Neuroprotective efficacy of P7C3 compounds in primate hippocampus.

There is a critical need for translating basic science discoveries into new therapeutics for patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, a target-agnostic in vivo screen in mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude of postnatal neurogenesis by protecting young neurons from death. Subsequently, neuroprotective efficacy of P7C3 compounds in a broad spectrum of preclinical rodent models has also been observed. An important next step in translating this work to patients is to determine whether P7C3 compounds exhibit similar efficacy in primates. Adult male rhesus monkeys received daily oral P7C3-A20 or vehicle for 38 weeks. During weeks 2-11, monkeys received weekly injection of 5'-bromo-2-deoxyuridine (BrdU) to label newborn cells, the majority of which would normally die over the following 27 weeks. BrdU+ cells were quantified using unbiased stereology. Separately in mice, the proneurogenic efficacy of P7C3-A20 was compared to that of NSI-189, a proneurogenic drug currently in clinical trials for patients with major depression. Orally-administered P7C3-A20 provided sustained plasma exposure, was well-tolerated, and elevated the survival of hippocampal BrdU+ cells in nonhuman primates without adverse central or peripheral tissue effects. In mice, NSI-189 was shown to be pro-proliferative, and P7C3-A20 elevated the net magnitude of hippocampal neurogenesis to a greater degree than NSI-189 through its distinct mechanism of promoting neuronal survival. This pilot study provides evidence that P7C3-A20 safely protects neurons in nonhuman primates, suggesting that the neuroprotective efficacy of P7C3 compounds is likely to translate to humans as well

Support for the higher-order factor structure of the WHODAS 2.0 self-report version in a Dutch outpatient psychiatric setting

PURPOSE: Previous studies of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) interview version suggested a second-order model, with a general disability factor and six factors on a lower level. The goal of this study is to investigate if we can find support for a similar higher-order factor structure of the 36-item self-report version of the WHODAS 2.0 in a Dutch psychiatric outpatient sample. We aim to give special attention to the differences between the non-working group sample and the working group sample. Additionally, we intend to provide preliminary norms for clinical interpretation of the WHODAS 2.0 scores in psychiatric settings. METHODS: Patients seeking specialized ambulatory treatment, primarily for depressive or anxiety symptoms, completed the WHODAS 2.0 as part of the initial interview. The total sample consisted of 770 patients with a mean age of 37.5 years (SD = 13.3) of whom 280 were males and 490 were females. Several factorial compositions (i.e., one unidimensional model and two second-order models) were modeled using confirmatory factor analysis (CFA). Descriptive statistics, model-fit statistics, reliability of the (sub)scales, and preliminary norms for interpreting test scores are reported. RESULTS: For the non-working group, the second-order model with a general disability factor and six factors on a lower level, provided an adequate fit. Whereas, for the working group, the second-order model with a general disability factor and seven factors on a lower level seemed more appropriate. The WHODAS 2.0 36-item self-report form showed adequate levels of reliability. Percentile ranks and normalized T-scores are provided to aid clinical evaluations. CONCLUSION: Our results lend support for a factorial structure of the WHODAS 2.0 36-item self-report version that is comparable to the interview version. While we conjecture that a seven-factor solution might give a better reflection of item content and item variance, further research is needed to assess the clinical relevance of such a model. At this point, we recommend using the second-order structure with six factors that matches past findings of the interview form

The Judas Iscariot Syndrome and Its Implication for Accounting Educators

The study is qualitative and applied the appreciative inquiry approach to address the "Judas Iscariot syndrome" of misappropriation and wrong assumptions among accountants and treasurers. It is believed that Seventh-day Adventist universities integrate faith and learning in their educational curriculum to cause a behavioral change. There seems to be a gap between knowledge, values, and the practice of accounting and financial management. From the biblical perspective, Judas Iscariot was the treasurer among the twelve disciples of Jesus Christ, but he was said to be a thief (see John 12:4-6). This study utilized a semi-structured, self-developed, open-ended questions in interviewing ten accounting educators at Valley View University, Ghana from the Oyibi and Techiman campuses and based on the triangulation method and the 5-D cycle approach of appreciative inquiry (Define, Discover, Dream, Design, and Delivery). The study revealed that in order to generate positive change, self-discipline, truthfulness, and conscience to duty must be inculcated into the current accounting education to make the student dream to have contentment. The achievement of contentment is based on a design of biblical and ethical discussion, sharing of examples and personal experiences, truth writing and telling, and audiovisual presentation. The study recommends that accounting educators must live an exemplary life, mentor students, use ethical simulations and debates to instill self-discipline, truthfulness, and conscience to duty. A roadmap of Christian Behavior Change for Accounting Educators is developed. 

Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning

Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC. We show that TBI-induced migration of megakaryocytes to the endosteal niche depends on thrombopoietin signaling through the c-MPL receptor on megakaryocytes, as well as CD41 integrin-mediated adhesion. Moreover, niche osteoblast proliferation post-TBI required megakaryocyte-secreted platelet-derived growth factor-BB. Furthermore, blockade of c-MPL-dependent megakaryocyte migration and function after TBI resulted in a significant decrease in donor HSC engraftment in primary and competitive secondary transplantation assays. Finally, we administered thrombopoietin to mice beginning 5 days before marrow radioablation and ending 24 hours before transplant to enhance megakaryocyte function post-TBI, and found that this strategy significantly enhanced donor HSC engraftment, providing a rationale for improving hematopoietic recovery and perhaps overall outcome after clinical HSC transplantation.Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC. We show that TBI-induced migration of megakaryocytes to the endosteal niche depends on thrombopoietin signaling through the c-MPL receptor on megakaryocytes, as well as CD41 integrin-mediated adhesion. Moreover, niche osteoblast proliferation post-TBI required megakaryocyte-secreted platelet-derived growth factor-BB. Furthermore, blockade of c-MPL-dependent megakaryocyte migration and function after TBI resulted in a significant decrease in donor HSC engraftment in primary and competitive secondary transplantation assays. Finally, we administered thrombopoietin to mice beginning 5 days before marrow radioablation and ending 24 hours before transplant to enhance megakaryocyte function post-TBI, and found that this strategy significantly enhanced donor HSC engraftment, providing a rationale for improving hematopoietic recovery and perhaps overall outcome after clinical HSC transplantation

The Ionization Fraction in Dense Molecular Gas II: Massive Cores

We present an observational and theoretical study of the ionization fraction in several massive cores located in regions that are currently forming stellar clusters. Maps of the emission from the J = 1-> O transitions of C18O, DCO+, N2H+, and H13CO+, as well as the J = 2 -> 1 and J = 3 -> 2 transitions of CS, were obtained for each core. Core densities are determined via a large velocity gradient analysis with values typically 10^5 cm^-3. With the use of observations to constrain variables in the chemical calculations we derive electron fractions for our overall sample of 5 cores directly associated with star formation and 2 apparently starless cores. The electron abundances are found to lie within a small range, -6.9 < log10(x_e) < -7.3, and are consistent with previous work. We find no difference in the amount of ionization fraction between cores with and without associated star formation activity, nor is any difference found in electron abundances between the edge and center of the emission region. Thus our models are in agreement with the standard picture of cosmic rays as the primary source of ionization for molecular ions. With the addition of previously determined electron abundances for low mass cores, and even more massive cores associated with O and B clusters, we systematically examine the ionization fraction as a function of star formation activity. This analysis demonstrates that the most massive sources stand out as having the lowest electron abundances (x_e < 10^-8).Comment: 35 pages (8 figures), using aaspp4.sty, to be published in Astrophysical Journa

Propagating transverse waves in soft X-ray coronal jets

Aims. The theoretical model for magnetohydrodynamic (MHD) modes guided by a field-aligned plasma cylinder with a steady flow is adapted to interpret transverse waves observed in solar coronal hot jets, discovered with Hinode/XRT in terms of fast magnetoacoustic kink modes. Methods. Dispersion relations for linear magnetoacoustic perturbations of a plasma jet of constant cross-section surrounded by static magnetised plasma are used to determine the phase and group speeds of guided transverse waves and their relationship with the physical parameters of the jet and the background plasma. The structure of the perturbations in the macroscopic parameters of the plasma inside and outside the jet, and the phase relations between them are also established. Results. We obtained a convenient expansion for the long wave-length limit of the phase and group speeds and have shown that transverse waves observed in soft-X-ray solar coronal jets are adequately described in terms of fast magnetoacoustic kink modes by a magnetic cylinder model, which includes the effect of a steady flow. In the observationally determined range of parameters, the waves are not found to be subject to either the Kelvin-Helmholtz instability or the negative energy wave instability, and hence they are likely to be excited at the source of the jet

GCIP water and energy budget synthesis (WEBS)

As part of the World Climate Research Program\u27s (WCRPs) Global Energy and Water-Cycle Experiment (GEWEX) Continental-scale International Project (GCIP), a preliminary water and energy budget synthesis (WEBS) was developed for the period 1996–1999 from the “best available” observations and models. Besides this summary paper, a companion CD-ROM with more extensive discussion, figures, tables, and raw data is available to the interested researcher from the GEWEX project office, the GAPP project office, or the first author. An updated online version of the CD-ROM is also available at http://ecpc.ucsd.edu/gcip/webs.htm/. Observations cannot adequately characterize or “close” budgets since too many fundamental processes are missing. Models that properly represent the many complicated atmospheric and near-surface interactions are also required. This preliminary synthesis therefore included a representative global general circulation model, regional climate model, and a macroscale hydrologic model as well as a global reanalysis and a regional analysis. By the qualitative agreement among the models and available observations, it did appear that we now qualitatively understand water and energy budgets of the Mississippi River Basin. However, there is still much quantitative uncertainty. In that regard, there did appear to be a clear advantage to using a regional analysis over a global analysis or a regional simulation over a global simulation to describe the Mississippi River Basin water and energy budgets. There also appeared to be some advantage to using a macroscale hydrologic model for at least the surface water budgets