Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EX-FAST) study

In this randomized, double-blind, multicenter study, patients whose blood pressure (BP) was uncontrolled by monotherapy were switched directly to amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in 72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BP were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg; P=.0046). Incremental BP reductions were also achieved with both regimens irrespective of previous monotherapy, hypertension severity, diabetic status, body mass index, and age. Peripheral edema was the most frequent adverse event. These results provide support for the BP-lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy.

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, -2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy.

Characterization of thermal and mechanical properties of polypropylene-based composites for fuel cell bipolar plates and development of educational tools in hydrogen and fuel cell technologies

In this project we developed conductive thermoplastic resins by adding varying amounts of three different carbon fillers: carbon black (CB), synthetic graphite (SG) and multi-walled carbon nanotubes (CNT) to a polypropylene matrix for application as fuel cell bipolar plates. This component of fuel cells provides mechanical support to the stack, circulates the gases that participate in the electrochemical reaction within the fuel cell and allows for removal of the excess heat from the system. The materials fabricated in this work were tested to determine their mechanical and thermal properties. These materials were produced by adding varying amounts of single carbon fillers to a polypropylene matrix (2.5 to 15 wt.% Ketjenblack EC-600 JD carbon black, 10 to 80 wt.% Asbury Carbon's Thermocarb TC-300 synthetic graphite, and 2.5 to 15 wt.% of Hyperion Catalysis International's FIBRILTM multi-walled carbon nanotubes) In addition, composite materials containing combinations of these three fillers were produced. The thermal conductivity results showed an increase in both through-plane and in-plane thermal conductivities, with the largest increase observed for synthetic graphite. The Department of Energy (DOE) had previously set a thermal conductivity goal of 20 W/m·K, which was surpassed by formulations containing 75 wt.% and 80 wt.% SG, yielding in-plane thermal conductivity values of 24.4 W/m·K and 33.6 W/m·K, respectively. In addition, composites containing 2.5 wt.% CB, 65 wt.% SG, and 6 wt.% CNT in PP had an in–plane thermal conductivity of 37 W/m·K. Flexural and tensile tests were conducted. All composite formulations exceeded the flexural strength target of 25 MPa set by DOE. The tensile and flexural modulus of the composites increased with higher concentration of carbon fillers. Carbon black and synthetic graphite caused a decrease in the tensile and flexural strengths of the composites. However, carbon nanotubes increased the composite tensile and flexural strengths. Mathematical models were applied to estimate through-plane and in-plane thermal conductivities of single and multiple filler formulations, and tensile modulus of single-filler formulations. For thermal conductivity, Nielsen's model yielded accurate thermal conductivity values when compared to experimental results obtained through the Flash method. For prediction of tensile modulus Nielsen's model yielded the smallest error between the predicted and experimental values. The second part of this project consisted of the development of a curriculum in Fuel Cell and Hydrogen Technologies to address different educational barriers identified by the Department of Energy. By the creation of new courses and enterprise programs in the areas of fuel cells and the use of hydrogen as an energy carrier, we introduced engineering students to the new technologies, policies and challenges present with this alternative energy. Feedback provided by students participating in these courses and enterprise programs indicate positive acceptance of the different educational tools. Results obtained from a survey applied to students after participating in these courses showed an increase in the knowledge and awareness of energy fundamentals, which indicates the modules developed in this project are effective in introducing students to alternative energy sources.

The coevolution of cooperation and dispersal in social groups and its implications for the emergence of multicellularity

Background Recent work on the complexity of life highlights the roles played by evolutionary forces at different levels of individuality. One of the central puzzles in explaining transitions in individuality for entities ranging from complex cells, to multicellular organisms and societies, is how different autonomous units relinquish control over their functions to others in the group. In addition to the necessity of reducing conflict over effecting specialized tasks, differentiating groups must control the exploitation of the commons, or else be out-competed by more fit groups. Results We propose that two forms of conflict – access to resources within groups and representation in germ line – may be resolved in tandem through individual and group-level selective effects. Specifically, we employ an optimization model to show the conditions under which different within-group social behaviors (cooperators producing a public good or cheaters exploiting the public good) may be selected to disperse, thereby not affecting the commons and functioning as germ line. We find that partial or complete dispersal specialization of cheaters is a general outcome. The propensity for cheaters to disperse is highest with intermediate benefit:cost ratios of cooperative acts and with high relatedness. An examination of a range of real biological systems tends to support our theory, although additional study is required to provide robust tests. Conclusion We suggest that trait linkage between dispersal and cheating should be operative regardless of whether groups ever achieve higher levels of individuality, because individual selection will always tend to increase exploitation, and stronger group structure will tend to increase overall cooperation through kin selected benefits. Cheater specialization as dispersers offers simultaneous solutions to the evolution of cooperation in social groups and the origin of specialization of germ and soma in multicellular organisms.

An outline of competencies and the appropriate postgraduate educational pathways in implant dentistry

The use of dental implants has become a widely accepted and well-documented treatment option offering to both patients and dentists an alternative to traditional treatment modalities and at the same time opening a brand new area in dental postgraduate education. As such, it is necessary to define the competencies that the graduate student/dentist will need at the different levels of clinical practice in Implant Dentistry and the educational pathways that are required to convey those competencies in a structured manner. The present position paper provides an initial suggestion for the knowledge, skills and behaviour necessary for a graduate student to practice implant dentistry at the different levels of clinical complexity. An outline of the necessary competencies and structure of various levels of postgraduate university courses is provided together with different educational approaches to support them. The present paper should be evaluated as a platform for discussion for future development of postgraduate curricula in implant dentistry rather than a manual on how to design and operate such curricula.

Long-term evaluation of anatomic and functional results after complicated retinal detachment treated with pars plana vitrectomy and heavy silicone oil tamponade

BACKGROUND: Heavier than water tamponades offer the possibility to support the inferior part of the fundus after retinal detachment. The aim of this study was to evaluate the anatomic and functional outcome of complicated retinal detachment treated with vitreous surgery and heavy silicone oil (HSO) tamponade. Surgery was performed in eyes with rhegmatogenous retinal detachment (RD) predominantly in the lower hemisphere or with penetrating injury (either as primary intervention or after development of proliferative vitreoretinopathy [PVR]). MATERIALS AND METHODS: Sixty-one eyes of 61 patients with RD - mostly complicated by PVR - and a minimum follow-up of 12 months were included in this study. Vitreoretinal surgery with HSO (Oxane HD) tamponade was performed in all patients. In 52 patients, heavy silicone oil was used in the management of complicated RD. 9 patients had surgery for complicated RD after penetrating eye injury.The mean follow-up period was 30.3 +/- 10.2 months. RESULTS: The overall final anatomic success rate was 79 %. In 39 % of the cases the retina remained attached during the entire follow-up period. CONCLUSIONS: The anatomic success rate after surgery with HSO (Oxane HD) was relatively low; however, only complex cases bearing a higher risk of retinal re-detachment received HSO in this study. Oxane HD does not appear to have major advantages compared to conventional silicone oil or other new-generation heavy silicone oils in these cases.

Changing Europe and The Relevance of Care and The Caring Professions

The aim of the paper is to introduce the challenges of the international care debate of the last ten years in order to grasp basic social needs, to analyse their treatment in the public and private sphere and to look at the orientation of professional answers by the care-professions. The concept of care enhances the societal dealing with - or ignoring of - different forms of dependency on informal and formal personal and social services throughout the life-cycle (child-care, nursing sick or handicapped persons, supporting the elderly) and in special life situations (from help to lone mothers and their children, via help to drug-addicts to help for homeless people). All societies have different approaches to deal with these life-situations, they do so by employ-ing various mixtures of: familial support, mostly provided by women, social politics, organized by the state, public and/or private social services. This welfare-mix shows different combinations of private and public obligations, paid and und unpaid work, professional and laymen's tasks based on a specific understanding of mo-rality and justice embedded in the gender structure and intergenerational relationships. The importance of social work as a profession in this context differs according to the historical developments and cultural traditions. Characteristic for the profile of social work is the rele-vance of a care ethics and the existence of social rights, the tension of mothering and profes-sional methods, the relationship between help, denial and punishment and the ways of institu-tionalisation. The actuality of this debate is closely intertwined with the restructuring of societal bonds in the face of globalisation, the political reorganisation of states, the changes in the living to-gether of different generations and both sexes and the consequences for the organisation and contents of welfare. Looking at Germany and Eastern Europe two new phenomena of social relevance for the dis-cussion of care work and care needs can be taken as an example: the extent of cheap illegal women laborers travelling between east and west, especially Polish women working intermit-tendly in private care for old people and the highly organized traffiking of women from Russia to Germany to work in the sex business. The care debate entails a reframing of welfare issues in the light of social justice between classes, ethnicities and gender groups.

Probing the function of ionotropic and G protein-coupled receptors in surface-confined membranes

This article reports on recent electrical and optical techniques for investigating cellular signaling reactions in artificial and native membranes immobilized on solid supports. The first part describes the formation of planar artificial lipid bilayers on gold electrodes, which reveal giga-ohm electrical resistance and the insertion and characterization of ionotropic receptors therein. These membranes are suited to record a few or even single ion channels by impedance spectroscopy. Such tethered membranes on planar arrays of microelectrodes offer mechanically robust, long-lasting measuring devices to probe the influence of different chemistries on biologically important ionotropic receptors and therefore will have a future impact to probe the function of channel proteins in basic science and in biosensor applications. In a second part, we present complementary approaches to form inside-out native membrane sheets that are immobilized on micrometer-sized beads or across submicrometer-sized holes machined in a planar support. Because the native membrane sheets are plasma membranes detached from live cells, these approaches offer a unique possibility to investigate cellular signaling processes, such as those mediated by ionotropic or G protein-coupled receptors, with original composition of lipids and proteins.

The Integration of Formal and Non-formal Education: The Dutch “brede school”

The Dutch “brede school” (BS) development originates in the 1990s and has spread unevenly since: quicker in the primary than secondary educational sector. In 2007, there were about 1000 primary and 350 secondary BS schools and it is the intention of the government as well as the individual municipalities to extend that number and make the BS the dominant school form of the near future. In the primary sector, a BS cooperates with crèche and preschool facilities, besides possible other neighborhood partners. The main targets are, first, to enhance educational opportunities, particularly for children with little (western-) cultural capital, and secondly to increase women’s labor market participation by providing extra familial care for babies and small children. All primary schools are now obliged to provide such care. In the secondary sector, a BS is less neighborhood-orientated than a primary BS because those schools are bigger and more often located in different buildings. As in the primary sector, there are broad and more narrow BS, the first profile cooperating with many non-formal and other partners and facilities and the second with few. On the whole, there is a wide variety of BS schools, with different profiles and objectives, dependent on the needs and wishes of the initiators and the neighborhood. A BS is always the result of initiatives of the respective school and its partners: parents, other neighborhood associations, municipality etc. BS schools are not enforced by the government although the general trend will be that existing school organizations transform into BS. The integration of formal and non-formal education and learning is more advanced in primary than secondary schools. In secondary education, vocational as well as general, there is a clear dominance of formal education; the non-formal curriculum serves mainly two lines and objectives: first, provide attractive leisure activities and second provide compensatory courses and support for under-achievers who are often students with migrant background. In both sectors, primary and secondary, it is the formal school organization with its professionals which determines the character of a BS; there is no full integration of formal and non-formal education resulting in one non-disruptive learning trajectory, nor is there the intention to go in that direction. Non-formal pedagogues are partly professionals, like youth- and social workers, partly volunteers, like parents, partly non-educational partners, like school-police, psycho-medical help or commercial leisure providers. Besides that, the BS is regarded by government educational and social policy as a potential partner and anchor for community development. It is too early to make reliable statements about the effects of the BS movement in the Netherlands concerning the educational opportunities for disadvantaged children and their families, especially those with migrant background, and combat further segregation. Evaluation studies made so far are moderately positive but also point to problems of overly bureaucratized structures and layers, lack of sufficient financial resources and, again, are uncertain about long-term effects.

Maternal transfer of IgE and subsequent development of IgE responses in the horse (Equus callabus)

Immunoglobulin E (IgE) mediates the immune response to parasites, but can also cause allergies. In humans maternal IgE is not transferred to cord blood and high levels of cord blood IgE are associated with subsequent allergy. In horses, both maternal IgG and IgE are transferred via colostrum; the IgE levels in the mare's serum, the colostrum and the foal's serum are correlated but the consequences of IgE transfer to foals are not known. By about 6 weeks of age the levels of IgE in foal serum have dropped to a nadir, at 6 months of age the level of IgE has risen only very slightly and is no longer correlated with the levels seen at birth, IgE(+) B-cells could be detected in lymphoid follicles of some foals at this age. Surprisingly, the levels of total IgE detected in a foals serum at 6 months of age are significantly correlated with the level in its serum at 1, 2 and even 3 years of age suggesting that by 6 months of age the foals are synthesizing IgE and that a pattern of relatively higher or lower total serum IgE has been established. The neonatal intestinal mucosa contained connective tissue mast cells which stained for bound IgE in foals up to 9 weeks of age but not mucosal mast cells, thereafter, the intestinal mast cells were IgE negative until 6 months of age. IgE antibodies to Culicoides nubeculosus salivary antigens were detected in Swiss born foals from imported Icelandic mares allergic to Culicoides spp. yet the foals showed no signs of skin sensitization and such second generation foals are known not to have an increased risk of developing allergy to Culicoides. Overall this evidence suggests there is a minimal effector role of maternal IgE also that maternal IgE has waned prior to the onset of IgE synthesis in foals and does not support maternal priming of IgE responses in foals. Furthermore the total levels of IgE in any given foal are seen to be relatively high or low from soon after the onset of IgE synthesis, and most likely they are determined by genetic factors.

Diseases in neonatal foals. Part 1: the 30 day incidence of disease and the effect of prophylactic antimicrobial drug treatment during the first three days post partum

REASONS FOR PERFORMING STUDY: Neonatal diseases have been grouped and analysed but up-to-date statistically significant information about the incidence and prevalence of diseases in foals is limited. Since the 1950s it has been a common management practice to administer a 3 day course of antimicrobial drugs to neonatal foals. This was shown to significantly reduce the incidence of infections (Platt 1977). Since then management practices have improved and it is widely believed that prophylactic antimicrobial drugs are no longer necessary in foal rearing. OBJECTIVES: To determine the 30 day incidences or prevalences (depending on case definition) of various diseases and conditions in the neonatal foal and ascertain the influence of a prophylactic 3 day treatment on the frequency of infections. METHODS: The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). Depending on the stud farm's practice in the use of prophylactic antimicrobial drugs, 2 groups of newborn foals (treated and untreated) were identified and followed for 30 days. RESULTS: The 30 day incidences of infectious diseases under study were between 0.2% (osteomyelitis) and 5.85% (systemic disease with diarrhoea). The overall incidence for 'total infectious diseases' was 8.27%. The most commonly observed noninfectious condition was limb deformities (12.11% of all foals). There was no significant difference in the incidence of infectious diseases between the 2 groups. CONCLUSION: Infectious diseases are still an important problem in neonatal foals requiring further investigation as to which factors other than antimicrobial prophylaxis are relevant for disease prevention. POTENTIAL RELEVANCE: The results provide an up-to-date overview about the frequencies of various neonatal foal diseases. They do not support the traditional prophylactic use of antimicrobials to prevent infectious diseases in healthy newborn foals. However, it should be noted that this study was not a randomised controlled trial and therefore does not provide the strongest possible evidence for this conclusion.

Global Standards: Recent Developments betweend the Poles of Privacy and Cloud Computing

The development of the Internet has made it possible to transfer data ‘around the globe at the click of a mouse’. Especially fresh business models such as cloud computing, the newest driver to illustrate the speed and breadth of the online environment, allow this data to be processed across national borders on a routine basis. A number of factors cause the Internet to blur the lines between public and private space: Firstly, globalization and the outsourcing of economic actors entrain an ever-growing exchange of personal data. Secondly, the security pressure in the name of the legitimate fight against terrorism opens the access to a significant amount of data for an increasing number of public authorities.And finally,the tools of the digital society accompany everyone at each stage of life by leaving permanent individual and borderless traces in both space and time. Therefore, calls from both the public and private sectors for an international legal framework for privacy and data protection have become louder. Companies such as Google and Facebook have also come under continuous pressure from governments and citizens to reform the use of data. Thus, Google was not alone in calling for the creation of ‘global privacystandards’. Efforts are underway to review established privacy foundation documents. There are similar efforts to look at standards in global approaches to privacy and data protection. The last remarkable steps were the Montreux Declaration, in which the privacycommissioners appealed to the United Nations ‘to prepare a binding legal instrument which clearly sets out in detail the rights to data protection and privacy as enforceable human rights’. This appeal was repeated in 2008 at the 30thinternational conference held in Strasbourg, at the 31stconference 2009 in Madrid and in 2010 at the 32ndconference in Jerusalem. In a globalized world, free data flow has become an everyday need. Thus, the aim of global harmonization should be that it doesn’t make any difference for data users or data subjects whether data processing takes place in one or in several countries. Concern has been expressed that data users might seek to avoid privacy controls by moving their operations to countries which have lower standards in their privacy laws or no such laws at all. To control that risk, some countries have implemented special controls into their domestic law. Again, such controls may interfere with the need for free international data flow. A formula has to be found to make sure that privacy at the international level does not prejudice this principle.

The use of mechanisms and modes of toxic action in integrated testing strategies: the report and recommendations of a workshop held as part of the European Union OSIRIS Integrated Project

This report on The Potential of Mode of Action (MoA) Information Derived from Non-testing and Screening Methodologies to Support Informed Hazard Assessment, resulted from a workshop organised within OSIRIS (Optimised Strategies for Risk Assessment of Industrial Chemicals through Integration of Non-test and Test Information), a project partly funded by the EU Commission within the Sixth Framework Programme. The workshop was held in Liverpool, UK, on 30 October 2008, with 35 attendees. The goal of the OSIRIS project is to develop integrated testing strategies (ITS) fit for use in the REACH system, that would enable a significant increase in the use of non-testing information for regulatory decision making, and thus minimise the need for animal testing. One way to improve the evaluation of chemicals may be through categorisation by way of mechanisms or modes of toxic action. Defining such groups can enhance read-across possibilities and priority settings for certain toxic modes or chemical structures responsible for these toxic modes. Overall, this may result in a reduction of in vivo testing on organisms, through combining available data on mode of action and a focus on the potentially most-toxic groups. In this report, the possibilities of a mechanistic approach to assist in and guide ITS are explored, and the differences between human health and environmental areas are summarised.

Does organic grassland farming benefit plant and arthropod diversity at the expense of yield and soil fertility?

Organic management is one of the most popular strategies to reduce negative environmental impacts of intensive agriculture. However, little is known about benefits for biodiversity and potential worsening of yield under organic grasslands management across different grassland types, i.e. meadow, pasture and mown pasture. Therefore, we studied the diversity of vascular plants and foliage-living arthropods (Coleoptera, Araneae, Heteroptera, Auchenorrhyncha), yield, fodder quality, soil phosphorus concentrations and land-use intensity of organic and conventional grasslands across three study regions in Germany. Furthermore, all variables were related to the time since conversion to organic management in order to assess temporal developments reaching up to 18 years. Arthropod diversity was significantly higher under organic than conventional management, although this was not the case for Araneae, Heteroptera and Auchenorrhyncha when analyzed separately. On the contrary, arthropod abundance, vascular plant diversity and also yield and fodder quality did not considerably differ between organic and conventional grasslands. Analyses did not reveal differences in the effect of organic management among grassland types. None of the recorded abiotic and biotic parameters showed a significant trend with time since transition to organic management, except soil organic phosphorus concentrations which decreased with time. This implies that permanent grasslands respond slower and probably weaker to organic management than crop fields do. However, as land-use intensity and inorganic soil phosphorus concentrations were significantly lower in organic grasslands, overcoming seed and dispersal limitation by re-introducing plant species might be needed to exploit the full ecological potential of organic grassland management. We conclude that although organic management did not automatically increase the diversity of all studied taxa, it is a reasonable and useful way to support agro-biodiversity.

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

OBJECTIVE: To evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Forty horses undergoing elective surgery. METHODS: After sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg(-1) initially, then 2 mg kg(-1) hour(-1)) and ketamine (2 mg kg(-1) hour(-1)), both CRIs reducing to 1.5 mg kg(-1) hour(-1) after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 mug kg(-1) hour(-1), reducing after 50 minutes to 2.75 mug kg(-1) hour(-1), and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE'ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 mug kg(-1) ) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05. RESULTS: FE'ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE'ISO in MILK was 0.65 (0.4-1.0) %, and in ILK was 1 (0.62-1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups. CONCLUSION AND CLINICAL RELEVANCE: A CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.