Changing Fecundity and Reproductive Output in Females of a Chesapeake Bay Population of Blue Crab, \u3ci\u3eCallinectes sapidus\u3c/i\u3e

The Chesapeake Bay blue crab, Callinectes sapidus, is an important species both ecologically and as a fishery. Fishery dependent and independent data indicate that the population declined abruptly in the mid-1990s and has remained low. Previous work prior to the decline in population abundance found a significant relationship between size and fecundity for mature females. As with many heavily fished populations, this population has experienced a reduction in the size at maturity. The objectives of this study were to reassess the fecundity of the population, determine the lipid and protein energy allocated for reproduction, and to examine the concentrations of lipid fractions in eggs. This study indicated that the size-fecundity relationship is absent or very weak. Fecundity estimates indicate that individual female fecundity has decreased by an order of magnitude from previously reported values. Egg production varied both inter- and intra-annually with a greater number of smaller eggs produced later in each season. This all suggests that allometric regulation is no longer the primary factor determining egg production in this population. Negative changes in the allocation or availability of energetic resources may be having a significant impact on this population. Lipid and protein concentrations measured from the hepatopancreas, ovaries and eggs of mature female blue crabs demonstrated that first brood production is derived from stored resources in the hepatopancreas. Later brood production is likely allocated for directly from ingested food. Egg lipid and protein concentrations showed considerable inter- and intra-annual variation, suggesting that there were trade offs between lipid and protein allocation. Concentrations of lipid fractions (triglyceride, phospholipid, and cholesterol) also showed variation within and between spawning seasons suggesting significant differences in egg quality. Decreases in population fecundity in conjunction with observed variation in the biochemical content of eggs can have far reaching impacts on the population including larval survivability and recruitment. My results suggest that there are significant shifts in maternal effort, and potentially reproductive success, both inter-annually and seasonally. Fluctuations in energy available to an embryo, as well as the production of fewer embryos have significantly lowered the reproductive output of this population

What is English now? The construction of subject English in contemporary textbooks for Australian secondary schools

Australian educators are currently engaged in widening debates about the performance of the nation’s schools, teachers and students. Perceived literacy deficits among secondary students have fuelled the debate, and this has precipitated reforms to English curricula at both National and State levels. The newly revised curricula attempt to improve student achievement through more systematic teaching about the English language and language skills. In response to the changes, major education publishers in Australia have released revised textbooks for English that purport to engage with the new curriculum. This research study considered whether such new resources offer genuinely fresh and effective approaches to English, or whether they reproduce established conceptions and methods in new packaging. Guided by Michel Foucault’s concepts of social technology and discursive practice, and Ian Hunter’s detailed historical-theoretical analysis of English, this inquiry used a combination of content analysis and theorisation to identify the models of English embodied in textbooks. Five recent publications were studied to expose both the content and the underlying ideas and pedagogical assumptions about English contained within. Hunter’s historical matrix was applied to categorise the content and quantify the overall proportions of rhetorical, ethical and aesthetical instruction evident in the resources. The findings were interpreted according to Hunter’s genealogy of English and its prevailing discourses, in an effort to offer some clarification about the assumptions that shape school English, and its direction now and in the future. The findings suggest that despite attempts to reconstruct English around the teaching of language skills, established conceptions of English have resurfaced, pulling the subject back toward the ethical domain and distorting the overall balance of content. While the data appears to reflect an apparent prominence of rhetorical skilling, analysis of the content demonstrates how this initiative is obscured by a superficial and mechanical treatment of language and a subsequent preoccupation with the ethical. The oscillation between rhetoric and ethics further reveals a visible circumvention of aesthetics, which is unvaryingly the most neglected category. The thesis concludes that change in English is likely being impeded by teaching materials, conceptual frameworks and assumptions that continue to frame English as a primarily ethical activity, in which linguistic skilling is subordinated to self-formation

Characterization of 7A7, an anti-mouse EGFR monoclonal antibody proposed to be the mouse equivalent of cetuximab.

The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer. However, only 15-20% patients benefit from this drug, thus new strategies to improve cetuximab efficiency are required. We aimed to develop a reliable and easy preclinical mouse model to evaluate the efficacy of EGFR-targeted antibodies and examine the immune mechanisms involved in tumour regression. We selected an anti-mouse EGFR mAb, 7A7, which has been reported to be "mouse cetuximab" and to exhibit similar properties to its human counterpart. Unfortunately, we were unable to reproduce previous results obtained with the 7A7 mAb. In our hands, 7A7 failed to recognize mouse EGFR, both in native and reducing conditions. Moreover, in vivo administration of 7A7 in an EGFR-expressing HPV38 tumour model did not have any impact on tumour regression or animal survival. We conclude that 7A7 does not recognize mouse EGFR and therefore cannot be used as the mouse equivalent of cetuximab use in humans. As a number of groups have spent effort and resources with similar issues we feel that publication is a responsible approach

What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

Investigation of chemistry graduate teaching assistants’ teacher knowledge and teacher identity

Graduate students play an integral role in undergraduate chemistry education at doctoral granting institutions where they routinely serve as instructors of laboratories and supplementary discussion sessions. Simultaneously, graduate teaching assistants (GTAs) balance major research and academic responsibilities. Although GTAs have substantial instructional facetime with large numbers of undergraduate students, little is known about their conceptions of teaching or their identities as teachers. To investigate the knowledge that GTAs have regarding teaching in this unique context, their teaching identities, and how these developed, we conducted 22 interviews with graduate students from several universities at various levels in their graduate school career using a modified Teacher Beliefs Interview. Interviews were analyzed for two overarching teacher learning constructs: teacher knowledge and teacher identity. We characterized chemistry GTAs’ teacher knowledge and identity and determined major influencing factors. We found that chemistry GTAs often identified as a tutor or lab manager, which hindered their self‐investment in developing as teachers. The results presented herein contribute to an understanding of GTAs’ teacher knowledge, teacher identity, and their teaching context, from which training can be designed to best support GTA development.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155950/1/tea21618_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155950/2/tea21618.pd

Langerhans cell histiocytosis of the sternum

We report a rare case of Langerhans cell histiocytosis involving the sternum. The patient was a 12-year-old girl presenting with anterior chest pain and swelling. Radiographs and computed tomography showed an osteolytic lesion in the sternum. Technetium bone scintigraphy revealed increased uptakes in the sternum, the greater trochanter of the right femur, and the right distal tibia. Incisional biopsy for the sternum lesion was performed, and the histopathologic diagnosis was Langerhans cell histiocytosis. She was treated with chemotherapy and the symptoms disappeared

Physical activity characterization:Does one site fit all?

Background: It is evident that a growing number of studies advocate a wrist-worn accelerometer for the assessment of patterns of physical activity a priori, yet the veracity of this site rather than any other body-mounted location for its accuracy in classifying activity is hitherto unexplored. Objective: The objective of this review was to identify the relative accuracy with which physical activities can be classified according to accelerometer site and analytical technique. Methods: A search of electronic databases was conducted using Web of Science, PubMed and Google Scholar. This review included studies written in the English language, published between database inception and December 2017, which characterized physical activities using a single accelerometer and reported the accuracy of the technique. Results: A total of 118 articles were initially retrieved. After duplicates were removed and the remaining articles screened, 32 full-text articles were reviewed, resulting in the inclusion of 19 articles that met the eligibility criteria. Conclusion: There is no 'one site fits all' approach to the selection of accelerometer site location or analytical technique. Research design and focus should always inform the most suitable location of attachment, and should be driven by the type of activity being characterized

Combination therapy in a xenograft model of glioblastoma: enhancement of the antitumor activity of temozolomide by an MDM2 antagonist

OBJECTIVE Improvement in treatment outcome for patients with glioblastoma multiforme (GBM) requires a multifaceted approach due to dysregulation of numerous signaling pathways. The murine double minute 2 (MDM2) protein may fulfill this requirement because it is involved in the regulation of growth, survival, and invasion. The objective of this study was to investigate the impact of modulating MDM2 function in combination with front-line temozolomide (TMZ) therapy in GBM. METHODS The combination of TMZ with the MDM2 protein-protein interaction inhibitor nutlin3a was evaluated for effects on cell growth, p53 pathway activation, expression of DNA repair proteins, and invasive properties. In vivo efficacy was assessed in xenograft models of human GBM. RESULTS In combination, TMZ/nutlin3a was additive to synergistic in decreasing growth of wild-type p53 GBM cells. Pharmacodynamic studies demonstrated that inhibition of cell growth following exposure to TMZ/nutlin3a correlated with: 1) activation of the p53 pathway, 2) downregulation of DNA repair proteins, 3) persistence of DNA damage, and 4) decreased invasion. Pharmacokinetic studies indicated that nutlin3a was detected in human intracranial tumor xenografts. To assess therapeutic potential, efficacy studies were conducted in a xenograft model of intracranial GBM by using GBM cells derived from a recurrent wild-type p53 GBM that is highly TMZ resistant (GBM10). Three 5-day cycles of TMZ/nutlin3a resulted in a significant increase in the survival of mice with GBM10 intracranial tumors compared with single-agent therapy. CONCLUSIONS Modulation of MDM2/p53-associated signaling pathways is a novel approach for decreasing TMZ resistance in GBM. To the authors' knowledge, this is the first study in a humanized intracranial patient-derived xenograft model to demonstrate the efficacy of combining front-line TMZ therapy and an inhibitor of MDM2 protein-protein interactions

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function