Impact of GE Crop Adoption on Quality-Adjusted Herbicide Use in U.S. Corn Production

This paper presents findings on the use of HT corn and quality-adjusted herbicide use for 12 key corn producing states using a panel data set for 1986-2008. Our preliminary findings indicate an insignificant impact of HT corn on herbicide use, conditioning or accounting for HT corn with other important drivers of corn herbicide use: HT soy, corn output price, glyphoste price, nonherbicide glyponsate price, and percentage of continuous corn and low-till corn. However, we find a positive and significant impact of HT corn on herbicide use in selected states, using regional interaction terms. We use econometric techniques to avoid spurious regression results. Other preliminary runs indicated that the results hold when running the US and regional interactions on 1986-2006 and 1986-2007 data.HT-corn, herbicides, weed resistance, glyphosate, corn, Environmental Economics and Policy, Farm Management, Production Economics,

Valproic acid enhances the efficacy of radiation therapy by protecting normal hippocampal neurons and sensitizing malignant glioblastoma cells

Neurocognitive deficits are serious sequelae that follow cranial irradiation used to treat patients with medulloblastoma and other brain neoplasms. Cranial irradiation causes apoptosis in the subgranular zone of the hippocampus leading to cognitive deficits. Valproic acid (VPA) treatment protected hippocampal neurons from radiation-induced damage in both cell culture and animal models. Radioprotection was observed in VPA-treated neuronal cells compared to cells treated with radiation alone. This protection is specific to normal neuronal cells and did not extend to cancer cells. In fact, VPA acted as a radiosensitizer in brain cancer cells. VPA treatment induced cell cycle arrest in cancer cells but not in normal neuronal cells. The level of anti-apoptotic protein Bcl-2 was increased and the pro-apoptotic protein Bax was reduced in VPA treated normal cells. VPA inhibited the activities of histone deacetylase (HDAC) and glycogen synthase kinase-3β (GSK3β), the latter of which is only inhibited in normal cells. The combination of VPA and radiation was most effective in inhibiting tumor growth in heterotopic brain tumor models. An intracranial orthotopic glioma tumor model was used to evaluate tumor growth by using dynamic contrast-enhanced magnetic resonance (DCE MRI) and mouse survival following treatment with VPA and radiation. VPA, in combination with radiation, significantly delayed tumor growth and improved mouse survival. Overall, VPA protects normal hippocampal neurons and not cancer cells from radiation-induced cytotoxicity both in vitro and in vivo. VPA treatment has the potential for attenuating neurocognitive deficits associated with cranial irradiation while enhancing the efficiency of glioma radiotherapy

A statistical method for predicting splice variants between two groups of samples using GeneChip(® )expression array data

BACKGROUND: Alternative splicing of pre-messenger RNA results in RNA variants with combinations of selected exons. It is one of the essential biological functions and regulatory components in higher eukaryotic cells. Some of these variants are detectable with the Affymetrix GeneChip(® )that uses multiple oligonucleotide probes (i.e. probe set), since the target sequences for the multiple probes are adjacent within each gene. Hybridization intensity from a probe correlates with abundance of the corresponding transcript. Although the multiple-probe feature in the current GeneChip(® )was designed to assess expression values of individual genes, it also measures transcriptional abundance for a sub-region of a gene sequence. This additional capacity motivated us to develop a method to predict alternative splicing, taking advance of extensive repositories of GeneChip(® )gene expression array data. RESULTS: We developed a two-step approach to predict alternative splicing from GeneChip(® )data. First, we clustered the probes from a probe set into pseudo-exons based on similarity of probe intensities and physical adjacency. A pseudo-exon is defined as a sequence in the gene within which multiple probes have comparable probe intensity values. Second, for each pseudo-exon, we assessed the statistical significance of the difference in probe intensity between two groups of samples. Differentially expressed pseudo-exons are predicted to be alternatively spliced. We applied our method to empirical data generated from GeneChip(® )Hu6800 arrays, which include 7129 probe sets and twenty probes per probe set. The dataset consists of sixty-nine medulloblastoma (27 metastatic and 42 non-metastatic) samples and four cerebellum samples as normal controls. We predicted that 577 genes would be alternatively spliced when we compared normal cerebellum samples to medulloblastomas, and predicted that thirteen genes would be alternatively spliced when we compared metastatic medulloblastomas to non-metastatic ones. We checked the consistency of some of our findings with information in UCSC Human Genome Browser. CONCLUSION: The two-step approach described in this paper is capable of predicting some alternative splicing from multiple oligonucleotide-based gene expression array data with GeneChip(® )technology. Our method employs the extensive repositories of gene expression array data available and generates alternative splicing hypotheses, which can be further validated by experimental studies

Targeting Survivin with YM155 (Sepantronium Bromide): A novel therapeutic strategy for paediatric acute myeloid leukaemia

Despite aggressive chemotherapy, approximately one-third of children with acute myeloid leukaemia(AML) relapse. More effective treatments are urgently needed. Survivin is an inhibitor-of-apoptosis protein with key roles in regulating cell division, proliferation and apoptosis. Furthermore, high expression of Survivin has been associated with poor clinical outcome in AML. The Survivin suppressant YM155 (Sepantronium Bromide) has pre-clinical activity against a range of solid cancers and leukemias, although data in AML is limited. Therefore, we undertook a comprehensive pre-clinical evaluation of YM155 in paediatric AML. YM155 potently inhibited cell viability in a diverse panel of AML cell lines. All paediatric cell lines were particularly sensitive, with a median IC50 of 0.038 mu M. Cell cycle analyses demonstrated concentration-dependent increases in a sub-G1 population with YM155 treatment, suggestive of apoptosis that was subsequently confirmed by an increase in annexin-V positivity. YM155-mediated apoptosis was confirmed across a panel of 8 diagnostic bone marrow samples from children with AML. Consistent with the proposed mechanism of action, YM155 treatment was associated with down-regulation of Survivin mRNA and protein expression and induction of DNA damage

Body composition, dietary intake and physical activity of young survivors of childhood cancer

To describe the body composition, dietary intake and physical activity and of paediatric, adolescent and young adult childhood cancer survivors (CCS) and examine the factors that impact body composition after treatment.This prospective cross-sectional study involved 74 subjects who were at least three years post treatment. Measurements included anthropometry, whole body potassium counting, air displacement plethysmography, and three day physical activity and diet diaries.The CCS had significantly reduced body cell mass index Z-scores compared to controls (p\ua0=\ua00.0001), with 59% considered undernourished. The CCS had a significantly higher percent fat (p\ua0=\ua00.002) than the controls, with 27% classified as obese. The intake of 60% of CCS met estimated energy requirements, but the CCS consumed high amount of energy from fat and low amount of energy from carbohydrates. A high percentage of CCS did not meet their dietary requirements for calcium (61%), magnesium (46%), folate (38%) and iodine (38%). The CCS group had a light active lifestyle with 64% spending more than 2\ua0h daily on screen time. Receiving a bone marrow transplant (r\ua0=\ua0-0.27; p\ua0=\ua00.02) and physical activity level (r\ua0=\ua00.49; p\ua0=\ua00.0001) were significantly correlated with body cell mass index.This study demonstrates that increased fat mass and decreased body cell mass is a concern for CCS and that CCS have poor health behaviours including light active lifestyles, excessive screentime, high fat intake, and poor intake of essential nutrients. This study has highlighted that CCS are at risk of both obesity and undernutrition and that increasing body cell mass as well as decreasing fat mass should be a focus of energy balance interventions in survivorship. There is a need for parents and children undergoing treatment for cancer to be educated about diet quality and importance of daily physical activity to ensure healthy habits are established and maintained into survivorship

Proteomic profiling of high risk medulloblastoma reveals functional biology

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior

Assessing the appropriateness of the management of otitis media in Australia: A population-based sample survey.

AIM: Acute otitis media (AOM) is the most common infectious disease for which antibiotics are prescribed; its management is costly and has the potential to increase the antimicrobial resistance of this infection. This study measured the levels of adherence to the clinical practice guidelines (CPGs) of AOM and otitis media with effusion (OME) management in Australian children. METHODS: We searched for national and international CPGs relating to AOM and OME in children and created 37 indicators for assessment. We reviewed medical records for adherence to these indicators in 120 locations, across one inpatient and three ambulatory health-care settings. Our review sample was obtained from three Australian states that contain 60% of the nation's children. RESULTS: We reviewed the records of 1063 children with one or more assessments of CPG adherence for otitis media. Of 22 indicators with sufficient data, estimated adherence ranged from 7.4 to 99.1%. Overuse of treatment, particularly overprescribing of antibiotics, was more common than underuse. A frequent lack of adherence with recommended care was observed for children aged between 1 and 2 years with AOM. Adherence varied by health-care setting, with emergency departments and inpatient settings more adherent to CPGs than general practices. CONCLUSIONS: Our assessment of a number of indicators in the common settings in which otitis media is treated found that guideline adherence varied widely between individual indicators. Internationally agreed standards for diagnosis and treatment, coupled with clinician education on the existence and content of CPGs and clinical decision support, are needed to improve the management of children presenting with AOM and OME

Characterising the types of paediatric adverse events detected by the global trigger tool - CareTrack Kids

Introduction A common method of learning about adverse events (AEs) is by reviewing medical records using the global trigger tool (GTT). However, these studies generally report rates of harm. The aim of this study is to characterise paediatric AEs detected by the GTT using descriptive and qualitative approaches. Methods Medical records of children aged 0–15 were reviewed for presence of harm using the GTT. Records from 2012–2013 were sampled from hospital inpatients, emergency departments, general practice and specialist paediatric practices in three Australian states. Nurses undertook a review of each record and if an AE was suspected a doctor performed a verification review of a summary created by the nurse. A qualitative content analysis was undertaken on the summary of verified AEs. Results A total of 232 AEs were detected from 6,689 records reviewed. Over four-fifths of the AEs (193/232, 83%) resulted in minor harm to the patient. Nearly half (112/232, 48%) related to medication/intravenous (IV) fluids. Of these, 83% (93/112) were adverse drug reactions. Problems with medical devices/equipment were the next most frequent with nearly two-thirds (32/51, 63%) of these related to intravenous devices. Problems associated with clinical processes/procedures comprise one in six AEs (38/232, 16%), of which diagnostic problems (12/38, 32%) and procedural complications (11/38, 29%) were the most frequent. Conclusion Adverse drug reactions and issues with IVs are frequently identified AEs reflecting their common use in paediatrics. The qualitative approach taken in this study allowed AE types to be characterised, which is a prerequisite for developing and prioritising improvements in practice

Proteomic profiling of high risk medulloblastoma reveals functional biology

Genomic characterization of medulloblastoma has improved molecular risk classification but struggles to define functional biological processes, particularly for the most aggressive subgroups. We present here a novel proteomic approach to this problem using a reference library of stable isotope labeled medulloblastoma-specific proteins as a spike-in standard for accurate quantification of the tumor proteome. Utilizing high-resolution mass spectrometry, we quantified the tumor proteome of group 3 medulloblastoma cells and demonstrate that high-risk MYC amplified tumors can be segregated based on protein expression patterns. We cross-validated the differentially expressed protein candidates using an independent transcriptomic data set and further confirmed them in a separate cohort of medulloblastoma tissue samples to identify the most robust proteogenomic differences. Interestingly, highly expressed proteins associated with MYC-amplified tumors were significantly related to glycolytic metabolic pathways via alternative splicing of pyruvate kinase (PKM) by heterogeneous ribonucleoproteins (HNRNPs). Furthermore, when maintained under hypoxic conditions, these MYC-amplified tumors demonstrated increased viability compared to non-amplified tumors within the same subgroup. Taken together, these findings highlight the power of proteomics as an integrative platform to help prioritize genetic and molecular drivers of cancer biology and behavior

Investigating the cost-effectiveness of videotelephone based support for newly diagnosed paediatric oncology patients and their families: design of a randomised controlled trial

BACKGROUND: Providing ongoing family centred support is an integral part of childhood cancer care. For families living in regional and remote areas, opportunities to receive specialist support are limited by the availability of health care professionals and accessibility, which is often reduced due to distance, time, cost and transport. The primary aim of this work is to investigate the cost-effectiveness of videotelephony to support regional and remote families returning home for the first time with a child newly diagnosed with cancer METHODS/DESIGN: We will recruit 162 paediatric oncology patients and their families to a single centre randomised controlled trial. Patients from regional and remote areas, classified by Accessibility/Remoteness Index of Australia (ARIA+) greater than 0.2, will be randomised to a videotelephone support intervention or a usual support control group. Metropolitan families (ARIA+ ≤ 0.2) will be recruited as an additional usual support control group. Families allocated to the videotelephone support intervention will have access to usual support plus education, communication, counselling and monitoring with specialist multidisciplinary team members via a videotelephone service for a 12-week period following first discharge home. Families in the usual support control group will receive standard care i.e., specialist multidisciplinary team members provide support either face-to-face during inpatient stays, outpatient clinic visits or home visits, or via telephone for families who live far away from the hospital. The primary outcome measure is parental health related quality of life as measured using the Medical Outcome Survey (MOS) Short Form SF-12 measured at baseline, 4 weeks, 8 weeks and 12 weeks. The secondary outcome measures are: parental informational and emotional support; parental perceived stress, parent reported patient quality of life and parent reported sibling quality of life, parental satisfaction with care, cost of providing improved support, health care utilisation and financial burden for families. DISCUSSION: This investigation will establish the feasibility, acceptability and cost-effectiveness of using videotelephony to improve the clinical and psychosocial support provided to regional and remote paediatric oncology patients and their families