and workshop may serve as useful tools for those searching for methods to develop leadership in contemporary organizations.
Sphaeranthus indicus Induces Apoptosis Through Mitochondrial-Dependent Pathway in HL-60 Cells and Exerts Cytotoxic Potential on Several Human Cancer Cell Lines
Authors: Nahata Alok , Saxena Arpita , Suri Nitasha , Saxena Ajit Kumar , Dixit Vinod Kumar
Published: August 2012

Purpose. The study was designed to screen Sphaeranthus indicus, Ganoderma lucidum, and Urtica dioica for their anticancer activity against human cancer cell lines. Phytochemical screening of active extracts was also planned. Methods. Petroleum ether, ethanolic, and aqueous extracts of S indicus Linn, G lucidum P Karst, and U dioica Linn were subjected to cytotoxicity studies using 7 different cancer cell lines. Potent cytotoxicity was noted in petroleum ether extract of S indicus (SIP), which inhibited proliferation of various cancer cell lines. Growth inhibition was determined by sulforhodamine B assay. Two biochemical markers, namely β-sitosterol and 7-hydroxyfrullanolide were isolated and characterized using high-performance thin layer chromatography, melting point, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass analysis. Cytotoxicity of isolated β-sitosterol and 7-hydroxyfrullanolide were also determined. The IC50 of SIP was calculated in the HL-60 cells and was found to be 53 µg/mL. Furthermore, SIP induced apoptosis in human leukemia HL-60 cells as measured by several biological end points. Cell cycle analysis and change in mitochondrial membrane potential was quantified by flow cytometry. Subsequently, using annexin V/PI assay, proportion of cells actively undergoing apoptosis was determined. Changes in DNA were observed by DNA ladder assay. Results. SIP induced apoptotic bodies formation, induced DNA laddering, enhanced annexin-V-FITC binding of the cells, increased sub-G0 DNA fraction, and induced loss of mitochondrial membrane potential (ΔΨm) in HL-60 cells. SIP also elevated the caspase 3 and caspase 9 levels in the HL-60 cells, which clearly indicates the involvement of the intrinsic proteins in inducing apoptosis. Discussion. All the above parameters revealed that SIP induced apoptosis through the mitochondrial-dependent pathway in HL-60 cells. The criterion for anticancer activity in cytotoxicity assay was ≥70% growth inhibition at 100 µg/mL against at least 4 cell lines. As G lucidum and U dioica did not exhibit appreciable inhibitory activity against human cancer cell lines (less than 50%), they were not included in the study thereafter. The results established that SIP has apoptosis-inducing effect against HL-60 cells in vitro and is a promising candidate for further anticancer study. β-Sitosterol and 7-hydroxyfrullanolide can be considered to be potent anticancer compounds isolated from SIP on the basis of present studies.
Does Training of the Nondominant Upper Extremity Reduce the Surgeon’s Muscular Strain During Laparoscopy?
Authors: Nieboer Theodoor E. , Massa Mark , Weinans Martin J. N. , Vierhout Mark E. , Kluivers Kirsten B. , Stegeman Dick F.
Published: August 2012

Introduction. In laparoscopy, suboptimal ergonomics frequently lead to morbidity for surgeons. Physical complaints are more commonly reported on the dominant upper extremity. This may be the consequence of challenging laparoscopic tasks being easier to perform with the dominant side. The authors hypothesized that specific training of the nondominant upper extremity may equip this side better and lead to a more equal distribution of physical load. Materials and methods. Participants (medical doctors) were randomized to a 3-week training schedule or no training. The training program consisted of training the nondominant upper extremity. Participants were not allowed to train on a laparoscopic box or virtual reality trainer during the study period. Baseline and outcome measurements after 3 weeks were examined with the use of EMG measurements during a validated task on a laparoscopic box trainer. Muscle strain of the trapezius and deltoid muscles and effective alternation of brachioradial and abductor pollicis brevis muscles were used as outcome variables. Results. In all, 26 participants were included. EMG analysis revealed that participants in both intervention and control groups showed a decrease in muscle strain of trapezius and deltoid muscles. However, there were no significant differences between groups. Those in the intervention group showed significantly better alternation in the brachioradial muscle. Conclusion. Training the nondominant upper extremity leads to better alternated use of lower-arm muscles during a validated box trainer task. Repeating the task after 3 weeks led to less muscle tension in the trapezius and deltoid muscles.
Nanoclay modified with nonionic surfactants as reinforcement for styrene–butadiene rubber
Authors: Rozik Nehad N , El-Nashar Doaa E , Younan Adel F
Published: August 2012

In this study, the preparation of organobentonite using nonionic surfactants has been investigated. The organophilic clay has been characterized using Fourier transform infrared spectroscopy, transmission electron microscopy and X-ray diffraction. The X-ray results suggest that the inter-gallery spacing of pristine clay increases with the incorporation of the surfactant where the nonionic surfactants intercalate into the interlamellar space of bentonite. The nanocomposites of SBR with various amounts of organoclay were prepared through the two roll mill. The X-ray diffraction peak observed for the modified clay also disappears in the rubber nanocomposites at low loading indicating exfoliation. Excellent improvement in mechanical properties, such as tensile strength, elongation at break and hardness, are observed on incorporation of the nanoclay. The results could be explained with the help of morphology, dispersion of the nanofiller and its interaction with the rubber. The formation of the intercalated nanocomposites was also indicated by scanning electron microscopy, used to study the surface morphology, which showed that the distribution of the organoclay in the polymer matrix was homogeneous. Thermal gravimetric analysis is also examined and the outcome of these results is discussed in this paper.
Utilizing the integrated difference of two survival functions to quantify the treatment contrast for designing, monitoring, and analyzing a comparative clinical study
Authors: Zhao Lihui , Tian Lu , Uno Hajime , Solomon Scott D , Pfeffer Marc A , Schindler Jerald S , Wei Lee Jen
Published: August 2012

Background

Consider a comparative, randomized clinical study with a specific event time as the primary end point. In the presence of censoring, standard methods of summarizing the treatment difference are based on Kaplan–Meier curves, the logrank test, and the point and interval estimates via Cox’s procedure. Moreover, for designing and monitoring the study, one usually utilizes an event-driven scheme to determine the sample sizes and interim analysis time points.

Purpose

When the proportional hazards (PHs) assumption is violated, the logrank test may not have sufficient power to detect the difference between two event time distributions. The resulting hazard ratio estimate is difficult, if not impossible, to interpret as a treatment contrast. When the event rates are low, the corresponding interval estimate for the ‘hazard ratio’ can be quite large due to the fact that the interval length depends on the observed numbers of events. This may indicate that there is not enough information for making inferences about the treatment comparison even when there is no difference between two groups. This situation is quite common for a postmarketing safety study. We need an alternative way to quantify the group difference.

Methods

Instead of quantifying the treatment group difference using the hazard ratio, we consider an easily interpretable and model-free parameter, the integrated survival rate difference over a prespecified time interval, as an alternative. We present the inference procedures for such a treatment contrast. This approach is purely nonparametric and does not need any model assumption such as the PHs. Moreover, when we deal with equivalence or noninferiority studies and the event rates are low, our procedure would provide more information about the treatment difference. We used a cardiovascular trial data set to illustrate our approach.

Results

The results using the integrated event rate differences have a heuristic interpretation for the treatment difference even when the PHs assumption is not valid. When the event rates are low, for example, for the cardiovascular study discussed in this article, the procedure for the integrated event rate difference provides tight interval estimates in contrast to those based on the event-driven inference method.

Limitations

The design of a trial with the integrated event rate difference may be more complicated than that using the event-driven procedure. One may use simulation to determine the sample size and the estimated duration of the study.

Conclusions

The procedure discussed in this article can be a useful alternative to the standard PHs method in the survival analysis.
The effects of 5-fluorouracil on flexor tendon healing by using a biodegradable gelatin, slow releasing system: experimental study in a hen model
Authors: Karaaltin M. V. , Ozalp B. , Dadaci M. , Kayıkcıoglu A. , Kecik A. , Oner F.
Published: August 2012

This study investigated the effects of 5-fluorouracil in a slow-release biodegradable gelatin system on tendon healing. Gelatin blocks prepared in a size of 10 × 20 × 1 mm were loaded with 10, 20, and 30 mg of 5–fluorouracil, and 30 adult white Leghorn chickens were used. The tendons to the third and fourth toes were severed and repaired. The extremities were casted for three weeks. After sacrifice, the tendons were examined histologically and biomechanically for adhesion formation. The 10 mg-loaded gelatin group showed a decrease in adhesion formation when compared with the operative control group; the 20 and 30 mg groups showed signs of severe inflammation. Low doses of 5-fluorouracil applied via a slow-release gelatin system reduced adhesion formation in flexor tendon healing.
Successful ICU Care of a 14-Year-Old With Total Artificial Circulation Using Two Ventricular Assist Devices for 118 Days
Authors: Silverman Richard B. , Quinn Sean M.
Published: August 2012

Within the first year following orthotopic heart transplantation, the patient is at risk of graft failure, rejection, and infection. Late mortality is often due to allograph vasculopathy. Most of the patients with primary graft failure will usually recover with temporary mechanical ventricular assist support; however, on occasion the patient must be retransplanted. For the patient who suffers primary graft failure necessitating explanation and bridging until a new suitable graft is found, there are several total artificial heart options. However, in the pediatric population these options are limited. The authors’ surgical colleagues were able to fashion a paracorporeal total artificial heart constructed with 2 ventricular assist devices. In this case report, the authors discuss a pediatric patient who had to be explanted and supported for an extended amount of time. This article describes the incidence of cardiomyopathy in juvenile rheumatoid arthritis patients, the choice of extracorporeal membrane oxygenation/extracorporeal complete life support versus ventricular assist devices for support, the major causes of primary graft failure, and the authors’ experience in caring for an adolescent with such a device for a protracted length of time (118 days).
Incentives for Healthy Behaviors
Authors: Hall Allyson G. , Lemak Christy Harris , Landry Amy Yarbrough , Duncan R. Paul
Published: August 2012

Objective: Engaging individuals in their own health care proves challenging for policy makers, health plans, and providers. Florida Medicaid introduced the Enhanced Benefits Rewards (EBR) program in 2006, providing financial incentives as rewards to beneficiaries who engage in health care seeking and healthy behaviors. Methods: This study analyzed beneficiary survey data from 2009 to determine predictors associated with awareness of and participation in the EBR program. Results: Non-English speakers, those in a racial and ethnic minority group, those with less than a high school education, and those with limited or no connection to a health care provider were associated with lower awareness of the program. Among those aware of the program, these factors were also associated with reduced likelihood of engaging in the program. Individuals in fair or poor health were also less likely to engage in an approved behavior. Individuals who speak Spanish at home and those without a high school diploma were more likely than other groups to spend their earned program credits. Conclusions: Findings underscore the fact that initial engagement in such a program can prove challenging as different groups are not equally likely to be aware of or participate in an approved activity or redeem a credit. Physicians may play important roles in encouraging participation in programs to incentivize healthy behaviors.
Career and Technical Education
Authors: Blowe Eleanor Hearst , Price Ted
Published: August 2012

The No Child Left Behind legislation was signed into law to ensure children in the United States receive quality education and learn the skills needed to be successful. Career and technical education (CTE) is not mentioned in the legislation, which suggests that more CTE courses may be dropped from high school master schedules, which makes the topic a concern for educational leaders. The purpose of this study was to investigate the academic performance of CTE completers and non-CTE completers in the Commonwealth of Virginia on the standards of learning English reading and mathematics assessments as well as cohort graduation rates. Findings indicate that statistically ( p < .05), CTE completers had higher mathematics and Grade 11 English reading pass rates as well as higher cohort graduation rates than those of non-CTE completers.
Disciplinary Images of “Korean-Ness”
Authors: Moon Seungho
Published: August 2012

The purpose of this study is to generate complicated conversations about identity and culture with an examination of various panoptic technologies, including separation, invisibility, control, and productivity. Drawn from Foucault’s panopticism, the author examines how discipline operates as a controlling power in several Korean institutions of schools, the seminary, and the military. This autobiographical self-reflexive research explores disciplinary images of “Korean-ness,” which has been discursively and materially constructed and embodied via panoptic technologies. These counter-narratives do not support for the advancement of the universalized version of the “Korean” identity. Rather, the author theorizes Korean identity as discursive practices in modern power structures, while dealing with the “political ‘double bind’” of (a) individualization through instruments of discipline and (b) the reinforcement of Confucian ideal of proper human relationships. This article provides educators with a lens to examine the ways in which disciplinary power/knowledge operates to control students’ ways of thinking, behaving, and living, in relation to “self,” “others,” and institutions. By opening possibilities to examine cultural identity beyond discovering “true” self, the author emphasizes the analyses of power in its examination of cultural sameness/difference in multicultural curriculum studies.
Families Coping With Disability Due to Brain Injury in Oman
Authors: Al-Adawi Samir , Al-Busaidi Zakiya , Al-Adawi Sara , Burke David T.
Published: August 2012

Little is known about primary caregivers’ perceptions of a relative who has sustained abruptly personality changes following traumatic brain injury (TBI) in non-Western populations. To help appreciate the diversity of perceptions of disability outside the biomedical setting, the present discourse highlights how primary caregivers construct sequelae of TBI in Oman. A qualitative case study with an ethnographic approach was conducted using semistructured interviews. Six caregivers from two families of patients with TBI were interviewed to garner description of lay beliefs within a rural community in Oman related to the experience of family carers with a relative suffering from a brain injury. The caregivers interpreted their relatives’ predicament through the local idiom of distress involving belief in spirit infestation and ensorcellment. The present qualitative study supports the view that when a family member incurs neurobehavioral impairments, the coping processes of the caregivers are heavily influenced by cultural concepts of health and illness. Such attributions are discussed in terms of specific sociocultural forces within Omani society.
A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia
Authors: Radich Jerald P. , Kopecky Kenneth J. , Appelbaum Frederick R. , Kamel-Reid Suzanne , Stock Wendy , Malnassy Greg , Paietta Elisabeth , Wadleigh Martha , Larson Richard A. , Emanuel Peter , Tallman Martin , Lipton Jeff , Turner A. Robert , Deininger Michael , Druker Brian J.
Published: August 2012

Tyrosine kinase inhibitor therapy with imatinib (IM), dasatinib (DAS), or nilotinib is very effective in chronic-phase chronic myeloid leukemia. Two hundred fifty-three patients with newly diagnosed chronic-phase chronic myeloid leukemia were randomized to IM 400 mg/day or DAS 100 mg/day. The proportion of patients achieving a complete cytogenetic remission rate was superior with DAS (84% vs 69%), as was the 12-month molecular response by the proportions of patients achieving > 3-log, > 4-log, and > 4.5-log reduction in BCR-ABL transcript levels. Overall and progression-free survival was similar in the 2 arms. Among patients who achieved hematologic CR, 3-year relapse-free survival was 91% with DAS and 88% with IM 400 mg. Grade 3 and 4 toxicities were most commonly hematologic, including thrombocytopenia in 18% and 8% of DAS and IM patients, respectively. DAS induced more complete cytogenetic response and deeper molecular responses after 12 months, compared with IM 400 mg, and with a median follow-up of 3.0 years there have been very few deaths, relapses, or progressions in the 2 arms. In summary, DAS compared with IM appeared to have more short-term cytogenetic and molecular response, more hematologic toxicity, and similar overall survival. This trial is registered at www.clinicaltrials.gov as NCT00070499.
Erythrocyte density in sickle cell syndromes is associated with specific clinical manifestations and hemolysis
Authors: Bartolucci Pablo , Brugnara Carlo , Teixeira-Pinto Armando , Pissard Serge , Moradkhani Kamran , Jouault Hélène , Galacteros Frederic
Published: August 2012

Dense, dehydrated red blood cells (DRBCs) are a characteristic feature of sickle-cell disease (SCD). DRBCs play a role in the pathophysiology of SCD acute and chronic organ damage because of heightened tendency to undergo polymerization and sickling because of their higher hemoglobin S concentration. Relations between red cell density (assessed with phthalate density-distribution profile method) and several hematologic, biochemical, genetic parameters, and clinical manifestations were studied in a large cohort of homozygous patients. The percentage of DRBCs was significantly higher in patients who experienced skin ulcers, priapism, or renal dysfunction. Presence of α-thalassemia deletions was associated with fewer DRBCs. A multivariable analysis model showed DRBCs to be positively associated with hemolytic parameters such as lactate dehydrogenase and bilirubin and negatively with fetal hemoglobin. The percentage of DRBCs decreased by 34% at 6 months of hydroxycarbamide (xydroxyurea) therapy. Thus, DRBCs are associated with specific clinical manifestations and biologic markers and may be a useful addition to the biologic and clinical evaluation of patients with SCD, because they can easily be measured in a hematocrit tube.
Exhaled volatile organic compounds for phenotyping chronic obstructive pulmonary disease: a cross-sectional study
Authors: Basanta Maria , Ibrahim Baharudin , Dockry Rachel , Douce David , Morris Mike , Singh Dave , Woodcock Ashley , Fowler Stephen J
Published: August 2012

Background

Non-invasive phenotyping of chronic respiratory diseases would be highly beneficial in the personalised medicine of the future. Volatile organic compounds can be measured in the exhaled breath and may be produced or altered by disease processes. We investigated whether distinct patterns of these compounds were present in chronic obstructive pulmonary disease (COPD) and clinically relevant disease phenotypes.

Methods

Breath samples from 39 COPD subjects and 32 healthy controls were collected and analysed using gas chromatography time-of-flight mass spectrometry. Subjects with COPD also underwent sputum induction. Discriminatory compounds were identified by univariate logistic regression followed by multivariate analysis: 1. principal component analysis; 2. multivariate logistic regression; 3. receiver operating characteristic (ROC) analysis.

Results

Comparing COPD versus healthy controls, principal component analysis clustered the 20 best-discriminating compounds into four components explaining 71% of the variance. Multivariate logistic regression constructed an optimised model using two components with an accuracy of 69%. The model had 85% sensitivity, 50% specificity and ROC area under the curve of 0.74. Analysis of COPD subgroups showed the method could classify COPD subjects with far greater accuracy. Models were constructed which classified subjects with ≥2% sputum eosinophilia with ROC area under the curve of 0.94 and those having frequent exacerbations 0.95. Potential biomarkers correlated to clinical variables were identified in each subgroup.

Conclusion

The exhaled breath volatile organic compound profile discriminated between COPD and healthy controls and identified clinically relevant COPD subgroups. If these findings are validated in prospective cohorts, they may have diagnostic and management value in this disease.
Accuracy of RNA-Seq and its dependence on sequencing depth
Authors: Cai Guoshuai , Li Hua , Lu Yue , Huang Xuelin , Lee Juhee , Müller Peter , Ji Yuan , Liang Shoudan
Published: August 2012

Background

The cost of DNA sequencing has undergone a dramatical reduction in the past decade. As a result, sequencing technologies have been increasingly applied to genomic research. RNA-Seq is becoming a common technique for surveying gene expression based on DNA sequencing. As it is not clear how increased sequencing capacity has affected measurement accuracy of mRNA, we sought to investigate that relationship.

Result

We empirically evaluate the accuracy of repeated gene expression measurements using RNA-Seq. We identify library preparation steps prior to DNA sequencing as the main source of error in this process. Studying three datasets, we show that the accuracy indeed improves with the sequencing depth. However, the rate of improvement as a function of sequence reads is generally slower than predicted by the binomial distribution. We therefore used the beta-binomial distribution to model the overdispersion. The overdispersion parameters we introduced depend explicitly on the number of reads so that the resulting statistical uncertainty is consistent with the empirical data that measurement accuracy increases with the sequencing depth. The overdispersion parameters were determined by maximizing the likelihood. We shown that our modified beta-binomial model had lower false discovery rate than the binomial or the pure beta-binomial models.

Conclusion

We proposed a novel form of overdispersion guaranteeing that the accuracy improves with sequencing depth. We demonstrated that the new form provides a better fit to the data.
Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells
Authors: Arutyunyan Anna , Stoddart Sonia , Yi Sun-ju , Fei Fei , Lim Min , Groffen Paula , Feldhahn Niklas , Groffen John , Heisterkamp Nora
Published: August 2012

Background

Acute lymphoblastic leukemia (ALL) cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs).

Results

We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the presence of drug-treated ALL cells. These mitotically inactivated MEFs showed few changes in gene expression, but a family of sequences of which transcription is significantly increased was identified. A sequence related to this family, which we named cassini, was selected for further characterization. We found that cassini was highly upregulated in drug-treated ALL cells. Analysis of RNAs from different normal mouse tissues showed that cassini expression is highest in spleen and thymus, and can be further enhanced in these organs by exposure of mice to bacterial endotoxin. Heat shock, but not other types of stress, significantly induced the transcription of this locus in ALL cells. Transient overexpression of cassini in human 293 embryonic kidney cells did not increase the cytotoxic or cytostatic effects of chemotherapeutic drugs but provided some protection. Database searches revealed that sequences highly homologous to cassini are present in rodents, apicomplexans, flatworms and primates, indicating that they are conserved in evolution. Moreover, CASSINI RNA was induced in human ALL cells treated with vincristine. Surprisingly, cassini belongs to the previously reported murine family of γ-satellite/major satellite DNA sequences, which were not known to be present in other species.

Conclusions

Our results show that the transcription of at least one member of these sequences is regulated, suggesting that this has a function in normal and transformed immune cells. Expression of these sequences may protect cells when they are exposed to specific stress stimuli.
A nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female survivors of childhood cancer: design and methodological challenges
Authors: Overbeek Annelies , van den Berg Marleen H , Kremer Leontien CM , van den Heuvel-Eibrink Marry M , Tissing Wim JE , Loonen Jacqueline J , Versluys Birgitta , Bresters Dorine , Kaspers Gertjan JL , Lambalk Cornelis B , van Leeuwen Flora E , van Dulmen-den Broeder Eline
Published: August 2012

Background

Advances in childhood cancer treatment over the past decades have significantly improved survival, resulting in a rapidly growing group of survivors. However, both chemo- and radiotherapy may adversely affect reproductive function. This paper describes the design and encountered methodological challenges of a nationwide study in the Netherlands investigating the effects of treatment on reproductive function, ovarian reserve, premature menopause and pregnancy outcomes in female childhood cancer survivors (CCS), the DCOG LATER-VEVO study.

Methods

The study is a retrospective cohort study consisting of two parts: a questionnaire assessing medical, menstrual, and obstetric history, and a clinical assessment evaluating ovarian and uterine function by hormonal analyses and transvaginal ultrasound measurements. The eligible study population consists of adult female 5-year survivors of childhood cancer treated in the Netherlands, whereas the control group consists of age-matched sisters of the participating CCS. To date, study invitations have been sent to 1611 CCS and 429 sister controls, of which 1215 (75%) and 333 (78%) have responded so far. Of these responders, the majority consented to participate in both parts of the study (53% vs. 65% for CCS and sister controls respectively). Several challenges were encountered involving the study population: dealing with bias due to the differences in characteristics of several types of (non-) participants and finding an adequately sized and well-matched control group. Moreover, the challenges related to the data collection process included: differences in response rates between web-based and paper-based questionnaires, validity of self-reported outcomes, interpretation of clinical measurements of women using hormonal contraceptives, and inter- and intra-observer variation of the ultrasound measurements.

Discussion

The DCOG LATER-VEVO study will provide valuable information about the reproductive potential of paediatric cancer patients as well as long-term survivors of childhood cancer. Other investigators planning to conduct large cohort studies on late effects may encounter similar challenges as those encountered during this study. The solutions to these challenges described in this paper may be useful to these investigators.

Trial registration

NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922
Reovirus exerts potent oncolytic effects in head and neck cancer cell lines that are independent of signalling in the EGFR pathway
Authors: Twigger Katie , Roulstone Victoria , Kyula Joan , Karapanagiotou Eleni M , Syrigos Konstantinos N , Morgan Richard , White Christine , Bhide Shreerang , Nuovo Gerard , Coffey Matt , Thompson Brad , Jebar Adel , Errington Fiona , Melcher Alan A , Vile Richard G , Pandha Hardev S , Harrington Kevin J
Published: August 2012

Background

Reovirus exploits aberrant signalling downstream of Ras to mediate tumor-specific oncolysis. Since ~90% squamous cell carcinomas of the head and neck (SCCHN) over-express EGFR and SCCHN cell lines are sensitive to oncolytic reovirus, we conducted a detailed analysis of the effects of reovirus in 15 head and neck cancer cell lines. Both pre- and post-entry events were studied in an attempt to define biomarkers predictive of sensitivity/resistance to reovirus. In particular, we analysed the role of EGFR/Ras signalling in determining virus-mediated cytotoxicity in SCCHN.

Methods

To test whether EGFR pathway activity was predictive of increased sensitivity to reovirus, correlative analyses between reoviral IC50 by MTT assay and EGFR levels by western blot and FACS were conducted. Inhibition or stimulation of EGFR signalling were analysed for their effect on reoviral oncolysis by MTT assay, and viral growth by TCID50 assay. We next analysed the effects of inhibiting signalling downstream of Ras, by specific inhibitors of p38MAPK, PI3-K or MEK, on reoviral killing examined by MTT assay. The role of PKR in reoviral killing was also determined by blockade of PKR using 2-aminopurine and assaying for cell survival by MTT assay. The apoptotic response of SCCHN to reovirus was examined by western blot analysis of caspase 3 cleavage.

Results

Correlative analyses between reoviral sensitivity and EGFR levels revealed no association. Intermediate sub-viral and core particles showed the same infectivity/cytotoxicity as intact reovirus. Therefore, sensitivity was not determined by cell entry. In 4 cell lines, oncolysis and viral growth were both unaffected by inhibition or stimulation of EGFR signalling. Inhibition of signalling downstream of Ras did not abrogate reoviral oncolysis and, in addition, modulation of PKR using 2-aminopurine did not alter reovirus sensitivity in resistant cell lines. Caspase 3 cleavage was not detected in infected cells and oncolysis was observed in pan-caspase inhibited cells.

Conclusions

In summary, reovirus is potently oncolytic in a broad panel of SCCHN cell lines. Attempts to define sensitivity/resistance by analysis of the EGFR/Ras/MAPK pathway have failed to provide a clear predictive biomarker of response. Further analysis of material from in vitro and clinical studies is ongoing in an attempt to shed further light on this issue.
Fecal calprotectin levels are higher in rural than in urban Chinese infants and negatively associated with growth
Authors: Liu Jin-Rong , Sheng Xiao-Yang , Hu Yan-Qi , Yu Xiao-Gang , Westcott Jamie E , Miller Leland V , Krebs Nancy F , Hambidge K Michael
Published: August 2012

Background

Fecal calprotectin (FC) is an established simple biomarker of gut inflammation. To examine a possible relationship between linear growth and gut inflammation, we compared fecal calprotectin levels in 6 month old infants from poor rural vs affluent urban families.

Methods

The project was a cross-sectional comparison of FC from rural and urban populations in China. The relationship between length-for-age Z-score (LAZ) and FC concentrations were also compared. Single fecal samples were assayed for FC using EK-CAL ELISA kits.

Results

The age of subjects for both locations was 6.1 ± 0.2 mo; all were apparently healthy. The mean ± SD of the LAZ for the rural and urban infants were −0.6 ± 0.9 and 0.4 ± 0.9, respectively. FC had a non-normal distribution. The median FC of 420.9 and 140.1 μg/g for rural and urban infants, respectively, were significantly different (P < 0.0001). For the rural group, linear regression analysis showed that an increase in FC of 100 μg/g was associated with a decrease of 0.06 in LAZ.

Conclusion

FC levels were significantly elevated in the rural infants and high concentrations accounted for approximately one-third of the low LAZ scores of these infants.
Prenatal polychlorinated biphenyl exposure is associated with decreased gestational length but not birth weight: archived samples from the Child Health and Development Studies pregnancy cohort
Authors: Kezios Katrina L , Liu Xinhua , Cirillio Piera M , Kalantzi Olga I , Wang Yunzhu , Petreas Myrto X , Park June-Soo , Bradwin Gary , Cohn Barbara A , Factor-Litvak Pam
Published: August 2012

Background

Polychlorinated biphenyls (PCBs), known endocrine disruptors, were banned in 1979 but persist in the environment. Previous studies are inconsistent regarding prenatal exposure to PCBs and pregnancy outcomes. We investigated associations between prenatal exposure to PCBs and gestational length and birth weight.

Methods

In a sample of 600 infants (born between 1960 and 1963) randomly selected from Child Health and Development Studies participants followed through adolescence we measured 11 PCB congeners in maternal post partum sera (within three days of delivery). Length of gestation was computed from the reported first day of the last menstrual period (LMP) and delivery date. Linear regression was used to estimate associations between PCB exposure and gestational age and birth weight, adjusting for potential confounders. PCBs were grouped according to hypothesized biological action (1b (sum of weak phenobarbital inducers), 2b (sum of limited dioxin activity), and 3 (sum of CYP1A and CYP2b inducers)) or degree of ortho- substitution (mono, di, tri). Secondary analyses examined associations between total PCB exposure and exposure to individual congeners.

Results

Each unit increase in mono-ortho substituted PCBs was associated with a 0.30 week decrease (95% confidence interval (CI) -0.59, -0.016), corresponding to a 2.1 (95% CI −4.13, -0.11) day decrease in length of gestation. Similar associations were estimated for di-ortho substituted PCBs, (1.4 day decrease; (95% CI −2.9, 0.1)) and group 3 PCBs (0.84 day decrease; (95% CI −1.8, 0.11). We found similar associations in congener specific analyses and for the sum of congeners.

Conclusions

Our study provides new evidence that PCB exposure shortens length of gestation in humans. This may have public health implications for population exposures.
Non-occupational exposure to paint fumes during pregnancy and risk of congenital anomalies: a cohort study
Authors: Hjortebjerg Dorrit , Andersen Anne-Marie Nybo , Garne Ester , Raaschou-Nielsen Ole , Sørensen Mette
Published: August 2012

Background

Occupational exposure to organic solvents during the 1sttrimester of pregnancy has been associated with congenital anomalies. Organic solvents are also used in the home environments in paint products, but no study has investigated the effect of such exposure in a general population.

Methods

We studied associations between residential exposure to paint fumes during the 1sttrimester of pregnancy and predefined subgroups of congenital anomalies, using data from the Danish National Birth Cohort (DNBC). During 2001 and 2003, a total of 20 103 pregnant women, enrolled in the DNBC, were interviewed in the 30thweek of gestation about the use of paint in their residence during pregnancy. By the end of first trimester, information about smoking habits, alcohol consumption and occupation were collected. Information on congenital anomalies was obtained from national registers. Associations were examined by estimating odds ratios (OR) using logistic regression.

Results

In total 1404 women (7%) had been exposed to paint fumes during the 1sttrimester of pregnancy and 1086 children were diagnosed with congenital anomalies; 73 children with congenital anomalies had been exposed to paint fumes in utero. Exposure to paint fumes seemed positively associated with congenital anomalies of the nervous system (OR 2.19, 95% confidence interval (CI) 0.76 to 6.32), ear, face and neck (OR 2.15, 95% CI 0.84 to 5.55) and the renal system (OR 2.16, 95% CI 1.02 to 4.58) after adjustment for maternal age, smoking, alcohol consumption and occupational solvent exposure. Congenital anomalies in the remaining subgroups were not associated with the exposure.

Conclusions

Our results suggest that in the general population, exposure to paint fumes during the 1sttrimester of pregnancy may increase the risk of some types of congenital anomalies, but the findings need to be confirmed.
The bidirectional interation between pancreatic cancer and diabetes
Authors: Li Junhui , Cao Gang , Ma Qingyong , Liu Han , Li Wei , Han Liang
Published: August 2012

The bidirectional interation between pancreatic cancer (PanCa) and diabetes has been confirmed by epidemiological studies, which provide evidence-based medical support for further research into the mechanisms involved in the interaction. We reviewed the literature regarding the role of diabetes in the generation and progression of PanCa and the mechanism by which PanCa induces diabetes for its malignant progression. The effect of antidiabetic drugs on the occurrence and prognosis of PanCa was also reviewed. Diabetes may directly promote the progression of PanCa by pancreatic duct enlargement and hypertension, as well as by enabling an increased tumor volume. Hyperinsulinemia, insulin resistance, cytokines, hyperglycemia and genotype change are also important factors in the progression of PanCa with diabetes. Hyperglycemia may be the first clinical manifestation and is helpful in the early diagnosis of PanCa. Furthermore, antidiabetic drugs can have different effects on the occurrence and prognosis of PanCa. The bidirectional interation between PanCa and diabetes is involved in the occurrence, proliferation, invasion, metastasis and prognosis of PanCa with diabetes. The discovery of biomarkers for the early diagnosis of PanCa, as well as the novel usage of metformin for its antitumor effects and determining the potential mechanisms of these effects, may be the next direction for PanCa research and treatment.
Chloroplasts-mediated biosynthesis of nanoscale Au-Ag alloy for 2-butanone assay based on electrochemical sensor
Authors: Zhang Yixia , Gao Guo , Qian Qirong , Cui Daxiang
Published: August 2012

We reported a one-pot, environmentally friendly method for biosynthesizing nanoscale Au-Ag alloy using chloroplasts as reducers and stabilizers. The prepared nanoscale Au-Ag alloy was characterized by UV–visible spectroscopy, X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM). Fourier transform infrared spectroscopy (FTIR) analysis was further used to identify the possible biomolecules from chloroplasts that are responsible for the formation and stabilization of Au-Ag alloy. The FTIR results showed that chloroplast proteins bound to the nanoscale Au-Ag alloy through free amino groups. The bimetallic Au-Ag nanoparticles have only one plasmon band, indicating the formation of an alloy structure. HR-TEM images showed that the prepared Au-Ag alloy was spherical and 15 to 20 nm in diameter. The high crystallinity of the Au-Ag alloy was confirmed by SAED and XRD patterns. The prepared Au-Ag alloy was dispersed into multiwalled carbon nanotubes (MWNTs) to form a nanosensing film. The nanosensing film exhibited high electrocatalytic activity for 2-butanone oxidation at room temperature. The anodic peak current (Ip) has a linear relationship with the concentrations of 2-butanone over the range of 0.01% to 0.075% (v/v), when analyzed by cyclic voltammetry. The excellent electronic catalytic characteristics might be attributed to the synergistic electron transfer effects of Au-Ag alloy and MWNTs. It can reasonably be expected that this electrochemical biosensor provided a promising platform for developing a breath sensor to screen and pre-warn of early cancer, especially gastric cancer.
Tripled fixed point of W-compatible mappings in abstract metric spaces
Authors: Aydi Hassen , Abbas Mujahid , Sintunavarat Wutiphol , Kumam Poom
Published: August 2012

In this paper, we introduce the concepts ofW-compatible mappings for mappingsF:X×X×X→Xandg:X→X, where(X,d)is an abstract metric space. We establish tripled coincidence and common tripled fixed point theorems in such spaces. The presented theorems generalize and extend several well-known comparable results in literature, in particular the results of Abbas, Ali and Radenović (Appl. Math. Comput. 217:195-202, 2010). We also provide an example to illustrate our obtained results.

MSC:54H25, 47H10.
Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans
Authors: Wang Qi , Schwarzenberger Paul , Yang Fang , Zhang Jingjing , Su Jianjia , Yang Chun , Cao Ji , Ou Chao , Liang Liang , Shi Junlin , Yang Fang , Wang Duoping , Wang Jia , Wang Xiaojuan , Ruan Ping , Li Yuan
Published: August 2012

Background

Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period.

Results

Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew.

Conclusions

Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.