Addendum: "The Dynamics of M15: Observations of the Velocity Dispersion Profile and Fokker-Planck Models" (ApJ, 481, 267 [1997])

It has recently come to our attention that there are axis scale errors in three of the figures of Dull et al. (1997, hereafter D97). D97 presented Fokker-Planck models for the collapsed-core globular cluster M15 that include a dense, centrally concentrated population of neutron stars and massive white dwarfs, but do not include a central black hole. In this Addendum, we present corrected versions of Figures 9, 10, and 12, and an expanded version of Figure 6. This latter figure, which shows the full run of the velocity dispersion profile, indicates that the D97 model predictions are in good agreement with the moderately rising HST-STIS velocity dispersion profile for M15 reported by Gerssen et al. (2002, astro-ph/0209315). Thus, a central black hole is not required to fit the new STIS velocity measurements, provided that there is a sufficient population of neutron stars and massive white dwarfs. This conclusion is consistent with the findings of Gerssen et al. (2002, astro-ph/0210158), based on a reapplication of their Jeans equation analysis using the corrected mass-to-light profile (Figure 12) for the D97 models.Comment: 4 pages, 4 figures, submitted to Ap

Evaluating The Importance Of Competencies Within Accounting Information Systems Curricula

In International Education Guideline No. 11, the International Federation of Accountants identified the essential information technology (IT) competencies, knowledge, and skills required for entry-level accounting positions. These IT competencies are classified into three categories:  (1) IT concepts for business systems (nine competencies), (2) internal control in computer-based business systems (six competencies), and (3) the roles of the professional accountant in information systems (18 competencies classified into three subcategories). In this exploratory study, we surveyed accounting information systems educators about the relative importance of the IFAC competencies to prepare undergraduate students for entry-level accounting positions. The results provide accounting educators with an understanding of current practice regarding the relative emphasis placed on IT competencies in AIS courses.  Using this information, the results may be used to guide the allocation of resources within the AIS curriculum

Identification of Four Potential Epigenetic Modulators from the NCI Structural Diversity Library Using a Cell-Based Assay

Epigenetic pathways help control the expression of genes. In cancer and other diseases, aberrant silencing or overexpression of genes, such as those that control cell growth, can greatly contribute to pathogenesis. Access to these genes by the transcriptional machinery is largely mediated by chemical modifications of DNA or histones, which are controlled by epigenetic enzymes, making these enzymes attractive targets for drug discovery. Here we describe the characterization of a locus derepression assay, a fluorescence-based mammalian cellular system which was used to screen the NCI structural diversity library for novel epigenetic modulators using an automated imaging platform. Four structurally unique compounds were uncovered that, when further investigated, showed distinct activities. These compounds block the viability of lung cancer and melanoma cells, prevent cell cycle progression, and/or inhibit histone deacetylase activity, altering levels of cellular histone acetylation

Fokker-Planck Models for M15 without a Central Black Hole: The Role of the Mass Function

We have developed a set of dynamically evolving Fokker-Planck models for the collapsed-core globular star cluster M15, which directly address the issue of whether a central black hole is required to fit Hubble Space Telescope (HST) observations of the stellar spatial distribution and kinematics. As in our previous work reported by Dull et al., we find that a central black hole is not needed. Using local mass-function data from HST studies, we have also inferred the global initial stellar mass function. As a consequence of extreme mass segregation, the local mass functions differs from the global mass function at every location. In addition to reproducing the observed mass functions, the models also provide good fits to the star-count and velocity-dispersion profiles, and to the millisecond pulsar accelerations. We address concerns about the large neutron star populations adopted in our previous Fokker-Planck models for M15. We find that good model fits can be obtained with as few as 1600 neutron stars; this corresponds to a retention fraction of 5% of the initial population for our best fit initial mass function. The models contain a substantial population of massive white dwarfs, that range in mass up to 1.2 solar masses. The combined contribution by the massive white dwarfs and neutron stars provides the gravitational potential needed to reproduce HST measurements of the central velocity dispersion profile.Comment: 10 pages, 7 figure

Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase

BACKGROUND Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. METHODS NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. RESULTS Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). CONCLUSIONS At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasi

Preventing dispensing errors by alerting for drug confusions in the pharmacy information system—A survey of users

Introduction Drug confusion is thought to be the most common type of dispensing error. Several strategies can be implemented to reduce the risk of medication errors. One of these are alerts in the pharmacy information system. Objective To evaluate the experiences of pharmacists and pharmacy technicians with alerts for drug name and strength confusion. Methods In May 2017, a cross-sectional survey of pharmacists and pharmacy technicians was performed in community pharmacies in the Netherlands using an online questionnaire. Results Of the 269 respondents, 86% (n = 230) had noticed the alert for drug name confusion, and 26% (n = 67) for drug strength confusion. Of those 230, 9% (n = 20) had experienced that the alert had prevented dispensing the wrong drug. For drug strength confusion, this proportion was 12% (n = 8). Respondents preferred to have an alert for drug name and strength confusion in the pharmacy information system. ‘Alert fatigue’ was an important issue, so alerts should only be introduced for frequent confusions or confusions with serious consequences. Conclusion Pharmacists and pharmacy technicians were positive about having alerts for drug confusions in their pharmacy information system and experienced that alerts contributed to the prevention of dispensing errors. To prevent alert fatigue, it was considered important not to include all possible confusions as a new alert: the potential contribution to the prevention of drug confusion should be weighed against the risk of alert fatigue

Lentiviral gene transfer into the dorsal root ganglion of adult rats

<p>Abstract</p> <p>Background</p> <p>Lentivector-mediated gene delivery into the dorsal root ganglion (DRG) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells <it>in vitro </it>and adult rat DRG <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro</it>, lentivectors expressing enhanced green fluorescent protein (EGFP) under control of the human elongation factor 1α (EF1α) promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G) envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs), and into primary cultured DRG neurons at higher MOIs. <it>In vivo</it>, injection of either first or second-generation EF1α-EGFP lentivectors directly into adult rat DRGs led to transduction rates of 19 ± 9% and 20 ± 8% EGFP-positive DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells included a full range of neuronal phenotypes, including myelinated neurons as well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons.</p> <p>Conclusion</p> <p>VSV-G pseudotyped lentivectors containing the human elongation factor 1α (EF1α)-EGFP expression cassette demonstrated relatively efficient transduction to sensory neurons following direct injection into the DRG. These results clearly show the potential of lentivectors as a viable system for delivering target genes into DRGs to explore basic mechanisms of neuropathic pain, with the potential for future clinical use in treating chronic pain.</p

An overview of the Michigan Positron Microscope Program

An overview of the Michigan Positron Microscope Program is presented with particular emphasis on the second generation microscope that is presently near completion. The design and intended applications of this microscope will be summarized.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87602/2/391_1.pd

Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial

Background Neonates born to women infected with HIV are at increased risk for invasive group B streptococcus (GBS) disease. We aimed to compare safety and immunogenicity of trivalent glycoconjugate GBS vaccine in pregnant women with and without HIV in Malawi and South Africa. Methods In our non-randomised phase 2, open-label, multicentre study, we recruited pregnant women attending two antenatal clinics, one in Blantyre, Malawi, and one in Soweto, Johannesburg, South Africa. Participants were divided into three groups on the basis of their HIV infection status (no infection, infection and high CD4 cell count [>350 cells per mu L], and infection and low CD4 cell count [>50 to <= 350 cells per mu L]) and received a 5 mu g dose of glycoconjugate GBS vaccine (serotypes Ia, Ib, and III, with CRM197 [Novartis Vaccines, Siena, Italy]) intramuscularly at 24-35 weeks' gestation. GBS serotype-specific antibody concentrations were measured before vaccination (day 1), day 15, day 31, and at delivery, and in infants at birth and day 42 of life. The primary outcomes were safety in mothers and infants and the amount of placental transfer of GBS serotype-specific antibodies from mothers to their infants. All immunogenicity and safety analyses were done on the full analysis set, including participants who, or whose mother, correctly received the vaccine and who provided at least one valid assessable serum sample. This study is registered with ClinicalTrials.gov, number NCT01412801. Findings 270 women and 266 infants were enrolled between Sept 26, 2011, and Dec 4, 2012 (90 women and 87 infants without HIV, 89 and 88 with HIV and high CD4 cell counts, and 91 and 91 with HIV and low CD4 cell counts, respectively). Seven women were lost to follow-up, six withdrew consent, one died, and two relocated. Eight infants died or were stillborn and two were lost to follow-up. Across serotypes, fold change in antibody concentrations were higher for the HIV-uninfected group than the HIV-infected groups. Transfer ratios were similar across all three groups (0.49-0.72; transfer ratio is infant geometric mean antibody concentration in blood collected within 72 h of birth divided by maternal geometric mean antibody concentration in blood collected at delivery); however, at birth, maternally derived serotype-specific antibody concentrations were lower for infants born to women infected with HIV (0.52-1.62 mu g/mL) than for those born to women not infected with HIV (2.67-3.91 mu g/mL). 151 (57%) of 265 women reported at least one solicited adverse reaction: 39 (45%) of 87 women with HIV and low CD4 cell counts, 52 (59%) of 88 women with HIV and high CD4 cell counts, and 60 (67%) of 90 women in the HIV-uninfected group. 49 (18%) of 269 women had at least one adverse event deemed possibly related to the vaccine (six [7%] in the HIV and low CD4 cell count group, 12 [13%] in the HIV and high CD4 cell count group, and 21 [23%] in the HIV-uninfected group), as did three (1%) of 266 neonates (zero, two [1%], and one [1%]); none of these events was regarded as serious. Interpretation The vaccine was less immunogenic in women infected with HIV than it was in those not infected, irrespective of CD4 cell count, resulting in lower levels of serotype-specific maternal antibody transferred to infants, which could reduce vaccine protection against invasive GBS disease. A validated assay and correlate of protection is needed to understand the potential protective value of this vaccine. Copyright (C) Heyderman et al. Open Access article distributed under the terms of CC BY