64 resultados para systematic pharmacology


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The increased frequency in reporting UK property performance figures, coupled with the acceptance of the IPD database as the market standard, has enabled property to be analysed on a comparable level with other more frequently traded assets. The most widely utilised theory for pricing financial assets, the Capital Asset Pricing Model (CAPM), gives market (systematic) risk, beta, centre stage. This paper seeks to measure the level of systematic risk (beta) across various property types, market conditions and investment holding periods. This paper extends the authors’ previous work on investment holding periods and how excess returns (alpha) relate to those holding periods. We draw on the uniquely constructed IPD/Gerald Eve transactions database, containing over 20,000 properties over the period 1983-2005. This research allows us to confirm our initial findings that properties held over longer periods perform in line with overall market performance. One implication of this is that over the long-term performance may be no different from an index tracking approach.

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The incorporation of potentially catalytic groups in DNA is of interest for the in vitro selection of novel deoxyribozymes, A series of 10 C5-modified analogues of 2'-deoxyuridine triphosphate have been synthesised that possess side chains of differing flexibility and bearing a primary amino or imidazole functionality, For each series of nucleotide analogues differing degrees of flexibility of the C5 side chain was achieved through the use of alkynyl, alkenyl and alkyl moieties, The imidazole function was conjugated to these CS-amino-modified nucleotides using either imidazole 4-acetic acid or imidazole 4-acrylic acid (urocanic acid), The substrate properties of the nucleotides (fully replacing dTTP) with Taq polymerase during PCR have been investigated in order to evaluate their potential applications for in vitro selection experiments, 5-(3-Aminopropynyl)dUTP and 5-(E-3-aminopropenyl)dUTP and their imidazole 4-acetic acid- and urocanic acid-modified conjugates were found to be substrates, In contrast, C5-amino-modified dUTPs with alkane or Z-alkene linkers and their corresponding conjugates were not substrates, The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XbaI and by mass spectrometry of the PCR products.

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Assimilation of temperature observations into an ocean model near the equator often results in a dynamically unbalanced state with unrealistic overturning circulations. The way in which these circulations arise from systematic errors in the model or its forcing is discussed. A scheme is proposed, based on the theory of state augmentation, which uses the departures of the model state from the observations to update slowly evolving bias fields. Results are summarized from an experiment applying this bias correction scheme to an ocean general circulation model. They show that the method produces more balanced analyses and a better fit to the temperature observations.

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Evolutionary developmental genetics brings together systematists, morphologists and developmental geneticists; it will therefore impact on each of these component disciplines. The goals and methods of phylogenetic analysis are reviewed here, and the contribution of evolutionary developmental genetics to morphological systematics, in terms of character conceptualisation and primary homology assessment, is discussed. Evolutionary developmental genetics, like its component disciplines phylogenetic systematics and comparative morphology, is concerned with homology concepts. Phylogenetic concepts of homology and their limitations are considered here, and the need for independent homology statements at different levels of biological organisation is evaluated. The role of systematics in evolutionary developmental genetics is outlined. Phylogenetic systematics and comparative morphology will suggest effective sampling strategies to developmental geneticists. Phylogenetic systematics provides hypotheses of character evolution (including parallel evolution and convergence), stimulating investigations into the evolutionary gains and losses of morphologies. Comparative morphology identifies those structures that are not easily amenable to typological categorisation, and that may be of particular interest in terms of developmental genetics. The concepts of latent homology and genetic recall may also prove useful in the evolutionary interpretation of developmental genetic data.

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Analysis of 20th century simulations of the High resolution Global Environment Model (HiGEM) and the Third Coupled Model Intercomparison Project (CMIP3) models shows that most have a cold sea-surface temperature (SST) bias in the northern Arabian Sea during boreal winter. The association between Arabian Sea SST and the South Asian monsoon has been widely studied in observations and models, with winter cold biases known to be detrimental to rainfall simulation during the subsequent monsoon in coupled general circulation models (GCMs). However, the causes of these SST biases are not well understood. Indeed this is one of the first papers to address causes of the cold biases. The models show anomalously strong north-easterly winter monsoon winds and cold air temperatures in north-west India, Pakistan and beyond. This leads to the anomalous advection of cold, dry air over the Arabian Sea. The cold land region is also associated with an anomalously strong meridional surface temperature gradient during winter, contributing to the enhanced low-level convergence and excessive precipitation over the western equatorial Indian Ocean seen in many models.

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Background & Aims: Malnutrition is prevalent in people diagnosed with dementia however ensuring adequate oral intake within this group is often problematic. It is important to determine whether providing nutritionally complete oral nutritional supplements (ONS) drinks is an effective way of improving clinical outcomes for older people with dementia. This paper systematically reviewed clinical, wellbeing and nutritional outcomes in people with long-term cognitive impairment. Methods: The CINAHL, Medline and EMBASE databases were searched from their inception until January 2012. Reference lists of the included papers, foreign language papers and review articles obtained were manually searched. Results: Twelve articles were included in the review containing 1076 people in the supplement groups (intervention) and 748 people in the control groups. Meta-analysis shows there was a significant improvement in weight (p=<0.0001), Body Mass Index (BMI) (p=<0.0001) and cognition at 6.5+/-3.9 month follow up (p=0.002) when supplements were given compared to the control group. Conclusions: Providing ONS drinks has a positive effect on weight gain and cognition at follow up in older people with dementia. Additional research is required in both comparing nutritional supplements to vitamin/mineral tablets and high protein/calorie shots and clinical outcomes relevant to hospitalised people with dementia.

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In recent years, there have been increasing concerns over the safety of the Chinese food supply. Although many of these have only raised concern internally within China, several major food safety issues have had international repercussions. In response, China has implemented new food safety laws and management systems to improve its national food safety control system and reduce public and international concerns. This paper has describes and discusses the components of the Chinese system using the five key elements of a national food control system identified by the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) as essential for an effective system. The latest Chinese national food safety control has made significantly improvement on its regulation framework, however, more work need to be done on standards, law enforcement, and information exchange.

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Abstract Objective: To systematically review the available evidence on whether national or international agricultural policies that directly affect the price of food influence the prevalence rates of undernutrition or nutrition-related chronic disease in children and adults. Design: Systematic review. Setting: Global. Search strategy: We systematically searched five databases for published literature (MEDLINE, EconLit, Agricola, AgEcon Search, Scopus) and systematically browsed other databases and relevant organisational websites for unpublished literature. Reference lists of included publications were hand-searched for additional relevant studies. We included studies that evaluated or simulated the effects of national or international food-price-related agricultural policies on nutrition outcomes reporting data collected after 1990 and published in English. Primary and secondary outcomes: Prevalence rates of undernutrition (measured with anthropometry or clinical deficiencies) and overnutrition (obesity and nutrition-related chronic diseases including cancer, heart disease and diabetes). Results: We identified a total of four relevant reports; two ex post evaluations and two ex ante simulations. A study from India reported on the undernutrition rates in children, and the other three studies from Egypt, the Netherlands and the USA reported on the nutrition related chronic disease outcomes in adults. Two of the studies assessed the impact of policies that subsidised the price of agricultural outputs and two focused on public food distribution policies. The limited evidence base provided some support for the notion that agricultural policies that change the prices of foods at a national level can have an effect on population-level nutrition and health outcomes. Conclusions: A systematic review of the available literature suggests that there is a paucity of robust direct evidence on the impact of agricultural price policies on nutrition and health.

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Massive open online courses (MOOCs) are a recent addition to the range of online learning options. Since 2008, MOOCs have been run by a variety of public and elite universities, especially in North America. Many academics have taken interest in MOOCs recognising the potential to deliver education around the globe on an unprecedented scale; some of these academics are taking a research-oriented perspective and academic papers describing their research are starting to appear in the traditional media of peer reviewed publications. This paper presents a systematic review of the published MOOC literature (2008-2012): Forty-five peer reviewed papers are identified through journals, database searches, searching the Web, and chaining from known sources to form the base for this review. We believe this is the first effort to systematically review literature relating to MOOCs, a fairly recent but massively popular phenomenon with a global reach. The review categorises the literature into eight different areas of interest, introductory, concept, case studies, educational theory, technology, participant focussed, provider focussed, and other, while also providing quantitative analysis of publications according to publication type, year of publication, and contributors. Future research directions guided by gaps in the literature are explored.

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We show that retrievals of sea surface temperature from satellite infrared imagery are prone to two forms of systematic error: prior error (familiar from the theory of atmospheric sounding) and error arising from nonlinearity. These errors have different complex geographical variations, related to the differing geographical distributions of the main geophysical variables that determine clear-sky brightness-temperatures over the oceans. We show that such errors arise as an intrinsic consequence of the form of the retrieval (rather than as a consequence of sub-optimally specified retrieval coefficients, as is often assumed) and that the pattern of observed errors can be simulated in detail using radiative-transfer modelling. The prior error has the linear form familiar from atmospheric sounding. A quadratic equation for nonlinearity error is derived, and it is verified that the nonlinearity error exhibits predominantly quadratic behaviour in this case.

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During glacial periods, atmospheric CO2 concentration increases and decreases by around 15 ppm. At the same time, the climate changes gradually in Antarctica. Such climate changes can be simulated in models when the AMOC (Atlantic Meridional Oceanic Circulation) is weakened by adding fresh water to the North Atlantic. The impact on the carbon cycle is less straightforward, and previous studies give opposite results. Because the models and the fresh water fluxes were different in these studies, it prevents any direct comparison and hinders finding whether the discrepancies arise from using different models or different fresh water fluxes. In this study we use the CLIMBER-2 coupled climate carbon model to explore the impact of different fresh water fluxes. In both preindustrial and glacial states, the addition of fresh water and the resulting slow-down of the AMOC lead to an uptake of carbon by the ocean and a release by the terrestrial biosphere. The duration, shape and amplitude of the fresh water flux all have an impact on the change of atmospheric CO2 because they modulate the change of the AMOC. The maximum CO2 change linearly depends on the time integral of the AMOC change. The different duration, amplitude, and shape of the fresh water flux cannot explain the opposite evolution of ocean and vegetation carbon inventory in different models. The different CO2 evolution thus depends on the AMOC response to the addition of fresh water and the resulting climatic change, which are both model dependent. In CLIMBER-2, the rise of CO2 recorded in ice cores during abrupt events can be simulated under glacial conditions, especially when the sinking of brines in the Southern Ocean is taken into account. The addition of fresh water in the Southern Hemisphere leads to a decline of CO2, contrary to the addition of fresh water in the Northern Hemisphere.

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Understanding the sources of systematic errors in climate models is challenging because of coupled feedbacks and errors compensation. The developing seamless approach proposes that the identification and the correction of short term climate model errors have the potential to improve the modeled climate on longer time scales. In previous studies, initialised atmospheric simulations of a few days have been used to compare fast physics processes (convection, cloud processes) among models. The present study explores how initialised seasonal to decadal hindcasts (re-forecasts) relate transient week-to-month errors of the ocean and atmospheric components to the coupled model long-term pervasive SST errors. A protocol is designed to attribute the SST biases to the source processes. It includes five steps: (1) identify and describe biases in a coupled stabilized simulation, (2) determine the time scale of the advent of the bias and its propagation, (3) find the geographical origin of the bias, (4) evaluate the degree of coupling in the development of the bias, (5) find the field responsible for the bias. This strategy has been implemented with a set of experiments based on the initial adjustment of initialised simulations and exploring various degrees of coupling. In particular, hindcasts give the time scale of biases advent, regionally restored experiments show the geographical origin and ocean-only simulations isolate the field responsible for the bias and evaluate the degree of coupling in the bias development. This strategy is applied to four prominent SST biases of the IPSLCM5A-LR coupled model in the tropical Pacific, that are largely shared by other coupled models, including the Southeast Pacific warm bias and the equatorial cold tongue bias. Using the proposed protocol, we demonstrate that the East Pacific warm bias appears in a few months and is caused by a lack of upwelling due to too weak meridional coastal winds off Peru. The cold equatorial bias, which surprisingly takes 30 years to develop, is the result of an equatorward advection of midlatitude cold SST errors. Despite large development efforts, the current generation of coupled models shows only little improvement. The strategy proposed in this study is a further step to move from the current random ad hoc approach, to a bias-targeted, priority setting, systematic model development approach.

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Diabatic processes can alter Rossby wave structure; consequently errors arising from model processes propagate downstream. However, the chaotic spread of forecasts from initial condition uncertainty renders it difficult to trace back from root mean square forecast errors to model errors. Here diagnostics unaffected by phase errors are used, enabling investigation of systematic errors in Rossby waves in winter-season forecasts from three operational centers. Tropopause sharpness adjacent to ridges decreases with forecast lead time. It depends strongly on model resolution, even though models are examined on a common grid. Rossby wave amplitude reduces with lead time up to about five days, consistent with under-representation of diabatic modification and transport of air from the lower troposphere into upper-tropospheric ridges, and with too weak humidity gradients across the tropopause. However, amplitude also decreases when resolution is decreased. Further work is necessary to isolate the contribution from errors in the representation of diabatic processes.