FGF9 can induce endochondral ossification in cranial mesenchyme

BACKGROUND: The flat bones of the skull (i.e., the frontal and parietal bones) normally form through intramembranous ossification. At these sites cranial mesenchymal cells directly differentiate into osteoblasts without the formation of a cartilage intermediate. This type of ossification is distinct from endochondral ossification, a process that involves initial formation of cartilage and later replacement by bone. RESULTS: We have analyzed a line of transgenic mice that expresses FGF9, a member of the fibroblast growth factor family (FGF), in cranial mesenchymal cells. The parietal bones in these mice show a switch from intramembranous to endochondral ossification. Cranial cartilage precursors are induced to proliferate, then hypertrophy and are later replaced by bone. These changes are accompanied by upregulation of Sox9, Ihh, Col2a1, Col10a1 and downregulation of CbfaI and Osteocalcin. Fate mapping studies show that the cranial mesenchymal cells in the parietal region that show a switch in cell fate are likely to be derived from the mesoderm. CONCLUSION: These results demonstrate that FGF9 expression is sufficient to convert the differentiation program of (at least a subset of) mesoderm-derived cranial mesenchyme cells from intramembranous to endochondral ossification

NGC 7789: An Open Cluster Case Study

We have obtained high-resolution spectra of 32 giants in the open cluster NGC 7789 using the Wisconsin-Indiana-Yale-NOAO Hydra spectrograph. We explore differences in atmospheric parameters and elemental abundances caused by the use of the linelist developed for the Gaia-ESO Survey (GES) compared to one based on Arcturus used in our previous work. [Fe/H] values decrease when using the GES linelist instead of the Arcturus-based linelist; these differences are probably driven by systematically lower (~ -0.1 dex) GES surface gravities. Using the GES linelist we determine abundances for 10 elements - Fe, Mg, Si, Ca, Ti, Na, Ni, Zr, Ba, and La. We find the cluster's average metallicity [Fe/H] = 0.03 +/- 0.07 dex, in good agreement with literature values, and a lower [Mg/Fe] abundance than has been reported before for this cluster (0.11 +/- 0.05 dex). We also find the neutron-capture element barium to be highly enhanced - [Ba/Fe] = +0.48 +/- 0.08 - and disparate from cluster measurements of neutron-capture elements La and Zr (-0.08 +/- 0.05 and 0.08 +/- 0.08, respectively). This is in accordance with recent discoveries of supersolar Ba enhancement in young clusters along with more modest enhancement of other neutron-capture elements formed in similar environments.Comment: 15 pages, 9 figures, Table 1 typo fixe

The Transnational Political Economy of Corporate Governance Regulation: A Research Outline

Corporate governance has become a buzzword of the global business community and is now receiving even wider attention given the repercussions of the Enron collapse. Although there is a burgeoning literature on this topic, the bulk of it is either highly normative or focused on corporate governance practices at the level of the firm. In contrast, our aim is to explain the current transformations of corporate governance regulation. Whereas this regulation used to be a distinctly national affair, it is now increasingly an area subject to both public and private (self-) regulation in multiple arenas, of which three are outstandingly important as well as closely interrelated and, therefore, form the empirical focus of the programme:- Europeanisation in the area of corporate governance regulation affects national regimes of corporate governance with a particular historical diversity, without entirely replacing them.- The EU, furthermore, does not operate in a vacuum but in a transatlantic and global context where it has to negotiate its choices with both state (mainly the US) and non-state actors. At the global level, private bodies such as the International Accounting Standards Board set many corporate governance standards, and international organisations like the OECD disseminate norms for good corporate governance.- Central and East European countries (CEEC) are exposed to the multiple (and partially conflicting) demands by global institutions and the EU when developing their corporat

Advance Care Planning In Frail Older People In The Netherlands

Advance Care Planning (ACP) enables individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and healthcare providers, and to record and review these preferences if appropriate. ACP may be especially relevant for frail older people since this population is most likely to develop physical and cognitive deficits in the near future and most likely to have to rely on others to communicate their treatment preferences. This thesis describes the effects of an ACP program in a randomized controlled trial among frail older people in the Netherlands, and concludes with recommendations for clinical practice and future research

An evaluation of exact matching and propensity score methods as applied in a comparative effectiveness study of inhaled corticosteroids in asthma

Peer reviewedPublisher PD

Brand and generic use of inhalation medication and frequency of switching in children and adults : a population-based cohort study

BACKGROUND: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. AIM: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. METHODS: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). CONCLUSION: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted

Many-body interactions and melting of colloidal crystals

We study the melting behavior of charged colloidal crystals, using a simulation technique that combines a continuous mean-field Poisson-Boltzmann description for the microscopic electrolyte ions with a Brownian-dynamics simulation for the mesoscopic colloids. This technique ensures that many-body interactions between the colloids are fully taken into account, and thus allows us to investigate how many-body interactions affect the solid-liquid phase behavior of charged colloids. Using the Lindemann criterion, we determine the melting line in a phase-diagram spanned by the colloidal charge and the salt concentration. We compare our results to predictions based on the established description of colloidal suspensions in terms of pairwise additive Yukawa potentials, and find good agreement at high-salt, but not at low-salt concentration. Analyzing the effective pair-interaction between two colloids in a crystalline environment, we demonstrate that the difference in the melting behavior observed at low salt is due to many-body interactions

Towards an E-Government Enterprise Architecture Framework for Developing Economies

The growth and uptake of e-government in developing economies are still affected by the interoperability challenge, which can be perceived as an orchestration of several issues that imply the existence of gaps in methods used for e-government planning and implementation. To a great extent, various counterparts in developed economies have succeeded in addressing the method-related gaps by developing e-government enterprise architectures, as blueprints for guiding e-government initiatives in a holistic and manageable way. However, existing e-government enterprise architectures are country-specific to appropriately serve their intended purpose, while enterprise architecture frameworks or methods are generic to accommodate several enterprise contexts. The latter do not directly accommodate the unique peculiarities of e-government efforts. Thus, a detailed method is lacking that can be adapted by developing economies to develop e-government enterprise architectures that fit their contexts. To address the gap, this article presents research that adopted a Design Science approach to develop an e-Government Enterprise Architecture Framework (EGEAF), as an explicit method for guiding the design of e-government enterprise architectures in a developing economy. EGEAF was designed by extending the Architecture Development Method of The Open Group Architecture Framework (TOGAF ADM) to address requirements for developing interoperable e-government solutions in a developing economy. EGEAF was evaluated using two scenarios in the Ugandan context, and findings indicate that it is feasible; its design is understandable to enable its adoption and extension to accommodate requirements for developing interoperable e-government solutions in other developing economies