Do Learners Fear More than Fear Itself: The Role of Fear in Law Students Educational Experiences

While previous research has examined the various relationships between fear and learning in K-12 academic settings, the relationship is surprisingly unexplored amongst law students. Using a descriptive qualitative approach, we examine the role fear plays in law students’ learning experiences. Through a series of semi-structured interviews a few areas of interest emerged including: fears related to disappointing family members and professors, as well as fears of peer judgment from classmates. The findings of this study demonstrate the unique relationship between the type of fear and how it influences academic motivation within this sample of law students. Based on our findings, we propose suggestions for future research that addresses the potentially detrimental effect of peer judgment on graduate students’ academic motivation

Metformin Treatment Does Not Inhibit Growth of Pancreatic Cancer Patient-Derived Xenografts

There is currently tremendous interest in developing anti-cancer therapeutics targeting cell signaling pathways important for both cancer cell metabolism and growth. Several epidemiological studies have shown that diabetic patients taking metformin have a decreased incidence of pancreatic cancer. This has prompted efforts to evaluate metformin, a drug with negligible toxicity, as a therapeutic modality in pancreatic cancer. Preclinical studies in cell line xenografts and one study in patient-derived xenograft (PDX) models were promising, while recently published clinical trials showed no benefit to adding metformin to combination therapy regimens for locally advanced and metastatic pancreatic cancer. PDX models in which patient tumors are directly engrafted into immunocompromised mice have been shown to be excellent preclinical models for biomarker discovery and therapeutic development. We evaluated the response of four PDX tumor lines to metformin treatment and found that all four of our PDX lines were resistant to metformin. We found that the mechanisms of resistance may occur through lack of sustained activation of adenosine monophosphate-activated protein kinase (AMPK) or downstream reactivation of the mammalian target of rapamycin (mTOR). Moreover, combined treatment with metformin and mTOR inhibitors failed to improve responses in cell lines, which further indicates that metformin alone or in combination with mTOR inhibitors will be ineffective in patients, and that resistance to metformin may occur through multiple pathways. Further studies are required to better understand these mechanisms of resistance and inform potential combination therapies with metformin and existing or novel therapeutics

NP108, an Antimicrobial Polymer with Activity against Methicillin- and Mupirocin-Resistant Staphylococcus aureus

D.K.M., L.K.K., D.W.S., J.R., and D.A.O. are employees of NovaBiotics Ltd. D.A.O. is a director and shareholder of NovaBiotics Ltd. D.K.M., L.K.K., F.H., D.W.S., and J.R. carried out the experiments described in the manuscript. D.K.M., L.K.K., and D.A.O. came up with the ideas and designed the experiments conducted in the manuscript. D.K.M., D.A.O., and L.K.K. wrote and edited the manuscript. Samples for electron microscopy were prepared by the microscopy and histology facility at the University of Aberdeen. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1). AUTHOR CORRECTION Volume 61, no. 9, e00502-17, 2017, https://doi.org/10.1128/AAC.00502-17. Page 1: Carol A. Munro should be added to the list of authors. The updated byline and affiliations are shown above. Page 11: the last paragraph of Acknowledgments should be replaced with the following sentences. The work of Laura K. Katvars was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (1091582). Carol Munro was supported by the MRC Centre for Medical Mycology (MR/N006364/1). Copyright © 2018 American Society for Microbiology.Peer reviewedPublisher PD

Preliminary Characterisation of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity

FUNDING SOURCE The study was funded by NovaBiotics with support from The UK Governments’ Department of Health and Social Care, delivered by Innovate UK. Shane Smith and Carol Munro’s contribution to the project was funded by a Scottish Universities Life Sciences Alliance Bioskape grant award.Peer reviewedPublisher PD

Research priorities in pediatric rheumatology: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus

<p>Abstract</p> <p>Background</p> <p>North American pediatric rheumatologists have created an investigator-initiated research network (the Childhood Arthritis and Rheumatology Research Alliance – CARRA) to facilitate multi-centre studies. One of the first projects undertaken by this network was to define, by consensus, research priorities for the group, and if possible a first group-sponsored clinical trial in which all members could participate.</p> <p>Methods</p> <p>We determined consensus using the Delphi approach. This approach has been used extensively in health research to reach consensus in large groups. It uses several successive iterations of surveys eliciting ideas and opinions from specialists in the field. Three surveys were designed based on this method and were distributed to members of CARRA to elicit and rank-order research priorities.</p> <p>Results</p> <p>A response rate of 87.6% was achieved in the final survey. The most highly ranked research suggestion was to study infliximab treatment of uveitis unresponsive to methotrexate. Other highly ranked suggestions were to study i) the treatment of systemic arthritis with anakinra and ii) the treatment of pediatric systemic lupus erythematosus with mycophenolate mofetil.</p> <p>Conclusion</p> <p>The Delphi approach was an effective and practical method to define research priorities in this group. Ongoing discussion and cooperation among pediatric rheumatologists in CARRA and others world-wide will help in developing further research priorities and to facilitate the execution of clinical trials in the future.</p

Evolution of a TRIM5-CypA Splice Isoform in Old World Monkeys

The TRIM family proteins share a conserved arrangement of three adjacent domains, an N-terminal RING domain, followed by one or two B-boxes and a coiled-coil, which constitutes the tripartite-motif for which the family is named. However, the C-termini of TRIM proteins vary, and include at least nine evolutionarily distinct, unrelated protein domains. Antiviral restriction factor TRIM5α has a C-terminal B30.2/SPRY domain, which is the major determinant of viral target specificity. Here, we describe the evolution of a cyclophilin-A encoding exon downstream of the TRIM5 locus of Asian macaques. Alternative splicing gives rise to chimeric transcripts encoding the TRIM motif fused to a C-terminal CypA domain (TRIM5-CypA). We detected TRIM5-CypA chimeric transcripts in primary lymphocytes from two macaque species. These were derived in part from a CypA pseudogene in the TRIM5 locus, which is distinct from the previously described CypA insertion in TRIM5 of owl monkeys. The CypA insertion is linked to a mutation in the 3′ splice site upstream of exon 7, which may prevent or reduce expression of the α-isoform. All pig-tailed macaques (M. nemestrina) screened were homozygous for the CypA insertion. In contrast, the CypA-containing allele was present in 17% (17/101) of rhesus macaques (M. mulatta). The block to HIV-1 infection in lymphocytes from animals bearing the TRIM5-CypA allele was weaker than that in cells from wild type animals. HIV-1 infectivity remained significantly lower than SIV infectivity, but was not rescued by treatment with cyclosporine A. Thus, unlike owl monkey TRIMCyp, expression of the macaque TRIM5-CypA isoform does not result in increased restriction of HIV-1. Despite its distinct evolutionary origin, Macaca TRIM5-CypA has a similar domain arrangement and shares ∼80% amino-acid identity with the TRIMCyp protein of owl monkeys. The independent appearance of TRIM5-CypA chimeras in two primate lineages constitutes a remarkable example of convergent evolution. Based on the presence of the CypA insertion in separate macaque lineages, and its absence from sooty mangabeys, we estimate that the Macaca TRIM5-CypA variant appeared 5–10 million years ago in a common ancestor of the Asian macaques. Whether the formation of novel genes through alternative splicing has played a wider role in the evolution of the TRIM family remains to be investigated

Nuclear Disks of Gas and Dust in Early Type Galaxies and the Hunt for Massive Black Holes: Hubble Space Telescope Observations of NGC 6251

We discuss Hubble Space Telescope optical images and spectra of NGC 6251, a giant E2 galaxy and powerful radio source at a distance of 106 Mpc (for H_0 = 70 km/s/Mpc). The galaxy is known to host a very well defined dust disk (O'Neil et al. 1994); the exceptional resolution of our V and I images allows a detailed study of the disk structure. Furthermore, narrow band images centered on the Halpha+[NII] emission lines, reveal the presence of ionized gas in the inner 0.3 arcsec of the disk. We used the HST/Faint Object Spectrograph with the 0.09 arcsec aperture to study the velocity structure of the disk. Dynamical models were constructed for two extreme (in terms of central concentration) analytical representations of the stellar surface brightness profile, from which the mass density and corresponding rotational velocity are derived assuming a constant mass-to-light ratio (M/L)_V ~ 8.5 M_solar/L_solar. For both representations of the stellar component, the models show that the gas is in Keplerian motion around a central mass ~ 4 - 8 X 10^8 solar masses, and that the contribution of radial flows to the velocity field is negligible.Comment: 45 pages, submitted to Ap

Relationship Stability After Traumatic Brain Injury Among Veterans and Service Members: A VA TBI Model Systems Study

Objective: To explore stability of relationships and predictors of change in relationship status 2 years following TBI/polytrauma. Setting: Five Department of Veterans Affairs Polytrauma Rehabilitation Centers (VA PRCs). Participants: A total of 357 active duty service members and Veterans enrolled in the Veterans Affairs Polytrauma Rehabilitation Centers Traumatic Brain Injury Model Systems database with complete marital status information at 2 years postinjury. Design: Prospective, longitudinal, multisite. Main Measures: Relationship status change was defined as change in marital status (single/never married; married; divorced/separated) at 2-year follow-up, compared with status at enrollment. Results: At the time of enrollment, 134 participants (38%) were single/never married; 151 (42%) were married, and 72 (20%) were divorced/separated. Of those married at enrollment, 78% remained married at year 2 while 22% underwent negative change. Multivariable analyses revealed that age and education at the time of injury and mental health utilization prior to injury were significant predictors of relationship change. Among those who were single/divorced/separated at the time of enrollment, 87% remained so at year 2 while 13% underwent positive change. Injury during deployment significantly predicted positive relationship change. Conclusions: The unmalleable, preinjury characteristics identified may be used as potential triggers for education, prevention, surveillance, and couples therapy, if needed

Evidence for Increased 5α-Reductase Activity During Early Childhood in Daughters of Women with Polycystic Ovary Syndrome

CONTEXT: Polycystic ovary syndrome (PCOS) is a heritable, complex genetic disease. Animal models suggest that androgen exposure at critical developmental stages contributes to disease pathogenesis. We hypothesized that genetic variation resulting in increased androgen production produces the phenotypic features of PCOS by programming during critical developmental periods. Although we have not found evidence for increased in utero androgen levels in cord blood in the daughters of women with PCOS (PCOS-d), target tissue androgen production may be amplified by increased 5α-reductase activity analogous to findings in adult affected women. It is possible to noninvasively test this hypothesis by examining urinary steroid metabolites. OBJECTIVE: We performed this study to investigate whether PCOS-d have altered androgen metabolism during early childhood. DESIGN, SETTING, AND PARTICIPANTS: Twenty-one PCOS-d, 1–3 years old, and 36 control girls of comparable age were studied at an academic medical center. MAIN OUTCOME MEASURES: Urinary steroid metabolites were measured by gas chromatography/mass spectrometry. Twenty-four hour steroid excretion rates and precursor to product ratios suggestive of 5α-reductase and 11β-hydroxysteroid dehydrogenase activities were calculated. RESULTS: Age did not differ but weight for length Z-scores were higher in PCOS-d compared to control girls (P = .02). PCOS-d had increased 5α-tetrahydrocortisol:tetrahydrocortisol ratios (P = .04), suggesting increased global 5α-reductase activity. There was no evidence for differences in 11β-hydroxysteroid dehydrogenase activity. Steroid metabolite excretion was not correlated with weight. CONCLUSIONS: Our findings suggest that differences in androgen metabolism are present in early childhood in PCOS-d. Increased 5α-reductase activity could contribute to the development of PCOS by amplifying target tissue androgen action