No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue

A single nucleotide polymorphism (SNP) rs6983267, located within the 8q24 region, is strongly associated with risk of colorectal and prostate cancer. It has been suggested that the mechanism of this association is related to differential interaction of TCF7L2 protein (previously known as TCF-4) with alleles of rs6983267, influencing the expression of a well-known oncogene, MYC, located 335 Kb telomeric. Here, we tested the correlation between mRNA expression of MYC and several alternatively spliced forms of TCF7L2 in 117 non-cancer colon samples. We observed a strong correlation (r = 0.60, p < 10-6) between expression of MYC and a unique splicing form of TCF7L2. The level of MYC expression in these samples was associated with expression of some TCF7L2 splicing forms but not with genotypes of rs6983267, or interaction of rs6983267 with TCF7L2 expression. These findings suggest that some splicing forms of TCF7L2 may be functionally important for regulation of MYC expression in colon tissue but this regulation is not directly dependent on rs6983267

What does it take to redesign a degree? A case study

BACKGROUND The Bachelor of Pharmaceutical Science course at Monash University is presently in the second year of a three-year redevelopment. Initiated to address the recommendations of a 2015 course review, the redevelopment has grown into a full course redesign with multiple aims including the deep embedding of skill development, authentic learning and lifelong learning skills into the curriculum; strengthening integrated and interdisciplinary learning; and improving the student experience. AIMS This case study maps the key stages in the full redesign of an applied science degree with the aim of identifying internal and external factors that have shaped its conception and implementation. METHODS Multiple data sources (institutional data, planning documents, personal notes and recollections) are used to describe the redesign process over a four-year period. The elements of the process are analysed with respect to literature examples and models of educational change and curriculum design. RESULTS AND CONCLUSIONS The present case has employed a mixed approach, addressing both institutional and individual practices, that is mostly consistent with an integration strategy of curriculum change

Kepler-16: A Transiting Circumbinary Planet

We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size, and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20% and 69% as massive as the sun, and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5 degree of a single plane, suggesting that the planet formed within a circumbinary disk.Comment: Science, in press; for supplemental material see http://www.sciencemag.org/content/suppl/2011/09/14/333.6049.1602.DC1/1210923.Doyle.SOM.pd

A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection.

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP

Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery: Enhanced Recovery After Surgery (ERAS\u3csup\u3e®\u3c/sup\u3e) Society Recommendations

Background: Enhanced Recovery After Surgery (ERAS®) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS® Society guidelines. We created an ERAS® guideline designed to enhance quality of care in neonatal intestinal resection surgery. Methods: A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. Results: Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. Discussion: We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties

The Siren Site and the Long Transition from Archaic to Late Prehistoric Lifeways on the Eastern Edwards Plateau of Central Texas

On behalf of the Texas Department of Transportation (TxDOT), SWCA Environmental Consultants (SWCA) conducted testing and data recovery investigations at the Siren site (41WM1126), a prehistoric multi-component site in the Interstate Highway 35 right-of-way along the South Fork of the San Gabriel River in Williamson County, Texas. The work was done to fulfill TxDOT’s compliance obligations under the National Historic Preservation Act and the Antiquities Code of Texas. The testing investigations were conducted under Antiquities Permit 3834, and the subsequent data recovery was under Permit 3938. Kevin Miller served as Principal Investigator on both permits. Though the site extends far beyond the area of potential effects both horizontally and vertically, the investigations focused on Late Archaic and Late Prehistoric components within a relatively limited area that would be subject to project impacts. The investigations were conducted in February 2006. The investigations identified five isolable components that were intermittently laid down from approximately 2600 to 900 years ago. A substantial Late Prehistoric Austin phase occupation is represented by Scallorn projectile points, stone tools, burned rock, faunal materials, and radiocarbon dates from cooking features. The component feature assemblage includes a cluster of discrete, well-preserved burned rock features that range from small fire-cracked rock concentrations to a large, slab-lined feature that dominates the cluster. The underlying components include four cultural strata representing a series of phases in the final millennium or so of the long Archaic period. These components span approximately 2600 to 1500 b.p., though earlier, deeply buried components were also noted on the site. These deeper deposits were not the focus of the investigations, however, since they would not be affected by the project. The Archaic components revealed a suite of small side-notched dart points such as Ensor, Fairland, and Frio, as well as many earlier broad-bladed styles such as Castroville, Montell, Marshall, and Pedernales. These robust components contained numerous burned rock features of varying size and function, abundant tools, well-preserved faunal materials, macrobotanical remains including geophytes from several earth ovens, and a large suite of radiocarbon dates. The features include an incipient burned rock midden, burned rock clusters, a debitage reduction area, a biface cache, slab-lined hearths, basin-shaped hearths, and small circular hearths. The distributions of artifacts and features within the Archaic components across the excavation blocks showed significant variations. These differences reflect sequential components that provide a view of diachronic trends in technology, subsistence, economy, and a suite of other behaviors and activities during the long transition from Archaic to Late Prehistoric adaptations. As previously determined by the testing excavations and further substantiated by the data recovery investigations, the Siren site, most notably the Late Archaic and Late Prehistoric components, is eligible for the National Register of Historic Places under Criterion D, 36 CFR 60.4, and eligible for State Archeological Landmark designation under Criteria 1 and 2 of the Rules of Practice and Procedure for the Antiquities Code of Texas, 13 TAC 26.8. The excavations and subsequent analysis have mitigated the adverse effects of the bridge construction by recovering the vast majority of the affected components within the area of potential effect. No further archaeological work is recommended. Portions of the site outside the area of potential effects have not been fully evaluated, and any future impacts beyond the mitigated areas warrant further assessment

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Optimization of percutaneous biopsy for diagnosis and pretreatment risk assessment of neuroblastoma

BackgroundImage- guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma.ProcedureA multi- institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3- year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children’s Oncology Group for risk stratification.ResultsA total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P = .314) or determine MYCN copy number (92.4% vs 97.8%, P = .111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P < .05; and 58.0% vs. 88.5%, P < .05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy.ConclusionsPCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real- time pathology assessment of specimen quality.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154667/1/pbc28153_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154667/2/pbc28153.pd

Optimization of percutaneous biopsy for diagnosis and pretreatment risk assessment of neuroblastoma

Background: Image-guided percutaneous core needle biopsy (PCNB) is increasingly utilized to diagnose solid tumors. The objective of this study is to determine whether PCNB is adequate for modern biologic characterization of neuroblastoma. Procedure: A multi-institutional retrospective study was performed by the Pediatric Surgical Oncology Research Collaborative on children with neuroblastoma at 12 institutions over a 3-year period. Data collected included demographics, clinical details, biopsy technique, complications, and adequacy of biopsies for cytogenetic markers utilized by the Children\u27s Oncology Group for risk stratification. Results: A total of 243 children were identified with a diagnosis of neuroblastoma: 79 (32.5%) tumor excision at diagnosis, 94 (38.7%) open incisional biopsy (IB), and 70 (28.8%) PCNB. Compared to IB, there was no significant difference in ability to accurately obtain a primary diagnosis by PCNB (95.7% vs 98.9%, P =.314) or determine MYCN copy number (92.4% vs 97.8%, P =.111). The yield for loss of heterozygosity and tumor ploidy was lower with PCNB versus IB (56.1% vs 90.9%, P \u3c.05; and 58.0% vs. 88.5%, P \u3c.05). Complications did not differ between groups (2.9 % vs 3.3%, P = 1.000), though the PCNB group had fewer blood transfusions and lower opioid usage. Efficacy of PCNB was improved for loss of heterozygosity when a pediatric pathologist evaluated the fresh specimen for adequacy. Conclusions: PCNB is a less invasive alternative to open biopsy for primary diagnosis and MYCN oncogene status in patients with neuroblastoma. Our data suggest that PCNB could be optimized for complete genetic analysis by standardized protocols and real-time pathology assessment of specimen quality