Survival rates and prognostic predictors of high grade brain stem gliomas in childhood : a systematic review and meta-analysis

Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the survival rates and assess potential prognostic factors including selected interventions. Studies included involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy reporting overall survival rates. Meta-analysis was undertaken using a binomial random effects model. Sixty-five studies (2336 participants) were included. Meta-analysis showed 1 year overall survival (OS) of 41% (95% confidence interval (CI) 38-44%, I-sq 52%, 2083 participants), 2 year OS of 15.3% (95% confidence interval 12-20%, I-sq 73.1%, 1329 participants) and 3 year OS of 7.3% (95% confidence interval 5.2-10%, I-sq 26%, 584 participants). Meta-analyses of median overall survival results was not possible due to the lack of reported measures of variance. Subgroup analysis comparing date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. There was insufficient data to undertake subgroup meta-analysis of patient age, duration of symptoms, K27M histone mutations and AVCR1 mutations. Survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or use of different therapeutic interventions. Future studies should harmonize outcome and prognostic variable reporting to enable accurate meta-analysis and better exploration of prognosis

Improving the Enhanced Journal Access through an Academic Library and Publisher Collaboration

In May 2017, the George A. Smathers Libraries (Libraries) at the University of Florida (UF) andElsevier delivered the Phase I findings of a pilot project that aimed to maximize visibility, impact and dissemination of articles by UF researchers who have published in Elsevier journals. Beginning April 2016, the collaboration provided metadata with article links automatically delivered toUF’s Institutional Repository, the IR@UF, in theIR@UF-Elsevier Collection. As of December 31, 2018, links to over 42,000 articles by UF authors published between 1949 and 2018 are available through integration of the IR@UF with theScienceDirect application programming interfaces (APIs) that are freely available to libraries. Access to full-text articles on ScienceDirect written by UF authors is available for all UF institutional repository users who are affiliated with a ScienceDirect subscribing institution

Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, But is Not Required for Infection in a Novel Male Murine Rectal Infection Model

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. Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection

Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology

PURPOSE: The incidence of invasive fungal disease (IFD) is rising, but its treatment in paediatric haematology and oncology patients is not yet standardised. This review aimed to critically appraise and analyse the clinical practice guidelines (CPGs) that are available for paediatric IFD. METHODS: Electronic searches of MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, the Guidelines International Network (GIN), guideline.gov and Google were performed and combined fungal disease (Fung* OR antifung*OR Candida* OR Aspergill*) with prophylaxis or treatment (prophyl* OR therap* OR treatment). All guidelines were assessed using the AGREE II tool and recommendations relating to prophylaxis, empirical treatment and specific therapy were extracted. RESULTS: Nineteen guidelines met the inclusion criteria. The AGREE II scores for the rigour of development domain ranged from 11 to 92 % with a median of 53 % (interquartile range 32-69 %). Fluconazole was recommended as antifungal prophylaxis in all nine of the included guidelines which recommended a specific drug. Liposomal amphotericin B was recommended in all five guidelines giving empirical therapy recommendations. Specific therapy recommendations were given for oral or genital candidiasis, invasive candida infection, invasive aspergillosis and other mould infections. CONCLUSIONS: In many areas, recommendations were clear about appropriate practice but further clarity was required, particularly relating to the decision to discontinue empirical antifungal treatment, the relative benefits of empiric and pre-emptive strategies and risk stratification. Future CPGs could consider working to published guideline production methodologies and sharing summaries of evidence appraisal to reduce duplication of effort, improving the quality and efficiency of CPGs in this area

Crystals of tryptophan indole-lyase and tyrosine phenol-lyase form stable quinonoid complexes.

The binding of substrates and inhibitors to wild-type Proteus vulgaris tryptophan indole-lyase and to wild type and Y71F Citrobacter freundii tyrosine phenol-lyase was investigated in the crystalline state by polarized absorption microspectrophotometry. Oxindolyl-lalanine binds to tryptophan indole-lyase crystals to accumulate predominantly a stable quinonoid intermediate absorbing at 502 nm with a dissociation constant of 35 microm, approximately 10-fold higher than that in solution. l-Trp or l-Ser react with tryptophan indole-lyase crystals to give, as in solution, a mixture of external aldimine and quinonoid intermediates and gem-diamine and external aldimine intermediates, respectively. Different from previous solution studies (Phillips, R. S., Sundararju, B.,Faleev, N. G. (2000) J. Am. Chem. Soc. 122, 1008-1114), the reaction of benzimidazole and l-Trp or l-Ser with tryptophan indole-lyase crystals does not result in the formation of an alpha-aminoacrylate intermediate, suggesting that the crystal lattice might prevent a ligand-induced conformational change associated with this catalytic step. Wild-type tyrosine phenol-lyase crystals bind l-Met and l-Phe to form mixtures of external aldimine and quinonoid intermediates as in solution. A stable quinonoid intermediate with lambda(max) at 502 nm is accumulated in the reaction of crystals of Y71F tyrosine phenol-lyase, an inactive mutant, with 3-F-l-Tyr with a dissociation constant of 1 mm, approximately 10-fold higher than that in solution. The stability exhibited by the quinonoid intermediates formed both by wild-type tryptophan indole-lyase and by wild type and Y71F tyrosine phenol-lyase crystals demonstrates that they are suitable for structural determination by x-ray crystallography, thus allowing the elucidation of a key species of pyridoxal 5'-phosphate-dependent enzyme catalysis

Being Motivated to Protect : The Influence of Sexual Communal Motivations on Sexual Risk Taking

College-aged students are a high-risk population for unplanned pregnancy with 40% of women between the ages of 18-20 experiencing an unplanned pregnancy. This can cause physical, mental, and emotional stress resulting in withdrawal from college for the student. Communal motivation (being oriented towards other’s needs) positively predicts condom use. WISE interventions, a simple yet impactful type of interventions targeted towards addressing a problem, have been shown to be successful. Participants completed a sexual risk behavior measure, sexual risk-taking measure and communal motivations (CM) measure following a sexual health video, and reflection activity were participants either applied the sexual health information to their relationship (experimental) or reflected on the sexual health material presented (control). CM was positively correlated with number of sexual partners in the past 3 months, r(262) = .162,

Academic Library and Publisher Collaboration: Utilizing an Institutional Repository to Maximize the Visibility and Impact of Articles by University Authors

The George A. Smathers Libraries (Libraries) (http://www.uflib.ufl.edu/) at the University of Florida (UF) (http://www.ufl.edu/) and Elsevier (http://www.elsevier.com) have embarked on a pilot project to maximize visibility, impact, and dissemination of articles by UF researchers who have published in Elsevier journals. Article links and metadata are automatically delivered to UF’s Institutional Repository, the IR@UF (http://ufdc.ufl.edu/ir), in the IR@UF-Elsevier Collection (http://ufdc.ufl.edu/ielsevier). The metadata, with links for approximately 31,000 articles by UF authors, is made possible through integration of the IR@UF with the ScienceDirect application programming interfaces (APIs) (https://www.elsevier.com/solutions/sciencedirect/support/institutional-repository) that are freely available to libraries. Access to the full text on ScienceDirect is available for all institutional repository users affiliated with a subscribing institution. In the next phase users without subscriptions will be able to access the manuscripts of articles published from 2013 forward. This will be done by embedding metadata and links to accepted manuscripts available on ScienceDirect into the IR@UF. We will conduct user and usability testing of this cross-platform user experience. This article provides an overview of the project’s current status, how it works, what it delivers, and next steps expanding the project to include articles by UF authors from other publishers. It concludes with strategic considerations, future developments, and reflections on the value of library/publisher collaboration

Observational Evidence from Supernovae for an Accelerating Universe and a Cosmological Constant

We present observations of 10 type Ia supernovae (SNe Ia) between 0.16 < z < 0.62. With previous data from our High-Z Supernova Search Team, this expanded set of 16 high-redshift supernovae and 34 nearby supernovae are used to place constraints on the Hubble constant (H_0), the mass density (Omega_M), the cosmological constant (Omega_Lambda), the deceleration parameter (q_0), and the dynamical age of the Universe (t_0). The distances of the high-redshift SNe Ia are, on average, 10% to 15% farther than expected in a low mass density (Omega_M=0.2) Universe without a cosmological constant. Different light curve fitting methods, SN Ia subsamples, and prior constraints unanimously favor eternally expanding models with positive cosmological constant (i.e., Omega_Lambda > 0) and a current acceleration of the expansion (i.e., q_0 < 0). With no prior constraint on mass density other than Omega_M > 0, the spectroscopically confirmed SNe Ia are consistent with q_0 <0 at the 2.8 sigma and 3.9 sigma confidence levels, and with Omega_Lambda >0 at the 3.0 sigma and 4.0 sigma confidence levels, for two fitting methods respectively. Fixing a ``minimal'' mass density, Omega_M=0.2, results in the weakest detection, Omega_Lambda>0 at the 3.0 sigma confidence level. For a flat-Universe prior (Omega_M+Omega_Lambda=1), the spectroscopically confirmed SNe Ia require Omega_Lambda >0 at 7 sigma and 9 sigma level for the two fitting methods. A Universe closed by ordinary matter (i.e., Omega_M=1) is ruled out at the 7 sigma to 8 sigma level. We estimate the size of systematic errors, including evolution, extinction, sample selection bias, local flows, gravitational lensing, and sample contamination. Presently, none of these effects reconciles the data with Omega_Lambda=0 and q_0 > 0.Comment: 36 pages, 13 figures, 3 table files Accepted to the Astronomical Journa

Stromal Derived Factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis

Renal cell carcinoma (RCC) is characterized by organ-specific metastases. The chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 have been suggested to regulate organ-specific metastasis in various other cancers. On this basis, we hypothesized that the biological axis of CXCL12 via interaction with its receptor, CXCR4, is a major mechanism for RCC metastasis. We demonstrated that CXCR4 was significantly expressed on circulating cytokeratin+ RCC cells from patients with known metastatic RCC. We detected up-regulation of CXCR4 mRNA and protein levels on a human RCC cell line by either knockdown of the von Hippel-Lindau (VHL) tumor suppressor protein, or incubating the cells under hypoxic conditions. The enhanced CXCR4 expression was mediated through the interaction of the Hypoxia Inducible Factor-1α (HIF-1α) with the promoter region of the CXCR4 gene. Furthermore, the expression of CXCR4 on human RCC directly correlated with their metastatic ability in vivo in both heterotopic and orthotopic SCID mouse models of human RCC. Neutralization of CXCL12 in SCID mice abrogated metastasis of RCC to target organs expressing high levels of CXCL12; without altering tumor cell proliferation, apoptosis, or tumor-associated angiogenesis. Therefore, our data suggest that the CXCL12/CXCR4 biological axis plays an important role in regulating the organ-specific metastasis of RCC

Clock-Comparison Tests of Lorentz and CPT Symmetry in Space

Clock-comparison experiments conducted in space can provide access to many unmeasured coefficients for Lorentz and CPT violation. The orbital configuration of a satellite platform and the relatively large velocities attainable in a deep-space mission would permit a broad range of tests with Planck-scale sensitivity.Comment: 4 page