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The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
The reaction of the German labor market to the Great Recession 2008/09 was relatively mild – especially compared to other countries. The reason lies not only in the specific type of the recession – which was favorable for the German economy structure – but also in a series of labor market reforms initiated between 2002 and 2005 altering, inter alia, labor supply incentives. However, irrespective of the mild response to the Great Recession, there are a number of substantial future challenges the German labor market will soon have to face. Female labor supply still lies well below that of other countries and a massive demographic change over the next 50 years will have substantial effects on labor supply as well as the pension system. In addition, due to a skill-biased technological change over the next decades, firms will face problems of finding employees with adequate skills. The aim of this paper is threefold. First, we outline why the German labor market reacted in such a mild fashion, describe current economic trends of the labor market in light of general trends in the European Union, and reveal some of the main associated challenges. Thereafter, the paper analyzes recent reforms of the main institutional settings of the labor market which influence labor supply. Finally, based on the status quo of these institutional settings, the paper gives a brief overview of strategies to combat adequately the challenges in terms of labor supply and to ensure economic growth in the future.
Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to integrate cell-level kinetic models and pharmacokinetic compartment models. Incorporating target dynamics into pharmacokinetic models is especially useful for the development of therapeutic antibodies because their effect and pharmacokinetics are inherently interdependent. The approach is illustrated by analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies targeting the epidermal growth factor receptor. We build a multi-level model for anti-EGFR antibodies by combining a systems biology model with in vitro determined parameters and a pharmacokinetic model based on in vivo pharmacokinetic data. Using this model, we investigated in silico the impact of biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect saturates with increasing drug-receptor affinity, thereby limiting the impact of increasing antibody affinity on improving the effect. This indicates that observed differences in the therapeutic effects of high affinity antibodies in the market and in clinical development may result mainly from Fc-mediated indirect mechanisms such as antibody-dependent cell cytotoxicity.
This study provides a detailed analysis of the mid-Holocene to present-day precipitation change in the Asian monsoon region. We compare for the first time results of high resolution climate model simulations with a standardised set of mid-Holocene moisture reconstructions. Changes in the simulated summer monsoon characteristics (onset, withdrawal, length and associated rainfall) and the mechanisms causing the Holocene precipitation changes are investigated. According to the model, most parts of the Indian subcontinent received more precipitation (up to 5 mm/day) at mid-Holocene than at present-day. This is related to a stronger Indian summer monsoon accompanied by an intensified vertically integrated moisture flux convergence. The East Asian monsoon region exhibits local inhomogeneities in the simulated annual precipitation signal. The sign of this signal depends on the balance of decreased pre-monsoon and increased monsoon precipitation at mid-Holocene compared to present-day. Hence, rainfall changes in the East Asian monsoon domain are not solely associated with modifications in the summer monsoon circulation but also depend on changes in the mid-latitudinal westerly wind system that dominates the circulation during the pre-monsoon season. The proxy-based climate reconstructions confirm the regional dissimilarities in the annual precipitation signal and agree well with the model results. Our results highlight the importance of including the pre-monsoon season in climate studies of the Asian monsoon system and point out the complex response of this system to the Holocene insolation forcing. The comparison with a coarse climate model simulation reveals that this complex response can only be resolved in high resolution simulations.
The closer the better
(2012)
A growing literature has suggested that processing of visual information presented near the hands is facilitated. In this study, we investigated whether the near-hands superiority effect also occurs with the hands moving. In two experiments, participants performed a cyclical bimanual movement task requiring concurrent visual identification of briefly presented letters. For both the static and dynamic hand conditions, the results showed improved letter recognition performance with the hands closer to the stimuli. The finding that the encoding advantage for near-hand stimuli also occurred with the hands moving suggests that the effect is regulated in real time, in accordance with the concept of a bimodal neural system that dynamically updates hand position in external space.
Duplicate detection is the task of identifying all groups of records within a data set that represent the same real-world entity, respectively. This task is difficult, because (i) representations might differ slightly, so some similarity measure must be defined to compare pairs of records and (ii) data sets might have a high volume making a pair-wise comparison of all records infeasible. To tackle the second problem, many algorithms have been suggested that partition the data set and compare all record pairs only within each partition. One well-known such approach is the Sorted Neighborhood Method (SNM), which sorts the data according to some key and then advances a window over the data comparing only records that appear within the same window. We propose several variations of SNM that have in common a varying window size and advancement. The general intuition of such adaptive windows is that there might be regions of high similarity suggesting a larger window size and regions of lower similarity suggesting a smaller window size. We propose and thoroughly evaluate several adaption strategies, some of which are provably better than the original SNM in terms of efficiency (same results with fewer comparisons).
Developing Critical Thinking
(2012)
Governments at central and sub-national levels are increasingly pursuing participatory mechanisms in a bid to improve governance and service delivery. This has been largely in the context of decentralization reforms in which central governments transfer (share) political, administrative, fiscal and economic powers and functions to sub-national units. Despite the great international support and advocacy for participatory governance where citizen’s voice plays a key role in decision making of decentralized service delivery, there is a notable dearth of empirical evidence as to the effect of such participation. This is the question this study sought to answer based on a case study of direct citizen participation in Local Authorities (LAs) in Kenya. This is as formally provided for by the Local Authority Service Delivery Action Plan (LASDAP) framework that was established to ensure citizens play a central role in planning and budgeting, implementation and monitoring of locally identified services towards improving livelihoods and reducing poverty. Influence of participation was assessed in terms of how it affected five key determinants of effective service delivery namely: efficient allocation of resources; equity in service delivery; accountability and reduction of corruption; quality of services; and, cost recovery. It finds that the participation of citizens is minimal and the resulting influence on the decentralized service delivery negligible. It concludes that despite the dismal performance of citizen participation, LASDAP has played a key role towards institutionalizing citizen participation that future structures will build on. It recommends that an effective framework of citizen participation should be one that is not directly linked to politicians; one that is founded on a legal framework and where citizens have a legal recourse opportunity; and, one that obliges LA officials both to implement what citizen’s proposals which meet the set criteria as well as to account for their actions in the management of public resources.
Developing critical thinking
(2012)