bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of cytotoxic T lymphocytes primed with Tumor RNA-loaded Dendritic Cells in esophageal squamous cell carcinoma: preliminary step for DC vaccine design
Authors: Gholamin Mehran , Moaven Omeed , Farshchian Moein , Mahmoudi Mahmoud , Sankian Mojtaba , Memar Bahram , Forghani Mohammad Naser , Malekzadeh Reza , Rajabi-Mashhadi Mohammad Taghi , Abbaszadegan Mohammad Reza
Published: May 2012

Background

Dendritic Cells (DC) are potent antigen presenting cells with the ability to prime naïve T cells and convert them to cytotoxic T-lymphocytes (CTL). We evaluated the capability of autologous DCs transfected with total tumor and normal RNA to induce cytotoxic CTL as the preliminary step to design a DC-based vaccine in the esophageal squamous cell carcinoma (ESCC).

Methods

Monocytes-derived DCs were electroporated with either total tumor RNA or normal RNA. T cells were then primed with tumor RNA transfected DCs and lytic effects of the generated CTL were measured with Cytotoxicity assay and IFN-γ Release Elispot assay.

Results

Cytotoxicity was induced against DCs loaded with tumoral RNA (%24.8 ± 5.2 SEM) while in normal RNA-loaded DCs, it was minimal (%6.1 ± 2.4 SEM) and significantly lower (p < 0.05). INF-γ secretion was more than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNA-loaded DCs (p < 0.05).

Conclusion

Electroporating DCs with tumor RNA generated tumor antigen presenting cells which in turn enhanced cytotoxic effects of the T cells against ESCC. This may be a useful autologous ex vivo screening tool for confirming the lytic effects of primed T cells on tumors and evaluate probable further adverse effects on noncancerous tissues. These data provide crucial preliminary information to establish a total tumor RNA-pulsed DC vaccine therapy of ESCC.
A prospective randomised trial comparing nasogastric with intravenous hydration in children with bronchiolitis (protocol) The comparative rehydration in bronchiolitis study (CRIB)
Authors:   The Paediatric Research in Emergency Departments International Collaborative (PREDICT), Oakley Ed , Babl Franz E , Acworth Jason , Borland Meredith , Kreiser David , Neutze Jocelyn , Theophilos Theane , Donath Susan , South Mike , Davidson Andrew
Published: May 2012

Background

Bronchiolitis is the most common reason for admission of infants to hospital in developed countries. Fluid replacement therapy is required in about 30% of children admitted with bronchiolitis. There are currently two techniques of fluid replacement therapy that are used with the same frequency-intravenous (IV) or nasogastric (NG).

The evidence to determine the optimum route of hydration therapy for infants with bronchiolitis is inadequate. This randomised trial will be the first to provide good quality evidence of whether nasogastric rehydration (NGR) offers benefits over intravenous rehydration (IVR) using the clinically relevant continuous outcome measure of duration of hospital admission.

Methods/Design

A prospective randomised multi-centre trial in Australia and New Zealand where children between 2 and 12 months of age with bronchiolitis, needing non oral fluid replacement, are randomised to receive either intravenous (IV) or nasogastric (NG) rehydration.

750 patients admitted to participating hospitals will be recruited, and will be followed daily during the admission and by telephone 1 week after discharge. Patients with chronic respiratory, cardiac, or neurological disease; choanal atresia; needing IV fluid resuscitation; needing an IV for other reasons, and those requiring CPAP or ventilation are excluded.

The primary endpoint is duration of hospital admission. Secondary outcomes are complications, need for ICU admission, parental satisfaction, and an economic evaluation. Results will be analysed using t-test for continuous data, and chi squared for categorical data. Non parametric data will be log transformed.

Discussion

This trial will define the role of NGR and IVR in bronchiolitis

Trail registration

The trial is registered with the Australian and New Zealand Clinical Trials Registry - ACTRN12605000033640
Epidemic modeling with discrete-space scheduled walkers: extensions and research opportunities
Authors: Borkowski Maciej , Podaima Blake W , McLeod Robert D
Published: May 2012

Background

This exploratory paper outlines an epidemic simulator built on an agent-based, data-driven model of the spread of a disease within an urban environment. An intent of the model is to provide insight into how a disease may reach a tipping point, spreading to an epidemic of uncontrollable proportions.

Methods

As a complement to analytical methods, simulation is arguably an effective means of gaining a better understanding of system-level disease dynamics within a population and offers greater utility in its modeling capabilities. Our investigation is based on this conjecture, supported by data-driven models that are reasonable, realistic and practical, in an attempt to demonstrate their efficacy in studying system-wide epidemic phenomena. An agent-based model (ABM) offers considerable flexibility in extending the study of the phenomena before, during and after an outbreak or catastrophe.

Results

An agent-based model was developed based on a paradigm of a 'discrete-space scheduled walker' (DSSW), modeling a medium-sized North American City of 650,000 discrete agents, built upon a conceptual framework of statistical reasoning (law of large numbers, statistical mechanics) as well as a correct-by-construction bias. The model addresses where, who, when and what elements, corresponding to network topography and agent characteristics, behaviours, and interactions upon that topography. The DSSW-ABM has an interface and associated scripts that allow for a variety of what-if scenarios modeling disease spread throughout the population, and for data to be collected and displayed via a web browser.

Conclusion

This exploratory paper also presents several research opportunities for exploiting data sources of a non-obvious and disparate nature for the purposes of epidemic modeling. There is an increasing amount and variety of data that will continue to contribute to the accuracy of agent-based models and improve their utility in modeling disease spread. The model developed here is well suited to diseases where there is not a predisposition for contraction within the population. One of the advantages of agent-based modeling is the ability to set up a rare event and develop policy as to how one may mitigate damages arising from it.
The diagnostic role of glycosaminoglycans in pleural effusions: A pilot study
Authors: Vavetsi Rozina , Bonovas Stefanos , Polizou Paraskevi , Papanastasopoulou Chrysanthi , Dougekou Georgia , Sitaras Nikolaos M
Published: May 2012

Background

Pleural effusions are classified into transudates and exudates. Various criteria have been used with Light's et al being the most accepted ones. Glycosaminoglycans (GAGs) have been detected during pleural fluids (PF) analysis in various causes. In this pilot study, we investigated: (a) the usefulness of GAGs in the assessment of pleural effusions, and (b) whether and in what way GAGs correlate with established criteria used to indicate an exudate.

Methods

LDH, total protein, cholesterol and GAG levels were measured in pleural fluid and serum from 50 patients with pleural effusion. GAG levels were defined by the photometric method of Hata. The discriminative properties of pleural GAGs (pGAG), pleural fluid/serum GAG ratio (GAGR), serum GAGs (sGAG) and serum LDH (sLDH) were explored with ROC analysis.

Results

According to ROC analysis, pGAG and GAGR exhibited satisfactory discriminative properties in the separation of pleural effusions. For GAGR, at a 1.1 cut off point, sensitivity and specificity reached 75.6%; 95%CI: 60.5–87.1 and 100%; 95%CI: 47.8–100, respectively. For pGAG at a cut off value of 8.4 μg/ml, these percentages changed to 86.7%; 95%CI: 73.2–94.9 and 100%; 95%CI: 47.8–100. The study also revealed the differential role of sGAG between malignancies and benign cases, scoring 68.8%; 95%CI: 50.0–83.9 for sensitivity, and 84.6%; 95%CI: 54.5–97.6 for specificity at a 7.8 μg/ml cut off.

Conclusion

Our results suggest that glycosaminoglycan measurement of both serum and pleural effusions could be useful for simultaneous differentiation of exudates from transudates, and of malignant from benign exudates.
Leveraging H1N1 infection transmission modeling with proximity sensor microdata
Authors: Hashemian Mohammad , Stanley Kevin , Osgood Nathaniel
Published: May 2012

Background

The contact networks between individuals can have a profound impact on the evolution of an infectious outbreak within a network. The impact of the interaction between contact network and disease dynamics on infection spread has been investigated using both synthetic and empirically gathered micro-contact data, establishing the utility of micro-contact data for epidemiological insight. However, the infection models tied to empirical contact data were highly stylized and were not calibrated or compared against temporally coincident infection rates, or omitted critical non-network based risk factors such as age or vaccination status.

Methods

In this paper we present an agent-based simulation model firmly grounded in disease dynamics, incorporating a detailed characterization of the natural history of infection, and 13 weeks worth of micro-contact and participant health and risk factor information gathered during the 2009 H1N1 flu pandemic.

Results

We demonstrate that the micro-contact data-based model yields results consistent with the case counts observed in the study population, derive novel metrics based on the logarithm of the time degree for evaluating individual risk based on contact dynamic properties, and present preliminary findings pertaining to the impact of internal network structures on the spread of disease at an individual level.

Conclusions

Through the analysis of detailed output of Monte Carlo ensembles of agent based simulations we were able to recreate many possible scenarios of infection transmission using an empirically grounded dynamic contact network, providing a validated and grounded simulation framework and methodology. We confirmed recent findings on the importance of contact dynamics, and extended the analysis to new measures of the relative risk of different contact dynamics. Because exponentially more time spent with others correlates to a linear increase in infection probability, we conclude that network dynamics have an important, but not dominant impact on infection transmission for H1N1 transmission in our study population.
Tomato juice intake suppressed serum concentration of 8-oxodG after extensive physical activity
Authors: Harms-Ringdahl Mats , Jenssen Dag , Haghdoost Siamak
Published: May 2012

Background

DNA is constantly exposed to reactive oxygen species (ROS), spontaneously arising during the normal oxygen metabolism. ROS may result in temporary as well as permanent modifications in various cellular components such as lipids, proteins and DNA, which may have deleterious consequences. Demonstrating that a dietary supplementation of antioxidants can reduce oxidative DNA damage may provide evidence for the value of such supplementation in prevention of cancer and age related diseases.

Findings

The present study was conducted to address whether tomato juice protects against ROS induced by extensive physical exercise in untrained individuals. As a marker of oxidative stress, serum levels of 8-oxodG were monitored using a modified ELISA. An intervention was performed involving 15 untrained healthy subjects who performed a 20 min physical exercise at 80% of maximum pulse using an ergometer bicycle. Blood samples were taken before and one hour after the exercise. The procedure was repeated after 5 weeks with a daily intake of 150 ml tomato juice and followed by a 5 weeks wash-out period and another 5 weeks with a daily intake of tomato juice. The results indicated that a daily intake of tomato juice, equal to 15 mg lycopene per day, for 5 weeks significantly reduced the serum levels of 8-oxodG after an extensive physical exercise.

Conclusion

These data strongly suggest that tomato juice has a potential antioxidant effect and may reduce the elevated level of ROS induced by oxidative stress.
Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line
Authors: Intarasunanont Ponpat , Navasumrit Panida , Waraprasit Somchamai , Chaisatra Krittinee , Suk William A , Mahidol Chulabhorn , Ruchirawat Mathuros
Published: May 2012

Background

Accumulating evidence indicates that in utero exposure to arsenic is associated with congenital defects and long-term disease consequences including cancers. Recent studies suggest that arsenic carcinogenesis results from epigenetic changes, particularly in DNA methylation. This study aimed to investigate DNA methylation changes as a result of arsenic exposure in utero and in vitro.

Methods

For the exposure in utero study, a total of seventy-one newborns (fifty-five arsenic-exposed and sixteen unexposed newborns) were recruited. Arsenic concentrations in the drinking water were measured, and exposure in newborns was assessed by measurement of arsenic concentrations in cord blood, nails and hair by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In the in vitro study, human lymphoblasts were treated with arsenite at 0-100 μM for two, four and eight hours (short-term) and at 0, 0.5 and 1.0 μM for eight-weeks period (long-term). DNA methylation was analyzed in cord blood lymphocytes and lymphoblasts treated with arsenite in vitro. Global DNA methylation was determined as LINE-1 methylation using combined bisulfite restriction analysis ( COBRA) and total 5-methyldeoxycytidine (5MedC) content which was determined by HPLC-MS/MS. Methylation of p53 was determined at the promoter region using methylation-specific restriction endonuclease digestion with MspI and HpaII.

Results

Results showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged. Short-term in vitro arsenite treatment in lymphoblastoid cells clearly demonstrated a significant global hypomethylation, determined as reduction in LINE-1 methylation and total 5-MedC content, and p53 hypermethylation (p < 0.05). However, a slight LINE-1 hypomethylation and transient p53 promoter hypermethylation were observed following long-term in vitro treatment.

Conclusions

This study provides an important finding that in utero arsenic exposure affects DNA methylation, particularly at the p53 promoter region, which may be linked to the mechanism of arsenic carcinogenesis and the observed increased incidence of cancer later in life.
New iterative schemes for a finite family of nonself uniformly quasi-Lipschitzian mappings in Banach spaces
Authors: Wang Chao , Li Jin , Hu Liang-gen
Published: May 2012

In this article, we introduce the concept of nonself uniformly quasi-Lipschitzian mapping and consider a new iterative scheme with errors to converge to a common fixed point for a finite family of nonself uniformly quasi-Lipschitzian mappings in Banach spaces. The results of this article improve and extend many known results.
HIV taken by STORM: Super-resolution fluorescence microscopy of a viral infection
Authors: Pereira Cândida F , Rossy Jérémie , Owen Dylan M , Mak Johnson , Gaus Katharina
Published: May 2012

Background

The visualization of viral proteins has been hindered by the resolution limit of conventional fluorescent microscopes, as the dimension of any single fluorescent signal is often greater than most virion particles. Super-resolution microscopy has the potential to unveil the distribution of proteins at the resolution approaching electron microscopy without relying on morphological features of existing characteristics of the biological specimen that are needed in EM.

Results

Using direct stochastic optical reconstruction microscopy (dSTORM) to achieve a lateral resolution of 15–20 nm, we quantified the 2-D molecular distribution of the major structural proteins of the infectious human immunodeficiency virus type 1 (HIV-1) before and after infection of lymphoid cells. We determined that the HIV-1 matrix and capsid proteins undergo restructuring soon after HIV-1 infection.

Conclusions

This study provides the proof-of-concept for the use of dSTORM to visualize the changes in the molecular distribution of viral proteins during an infection.
Sternal reconstruction for unusual chondrosarcoma: innovative technique
Authors: Nosotti Mario , Rosso Lorenzo , Mendogni Paolo , Tosi Davide , Palleschi Alessandro , Parafioriti Antonina , Santambrogio Luigi
Published: May 2012

The authors report a clinical case of a primary sternal chondrosarcoma, presented as a mass in the anterior mediastinum. The patient was treated with subtotal sternectomy and sternal transplantation followed by radiotherapy. Twelve months after surgery, the patient is in good clinical condition, without any sign of tumor relapse and with normal respiratory mechanics.

Primary malignant tumors of the sternum are uncommon and a presentation mimicking thymoma is rare and unreported. The stermal replacement with a cryopreserved allograft sternum is an innovative technique that overcomes the problems related to the prosthetic biocompatibility or to the bone autograft.
A quantitative structure- property relationship of gas chromatographic/mass spectrometric retention data of 85 volatile organic compounds as air pollutant materials by multivariate methods
Authors: Sarkhosh Maryam , Ghasemi Jahan B , Ayati Mahnaz
Published: May 2012

A quantitative structure-property relationship (QSPR) study is suggested for the prediction of retention times of volatile organic compounds. Various kinds of molecular descriptors were calculated to represent the molecular structure of compounds. Modeling of retention times of these compounds as a function of the theoretically derived descriptors was established by multiple linear regression (MLR) and artificial neural network (ANN). The stepwise regression was used for the selection of the variables which gives the best-fitted models. After variable selection ANN, MLR methods were used with leave-one-out cross validation for building the regression models. The prediction results are in very good agreement with the experimental values. MLR as the linear regression method shows good ability in the prediction of the retention times of the prediction set. This provided a new and effective method for predicting the chromatography retention index for the volatile organic compounds.
Respiratory syncytial virus outbreak in neonatal intensive care unit: Impact of infection control measures plus palivizumab use
Authors: Silva Camila de A , Dias Lívio , Baltieri Sandra R , Rodrigues Tatiane T , Takagi Neusa Brandolise , Richtmann Rosana
Published: May 2012

Background

The occurrence of a respiratory syncytial virus (RSV) outbreak in a Neonatal Intensive Care Unit (NICU) is related to unfavorable outcomes, as this infection can lead to respiratory distress and death in premature in infants. Report the successful control of an outbreak that occurred in April 2010 in a NICU.

Methods

After the index case, of 18 premature infants placed in the same room 10 infants were infected. Of those 10, 6 developed mild to moderate respiratory symptoms, 4 persisted asymptomatic and no death occurred. Contact and respiratory precautions were rapidly initiated, the infants were cohorted in 3 different rooms and palivizumab was administered to all contacts.

Results

The outbreak was controlled and no new cases were subsequently indentified.

Conclusion

Standard infection control measures plus palivizumab prophylaxis were efficient in rapid control of the outbreak.
Prognostic and predictive value of TP53mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial
Authors: Fernández-Cuesta Lynnette , Oakman Catherine , Falagan-Lotsch Priscila , Smoth Ke-seay , Quinaux Emmanuel , Buyse Marc , Dolci M Stella , Azambuja Evandro De , Hainaut Pierre , Dell'Orto Patrizia , Larsimont Denis , Francis Prudence A , Crown John , Piccart-Gebhart Martine , Viale Giuseppe , Leo Angelo Di , Olivier Magali
Published: May 2012

Introduction

Pre-clinical data suggest p53-dependent anthracycline-induced apoptosis and p53-independent taxane activity. However, dedicated clinical research has not defined a predictive role for TP53 gene mutations. The aim of the current study was to retrospectively explore the prognosis and predictive values of TP53 somatic mutations in the BIG 02-98 randomized phase III trial in which women with node-positive breast cancer were treated with adjuvant doxorubicin-based chemotherapy with or without docetaxel.

Methods

The prognostic and predictive values of TP53 were analyzed in tumor samples by gene sequencing within exons 5 to 8. Patients were classified according to p53 protein status predicted from TP53 gene sequence, as wild-type (no TP53 variation or TP53 variations which are predicted not to modify p53 protein sequence) or mutant (p53 nonsynonymous mutations). Mutations were subcategorized according to missense or truncating mutations. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Cox-regression analysis was used to identify independent predictors of outcome.

Results

TP53 gene status was determined for 18% (520 of 2887) of the women enrolled in BIG 02-98. TP53 gene variations were found in 17% (90 of 520). Nonsynonymous p53 mutations, found in 16.3% (85 of 520), were associated with older age, ductal morphology, higher grade and hormone-receptor negativity. Of the nonsynonymous mutations, 12.3% (64 of 520) were missense and 3.6% were truncating (19 of 520). Only truncating mutations showed significant independent prognostic value, with an increased recurrence risk compared to patients with non-modified p53 protein (hazard ratio = 3.21, 95% confidence interval = 1.740 to 5.935, P = 0.0002). p53 status had no significant predictive value for response to docetaxel.

Conclusions

p53 truncating mutations were uncommon but associated with poor prognosis. No significant predictive role for p53 status was detected.

Trial registration

ClinicalTrials.gov NCT00174655
The secretome of stem cells isolated from the adipose tissue and Wharton jelly acts differently on central nervous system derived cell populations
Authors: Ribeiro Carlos A , Fraga Joana S , Grãos Mário , Neves Nuno M , Reis Rui L , Gimble Jeffrey M , Sousa Nuno , Salgado António J
Published: May 2012

Introduction

It is hypothesized that administration of stromal/stem cells isolated from the adipose tissue (ASCs) and umbilical cord (HUCPVCs) can ameliorate the injured central nervous system (CNS). It is still not clear, however, whether they have similar or opposite effects on primary cultures of neuronal populations. The objective of the present work was to determine if ASCs and HUCPVCs preferentially act, or not, on specific cell populations within the CNS.

Methods

Primary cultures of hippocampal neurons were exposed to ASCs and HUCPVCs conditioned media (CM) (obtained 24, 48, 72 and 96 hours after three days of culture) for one week.

Results

Cell viability experiments (MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2H tetrazolium) test) revealed that CM obtained from both cell populations at all time points did not cause any deleterious effects on neuronal cells. In fact, it was determined that whenever the ASCs CM were supplemented with basic fibroblast growth factor (bFGF) and B27, there was a significant increase in the metabolic viability and neuronal cell density of the cultures. On the other hand, in the absence of CM supplementation, it was the HUCPVCs secretome that had the highest impact on the metabolic viability and cell density. In an attempt to unveil which factors could be involved in the observed effects, a screening for the presence of bFGF, nerve growth factor (NGF), stem cell factor (SCF), hepatocyte growth factors (HGF) and vascular endothelial growth factor (VEGF) in the CM was performed. Results revealed the presence of all these factors in ASCs CM, except bFGF; in contrast, in HUCPVCs CM it was only possible to detect robust NGF expression.

Conclusions

Overall, the results confirm important differences on the secretome of ASCs and HUCPVCs, which lead to distinct effects on the metabolic viability and neuronal cell densities in primary cultures of hippocampal neurons; however, the factor(s) that promote the stronger effect of the HUCPVCs CM in neuronal survival is(are) still to be identified.
Exploring the model space and ranking a best class of models in surface-wave dispersion inversion: Application at European strong-motion sites
Authors: Di Giulio Giuseppe , Savvaidis Alexandros , Ohrnberger Matthias , Wathelet Marc , Cornou Cecile , Knapmeyer-Endrun Brigitte , Renalier Florence , Theodoulidis Nikos , Bard Pierre-Yves
Published: May 2012

The inversion of surface-wave dispersion curve to derive shear-wave velocity profile is a very delicate process dealing with a nonunique problem, which is strongly dependent on the model space parameterization. When independent and reliable information is not available, the selection of most representative models within the ensemble produced by the inversion is often difficult. We implemented a strategy in the inversion of dispersion curves able to investigate the influence of the parameterization of the model space and to select a “best” class of models. We analyzed surface-wave dispersion curves measured at 14 European strong-motion sites within the NERIES EC-Project. We focused on the inversion task exploring the model space by means of four distinct parameterization classes composed of layers progressively added over a half-space. The classes differ in the definition of the shear-wave velocity profile; we considered models with uniform velocity as well as models with increasing velocity with depth. At each site and for each model parameterization, we performed an extensive surface-wave inversion (200,100 models for five seeds) using the conditional neighborhood algorithm. We addressed the model evaluation following the corrected Akaike’s information criterion (AICc) that combines the concept of misfit to the number of degrees of freedom of the system. The misfit was computed as least-squares estimation between theoretical and observed dispersion curve. The model complexity was accounted in a penalty term by AICc. By applying such inversion strategy on 14 strong-motion sites, we found that the best parameterization of the model space is mostly three to four layers over a half-space; where the shear-wave velocity of the uppermost layers can follow uniform or power-law dependence with depth. The shear-wave velocity profiles derived by inversion agree with shear-wave velocity profiles provided by borehole surveys at approximately 80% of the sites.
A Novel Therapeutic Approach to Treating Obesity through Modulation of TGFβ Signaling
Authors: Koncarevic Alan , Kajimura Shingo , Cornwall-Brady Milton , Andreucci Amy , Pullen Abigail , Sako Dianne , Kumar Ravindra , Grinberg Asya V. , Liharska Katia , Ucran Jeffrey A. , Howard Elizabeth , Spiegelman Bruce M. , Seehra Jasbir , Lachey Jennifer
Published: May 2012

Obesity results from disproportionately high energy intake relative to energy expenditure. Many therapeutic strategies have focused on the intake side of the equation, including pharmaceutical targeting of appetite and digestion. An alternative approach is to increase energy expenditure through physical activity or adaptive thermogenesis. A pharmacological way to increase muscle mass and hence exercise capacity is through inhibition of the activin receptor type IIB (ActRIIB). Muscle mass and strength is regulated, at least in part, by growth factors that signal via ActRIIB. Administration of a soluble ActRIIB protein comprised of a form of the extracellular domain of ActRIIB fused to a human Fc (ActRIIB-Fc) results in a substantial muscle mass increase in normal mice. However, ActRIIB is also present on and mediates the action of growth factors in adipose tissue, although the function of this system is poorly understood. In the current study, we report the effect of ActRIIB-Fc to suppress diet-induced obesity and linked metabolic dysfunctions in mice fed a high-fat diet. ActRIIB-Fc induced a brown fat-like thermogenic gene program in epididymal white fat, as shown by robustly increased expression of the thermogenic genes uncoupling protein 1 and peroxisomal proliferator-activated receptor-γ coactivator 1α. Finally, we identified multiple ligands capable of reducing thermogenesis that represent likely target ligands for the ActRIIB-Fc effects on the white fat depots. These data demonstrate that novel therapeutic ActRIIB-Fc improves obesity and obesity-linked metabolic disease by both increasing skeletal muscle mass and by inducing a gene program of thermogenesis in the white adipose tissues.
Zebrafish homologs of 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes
Authors: Blaker-Lee Alicia , Gupta Sunny , McCammon Jasmine M. , DeRienzo Gianluca , Sive Hazel
Published: May 2012

Deletion or duplication of one copy of the human 16p11.2 interval is tightly associated with impaired brain function, including autism spectrum disorders (ASD), intellectual disability disorder (IDD), and other phenotypes, indicating the importance of gene dosage in this copy number variant region (CNV). The core of this CNV includes 25 genes, however, the number of genes that contribute to these phenotypes is not known. Further, genes whose functional levels change with deletion or duplication (termed 'dosage sensors'), which may associate the CNV with pathologies, have not been identified. Using the zebrafish as a tool, a set of 16p11.2 homologs was identified, primarily on chromosomes 3 and 12. Use of eleven phenotypic assays, spanning the first five days of development, demonstrates that this set of genes is highly active, such that 21 out of 22 homologs tested show loss of function phenotypes. Most genes are required for nervous system development − impacting brain morphology, eye development, axonal density or organization, and motor response. In general, human genes can substitute for the fish homolog, demonstrating orthology, and consistent with conserved molecular pathways. In a screen for 16p11.2 genes whose function is sensitive to hemizygosity, the aldolase a (aldoa) and kinesin family member 22 (kif22) genes were identified as giving clear phenotypes when RNA levels are reduced by ~50%, suggesting that these genes are deletion dosage sensors. This study leads to two major findings. The first is that the 16p11.2 region comprises a highly active set of genes, which may present a large genetic target, and may explain why multiple brain function and other phenotypes are associated with this interval. The second major finding is that there are (at least) two genes with deletion dosage sensor properties amongst the 16p11.2 set, which may link this CNV to brain disorders including ASD and IDD.
Clinical Outcomes Associated with Brand-to-Generic Phenytoin Interchange
Authors: Kinikar Shilpa A , Delate Thomas , Menaker-Wiener C Mindy , Bentley William H
Published: May 2012

Background:

Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. However, little within-patient evidence exists examining such interchanges.

Objective:

To compare within-patient seizure control before and after the interchange of a branded to a single-source generic Phenytoin among patients with seizures in a managed care organization.

Methods:

This was a pre-post, self-controlled, retrospective study. Adults with a history of seizure who used Dilantin Kapseals 100 mg extended Phenytoin sodium, USP, capsules and whose therapy was interchanged to Taro Pharmaceuticals’ AB-rated generic extended phenytoin sodium capsules, USP, 100 mg between July 2007 and May 2008 were included. Study outcomes included the comparisons of the proportions of patients with at least emergency department (ED) visit/inpatient hospitalization and medical office visit/nonoffice consultation for acute seizure in the 6 months before and after interchange. Outcomes were confirmed with manual chart reviews and adjusted for potential confounding medication use.

Results:

A total of 222 patients were included in the study. Patients were primarily middle-aged (mean 56 years), equally mixed by sex (47% female); most had nonintractable seizures. The majority of patients (~70%) were on phenytoin as monotherapy and had equivalent rates of purchases for potentially confounding medications in both pre- and postinterchange time periods (all p < 0.05). Low serum concentrations were detected more often in the postinterchange study period (adjusted p < 0.001). Despite this, there were low proportions of patients with confirmed seizure events that resulted in an ED visit/inpatient hospitalization in both pre- and postinterchange periods (both 6.3%, adjusted p = 0.937). The proportion of patients with confirmed seizure events diagnosed at a medical office visit was not significantly different between the preinterchange and postinterchange periods (12.2% vs 11.3%, adjusted p = 0.545).

Conclusions:

NO increased proportion of seizures was observed within patients when branded phenytoin was interchanged to an AB-rated, single-source, generic equivalent. More rigorous studies should be conducted to more thoroughly evaluate patient tolerability and drug efficacy when antiepileptic drugs are interchanged from brand to generic formulations.
Total synthesis of gelsemoxonine
Authors: Shimokawa Jun , Harada Takaaki , Yokoshima Satoshi , Fukuyama Tohru
Published: May 2012

The first total synthesis of gelsemoxonine has been accomplished. A divinylcyclopropane–cycloheptadiene rearrangement of the highly functionalized substrate successfully assembled the spiro-quaternary carbon center connected to the bicyclic seven-membered core structure. A one-pot isomerization reaction of the α,β-unsaturated aldehyde to the saturated ester via a trimethylsilyl cyanide–diazabicycloundecene (TMSCN–DBU) reagent combination allowed a facile and diastereoselective introduction of the latent nitrogen functionality in the unique azetidine moiety.
A unique, two-component sensing system for fluorescence detection of glucose and other carbohydrates
Authors: Cordes David B. , Singaram Bakthan
Published: May 2012

In our glucose-sensing system, a boronic acid-modified viologen molecule quenches the fluorescence of a separate dye molecule. When glucose or other monosaccharides are added and bind to the boronic acid, the quenching ability of the viologen is diminished and fluorescence increases. Thus, changes in the fluorescence of the dye can be correlated with changing glucose concentration. Quenching and sugar-sensing results are explained by an electrostatic interaction between dye and quencher. This modular system can be configured in a nearly unlimited number of ways through substitution and multiplexing of the two fundamental quencher and dye components. Significantly, fluorescent quantum dots (QDs) can also be used as the reporter component. The system can also be immobilized in a hydrogel polymer to provide real-time, reversible sugar sensing.
Pathways for Indigenous Education in the Australian Curriculum Framework
Authors: Nakata Martin
Published: May 2012

This article reflects on pathways for Indigenous
education in the developing agenda of the Australian
Curriculum, the cross-curriculum priorities, the general
capability area of intercultural understanding, and the
positioning of Indigenous learners within the diversity of
learners with English as an additional language or dialect
(EALD).
Embedding Indigenous Perspectives in Teaching School Science
Authors: Appanna Subhashni Devi
Published: May 2012

Some Indigenous students are at risk of academic failure
and science teachers have a role in salvaging these equally
able students. This article firstly elucidates the research
entailed in Indigenous science education in Australia and
beyond. Secondly, it reviews the cultural and language
barriers when learning science, faced by middle and senior
year students of Aboriginal and Torres Strait Islander
descent. Finally, it outlines the effective strategies that
science teachers could adopt to better engage these
students in learning school science. In summary, the
article will highlight the need for teachers to realise the
importance of crossing borders from teachers' school
science culture to students' culture. This holds
implications for teaching practice and teacher identity in
today's classroom.
The Components of Best-Practice Indigenous Education: A Comparative Review
Authors: Griffiths Andrew
Published: May 2012

Currently in Australia there is much activity and
expenditure in a field broadly defined as ‘Indigenous
education’. However, there is little by way of rigorous
research that has compared and evaluated different
approaches. This article draws together the existing
international evidence to develop a set of best-practice
components for Indigenous education. The author intends for
these components to provide practical guidance for program
developers who may currently be developing programs without
the benefit of an existing evidence base, while also
acknowledging the need to expand the evidence base and
continue to refine this set of components to maximise their
utility.
Refocusing on Oral Language and Rich Representations to Develop the Early Mathematical Understandings of Indigenous Students
Authors: McDonald Susan , Warren Elizabeth , DeVries Eva
Published: May 2012

This article examines the nature of oral language and
representations used by teachers as they instruct young
Indigenous Australian students at the beginning of formal
schooling during play-based activities in mathematics. In
particular, the use of Standard Australian English (SAE),
the mathematical register used, and the interplay with
mathematical representations during classroom instruction
are analysed based upon the teachers' selfreported
practices. The data are drawn from structured telephone
interviews with 40 teachers in 15 schools from rural and
remote or multicultural settings in Queensland at the
initial stage of a large, longitudinal study. The specific
aim of the study was the identification of effective
pedagogical practices that may assist young Australian
students from diverse ethnic and cultural backgrounds to
negotiate western mathematical understanding. The findings
indicate that despite experience in these settings and
focused professional learning sessions, the majority of
these teachers report practices which reflect a strong
emphasis on literacy acquisition rather than mathematical
understanding. It is the contention of the researchers that
the use of oral language with a rich selection of
mathematical representations strongly supports mathematical
understanding.
A New Net to Go Fishing: Messages From International Evidence-Based Research and Kaupapa Māori Research
Authors: Manning Richard F. , Macfarlane Angus H. , Skerrett Mere , Cooper Garrick , De Oliveira (Andreotti) Vanessa , Emery Tepora
Published: May 2012

This article draws upon a Māori metaphor to describe the
theoretical framework underpinning the methodology and
findings of a research project completed by researchers
from the University of Canterbury, New Zealand, in 2010. It
explains how and why the project required the research team
to synthesise key information from four New Zealand
Ministry of Education Best Evidence Synthesis (BES) reports
as well as
kaupapaMāori research associated with the
Ministry's
Ka HikitiaMāori Education Strategy. The
key messages outlined in this article were designed by the
research team to serve as a new tool to assist whānau
(family) and iwi (tribe) to actively engage in the New
Zealand schooling system and assert their rights in
accordance with the principles of the Treaty of Waitangi
(1840). Given the large number of Māori children attending
Australian schools, the findings of this research may be of
interest to Australian educationalists.
A Review of Foster Carer Allowances: Responding to Recommendation 16.9 of the Special Commission of Inquiry into Child Protection (NSW)
Authors: McHugh Marilyn
Published: May 2012

In the Report of the Special Commission of Inquiry into Child Protection in New South Wales, Recommendation 16.9 states: ‘Carer allowances should be reviewed periodically by an independent body and should more closely reflect the actual costs to the carer of providing care, according to the varying categories of need’ (Wood, 2008, p. 689). In 2000, estimates of the costs of foster children were developed (the Foster Care Estimates) by an ‘independent body’, the Social Policy Research Centre (SPRC). Using a budget standards approach, estimates representing the ‘basic’ subsidy were based on the costs of children not in care and adjusted to more closely reflect the day-to-day cost of fostering children in statutory care. Since 2000, the estimates have been updated annually (using the Consumer Price Index). This article examines the changes to levels of allowances for statutory foster and kinship carers in all Australian jurisdictions over the period 2000–2009. It argues that the use of the internationally recognised budget standards approach to estimate ‘actual costs to carers’ has been accepted by government and more than meets the requirements of Wood's Recommendation 16.9.
Parents With Mental Illness: The Cycle of Intergenerational Mental Illness
Authors: Boursnell Melanie
Published: May 2012

This article provides an insight into the under-explored lives of parents with mental illness. In particular, this article considers the experiences of parents with mental illness who grew up with parents who also had mental illness, or experienced issues related to violence, abuse and neglect during childhood. Due to the dearth of research in this area there is minimal insight into how parents experience mental illness and even less significance is placed on exploring how intergenerational mental illness and backgrounds of violence, abuse and neglect impact on parenthood. This qualitative study generates information about how intergenerational family mental illness, and other issues identified in the course of the study, affected the participants' experiences of being a parent.
Three Therapeutic Residential Care Models, the Sanctuary Model, Positive Peer Culture and Dyadic Developmental Psychotherapy and Their Application to the Theory of Congruence
Authors: Clarke Annaley
Published: May 2012

Therapeutic residential care for children and young people is a service model being implemented in the Queensland out-of-home care sector. Many therapeutic models for residential care exist; however, three that have research supporting their use include the Sanctuary model, positive peer culture model and the dyadic developmental psychotherapy residential model. This article will first outline the three models, with particular focus on the principles, strategies, current implementation and research related to each. It will then introduce Anglin's theory of congruence (2002) and outline how consistently each model corresponds to this theory.
Support in Kith and Kin Care: The Experience of Carers
Authors: O'Neill Cas
Published: May 2012

As a home-based care option for children at risk of significant harm, kinship care placements are steadily increasing in Australia as they are in other western countries. This article describes a qualitative research study undertaken with 65 kin (relative) and kith (nonrelative) carers in Victoria in the years 2004–2007. The aims of the research were to explore the lived experience of carers and to understand their support needs. The findings distinguish similarities and differences between the experience of formal and informal grandparent carers, non-grandparent relative carers and nonrelative carers. The article discusses the role of caregiving for the different groups, family relationships, finances (having enough money, as well as having too little), relationships with government agencies, respite and peer support.
Commentary: Child Protection Inquiries: Where are the Voices of Children and Young People?
Authors: Taylor Sandra , Ashford Aileen
Published: May 2012

Parliamentary Inquiries into the adequacy of child protection services, as well as best practice care and service delivery in child protection, have been a dominant feature of contemporary Australia in recent times. The direct voices of children and young people in such inquiries are usually missing, despite them being at the very centre of the child protection system and a range of government policies. In this paper we reflect upon this issue and consider why these voices are absent and what factors and barriers limit their inclusion. A review of relevant literature and empirical data indicates that the structures, agendas and processes of such Inquiries are intrinsically adult-oriented endeavours in which the contributions and inclusion of children and young people are not easily accommodated. Through adopting a shift in perspective, orientation and practice, the voices and experiences of children and young people can be included in child protection Inquiries that have critical implications for the quality of their lives and their life chances. Such inclusions uphold the rights of children and young people and support the implementation of government policy in practice.
Commentary: Therapeutic Reparenting: What Does it Take?
Authors: Doorn Michelle Van , Connolly Marilyn
Published: May 2012

The Circle Program is a therapeutic model of foster care in Victoria. Oz Child has delivered this model of foster care in partnership with The Australian Childhood Foundation and the Department of Human Services over the last four years. Therapeutic foster care is designed to assist children entering care to heal from the affects of trauma and abuse. A significant benefit of therapeutic care is the provision and emphasis on a supportive therapeutic environment for the child in everyday interactions with the carer. It is through the child's relationship with the carer that healing can begin. In order to provide such an environment carers are trained, assessed and accredited to have a working understanding of the impact of trauma and abuse, and are provided with tools and strategies to therapeutically re-parent these children. Carers are an integral part of the team and work alongside placement workers and clinicians to understand the impact of trauma and abuse. Together they develop strategies and interventions that are therapeutic and address the impact of trauma on all aspects of the child's development and wellbeing. While considering outcomes for children within a therapeutic model it is crucial to identify particular interpersonal and parenting characteristics held by carers. This commentary will consider the defining characteristics required to be a therapeutic foster carer.