bluuebunny/crossref_metadata_2025 huggingface dataset:
SEM evaluation of root canal debridement with Sonicare CanalBrush irrigation
Authors: Salman M. I. , Baumann M. A. , Hellmich M. , Roggendorf M. J. , Termaat S.
Published: April 2010

Salman MI, Baumann MA, Hellmich M, Roggendorf MJ, Termaat S. SEM evaluation of root canal debridement with Sonicare CanalBrush irrigation. International Endodontic Journal, 43, 363–369, 2010.

Aim  To determine the efficacy of Sonicare CanalBrush irrigation for root canal cleaning.

Methodology  Fifty human molar root canals were shaped with sequential NiTi rotary instruments up to size F3 (size 30, 0.09 taper; ProTaper system) and then enlarged apically with a Profile size 40, 0.04 taper. Five different irrigation protocols were tested (n = 10 canals per group) with 2 mL of distilled water (control, group I) or 2.5% NaOCl (control group II and test groups III, IV and V) between instrument size changes. Group III–IV received a final rinse with 17% EDTA for one min. This was extended by 30 s in group IV, whereas group V received this additional 30 s of 17% EDTA sonically dispersed with a Sonicare CanalBrush. For cleanliness evaluations, roots were split longitudinally, examined with scanning electron microscopy and scored according to Hülsmann et al. (1997) for debris and smear layer on the surface of the root canal wall. Walls were assessed at the coronal, middle and apical thirds. Data were analysed with the Kruskal–Wallis and Mann–Whitney tests.

Results  Irrigation with 17% EDTA significantly reduced debris and smear layer scores (P < 0.05) compared to controls. The coronal and middle thirds had lower debris and smear layer scores than the apical third (P < 0.05). In all thirds, sonic agitation of the irrigant with a CanalBrush (group V) resulted in significantly cleaner canal walls compared to all other groups (P < 0.05).

Conclusions  Irrigation by agitation with the Sonicare CanalBrush improved root canal debridement in the coronal, middle and particularly the apical thirds of the root canal.
Short‐ and long‐term sealing ability of Gutta‐flow and AH‐Plus using an ex vivo fluid transport model
Authors: Vasiliadis L. , Kodonas K. , Economides N. , Gogos C. , Stavrianos C.
Published: April 2010

Vasiliadis L, Kodonas K, Economides N, Gogos C, Stavrianos C. Short‐ and long‐term sealing ability of Gutta‐flow and AH‐Plus using an ex vivo fluid transport model. International Endodontic Journal, 43, 377–381, 2010.

Aim  To use the fluid transport model to evaluate the ex vivo short‐ and long‐term microleakage along root canals filled with Gutta‐flow or AH‐Plus using the cold lateral compaction technique.

Methodology  A total of 38 single‐rooted human teeth were used for the assessment of microleakage. The crowns of the teeth were sectioned below their cemento–enamel junctions to adjust the length of the roots to approximately 15 mm. The root canals were instrumented using the step‐back technique and filled using cold lateral condensation. The sealer employed was either Gutta‐flow (Group A) or AH‐Plus (Group B). Microleakage along the root canals was evaluated using a fluid transport model after periods of 1 week and 3 months.

Results  The microleakage values (μL h−1) for group A were 0.36 ± 0.33 at 1 week and 0.41 ± 0.36 at 3 months. Group B showed mean microleakage values 0.2 ± 0.31 at 1 week and 0.28 ± 0.38 at 3 months. Statistical analysis indicated no significant differences (P > 0.05) between the two groups after either 1 week or 3 months.

Conclusions  There was no significant difference between AH‐plus and Gutta‐flow in terms of sealing ability.
Irrigant flow in the root canal: experimental validation of an unsteady Computational Fluid Dynamics model using high‐speed imaging
Authors: Boutsioukis C. , Verhaagen B. , Versluis M. , Kastrinakis E. , Van Der Sluis L. W. M.
Published: April 2010

Boutsioukis C, Verhaagen B, Versluis M, Kastrinakis E, van der Sluis LWM. Irrigant flow in the root canal: experimental validation of an unsteady Computational Fluid Dynamics model using high‐speed imaging. International Endodontic Journal43, 393–403, 2010.

Aim  To compare the results of a Computational Fluid Dynamics (CFD) simulation of the irrigant flow within a prepared root canal, during final irrigation with a syringe and a needle, with experimental high‐speed visualizations and theoretical calculations of an identical geometry and to evaluate the effect of off‐centre positioning of the needle inside the root canal.

Methodology  A CFD model was created to simulate irrigant flow from a side‐vented needle inside a prepared root canal. Calculations were carried out for four different positions of the needle inside a prepared root canal. An identical root canal model was made from poly‐dimethyl‐siloxane (PDMS). High‐speed imaging of the flow seeded with particles and Particle Image Velocimetry (PIV) were combined to obtain the velocity field inside the root canal experimentally. Computational, theoretical and experimental results were compared to assess the validity of the computational model.

Results  Comparison between CFD computations and experiments revealed good agreement in the velocity magnitude and vortex location and size. Small lateral displacements of the needle inside the canal had a limited effect on the flow field.

Conclusions  High‐speed imaging experiments together with PIV of the flow inside a simulated root canal showed a good agreement with the CFD model, even though the flow was unsteady. Therefore, the CFD model is able to predict reliably the flow in similar domains.
Cytotoxicity of chlorhexidine on human osteoblastic cells is related to intracellular glutathione levels
Authors: Lee T.‐H. , Hu C.‐C. , Lee S.‐S. , Chou M.‐Y. , Chang Y.‐C.
Published: April 2010

Lee T‐H, Hu C‐C, Lee S‐S, Chou M‐Y, Chang Y‐C. Cytotoxicity of chlorhexidine on human osteoblastic cells is related to intracellular glutathione levels. International Endodontic Journal, 43, 430–435, 2010.

Aim  To evaluate the mechanisms of cytotoxicity of chlorhexidine (CHX) in human osteoblastic cells in vitro.

Methodology  Cytotoxicity, cell proliferation and collagen synthesis assays were performed to elucidate the toxic effects of CHX on the human osteoblastic cell line U2OS. To determine whether glutathione (GSH) levels were important in the cytotoxicity of CHX, cells were pre‐treated with 2‐oxothiazolidine‐4‐carboxylic acid (OTZ) to boost GSH levels or buthionine sulfoximine (BSO) to deplete GSH.

Results  CHX demonstrated a cytotoxic effect to U2OS cells in a dose‐dependent manner (P < 0.05). The 50% inhibition concentration of CHX was approximately 0.005%. CHX also inhibited cell proliferation and collagen synthesis (P < 0.05). The addition of OTZ acted as a protective effect on the CHX‐induced cytotoxicity (P < 0.05). In contrast, the addition of BSO enhanced the CHX‐induced cytotoxicity (P < 0.05).

Conclusions  The levels of CHX tested inhibited cell growth, proliferation and collagen synthesis on U2OS cells. CHX has significant potential for periapical toxicity. GSH depletion might be one of the mechanisms underlying CHX cytotoxicity.
Phytophthora andina sp. nov., a newly identified heterothallic pathogen of solanaceous hosts in the Andean highlands
Authors: Oliva R. F. , Kroon L. P. N. M. , Chacón G. , Flier W. G. , Ristaino J. B. , Forbes G. A.
Published: April 2010

A blight disease on fruits and foliage of wild and cultivated Solanum spp. was found to be associated with a new species of Phytophthora. The proposed novel species is named Phytophthora andina Adler & Flier, sp. nov. based on morphological characteristics, pathogenicity assays, mitochondrial DNA haplotyping, AFLP fingerprinting and nuclear and mitochondrial DNA sequence analyses. Isolates of P. andina (n = 48) from the Andean highland tropics of Ecuador were collected from 1995 to 2006. Phytophothora andina is closely related to P. infestans and has semipapillate, ellipsoidal sporangia borne on sympodially branched sporangiophores. It is heterothallic and produces amphigynous antheridia. The species consists of several clonal lineages, including the EC‐2 and EC‐3 RFLP lineages, which were described previously as P. infestans. Approximately 75% of isolates react as compatibility type A2 when paired with an A1 compatibility type isolate of P. infestans. However, when A2 isolates from the Anarrhichomenum section of Solanum were paired in all combinations, viable oospores were obtained in several crosses, suggesting that there is a unique compatibility interaction in P. andina that is complementary to that described in P. infestans. Nuclear and mitochondrial sequence analysis supported the species designation of P. andina. This newly identified heterothallic pathogen shares a common ancestor with P. infestans and may have arisen from hybridization events with sister taxa in the Andes.
Cardiospecific expression of AAV vectors
Authors: Kupatt C.
Published: April 2010

Adenoviral vectors have been set for cardiomyocyte gene therapy with considerable transfection rates. However, due to adenoviral immunogenicity, adenoviral transfected cells are frequently subject to specific cellular immune reactions leading to loss of cells and transgene expression. Non‐pathogenic adeno associated vectors lacking immunogenicity have been utilized alternately. Tropism of the most common AAV serotype 2, favoring liver of muscle transfection, has been altered by use of serotypes 1, 6 and 9.

We used a model of chronic (4 weeks) regional myocardial transfection of the pig to investigate transfection efficacy of AAV vectors, which were applied to the target region by retroinfusion. Cardiac restriction was ensured by utilization of an MLC‐2v promoter‐CMV‐enhancer construct, fused to a luciferase reporter gene, the activity of which was analyzed.

Compared to the wildtype (WT) AAV 2 vector, which barely exceeded background luciferase activity, a vector lacking the heparin binding site of the envelope (AAV2 ΔHep) improved expression only slightly. Substantial increase to 40 000 RLU/mg tissue) was achieved by the addition of VEGF‐A, which enhances vascular permeability. A further 15‐fold increase of luciferase activity was achieved by applying an equal amount of AAV6 virus particles to a pig heart, with a further 5–10 fold increase achieved by utilization of AAV serotype 9.

Functionally relevant gene transfer was ensured by applying AAV9 hVEGF/PDGF (0.2/0.4 × 1013 virus particles, respectively). 4 weeks after retroinfusion into pig hearts suffering from chronic total LAD‐occlusion (induced by a reduction stent), we found a significant increase of blood flow and regional myocardial function.

We conclude that AAV9 is a more efficient AAV vector when compared to WT‐ or ΔHep‐AAV2 or AAV6. Functionally relevant gene expression, as performed by VEGF‐A/PDGF transfection, opens the door for utilization of this vector system for xenotransplant organ priming.
Negative costimulation to prevent human anti‐pig T cell responses
Authors: Schwinzer R. , Plege A.
Published: April 2010

Genetic modification of pigs [e.g. transgenic expression of human complement regulatory molecules or inactivation of α(1,3)‐galactosyltransferase] enabled the development of promising strategies to overcome hyperacute rejection after pig‐to‐primate xenotransplantation. However, cellular rejection still remains a hurdle for successful xenograft survival. Our group focuses on the inhibition of human anti‐pig T cell responses by targeting ‘‘negative’’ costimulatory pathways. We tested the hypothesis that over‐expression of the human negative costimulatory ligands PD‐L1 and PD‐L2 on pig cells will result in reduced human anti‐pig T cell responses. To this end, pig cell lines stably over‐expressing human PD‐Ligands (L23‐PD‐L1/L2 cells) and appropriate controls (L23‐GFP cells) were generated and used for in vitro stimulation of purified human CD4+ T cells. Furthermore, the effect of PD‐L expression on cellular cytotoxicity was tested by 51Cr‐release assays using L23‐PD‐L1/L2 and L23‐GFP cells as targets and IL‐2‐activated human CD8+ T cells and NK cells as effector. CD4+ T cells responded with significantly reduced proliferation to L23‐PD‐L1 or L23‐PD‐L2 cells and produced less IL‐2, IFNγ, TNFα, IL‐4, and IL‐5 than cells stimulated with mock‐transfected B cells. The concentration of IL‐10, however, was increased in CD4+ T cells responding to stimulation with PD‐L1 or PD‐L2 transfectants. Furthermore, in cultures of CD4+ T cells stimulated for 3 weeks with PD‐L1 or PD‐L2 transfectants a CD4+CD25highFoxp3+ subset showed up that effectively suppressed the activation of conventional CD4+ T cells. CD8+ T cells and NK cells acquired cytolytic potential and up‐regulated the PD‐1 receptor during cultivation with IL‐2. Both cell types lysed L23‐GFP cells very effectively but were less potent on L23‐PD‐L1 targets (reduced cytotoxicity of about 50%). When cytotoxic effector cells were used that do not express PD‐1 (293‐95L cells), L23‐GFP and L23‐PD‐L1 cells were lysed with similar intensity suggesting that PD‐1/PD‐L1 interactions are required for PD‐L1 mediated protection. Flow cytometric studies revealed that a proportion of activated CD8+PD‐1+ T cells underwent apoptosis when exposed to PD‐L1 expressing L23 cells. Together these observations support the assumption that PD‐1/PD‐Ligand pathways are interesting targets to prevent human anti‐pig cellular immune responses after xenotransplantation [1]. PD‐L over‐expression might not only empede the initiation of a human anti‐pig T cell response by suppressing CD4+ T cells but may also protect pig cells from destruction by human cytotoxic effectors. Supported by the Deutsche Forschungsgemeinschaft (Transregio Forscher‐gruppe ‘‘Xenotransplantation’’, FOR 535).

Reference

1. Plege A, Borns K, Baars W, Schwinzer R. Suppression of human T‐cell activation and expansion of regulatory T cells by pig cells overexpressing PD‐ligands. Transplantation 2009; 87: 975–982.
Porcine pathogens and xenotransplantation: PERV and beyond!
Authors: Scobie L.
Published: April 2010

Concerns regarding the transmission of potentially zoonotic porcine viruses via a xenotransplant have prompted a significant number of studies on methods to eliminate or prevent expression and transmission of these viruses. The main focus of these studies, to date, has been the porcine endogenous retrovirus (PERV); PERV is a genetically acquired element and present in the genome of all swine. This situation is problematic as it cannot simply be eliminated from swine by using methods currently employed to exclude exogenous pathogens in barrier facilities. As such, alternative strategies have been sought to circumvent the potential risk of PERV expression and transmission via a xenotransplant, however, there are other existing and emerging pathogens of concern that should be addressed when using this novel technology in vivo.

Zoonotic porcine viruses have been identified that require specific diagnostic methods to confirm their absence. Animal husbandry and the exclusion of pathogens from SPF herds for use in xenotransplantation have been widely discussed and a number of organizations have issued guidelines on the screening for infectious agents. Although these recommendations on monitoring protocol and the identification of adventitious agents are clear, there is no comprehensive list of pathogens to be excluded from these animals that can be applied to all centres carrying out xenotransplantation. Currently, SPF animals used for research purposes are monitored for specific pathogens as defined by local guidelines, and may not be tested for all pathogens relevant to xenotransplantation.

As recent data has indicated the potential for certain porcine pathogens to cross the species barrier, it is clear that xenotransplantation is a unique situation which may require us to address a more comprehensive panel of microorganisms than is currently recommended for SPF animals. This presentation will discuss data on the presence of pathogens in pigs, other than PERV, that may cause concern during the clinical application of xenotransplantation and the issues regarding the potential transfer of new zoonotic microorganisms.
Cell therapeutic strategies to improve pig islet graft survival after xenotransplantation
Authors: Sattler C. , Steinsdörfer M. , Offers M. , Seissler J.
Published: April 2010

Transplantation of the whole pancreas organ or isolated Langerhans‐islets is the only methods to cure Type 1 diabetes. Transplantation is largely limited by the lack of organ donors and considerable side effects of immunosuppressive therapies. Porcine pancreas represents a promising cell source to overcome the shortage of islets. Due to the strong rejection of xenoantigens novel strategies such as the generation of transgenic pig islets are needed. Another complementary alternative is the co‐transplantation with immunomodulatory cells that mediate only local immunosuppression at the transplantation site.

Mesenchymal stem cells (MSCs) are unique cells residing in different tissues which possess pleiotropic immunoregulatory activities. We isolated murine and human MSCs from bone‐marrow (CD73+, CD105+) and used them for in vitro experiments (mixed lymphocyte reaction after mitogen, allogenic and xenogenic stimulation) and co‐transplantation studies in diabetic C57BL/6 mice.

Both murine and human MSCs exert strong immunosuppressive effects on lymphocyte proliferation (up to 75% and 80% respectively). Interestingly, there were major differences in the underlying mechanisms. We were able to demonstrate for the first time that mouse MSCs suppressed MLR by a combination of prostaglandin E2 production and adenosine formation. Only human but not mouse MSCs do express the tryptophan degrading enzyme indoleamine 2,3‐dioxygenase (IDO) upon stimulation with proinflammatory cytokines. Our features such as TGFβ and hepatocyte growth factor (HGF) production also contribute to the immunoregulatory effect. When human lymphocytes were challenges with porcine antigens there was a strong proliferative immune response which can be suppressed in a dose‐dependent manner by the addition of hMSCs (inhibition up to 95%). Co‐transplantation of allogenic islets with MSCs favoured islet cell function and survival. This effect was dependent on the MSC source as demonstrated by the fact that the use of donor MSCs resulted in longer survival rate as compared to syngenic MSCs. In current experiments we test the effect of hMSCs in the NOD SCID‐IL2R–/–mouse model to study immune response of human PBMCs towards porcine islets.

In conclusion, our results strongly support and extend the concept that MSCs are potent candidates to control cellular immune rejection. We observed surprising differences in the immunosuppressive properties between mouse and human MSCs. Since human MSCs also strongly suppress immune response against pig antigens, they are promising novel candidates to modulate the local microenviroment for islet cell xenotransplantation. The next step is to analyse survival of transgenic pig islets (CTLA‐4 Ig) with and without hMSC in diabetic NOD SCID‐IL2R–/–mice.

Supported by the Deutsche Forschungsgemeinschaft (Transregio Forschergruppe ‘‘Xenotransplantation’’, FOR 535).
Survival and function of CD47‐deficient thymic grafts in mice
Authors: Wang Yuantao , Wang Hui , Wang Shumei , Fu Yaowen , Yang Yong‐Guang
Published: April 2010

Wang Y, Wang H, Wang S, Fu Y, Yang Y‐G. Survival and function of CD47‐deficient thymic grafts in mice. Xenotransplataion 2010; 17: 160–165. © 2010 John Wiley & Sons A/S.

Abstract: Background:  We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, it remains unknown whether CD47 incompatibility also contributes to the rejection of non‐hematopoietic xenografts.

Aims:  Here, we investigated the role of CD47 in preventing macrophage‐mediated rejection of thymic epithelial cells in a mouse model of thymic transplantation across the CD47 barrier.

Methods:  Wild‐type (WT) and CD47 KO mice were thymectomized and treated with T cell‐depleting mAbs, and implanted with fetal thymus from syngeneic WT or CD47 KO donors.

Results:  Transplantation of CD47 KO mouse thymus led to T cell recovery in thymectomized, T cell‐depleted WT mice. Similar to the control WT mouse thymic grafts, CD47 KO mouse thymic grafts showed a normal distribution of thymocyte subsets, and almost all of the thymocytes were recipient origin. Furthermore, histological analysis confirmed long‐term survival of CD47 KO mouse thymic epithelial cells in WT mouse recipients.

Conclusions:  These results demonstrate that, unlike hematopoietic cells, CD47 KO mouse thymus can survive and function in WT mice. Furthermore, our data implicate that the role of CD47 in xenograft rejection may differ for different types of xenografts, and that CD47 incompatibility is unlikely to impede thymic xenotransplantation, a potential approach to inducing xenotolerance, by triggering macrophage‐mediated rejection.
Xenotransplantation literature update: November 2009–January 2010
Authors: Schneider Mårten K. J. , Seebach Jörg D.
Published: April 2010

Schneider MKJ, Seebach JD. Xenotransplantation literature update: November 2009–January 2010. Xenotransplantation 2010; 17: 166–170. © 2010 John Wiley & Sons A/S.
An Exceptional Response? Security, Development and Civil Society in Spanish Policy after 11‐M
Authors: Colás Alejandro
Published: April 2010

This article considers the ways in which Spanish state institutions responded to the Madrid bombings of 11 March 2004 in the context of the global ‘War on Terror’. It examines three inter‐related arenas of Spanish policy after 9/11 in which security and civil society are invoked in ways that impact upon the country's development agenda toward its southern Mediterranean partners. The first relates to Spain's external relations with its North African neighbours, and in particular the place of migration in shaping these relations over the last decade. The second concerns Spain's political relations with the representative organizations of its own Muslim populations. A third area of analysis pertains to the juridical‐institutional reactions of the state to the 11 March attacks: how have public authorities and civil society been affected and refashioned in the face of jihadist terrorism on the peninsula? The author argues that in each of these domains, the post‐9/11 context generally, and the 11 March attacks in particular, have elicited a securitization of civil society, which has in turn been associated with the country's international relations and domestic politics. Such securitization, however, has only been partially successful, thus vindicating the continuation of ‘politics as usual’ among Spain's state officials and its civil society.
Managing Dissent in a Post‐genocide Environment: The Challenge of Political Space in Rwanda
Authors: Beswick Danielle
Published: April 2010

This article analyses how political space, defined here as the ability of actors other than the government to critically engage in debate on government policy and practice, is being constituted in post‐genocide Rwanda. Using evidence from interviews with civil society activists and examples from the Rwandan Government's post‐genocide policies, it explores the kind of political space which results from an interplay of potentially competing influences. These include the promotion of a liberal approach to democracy, favoured by many of Rwanda's donors, and a more tightly‐managed and limited transition which is both preferred by and beneficial for the RPF Government. The article shows that although space could be seen in some areas as opening, this trend is hampered by government actions, including legislative and shadow methods, by donor reluctance to pressure the ruling RPF and by fear within civil society of tackling politically sensitive issues. In conclusion, the author suggests that this fear is reinforced by government policies which narrow perceptions of political space, exacerbated by perceived abandonment of civil society by donors, and that in combination these factors pose a long‐term challenge to more openly contested politics in Rwanda.
Accountability and Inaction: NGOs and Resource Lodging in Development
Authors: Harsh Matthew , Mbatia Paul , Shrum Wesley
Published: April 2010

From the late 1980s, research on NGOs had a normative focus and was vulnerable to changing donor preoccupations. This article contributes a new conceptual approach, analysing the practices through which relationships and resources are translated into programmes and projects. The theoretical justification for this move combines the new ethnography of development practice with a re‐agency approach to transactions across time and space. The study is based on data including thirty hours of video ethnography involving interviews and field visits with Kenyan NGOs in a variety of sectors. The analysis focuses on the problem of accountability that emerged through the interactions of donors and state corruption. We argue that NGOs operating in capital cities often provide organizational solutions to this problem. Depending on donor preferences, varying amounts of resources become ‘lodged’ or absorbed in ‘capital NGOs’ as they provide accounts of programmes that satisfy donors. However, no matter the donor preferences, capital NGOs provide accountability independently of increased action with communities or increased resources transferred to them. We conclude that the institutionalization of the NGO field as a well‐grounded specialization depends in part on the degree to which researchers can sideline the stories generated in inter‐organizational contexts such as workshops and policy meetings, and substitute understandings based on accounting practices, resource flows and social ties.
Counter‐terrorism and the Regulation of Civil Society in the USA
Authors: Sidel Mark
Published: April 2010

This article examines the impact of counter‐terrorism measures on non‐profit regulation in the USA, where some of the most interventionist legal and policy responses took hold soon after the brutal attacks of September 2001. It highlights the sternness of these measures by comparing the US approach to counter‐terrorism and charity regulation with that of the UK. It suggests that the different institutional arrangements for charity regulation in the two countries account in part for different treatment and policy choices, with implications for civil society groups working domestically and overseas. The article particularly analyses the impact of legislation and policy on the American philanthropic sector, and the responses of civil society to measures enacted and undertaken in the USA. It argues that groups directly affected by the new legislation and hardened policy, especially Muslim charities and some civil liberties group, have openly resisted these measures, while mainstream non‐profit sector and philanthropic institutions have often acquiesced in the introduction of new policies, ‘guidelines’ and legislation, opposing them only when they felt directly threatened.
Efavirenz directly modulates the oestrogen receptor and induces breast cancer cell growth
Authors: Sikora MJ , Rae JM , Johnson MD , Desta Z
Published: April 2010

Objectives

Efavirenz‐based HIV therapy is associated with breast hypertrophy and gynaecomastia. Here, we tested the hypothesis that efavirenz induces gynaecomastia through direct binding and modulation of the oestrogen receptor (ER).

Methods

To determine the effect of efavirenz on growth, the oestrogen‐dependent, ER‐positive breast cancer cell lines MCF‐7, T47D and ZR‐75‐1 were treated with efavirenz under oestrogen‐free conditions in the presence or absence of the anti‐oestrogen ICI 182,780. Cells treated with 17β‐oestradiol in the absence or presence of ICI 182,780 served as positive and negative controls, respectively. Cellular growth was assayed using the crystal violet staining method and an in vitro receptor binding assay was used to measure the ER binding affinity of efavirenz.

Results

Efavirenz induced growth in MCF‐7 cells with an estimated effective concentration for half‐maximal growth (EC50) of 15.7 μM. This growth was reversed by ICI 182,780. Further, efavirenz binds directly to the ER [inhibitory concentration for half maximal binding (IC50) of ∼52 μM] at a roughly 1000‐fold higher concentration than observed with 17β‐oestradiol.

Conclusions

Our data suggest that efavirenz‐induced gynaecomastia may be caused, at least in part, by drug‐induced ER activation in breast tissues.
The Transmission of US Monetary Policy to the Euro Area*
Authors: Neri Stefano , Nobili Andrea
Published: April 2010

This paper studies how changes in the federal funds rate by the US Federal Reserve affect the eurozone economy. In our analysis, the international transmission mechanism works through movements in the exchange rate, commodity prices, short‐term interest rates and the trade balance. We find that an increase in the federal funds rate causes the euro to immediately depreciate, while commodity, and in particular oil, prices decline sharply, reflecting a decline in demand. Lower commodity prices stimulate household consumption in the short run, and the higher aggregate demand induces an expansion of eurozone economic activity. Our results show that the effects of changes in the federal funds rate on commodity prices are greater than previously found in the literature. Our analysis also assesses the likely effects on the eurozone economy of the European Central Bank's (ECB's) own responses to macroeconomic developments. We find that the expansionary effect of lower commodity prices and a depreciated euro on the eurozone economy is partially offset by the ECB increasing short‐term nominal interest rates to curb inflationary pressures in an expanding economy. This result highlights the importance of commodity prices and the euro–dollar exchange rate as inputs into European monetary policy‐making, as seen, for example, in the Eurosystem staff macroeconomic projections used by the Governing Council to assess the risks to price stability.
Cross‐Border Diversification in Bank Asset Portfolios*
Authors: Buch Claudia M. , Driscoll John C. , Ostergaard Charlotte
Published: April 2010

We compute optimally diversified international asset portfolios for banks located in France, Germany, Italy, the United Kingdom and the United States using the mean–variance portfolio model with currency hedging. We compare these benchmark portfolios with the actual cross‐border asset positions of banks from 1995 to 2003 and ask whether the differences are best explained by regulations, institutions, cultural conditions or other financial frictions. Our results suggest that both culture and regulations affect the probability of a country's being overweighted in banks' portfolios: countries whose residents score higher on a survey measure of trust are more likely to be overweighted, while countries that have tighter capital controls are less likely to be overweighted. From a policy standpoint, the importance of culture suggests a limit to the degree of financial integration that may be achievable by the removal of formal economic barriers.
Reforming the Global Reserve Regime: The Role of a Substitution Account*
Authors: Kenen Peter B.
Published: April 2010

The governor of China's central bank recently revived a proposal for the creation of a ‘substitution account’, managed by the International Monetary Fund (IMF), into which central banks and governments could deposit dollar reserves in exchange for claims denominated in Special Drawing Rights (SDRs), the Fund's quasi‐currency. This paper summarizes simulations that measure the potential cost of such an arrangement to the United States were it to guarantee the solvency of the account. The simulations show that those costs would be small relative to the size of US external assets and of the US economy. The paper also shows how the costs could be shared with the depositors. Creation of a substitution account could make the SDRs the principal reserve asset in the international monetary system, achieving a major reform of the reserve regime and enhancing the role of the International Monetary Fund.
How political representatives earn legitimacy: a symbolic approach
Authors: Daloz Jean‐Pascal
Published: April 2010

This article explores the issue of political elites' symbolic legitimation from theoretical and comparative points of view. With the rise of democratic ideals, it can be argued that the image of political elites has been fundamentally transformed because the control of governments exercised by citizens as voters works to narrow the symbolic gap between the rulers and the ruled. However, efforts to explain the symbolic logics of political representation in present‐day democracies with one generalisable law would amount to denying important sources of difference. There are huge cultural variations, even among apparently similar democratic countries. Moving away from evolutionist interpretations that tend to rely on debatable socio‐political dichotomies and reductive causalities, this article attempts to improve our understanding of the legitimation processes at stake through a discussion of the conundrum of eminence versus proximity.
Legitimacy and the quality of democracy
Authors: Morlino Leonardo
Published: April 2010

This article discusses the connections between legitimacy and the quality of democracy. The multiple dimensions of the quality of democracy are presented and it is shown that legitimacy is at the core of the definition of responsiveness. Citizens' reactions to government policies are analysed. Also stressed are the limits and constraints of considering responsiveness only in relationship to citizens' attitudes towards government and institutions. Other dimensions are taken into account, particularly electoral accountability.
Political legitimacy: new criteria and anachronistic theories
Authors: Dogan Mattei
Published: April 2010

Two of the three types of legitimacy identified by Max Weber over a century ago, traditional and charismatic, are virtually inapplicable today. The third and only type that remains valid, rational legitimacy, has become an amalgamation of many different varieties, an incoherent collection of cases. Due to this diversity the type is no longer meaningful. Weber's typology is therefore out of touch with the contemporary world. The reasons behind this obsolescence are analysed empirically and the need for new distinctions demonstrated. The role of elites in the legitimation and delegitimation processes is given particular attention, as well as the links between illegitimacy and mistrust.
Evolution of development of vascular cambia and secondary growth
Authors: Spicer Rachel , Groover Andrew
Published: April 2010

Secondary growth from vascular cambia results in radial, woody growth of stems. The innovation of secondary vascular development during plant evolution allowed the production of novel plant forms ranging from massive forest trees to flexible, woody lianas. We present examples of the extensive phylogenetic variation in secondary vascular growth and discuss current knowledge of genes that regulate the development of vascular cambia and woody tissues. From these foundations, we propose strategies for genomics‐based research in the evolution of development, which is a next logical step in the study of secondary growth.

Contents

Summary
577

I.
Introduction
577

II.
Generalized function of vascular cambia and their developmental and evolutionary origins
578

III.
Variation in secondary vascular growth in angiosperms
581

IV.
Genes and mechanisms regulating secondary vascular growth and their evolutionary origins
584

V.
Evolution of development approaches for the study of secondary vascular growth
587

VI.
Conclusions
589

Acknowledgements
589

References
589
Reliability and validity of the attitudes to ageing questionnaire for Canadian and Norwegian older adults
Authors: Kalfoss Mary H. , Low Gail , Molzahn Anita E.
Published: April 2010

Scand J Caring Sci; 2010; 24; 75–85 Reliability and validity of the attitudes to ageing questionnaire for Canadian and Norwegian older adults

The aim of this study was to examine the reliability and validity of the Attitudes to Ageing Questionnaire (AAQ), a new scale designed for cross‐cultural comparisons of older adults. There are currently very few measures intended to measure the attitudes of older adults to their own ageing. The instrument was designed as part of a larger study to develop a measure of quality of life (QOL) of older adults and to assess factors related to QOL; it was hypothesized that attitudes to ageing would be related to QOL. Canadian (n = 202) and Norwegian (n = 490) data were used. In both study samples, a series of correlation analyses indicated that item scores correlated most strongly with their parent subscales (r=0.42–0.79; p < 0.01). Acceptable internal consistency was shown (Cronbach’s alpha of 0.70 or greater for all subscales). In a confirmatory factor analyses (CFA), all 24 items in the AAQ were retained (p < 0.001); the observed lack of goodness of fit and residual covariance patterns provided empirical support, in part, for the construct validity of the AAQ. Patterns of correlations of the AAQ subscales with WHOQOL‐OLD facets, WHOQOL‐BREF domains, a global QoL item and GDS scores provided evidence of convergent and divergent validity. Nonsignificant correlations were found between psychological growth and two facets of the WHOQOL‐OLD in the Canadian sample. Subscale scores also significantly discriminated between healthy and unhealthy groups. Further validation of the scale among older people, across countries, is recommended.
Conservation biogeography – foundations, concepts and challenges
Authors: Richardson David M. , Whittaker Robert J.
Published: April 2010

Conservation biogeography involves the application of biogeographical principles, theories, and analyses to problems regarding biodiversity conservation. The field was formally defined in 2005, and considerable research has been conducted in the ensuing 5 years.

This editorial sets the context for 16 contributions in a special issue of Diversity and Distributions on developments and challenges in conservation biogeography. Papers are grouped into the following main themes: species distribution modelling; data requirements; approaches for assigning conservation priorities; approaches for integrating information from numerous disparate sources; special challenges involving invasive species; and the crucial issue of determining how elements of biodiversity are likely to respond to rapid climate change. One paper provides a synthesis of requirements for a robust conservation biogeography for freshwater ecosystems.

Conservation biogeography is well poised to make a significant contribution to the process of providing policy makers with objectively formulated scenarios and options for the effective management of biodiversity. The editorial, and the papers in the special issue, deliberate on many of the exciting developments in play in the field, and the many complex challenges that lie ahead.
Adolescent endometriosis in the Waikato region of New Zealand – A comparative cohort study with a mean follow‐up time of 2.6 years
Authors: ROMAN Jose D
Published: April 2010

Study objective:  To describe our experience with laparoscopic excision of endometriosis on an adolescent population and to compare it with a non‐adolescent population treated during the same period.

Design:  Comparative cohort study of patients with endometriosis treated consecutively between July 2003 and January 2009 with a follow‐up between six months and six years.

Setting:  Braemar Hospital, Hamilton, New Zealand.

Results:  We treated 20 adolescents. Ninety‐five per cent (19/20) of adolescents were using pain relief other than Paracetamol, in contrast to only 59% (84/143) of non‐adolescents. Thirty per cent (6/20) of adolescents had a first‐degree relative with endometriosis, in contrast to 8% (11/143) of non‐adolescents. Endometriosis was found to be stage I in 40% (8/20) of patients, stage II in 45% (9/20) of patients, stage III in 5% (1/20) of patients and stage IV in 10% (2/20) of patients. The main type of endometriotic lesion in the adolescent was an atypical red vascular lesion, which was present in 60% (12/20) of adolescents; but it was present in only 20% (29/143) of non‐adolescents. There were no intra‐operative complications. Minor postoperative complications included one case of urinary tract infection and one case of port infection. The operative complications that developed when treating the non‐adolescent group are presented for comparison. Pain scores recorded at follow‐up revealed a significant reduction in dysmenorrhoea and pelvic pain and there was a positive effect on the quality of life of adolescents as measured by the EQ‐5D questionnaire tool.

Conclusion:  Adolescents with endometriosis use significantly more pain relief than non‐adolescents to control symptoms. They have a higher rate of a first degree relative with the disease and they present with more atypical endometriotic lesions when compared with an adult population with endometriosis. All the stages of disease are present in the adolescent, including stages III and IV. The laparoscopic excision of endometriosis has a positive effect on the relief of pain symptoms and on the improvement in quality of life in the adolescent.
Blood Glucose Control in the Intensive Care Unit: Benefits and Risks
Authors: Gunst Jan , Van den Berghe Greet
Published: April 2010

Abnormal blood glucose levels are common during critical illness and are associated with outcomes that correspond to a J‐shaped curve, the lowest risk associated with normoglycemia. Three proof‐of‐concept randomized‐controlled‐trials performed in the surgical, medical, and pediatric intensive care units of the Leuven University Hospital in Belgium demonstrated that maintaining strict age‐adjusted normal fasting levels of glycemia (80–110 mg/dl in adults, 70–100 mg/dl in children, 50–80 mg/dl in infants) with intensive insulin therapy reduced morbidity and mortality as compared with tolerating stress hyperglycemia as a potentially beneficial response. Recently, concern has risen about the safety of this intervention, as a multicenter adult study reported an, as yet unexplained, increased mortality with targeting normoglycemia as compared with an intermediate blood glucose level of around 140 mg/dl. This apparent contradiction may be explained by several methodological differences among studies, comprising, among others, different glucose target ranges in the control groups, different feeding policies, and variable accuracy of tools used for glucose measurement and insulin infusion. Hence, efficacy and safety of intensive insulin therapy may be affected by patient‐related and ICU setting‐related variables. Therefore, no single optimal blood glucose target range for ICU patients can be advocated. It appears safe not to embark on targeting “age‐normal” levels in intensive care units (ICUs) that are not equipped to accurately and frequently measure blood glucose, and have not acquired extensive experience with intravenous insulin administration using a customized guideline. A simple fallback position could be to control blood glucose levels as close to normal as possible without evoking unacceptable blood glucose fluctuations, hypoglycemia, and hypokalemia.
ASDIN: Percutaneous Retrieval of an Intravascular Fluency Stent‐Graft Using a Rigid Alligator Forceps: Case Report
Authors: Alomari Ahmad I.
Published: April 2010

The author reports a case of a successful retrieval of a stent‐graft in a young patient with a femoral dialysis graft. The stent‐graft was used to treat a resistant occluded segment of the arterial limb of the graft. However, the stent‐graft was inadvertently deployed partially into the superficial femoral artery. The stent‐graft was successfully retrieved utilizing a rigid alligator forceps. The resulting dissection/thrombosis of the artery was managed successfully with transcatheter thrombolysis and the function of the dialysis graft was restored.
A Quality Improvement Model for Optimizing Care of the Diabetic End‐Stage Renal Disease Patient
Authors: Mahnensmith Rex L. , Zorzanello Mary , Hsu Yueh‐Han , Williams Mark E.
Published: April 2010

Persons with diabetes mellitus whose kidney disease progresses to end‐stage requiring dialysis have poorer outcomes compared to nondiabetic patients who commence maintenance dialysis. In the diabetic patient without renal failure, sustained strict glycemic, lipid, and blood pressure (BP) control can retard or thwart diabetic complications such as retinopathy, neuropathy, coronary disease, and peripheral vascular disease. Achieving these outcomes requires multidisciplinary collaborative care. Best care of the diabetic person requires a dedicated clinician who knows the patient well, who closely follows the course of clinical problems, who provides frequent assessments and interventions, and who also directs care to other agencies, clinics, and specialized clinicians who provide expert focused evaluations and interventions aimed at specific clinical concerns. Diabetic patients who reach end‐stage renal disease (ESRD) have even greater clinical need of a dedicated principal care clinician than the diabetic patient who has minimal or moderate kidney disease. The diabetic patient with ESRD exhibits greater fluctuations in glucose and BP due to dialysis‐related diet patterns and fluid balances and has more active cardiovascular problems due to the combined influences of calcium, phosphorus, and lipid imbalances. These problems warrant exceptional care that includes frequent surveillance and monitoring with timely interventions if patient outcomes are to be improved. We present here a quality improvement model for optimizing care of the diabetic dialysis patient that relies on a dedicated practitioner who can evaluate and intervene on the multiple variables within and beyond the dialysis clinic that impact the patient’s health. We present three detailed clinical care pathways that the dedicated clinician can follow. We believe that patient outcomes can be improved with this approach that provides customized problem‐focused care, collaborates with the dialysis‐provider team, and extends and directs diabetic self‐care, home‐care, and specialized clinical care in the challenging areas of cardiac and peripheral vascular disease, glycemic control, lipid control, infection prevention, and BP management.
The Influence of Operational Protocol on the Fluid Dynamics in the 12 cc Penn State Pulsatile Pediatric Ventricular Assist Device: The Effect of End‐Diastolic Delay
Authors: Cooper Benjamin T. , Roszelle Breigh N. , Long Tobias C. , Deutsch Steven , Manning Keefe B.
Published: April 2010

The success of adult ventricular assist devices (VADs), coupled with the high transplant waiting list mortality of infants (40%) has prompted Penn State to develop a pediatric version of the clinically successful adult device. Although the primary use of this device will be bridge‐to‐transplant, there has been sufficient clinical data to demonstrate the efficacy of VADs in a bridge‐to‐recovery setting. However, removing the patient from the device, a process known as weaning, demands operation of the device at a lower beat rate and concomitant increased risk for thromboembolism. Previous studies have shown that the interrelated flow characteristics necessary for the prevention of thrombosis in a pulsatile VAD are a strong inlet jet, a late diastolic recirculating flow, and a wall shear rate greater than 500/s. In an effort to develop a strong inlet jet and rotational flow pattern at a lower beat and flow rate, we have compressed diastole by altering the end‐diastolic delay time (EDD). Particle image velocimetry was used to compare the flow fields and wall shear rates in the chamber of the 12 cc Penn State pulsatile pediatric VAD operated at 50 beats per minute using EDDs of 10, 50, and 100 ms. Although we expected the 100 ms EDD to have the best wall shear profiles, we found that the 50 ms EDD condition was superior to both the 10 and 100 EDD conditions, due to a longer sustained inlet jet.