bluuebunny/crossref_metadata_2025 huggingface dataset:
The link between antibodies to OxLDL and natural protection against pneumococci depends on DH gene conservation
Authors: Vale Andre M. , Kapoor Pratibha , Skibinski Greg A. , Elgavish Ada , Mahmoud Tamer I. , Zemlin Cosima , Zemlin Michael , Burrows Peter D. , Nobrega Alberto , Kearney John F. , Briles David E. , Schroeder Harry W.
Published: April 2013

Selection and physiological production of protective natural antibodies (NAbs) have been associated with exposure to endogenous antigens. The extent to which this association depends on germline NAb sequence is uncertain. Here we show that alterations in germline DH sequence can sever the association between the production of self-reactive NAbs and NAbs that afford protection against a pathogen. In unmanipulated hosts, the availability of the evolutionarily conserved DFL16.1 gene segment sequence profoundly affected the serum levels of NAbs against bacterial phosphorylcholine but not oxidized low-density lipoprotein. Mice with partially altered DFL16.1 sequence could use N nucleotides to recreate the amino acid sequence associated with the classical protective T15 idiotype–positive NAbs, whereas those without DFL16.1 could not. DFL16.1 gene–deficient mice proved more susceptible to challenge with live Streptococcus pneumoniae. Our findings indicate that although production of self-reactive NAbs can be independent of germline DH sequence, their capacity to provide protection against pathogens cannot. The potential relevance of these findings for the rational design of vaccines is discussed.
Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model
Authors: Kirchberger Stefanie , Royston Daniel J. , Boulard Olivier , Thornton Emily , Franchini Fanny , Szabady Rose L. , Harrison Oliver , Powrie Fiona
Published: April 2013

Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17+IL-22+ colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. Analysis of the functional role of distinct Type 17 cytokines shows that although blockade of IL-17 inhibits some parameters of intestinal inflammation, reduction in dysplasia and colorectal cancer (CRC) requires neutralization of IL-22 indicating a unique role for IL-22 in the maintenance of cancer in this model. Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. Importantly, we could detect IL-22+CD3+ and IL-22+CD3− cells in human CRC. Our results describe a new activity of IL-22 in the colon as a nonredundant mediator of the inflammatory cascade required for perpetuation of CRC, highlighting the IL-22 axis as a novel therapeutic target in colon cancer.
Cost of Annual Tuberculosis Screening of Healthcare Workers with Negative Tuberculin Skin Test Results
Authors: Jackson J. Brooks , Tao Xuguang , Sneed Laurie , Humphrey-Carothers Frances , Bernacki Edward
Published: April 2013

The Centers for Disease Control and Prevention (CDC) recommends annual screening for Mycobacterium tuberculosis infection using the tuberculin skin test (TST) for individuals working in hospitals with 200 or more inpatient beds that have at least 6 documented cases of active tuberculosis (TB) per year. The cost of annual TB screening programs is significant, but the cost per individual with TST conversion is unknown. Therefore, we evaluated the annual TB screening program at the Johns Hopkins Hospital and Medical School to determine (1) the proportion of individuals with TST conversion among individuals in the annual TB screening program with patient care exposure at the Johns Hopkins Hospital and Medical School, (2) which employment and demographic factors are associated with TST conversion, (3) the prevalence of active TB disease among those with TST conversion, and (4) the annual cost of subsequent screening of individuals with initial negative TST results and the screening cost per individual with TST conversion.

TST results were reviewed for individuals participating in the annual TB screening program during the previous 4 years (2007–2010) at the Johns Hopkins Hospital and Medical School, which has experienced an average of 12 documented cases of active TB per year. TST was performed before employment and then annually for healthcare providers according to CDC guidelines and the manufacturer's directions. Individuals in the testing program included anyone who had patient contact, such as physicians, nurses, technologists, students, phlebotomists, nutritionists, pharmacists, and clerks. All initial testing was 2-step testing if the individual was initially reactive.
Analyzing genome coverage profiles with applications to quality control in metagenomics
Authors: Lindner Martin S. , Kollock Maximilian , Zickmann Franziska , Renard Bernhard Y.
Published: April 2013

Motivation: Genome coverage, the number of sequencing reads mapped to a position in a genome, is an insightful indicator of irregularities within sequencing experiments. While the average genome coverage is frequently used within algorithms in computational genomics, the complete information available in coverage profiles (i.e. histograms over all coverages) is currently not exploited to its full extent. Thus, biases such as fragmented or erroneous reference genomes often remain unaccounted for. Making this information accessible can improve the quality of sequencing experiments and quantitative analyses.

Results: We introduce a framework for fitting mixtures of probability distributions to genome coverage profiles. Besides commonly used distributions, we introduce distributions tailored to account for common artifacts. The mixture models are iteratively fitted based on the Expectation-Maximization algorithm. We introduce use cases with focus on metagenomics and develop new analysis strategies to assess the validity of a reference genome with respect to (meta-) genomic read data. The framework is evaluated on simulated data as well as applied to a large-scale metagenomic study, for which we compute the validity of 75 microbial genomes. The results indicate that the choice and quality of reference genomes is vital for metagenomic analyses and that validation of coverage profiles is crucial to avoid incorrect conclusions.

Availability: The code is freely available and can be downloaded from http://sourceforge.net/projects/fitgcp/.

Contact:  RenardB@rki.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Persistent regimes and extreme events of the North Atlantic atmospheric circulation
Authors: Franzke Christian L. E.
Published: April 2013

Society is increasingly impacted by natural hazards which cause significant damage in economic and human terms. Many of these natural hazards are weather and climate related. Here, we show that North Atlantic atmospheric circulation regimes affect the propensity of extreme wind speeds in Europe. We also show evidence that extreme wind speeds are long-range dependent, follow a generalized Pareto distribution and are serially clustered. Serial clustering means that storms come in bunches and, hence, do not occur independently. We discuss the use of waiting time distributions for extreme event recurrence estimation in serially dependent time series.
Stochastic parametrizations and model uncertainty in the Lorenz ’96 system
Authors: Arnold H. M. , Moroz I. M. , Palmer T. N.
Published: April 2013

Simple chaotic systems are useful tools for testing methods for use in numerical weather simulations owing to their transparency and computational cheapness. The Lorenz system was used here; the full system was defined as ‘truth’, whereas a truncated version was used as a testbed for parametrization schemes. Several stochastic parametrization schemes were investigated, including additive and multiplicative noise. The forecasts were started from perfect initial conditions, eliminating initial condition uncertainty. The stochastically generated ensembles were compared with perturbed parameter ensembles and deterministic schemes. The stochastic parametrizations showed an improvement in weather and climate forecasting skill over deterministic parametrizations. Including a temporal autocorrelation resulted in a significant improvement over white noise, challenging the standard idea that a parametrization should only represent sub-gridscale variability. The skill of the ensemble at representing model uncertainty was tested; the stochastic ensembles gave better estimates of model uncertainty than the perturbed parameter ensembles. The forecasting skill of the parametrizations was found to be linked to their ability to reproduce the climatology of the full model. This is important in a seamless prediction system, allowing the reliability of short-term forecasts to provide a quantitative constraint on the accuracy of climate predictions from the same system.
On estimating local long-term climate trends
Authors: Chapman S. C. , Stainforth D. A. , Watkins N. W.
Published: April 2013

Climate sensitivity is commonly taken to refer to the equilibrium change in the annual mean global surface temperature following a doubling of the atmospheric carbon dioxide concentration. Evaluating this variable remains of significant scientific interest, but its global nature makes it largely irrelevant to many areas of climate science, such as impact assessments, and also to policy in terms of vulnerability assessments and adaptation planning. Here, we focus on local changes and on the way observational data can be analysed to inform us about how local climate has changed since the middle of the nineteenth century. Taking the perspective of climate as a constantly changing distribution, we evaluate the relative changes between different quantiles of such distributions and between different geographical locations for the same quantiles. We show how the observational data can provide guidance on trends in local climate at the specific thresholds relevant to particular impact or policy endeavours. This also quantifies the level of detail needed from climate models if they are to be used as tools to assess climate change impact. The mathematical basis is presented for two methods of extracting these local trends from the data. The two methods are compared first using surrogate data, to clarify the methods and their uncertainties, and then using observational surface temperature time series from four locations across Europe.
Statistical characteristics, circulation regimes and unstable periodic orbits of a barotropic atmospheric model
Authors: Gritsun A.
Published: April 2013

The theory of chaotic dynamical systems gives many tools that can be used in climate studies. The widely used ones are the Lyapunov exponents, the Kolmogorov entropy and the attractor dimension characterizing global quantities of a system. Another potentially useful tool from dynamical system theory arises from the fact that the local analysis of a system probability distribution function (PDF) can be accomplished by using a procedure that involves an expansion in terms of unstable periodic orbits (UPOs). The system measure (or its statistical characteristics) is approximated as a weighted sum over the orbits. The weights are inversely proportional to the orbit instability characteristics so that the least unstable orbits make larger contributions to the PDF. Consequently, one can expect some relationship between the least unstable orbits and the local maxima of the system PDF. As a result, the most probable system trajectories (or ‘circulation regimes’ in some sense) may be explained in terms of orbits. For the special classes of chaotic dynamical systems, there is a strict theory guaranteeing the accuracy of this approach. However, a typical atmospheric model may not qualify for these theorems. In our study, we will try to apply the idea of UPO expansion to the simple atmospheric system based on the barotropic vorticity equation of the sphere. We will check how well orbits approximate the system attractor, its statistical characteristics and PDF. The connection of the most probable states of the system with the least unstable periodic orbits will also be analysed.
A data-driven multi-cloud model for stochastic parametrization of deep convection
Authors: Dorrestijn J. , Crommelin D. T. , Biello J. A. , Böing S. J.
Published: April 2013

Stochastic subgrid models have been proposed to capture the missing variability and correct systematic medium-term errors in general circulation models. In particular, the poor representation of subgrid-scale deep convection is a persistent problem that stochastic parametrizations are attempting to correct. In this paper, we construct such a subgrid model using data derived from large-eddy simulations (LESs) of deep convection. We use a data-driven stochastic parametrization methodology to construct a stochastic model describing a finite number of cloud states. Our model emulates, in a computationally inexpensive manner, the deep convection-resolving LES. Transitions between the cloud states are modelled with Markov chains. By conditioning the Markov chains on large-scale variables, we obtain a conditional Markov chain, which reproduces the time evolution of the cloud fractions. Furthermore, we show that the variability and spatial distribution of cloud types produced by the Markov chains become more faithful to the LES data when local spatial coupling is introduced in the subgrid Markov chains. Such spatially coupled Markov chains are equivalent to stochastic cellular automata.
The hemopexin domain of MMP3 is responsible for mammary epithelial invasion and morphogenesis through extracellular interaction with HSP90β
Authors: Correia Ana Luísa , Mori Hidetoshi , Chen Emily I. , Schmitt Fernando C. , Bissell Mina J.
Published: April 2013

Matrix metalloproteinases (MMPs) are crucial mediators in sculpting tissue architecture and are required for many physiological and pathological processes. MMP3 has been shown to regulate branching morphogenesis in the mammary gland. Ectopic expression of proteolytically active MMP3 in mouse mammary epithelia triggers supernumerary lateral branching and, eventually, tumors. Using a three-dimensional collagen-I (Col-1) gel assay that simulates epithelial invasion and branching, we show that it is the hemopexin domain that directs these processes. Using three different engineered constructs containing a variation on MMP3 structural domains, we confirmed the importance of the hemopexin domain also in primary organoids of the mammary gland. A proteomic screen of MMP3-binding partners surprisingly revealed that the intracellular chaperone heat-shock protein 90 β (HSP90β) is present extracellularly, and its interaction with the hemopexin domain of MMP3 is critical for invasion. Blocking of HSP90β with inhibitory antibodies added to the medium abolished invasion and branching. These findings shift the focus from the proteolytic activity of MMP3 as the central player to its hemopexin domain and add a new dimension to HSP90β's functions by revealing a hitherto undescribed mechanism of MMP3 regulation. Our data also may shed light on the failure of strategies to use MMP inhibitors in cancer treatment and other related disorders.
Exploring host–microbiota interactions in animal models and humans
Authors: Kostic Aleksandar D. , Howitt Michael R. , Garrett Wendy S.
Published: April 2013

The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host–microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host–microbiota interactions and explore recent human microbiome studies.
In vivo live imaging of RNA polymerase II transcription factories in primary cells
Authors: Ghamari Alireza , van de Corput Mariëtte P.C. , Thongjuea Supat , van Cappellen Wiggert A. , van IJcken Wilfred , van Haren Jeffrey , Soler Eric , Eick Dirk , Lenhard Boris , Grosveld Frank G.
Published: April 2013

Transcription steps are marked by different modifications of the C-terminal domain of RNA polymerase II (RNAPII). Phosphorylation of Ser5 and Ser7 by cyclin-dependent kinase 7 (CDK7) as part of TFIIH marks initiation, whereas phosphorylation of Ser2 by CDK9 marks elongation. These processes are thought to take place in localized transcription foci in the nucleus, known as “transcription factories,” but it has been argued that the observed clusters/foci are mere fixation or labeling artifacts. We show that transcription factories exist in living cells as distinct foci by live-imaging fluorescently labeled CDK9, a kinase known to associate with active RNAPII. These foci were observed in different cell types derived from CDK9-mCherry knock-in mice. We show that these foci are very stable while highly dynamic in exchanging CDK9. Chromatin immunoprecipitation (ChIP) coupled with deep sequencing (ChIP-seq) data show that the genome-wide binding sites of CDK9 and initiating RNAPII overlap on transcribed genes. Immunostaining shows that CDK9-mCherry foci colocalize with RNAPII-Ser5P, much less with RNAPII-Ser2P, and not with CDK12 (a kinase reported to be involved in the Ser2 phosphorylation) or with splicing factor SC35. In conclusion, transcription factories exist in living cells, and initiation and elongation of transcripts takes place in different nuclear compartments.
Activation of BDNF signaling prevents the return of fear in female mice
Authors: Baker-Andresen Danay , Flavell Charlotte R. , Li Xiang , Bredy Timothy W.
Published: April 2013

There are significant sex differences in vulnerability to develop fear-related anxiety disorders. Females exhibit twice the rate of post-traumatic stress disorder (PTSD) as males and sex differences have been observed in fear extinction learning in both humans and rodents, with a failure to inhibit fear emerging as a precipitating factor in the development of PTSD. Here we report that female mice are resistant to fear extinction, and exhibit increased DNA methylation of Bdnf exon IV and a concomitant decrease in mRNA expression within the medial prefrontal cortex. Activation of BDNF signaling by the trkB agonist 7,8-dihydroxyflavone blocks the return of fear in female mice after extinction training, and thus represents a novel approach to treating fear-related anxiety disorders that are characterized by a resistance to extinction and increased propensity for renewal.
Two routes of MexS‐MexT‐mediated regulation of MexEF‐OprN and MexAB‐OprM efflux pump expression in Pseudomonas aeruginosa
Authors: Uwate Maki , Ichise Yu‐ki , Shirai Akihiro , Omasa Takeshi , Nakae Taiji , Maseda Hideaki
Published: April 2013

The NfxC‐type mutant of Pseudomonas aeruginosa produces the MexEF‐OprN efflux pump and down‐regulates expression of the quorum‐sensing‐dependent efflux pump MexAB‐OprM and production of virulence factors in the presence of an active transcriptional regulator, MexT. Consequently, these cells are resistant to chloramphenicol and hypersusceptible to β‐lactam antibiotics. An upper negative regulator, MexS, has been assumed to inactivate MexT in wild‐type strains, hence shutting down production of the MexEF‐OprN pump. This observation was, however, reported in only one clinical strain and not confirmed in well‐characterized laboratory strains. Moreover, it is not known whether MexS is involved in the quorum‐sensing‐dependent regulation of virulence factor production. To assess these issues, a plasmid carrying wild‐type mexS was introduced into three NfxC‐type mutants from laboratory strains, which carry an impaired mexS and unimpaired mexT. Unexpectedly, all the transformants produced an increased amount of MexEF‐OprN proteins. Three clinical NfxC strains were similarly transformed and although MexEF‐OprN was undetectable in two of these strains, one produced an increased amount of these proteins, similar to the laboratory strains. These results were interpreted to mean that P. aeruginosa takes two separate routes in MexT‐mediated regulation of mexEF‐oprN expression: the MexS‐bypassed pathway and MexS‐mediated pathway. On the other hand, the transformants of both the laboratory and clinically derived NfxC‐type cells produced increased amounts of MexAB‐OprM and virulence factors, suggesting that production of these proteins occurs via the MexS‐mediated pathway.
Murine macrophage inflammatory cytokine production and immune activation in response to Vibrio parahaemolyticus infection
Authors: Waters Stephanie , Luther Sanjana , Joerger Torsten , Richards Gary P. , Boyd E. Fidelma , Parent Michelle A.
Published: April 2013

Vibrio parahaemolyticus is the most common cause of bacterial, seafood‐related illness in the USA. Currently, there is a dearth of published reports regarding immunity to infection with this pathogen. Here, production of both pro‐ and anti‐inflammatory cytokines by V. parahaemolyticus‐infected RAW 264.7 murine macrophages was studied. It was determined that this infection results in increased concentrations of IL‐1α, IL‐6, TNF‐α and IL‐10. Additionally, decreases in cell surface TLR2 and TLR4 and increases in T‐cell co‐stimulatory molecules CD40 and CD86 were discovered. The data presented here begin to identify the immune variables required to eliminate V. parahaemolyticus from infected host tissues.
Taming wildlife disease: bridging the gap between science and management
Authors: Joseph Maxwell B. , Mihaljevic Joseph R. , Arellano Ana Lisette , Kueneman Jordan G. , Preston Daniel L. , Cross Paul C. , Johnson Pieter T. J.
Published: April 2013

Parasites and pathogens of wildlife can threaten biodiversity, infect humans and domestic animals, and cause significant economic losses, providing incentives to manage wildlife diseases. Recent insights from disease ecology have helped transform our understanding of infectious disease dynamics and yielded new strategies to better manage wildlife diseases. Simultaneously, wildlife disease management (WDM) presents opportunities for large‐scale empirical tests of disease ecology theory in diverse natural systems.

To assess whether the potential complementarity betweenWDMand disease ecology theory has been realized, we evaluate the extent to which specific concepts in disease ecology theory have been explicitly applied in peer‐reviewedWDMliterature.

While only half ofWDMarticles published in the past decade incorporated disease ecology theory, theory has been incorporated with increasing frequency over the past 40 years. Contrary to expectations, articles authored by academics were no more likely to apply disease ecology theory, but articles that explain unsuccessful management often do so in terms of theory.

Some theoretical concepts such as density‐dependent transmission have been commonly applied, whereas emerging concepts such as pathogen evolutionary responses to management, biodiversity–disease relationships and within‐host parasite interactions have not yet been fully integrated as management considerations.

Synthesis and applications. Theory‐based disease management can meet the needs of both academics and managers by testing disease ecology theory and improving disease interventions. Theoretical concepts that have received limited attention to date in wildlife disease management could provide a basis for improving management and advancing disease ecology in the future.
Cardiovascular disease in Australia: calm before a new storm?
Authors: Reid Christopher M
Published: April 2013

See original article on page 347
Distribution of Variants of Old English by, for, between
Authors: Alcorn Rhona
Published: April 2013

This paper attempts to systematise the distribution of variant forms of the Old English prepositions by, for and between. Using evidence from the variable positioning of their object personal pronouns, I argue that by and for each have two prosodically conditioned allomorphs; one that is phonologically dependent on its object (like French de ‘of’ as in Jean a beaucoup d'argent ‘John has lots of money’) and another that is not. Patterns in the distribution of variant forms of between have previously been noted but remain partially unexplained. I offer a novel analysis of the tendency for personal pronouns to occur to the left rather than the right of betweonum and of the tendency to use that particular variant of between when its complement is a personal pronoun.
New annual estimates of Swedish GDP, 1800–2010
Authors: Edvinsson Rodney
Published: April 2013

Although the historical national accounts of Sweden are among the most detailed in the world, there is scope for improvement. This study revises previous historical estimates of Swedish GDP. Agricultural output is upgraded for the nineteenth century following recent research by Swedish agrarian historians on the underestimation of official statistics. Estimates of annual fluctuations before 1861 are significantly improved by using new sources on yield ratios of harvests. For manufacturing, home industries are added, in accordance with modern international guidelines (2008 SNA). The study concludes that early nineteenth‐century Sweden was not as poor relative to other West European countries as previously thought.
The cost of railroad regulation: the disintegration of American agricultural markets in the interwar period
Authors: Federico Giovanni , Sharp Paul
Published: April 2013

This article investigates the costs of transport regulation using the example of agricultural markets in theUS. Using a large database of prices by state of agricultural commodities, we find that dispersion fell for many commodities until theFirstWorldWar. We demonstrate that this reflected changes in transport costs which in turn in the long run depended on productivity growth in railroads. The year 1920 marked a change in this relationship, however, and between theFirst andSecondWorldWars we find considerable disintegration of agricultural markets, ultimately as a consequence of the 1920TransportationAct. We argue that this benefited railroad companies in the 1920s and workers in the 1930s, and we put forward an estimate of the welfare losses for the consumers of railroad services (that is, agricultural producers and final consumers).
Efficacy of Continuous Oral Administration of Lanthanum Carbonate over 24 months
Authors: Ishizu Takashi , Hong Zhang , Matsunaga Tsuneaki , Kaneko Yoko , Taru Yoshinori
Published: April 2013

To examine the efficacy of long‐term administration of lanthanum carbonate, changes in serum Ca, phosphate, whole parathyroid hormone (wPTH), and ALP were examined in 40 patients who were able to tolerate dosage of lanthanum carbonate over a continuous period of 24 months. Concurrently, concomitant administration of other phosphate binders, cinacalcet, vitamin D, etc., was also examined. After 24 months, serum phosphorus levels (P levels) had decreased to within management target of guidelines, from 6.16 ± 1.44 mg/dL to 5.58 ± 1.15 mg/dL, and this effect was maintained for 2 years. There were no changes in Ca level. wPTH did not change significantly but tended to increase at 12 months. The dose of concomitantly administered calcium carbonate and sevelamer hydrochloride was reduced. The P‐lowering function of lanthanum carbonate still held steady at 24 months following the start of dosage. Because of the rising trend seen in wPTH, dose of cinacalcet and/or vitamin D need to be modulated. Reducing the number of concomitantly administered phosphate binder tablets was desirable from the standpoint of patient adherence.
Multicenter Study of Long‐Term (Two‐Year) Efficacy of Lanthanum Carbonate
Authors: Ando Ryoichi , Kimura Hitoshi , Sato Hidehiko , Iwamoto Shunsuke , Yoshizaki Yuki , Chida Yoshiko , Ishida Yuji , Takayama Masanobu , Yamada Kouei , Tachibana Ken , Ohtsuka Masakazu , Kikuchi Kan , Inoue Atsushi
Published: April 2013

Long‐term efficacy of lanthanum carbonate on hyperphosphatemia was examined in multicenter dialysis patients. Outcome and efficacy after 2 years was investigated in 101 patients who had undergone lanthanum carbonate administration. Thirty‐three cases dropped out by the 2‐year point; patients undergoing at least 2 years of administration totaled 68. Reasons for dropping out were as follows: improvement of hyperphosphatemia, nine cases; changing hospitals, seven cases; medical complications, five cases; digestive symptoms, four cases; poor compliance, four cases; parathyroidectomy, two cases; death, two cases. The mean dosage was increased from initial daily dosage of 744 mg to 1266 mg after 1 year, and to 1246 mg after 2 years. Serum phosphate concentration decreased significantly from the initial 6.15 mg to 5.57 mg/dL after 1 year, and to 5.45 mg/dL after 2 years. Although a lowering trend was observed in corrected calcium levels, the difference was not significant. Parathyroid hormone was unchanged. Achievement rate of Japanese Society for Dialysis Therapy (JSDT) management target values for both phosphorus and calcium improved from 32.7% to 50.0% after 1 year, and to 56.5% after 2 years. Lanthanum carbonate is useful as a therapeutic tool for hyperphosphatemia over long durations.
Improving Agricultural Productivity Sustainably at Global Level: The Role of Agricultural Innovation Policies
Authors: Moreddu Catherine , Van Tongeren Frank
Published: April 2013

summary

Improving Agricultural Productivity Sustainably at Global Level: The Role of Agricultural Innovation Policies

At the request of Mexican G20 presidency, a number of international organisations provided recommendations on how to improve agricultural productivity sustainably, in particular for small family farms. This article outlines current issues regarding developments in agricultural productivity and sustainability, and stresses the potential role of innovation in improving agricultural productivity growth sustainably. While average growth in total factor productivity tends to accelerate and to converge across major world regions, there are major differences across countries, regions and farms. Efforts to increase agricultural production and productivity face serious challenges in terms of sustainability as they take place within an environment characterised by the scarcity of natural resources and uncertainties regarding the impact of climate change. Innovation is seen as key to improving productivity sustainably. As major providers of research and innovation, G20 countries will have to help find innovative solutions better adapted to an evolving and diverse demand. Suggestions made to improve the relevance and cost‐efficiency of G20 agricultural innovation systems include: strengthening the governance of Agricultural Innovations Systems (AIS), cross‐country co‐operation, involvement of the private sector, including through public–private partnerships, linkages within multiple AIS actors, and regulations to foster innovation in the sector.
Intellectual Property Rights Systems and Innovation in the Plant Breeding Industry
Authors: (Hans) Dons J.J.M.
Published: April 2013

summary

Intellectual Property Rights Systems and Innovation in the Plant Breeding Industry

The debate on Intellectual Property Rights (IPR) in the plant breeding industry over the past 3 years has been important for the future of the plant breeding sector and for global food security in the coming decades. Intensive discussions have led to initiatives aimed at reducing the imbalance that appeared to have developed between two intellectual property systems: Plant Breeders Rights (PBR) on new plant varieties and patent rights on plant‐related inventions. A better balance can be achieved by a combination of several measures that will strengthen the PBR system as the most important instrument for IP protection in this sector. Patents on plant‐related inventions are important for encouraging innovation, but must be restricted to inventions meeting strict legal criteria. Access to such inventions (technologies, traits) can be realised via a limited breeder’s exemption and/or licences that can be negotiated in a Fair, Reasonable and Non‐Discriminatory (FRAND) way. Although the debate is not yet finalised, the sector has taken several initiatives at both a European and global level. All measures together form a major step forwards in safeguarding access to genetic variation. They also safeguard the IP position of the breeder, which is important for ensuring a fair return on investment and encouraging further innovation in the plant breeding sector.
Information and Communication Technology as a Driver for Change in Agri‐food Chains
Authors: Poppe Krijn J. , Wolfert Sjaak , Verdouw Cor , Verwaart Tim
Published: April 2013

summary

Information and Communication Technology as a Driver for Change in Agri‐food Chains

Agri‐food chains will be changed in the coming years by Information and Communication Technology (ICT). Technological trends and economic analysis suggest that ICT will be a major driver for innovation. Satellites and sensors make precision agriculture possible. More and more data are being generated in agriculture and the rest of the food chain, which helps to steer production processes with greater precision. However, there is a low level of integration of these data between actors in the food chain. By improving this ‘interoperability’ of data, processes in the food chain can be optimised and new business models developed. Data‐intensive food chains have the potential to alleviate many of the current sustainability and food safety issues and contribute to human health. The economic and policy effects of such developments still need to be explored. At first sight it could lead to more closely integrated supply chains that make the farmer act as a franchise taker with limited freedom. But the opposite could also be true, with more transparency and easier options for direct sales via consumer food webs, using smart solutions for the ‘last mile’ delivery. New issues like a trade‐off between transparency and privacy or pricing data might well arise.
Marked Reduction in Length of Stay for Patients With Psychiatric Emergencies After Implementation of a Comanagement Model
Authors: Polevoi Steven K. , Jewel Shim J. , McCulloch Charles E. , Grimes Barbara , Govindarajan Prasanthi
Published: April 2013

Objectives

Patients with psychiatric emergencies often spend excessive time in an emergency department (ED) due to limited inpatient psychiatric bed capacity. The objective was to compare traditional resident consultation with a new model (comanagement) to reduce length of stay (LOS) for patients with psychiatric emergencies. The costs of this model were compared to those of standard care.

Methods

This was a before‐and‐after study conducted in the ED of an urban academic medical center without an inpatient psychiatry unit from January 1, 2007, through December 31, 2009. Subjects were all adult patients seen by ED clinicians and determined to be a danger to self or others or gravely disabled. At baseline, psychiatry residents evaluated patients and made therapeutic recommendations after consultation with faculty. The comanagement model was fully implemented in September 2008. In this model, psychiatrists directly ordered pharmacotherapy, regularly monitored effects, and intensified efforts toward appropriate disposition. Additionally, increased attending‐level involvement expedited focused evaluation and disposition of patients. An interrupted time series analysis was used to study the effects of this intervention on LOS for all psychiatric patients transferred for inpatient psychiatric care. Secondary outcomes included mean number of hours on ambulance diversion per month and the mean number of patients who left without being seen (LWBS) from the ED.

Results

A total of 1,884 patient visits were considered. Compared to the preintervention phase, median LOS for patients transferred for inpatient psychiatric care decreased by about 22% (p < 0.0005, 95% confidence interval [CI] = 15% to 28%) in the postintervention phase. Ambulance diversion hours increased by about 40 hours per month (p = 0.008, 95% CI = 11 to 69 hours) and the mean number of patients who LWBS decreased by about 26 per month (p = 0.106; 95% CI = −60 to 5.9 visits per month) in the postintervention phase.

Conclusions

A comanagement model was associated with a marked reduction in the LOS for this patient population.
Guidelines for Safety of Trainees Rotating Abroad: Consensus Recommendations from the Global Emergency Medicine Academy of the Society for Academic Emergency Medicine, Council of Emergency Medicine Residency Directors, and the Emergency Medicine Residents' Association
Authors: Hansoti Bhakti , Douglass Kate , Tupesis Janis , Runyon Michael S. , Sanson Tracy , Babcock Christine , Jacquet Gabrielle , Schroeder Erika D. , Hoffelder David , Martin Ian B. K.
Published: April 2013

The goal of a global health elective is for residents and medical students to have safe, structured, and highly educational experiences. In this article, the authors have laid out considerations for establishing a safe clinical site; ensuring a traveler's personal safety, health, and wellness; and mitigating risk during a global health rotation. Adequate oversight, appropriate mentorship, and a well‐defined safety and security plan are all critical elements to a successful and safe experience.
Posted Emergency Department Wait Times Are Not Always Accurate
Authors: Jouriles Nicholas , Simon Erin L. , Griffin Peter , Williams Carolyn Jo , Haller Nairmeen Awad
Published: April 2013

Objectives

Hospitals around the United States are advertising emergency department (ED) wait times. The objective was to measure the difference between publicly posted and actual ED wait times and to compare these between ED site volumes.

Methods

This study was a retrospective consecutive sample of ED patients at one hospital system with four EDs. The wait times of 8,889 patients were included in this analysis. One ED was in a large teaching hospital with 5,000 ED patients per month; the other three were freestanding or community EDs without teaching and with fewer than 2,000 ED patients per month each. The publicly posted ED wait times at the time of patient arrival were recorded and compared to the actual wait times as retrieved from the ED tracking system. The difference between posted and actual wait times for each site was calculated. Separate one‐way analysis of variance (ANOVA) tests with post hoc testing were conducted to assess actual wait time and wait time difference between ED sites.

Results

Mean and standard deviation (SD) wait time difference at the main ED with a volume of 5,000 patients per month was 31.5 (±61.2) minutes. At the facilities with fewer than 2,000 ED patients per month each, the differences in wait times were 4.2 (±21.8), 8.6 (±23.8), and 1.3 (±11.9) minutes. ANOVA results revealed that the main ED had significantly different actual wait time and wait time differences (p < 0.05) when compared to the other three EDs.

Conclusions

In one hospital system, publicly posted ED wait times show better accuracy in EDs that see 2,000 or fewer patients per month and less accuracy for an ED that sees 5,000 patients per month, likely due to flow confounders.
A Survey of Emergency Department Resources and Strategies Employed in the Treatment of Pediatric Gastroenteritis
Authors: Kinlin Laura M. , Bahm Allison , Guttmann Astrid , Freedman Stephen B.
Published: April 2013

Objectives

Although leading organizations have developed gastroenteritis management guidelines, little is known about emergency department (ED) use of clinical tools to improve outcomes. Our objective was to describe pediatric gastroenteritis clinical decision tools employed in EDs in the province of Ontario and to determine if a greater number of clinical decision tools are employed in academic, high‐volume institutions staffed primarily by emergency medicine (EM)‐trained physicians.

Methods

A cross‐sectional, Internet‐based survey was distributed in the summer of 2010 to medical directors and managers of Ontario EDs. Domains included patient population, general resources, and gastroenteritis‐specific strategies. Copies were requested of all gastroenteritis‐specific strategies to enable a content review.

Results

A total of 133 (83%) of 160 eligible participants responded. Practice guidelines, pathways, or order sets; medical directives; and printed discharge instructions were reported to be in use at 38 of the 133 (29%), 69 of 133 (52%), and 105 of 133 (79%) of the responding institutions, respectively. Oral rehydration therapy (ORT) is routinely initiated at triage in only 51 of the 133 of the EDs (38%). High‐volume institutions are more likely to have clinical practice guidelines, pathways, or order sets (p = 0.001) than low‐ and medium‐volume EDs. Physician training in EM was associated with the presence of medical directives for nursing administration of antiemetics and antipyretics (p = 0.04). Review of clinical practice guidelines, pathways, and order sets showed that only six of 27 gastroenteritis‐specific strategies reviewed were correctly classified, and 20 (74%) met prespecified quality criteria.

Conclusions

Clinical decision tools designed to improve pediatric gastroenteritis management are not commonly implemented. Such strategies are more common in high‐volume EDs and those staffed primarily by physicians with EM training.
The Use of Delayed Telephone Informed Consent for Observational Emergency Medicine Research Is Ethical and Effective
Authors: Offerman Steven R. , Nishijima Daniel K. , Ballard Dustin W. , Chetipally Uli K. , Vinson David R. , Holmes James F.
Published: April 2013

Objectives

The objective was to describe the rate of successful consent using an altered (deferred telephone) consent process in emergency department (ED) patients.

Methods

This study evaluated the consent process employed during a prospective, multicenter, observational study of outcomes in anticoagulated patients with blunt head trauma. The study was approved by the institutional review boards (IRBs) at all participating centers. Patients were not informed of the study during their enrollment at their index ED visit. Patient names, clinical findings, and contact information were collected at the time of initial ED visits. The patients or their legally designated surrogates were contacted by telephone at least 14 days after ED discharge, given all the elements of informed consent, and then consented for study participation. Study results are presented with simple descriptive statistics.

Results

A total of 506 patients with a mean (±SD) age of 75.8 (±12.2) years including 274 female subjects (54.2%; 95% confidence interval [CI] = 49.7% to 58.6%) were enrolled into the study. Patients or their surrogates were successfully contacted by telephone in 501 of 506 cases (99.0%; 95% CI = 97.7% to 99.7%). Consent was obtained in 500 of 501 cases at time of telephone follow‐up (99.8%; 95% CI = 98.9% to 100.0%). Surrogates provided consent in 199 cases (39.7%; 95% CI = 35.4% to 44.2%). Median time from ED visit to phone contact was 21 days (interquartile range [IQR] = 17 to 27 days). The median number of phone attempts for successful contact was 1 (IQR = 1 to 2 attempts).

Conclusions

The authors achieved a very high rate of successful telephone follow‐up in this predominantly older ED population. Obtaining consent to participate in a research study using a deferred telephone contact process was effective and well received by both subjects and surrogates. IRBs should consider deferred telephone consent for minimal‐risk studies requiring telephone follow‐up, as opposed to a consent process requiring written documentation at the time of initial ED visit.
Working at the frontline in cases of elder abuse: ‘It keeps me awake at night’
Authors: Cairns Jane , Vreugdenhil Anthea
Published: April 2013

Aim

To explore the experiences of frontline health and welfare practitioners in working with older people experiencing abuse.

Methods

In‐depth interviews with 16 Tasmanian community‐based health and welfare practitioners regarding their experiences of working in 49 recent cases of elder abuse. Interview transcripts were analysed using thematic analysis.

Results

All participants found working in cases of elder abuse challenging and the work itself was perceived as difficult, complex and at times dangerous. The cumulative effect of intimidating work contexts, practice dilemmas and a lack of support resulted in frustration and stress for many practitioners. Nevertheless, participants were committed to providing ongoing services and support for older people experiencing abuse.

Conclusion

Frontline practitioners working in cases of elder abuse face significant challenges and could be better supported through strengthening organisational elder abuse policies, increased management support and more age‐inclusive family violence support services.
Prenatal diagnosis: array comparative genomic hybridization in fetuses with abnormal sonographic findings
Authors: Vestergaard Else Marie , Christensen Rikke , Petersen Olav B. , Vogel Ida
Published: April 2013

Objective

To evaluate the clinical value of a high‐resolution whole‐genome array method for examination of genomic imbalances in prenatal samples (46 amniotic fluid, 17 chorionic villus, and 26 products of conception) from fetuses with abnormal ultrasound, in a clinical setting where more than 90% of pregnant women receive first‐trimester combined screening and a second‐trimester anomaly scan.

Design

Cross‐sectional study.

Setting

Fetal medicine units (national healthcare system) in Central and North Denmark Regions from March 2009 to April 2012.

Samples

Eighty‐nine samples obtained at 11.5–35.0 (mean 19.3) gestational weeks, either during ongoing pregnancy or after termination.

Methods

DNA was extracted directly from amniotic fluid cells and chorionic villus samples, or from cultured cells, and examined with 80‐kb resolution oligonucleotide array‐based comparative genomic hybridization (aCGH).

Main outcome measures

Clinically significant copy number variations identified by aCGH.

Results

We detected clinically significant copy number variations in 11 fetuses (12%, confidence interval 6.0–19%) with structural malformations. Three fetuses (3.4%) had uncertain clinical significant variations and incidental findings.

Conclusions

aCGH is a valuable diagnostic tool when fetal malformations are detected. More affected fetuses may be diagnosed at an earlier gestational age providing better possibilities for postnatal treatment and allowing for women to decide earlier on termination of pregnancy. When a normal result has reduced the risk of significant chromosomal aberration, aCGH may facilitate parental decision‐making on whether to continue the pregnancy.