bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems
Authors: Ullal Anirudh J. , Pisetsky David S. , Reich Charles F.
Published: January 2010

Microparticles (MPs) are small membrane‐bound vesicles that are released from activated or dying cells by a blebbing process. These particles contain nuclear and cytoplasmic components and represent unique biomarkers for disease. The small size of particles, however, limits detection using flow cytometry with either light scatter or staining for surface markers. Because MPs contain DNA and RNA, we have explored the use of SYTO 13, a member of the class of SYTO dyes, for particle detection. SYTO 13 is cell permeable and has a high fluorescent yield when bound to DNA or RNA. In this study, we compared detection of MPs using either light scatter or SYTO 13 staining, testing the hypothesis that, with fluorescence detection with SYTO 13, problems of “noise” with light scatter are reduced and the range of MP sizes detected is increased. In these experiments, particles were obtained from lymphoid cell lines treated in vitro to undergo apoptosis. As these results showed, STYO 13 allowed the detection of 1.5–2.9 times as many particles as did light scatter. The increased sensitivity was observed with three different cell lines and was independent of inducing stimulus. Treatment of fixed and permeabilized MPs with DNase and RNase showed that SYTO 13 binding resulted from interaction with both DNA and RNA. Together, these findings indicate that the nucleic acid content of MPs provides the basis for their detection in in vitro systems and suggests the utility of fluorescent dyes like SYTO 13 for more sensitive quantitative assays. © 2010 International Society for Advancement of Cytometry
Ki‐67 staining for determination of rhesus macaque T cell proliferative responses ex vivo
Authors: Shedlock Devon J. , Talbott Kendra T. , Morrow Matthew P. , Ferraro Bernadette , Hokey David A. , Muthumani Karuppiah , Weiner David B.
Published: January 2010

The capacity for robust proliferation upon re‐infection is a hallmark of adaptive immunity and the basis of vaccination. A widely used animal model for the study of human disease is the rhesus macaque (RM), where capacity for proliferation can be assessed ex vivo using carboxyfluorescein succinimidyl ester (CFSE)‐based dilution assays. However, we show over the course of the standard ex vivo proliferation assay that CFSE‐labeling at commonly used dye concentrations induces significant cell death, but that this phenomenon is dose‐dependent. Here, we describe an alternative semiquantitative method for estimating T cell proliferative responses that avoids the putative biases associated with chemical modification. RM peripheral blood mononuclear cells were stimulated ex vivo with cognate peptides for 5 days, immunostained for intracellular Ki‐67, and then analyzed by flow cytometry. We describe a gating strategy using Ki‐67 and side light scatter, also a marker of blastogenesis, which correlates strongly with data from CFSE dilution. We show that this method is a valid tool for measuring RM antigen‐specific cellular proliferation ex vivo and can be used as an alternative to CFSE dilution assays. © 2010 International Society for Advancement of Cytometry
The climate learning ladder. A pragmatic procedure to support climate adaptation
Authors: Tàbara J. David , Dai Xingang , Jia Gensuo , McEvoy Darryn , Neufeldt Henry , Serra Anna , Werners Saskia , West Jennifer J.
Published: January 2010

We introduce a new pragmatic procedure called the ‘climate learning ladder’ to structure policy analysis, support reflection and identify critical decisions to support climate adaptation. This tool is the result of the reflexive learning process that occurred while developing innovative appraisal methods in the Alxa League of Inner Mongolia, China, and in the Guadiana river basin in the European Union. Building capacities to cope with climate change requires going beyond simply providing ‘more knowledge’ on climate impacts to policy makers. Instead, climate adaptation can be understood as a multi‐step social process in which individuals and organizations need to learn how to (1) manage different framings of the issues at stake while raising awareness of climate risks and opportunities, (2) understand different motives for, and generate adequate incentives or sanctions to ensure, action, (3) develop feasible options and resources for individual and collective transformation and collaboration and (4) institutionalize new rights, responsibilities and feedback learning processes for climate adaptation in the long term. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Ectopic GC in the thymus of myasthenia gravis patients show characteristics of normal GC
Authors: Zuckerman Neta S. , Howard Wendy A. , Bismuth Jacky , Gibson Kate , Edelman Hanna , Berrih‐Aknin Sonia , Dunn‐Walters Deborah , Mehr Ramit
Published: January 2010

Young patients with myasthenia gravis (MG) frequently have ectopic GC in their thymus. We investigated these ectopic GC by microdissection of GC B cells and analysis of their Ig gene characteristics, in comparison to normal GC. CDR3 length distribution, a measure of clonal variability, and Ig gene family usage were similar in MG and normal tonsil samples. Lineage tree analysis demonstrated similar diversification and mutations per cell compared with normal control trees. Mutations were observed in the framework regions, responsible for the structural integrity of the BCR; however, these mutations were mostly conservative or neutral, confirming that a functional BCR is conserved in MG. In the CDR, responsible for Ag binding, selection against replacement mutations was revealed. This may indicate that the MG clones analyzed are already highly Ag‐specific, and therefore potential affinity‐reducing replacement mutations in the CDR3 are not propagated, due to Ag‐driven selection. Somatic hypermutation (SHM) targeting motifs and aa substitution preferences in MG were similar to those of normal controls. Overall, these results suggest that B cells in the ectopic GC in MG appear to undergo normal diversification and selection, in spite of the chronic nature and different environment of the response.
Human β‐defensin 3 has immunosuppressive activity in vitro and in vivo
Authors: Semple Fiona , Webb Sheila , Li Hsin‐Ni , Patel Hetal B. , Perretti Mauro , Jackson Ian J. , Gray Mohini , Davidson Donald J. , Dorin Julia R.
Published: January 2010

β‐defensins are antimicrobial peptides with an essential role in the innate immune response. In addition β‐defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human β defensin‐3 (hBD3) was considered pro‐inflammatory. We present evidence here that hBD3 lacks pro‐inflammatory activity in human and mouse primary Mϕ. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF‐α and IL‐6 accumulation implying an anti‐inflammatory function. hBD3 also inhibits CD40/IFN‐γ stimulation of Mϕ and in vivo, hBD3 significantly reduces the LPS‐induced TNF‐α level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.
Reaction Diversity of the S–S Bond Promoted by Metal Coordination: From Discovery to Controllable Reactions
Authors: Zhu Hai‐Bin , Li Lei , Xu Gang , Gou Shao‐Hua
Published: January 2010

Promoted by NiCl2 coordination in the mixed solvent MeOH/CH2Cl2, diverse in situ S–S bond reactions, such as S‐oxidation and S–S and C–S bond scission, occurred in the disulfide ligand of 2‐ppds {bis[4‐(pyridin‐2‐yl)pyrimidin‐2‐yl]disulfane} to yield three new components identified as 2‐mpp [2‐methoxy‐4‐(pyridin‐2‐yl)pyrimidine], 2‐ppst {S‐[4‐(pyridin‐2‐yl)pyrimidin‐2‐yl] 4‐(pyridin‐2‐yl)pyrimidine‐2‐sulfonothioate} and 2‐pps {bis[4‐(pyridin‐2‐yl)pyrimidin‐2‐yl]sulfane}. More importantly, such in situ reactions could be efficaciously controlled so that they proceed in a highly selective manner. Thus, NiCl2‐mediated in situ reaction of 2‐ppds with the aid of continuous air bubbling through the reaction mixture exclusively led to 2‐pps, whereas replacement of NiCl2 by Cu(OAc)2 afforded 2‐mpp alone. A confirmatory experiment proved that 2‐ppst served as a decisive intermediate in these in situ reactions.
A Back‐to‐Back Ligand with Dipyrazolylpyridine and Dipicolylamine Metal‐Binding Domains
Authors: Tovee Clare A. , Kilner Colin A. , Barrett Simon A. , Thomas James A. , Halcrow Malcolm A.
Published: January 2010

Reaction of 4‐bromomethyl‐2,6‐bis(pyrazol‐1‐yl)pyridine with dipicolylamine yields 4‐bis(pyrid‐2‐ylmethyl)aminomethyl‐2,6‐bis(pyrazol‐1‐yl)pyridine (L). Treatment of L with [MCl2(NCPh)2] (M = Pd, Pt) in the presence of AgPF6 affords [MCl(L)]PF6, whose palladium or platinum centre is bound exclusively by the dipicolylamino moiety of L, as established by NMR spectroscopy. The pendant dipyrazolylpyridine residue in these compounds is complexed by iron(II) to form [Fe{MCl(μ‐L)}2][PF6]4 (M = Pd, 1; M = Pt, 2·nH2O). The nitromethane solvate crystal of 1 contains low‐spin iron centres at 150 K. However, dried 1 and 2·nH2O are predominantly high‐spin at room temperature, undergoing very gradual thermal spin transitions upon cooling to ≤ 50 % completeness. The platinum compound also undergoes a thermal spin transition in CD3NO2 solution, with T1/2 = 253 K.
Carolacton – A Macrolide Ketocarbonic Acid that Reduces Biofilm Formation by the Caries‐ and Endocarditis‐Associated Bacterium Streptococcus mutans
Authors: Jansen Rolf , Irschik Herbert , Huch Volker , Schummer Dietmar , Steinmetz Heinrich , Bock Martin , Schmidt Thomas , Kirschning Andreas , Müller Rolf
Published: January 2010

The macrolide ketocarbonic acid carolacton (1) was isolated from the myxobacterium Sorangium cellulosum, strainSo ce960, because of its antibiotic activity. Subsequently, carolacton (1) was discovered to be a highly potent agent against biofilms containing the caries‐ and endocarditis‐associated bacterium Streptococcus mutans. The 2D structure of 1 was elucidated by HRMS, IR and 2D NMR spectroscopy. Initially, the stereogenic centres were determined by chemical derivatization in combination with computional methods and finally verified by X‐ray analysis.
Electrical imaging of sliding geometry and fluids associated with a deep seated landslide (La Clapière, France)
Authors: Jomard H. , Lebourg T. , Guglielmi Y. , Tric E.
Published: January 2010

This paper deals with the applicability of electrical resistivity tomography (ERT) for the recognition of large landslide structures at depths, which have never previously been imaged accurately. One of the most studied and instrumented deep landslides in Europe is taken as an example: the La Clapière landslide.

The first stage of the study consisted of an accurate geological mapping taking into account a morphological analysis of gravitational deformations. This allowed a very fine definition of the landslide structure, that could be compared with three provided ERT profiles performed within the landslide body. Very good correlations were obtained for the determination of sub‐horizontal structures and associated fluid circulations. It confirmed the position of the sliding surface that reached a maximum depth of 100 m. Forward computing was however necessary to determine the influence and then the presence of vertical discontinuities. It supports the use of ERT as an efficient tool for large scale landslide imaging, such as deep seated landslides. Copyright © 2010 John Wiley & Sons, Ltd.
Raw materials: the importance of quality and safety. A review.
Authors: Salgueiro L. , Martins A. P. , Correia H.
Published: January 2010

Aromatic plants and spices are used throughout the world for flavouring food and beverages, as well as for food supplements, novel foods and as a source of essential oils and aromatic extracts. The non‐availability or inadequacy of standards for checking and assuring the quality of aromatic plants and spices is one of the main problems that arise for industry when using such raw materials. As many aromatic plants are harvested from the wild, standardization to assure their quality is important for their safe and effective utilization in food and beverage industries. On the other hand, there are numerous parameters that influence the chemical composition of plants, which play an important role in the final quality of the product and possibly in any risk arising to the consumer. Also, from a safety point of view, aromatic plants and spices should be free of undeclared contaminants and adulterants, such as toxic botanicals, pathogenic microorganisms and excessive levels of microbial toxins, pesticides or fumigation agents. We focus on these aspects and examine ways to assure their appropriate utilization from the quality and safety standpoint. The regulatory situation of medicinal and aromatic plants (MAPs) is very complicated; several differences in standards and regulations between countries can be found, a situation that can result in more health risks arising for consumers. To clarify some of the existing problems, the major regulations of the USA and the European Union (EU) and the borderlines between food supplements and medicines and other international standards, are briefly described and discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Functional methods for time series prediction: a nonparametric approach
Authors: Aneiros‐Pérez Germán , Cao Ricardo , Vilar‐Fernández Juan M.
Published: January 2010

The problem of prediction in time series using nonparametric functional techniques is considered. An extension of the local linear method to regression with functional explanatory variable is proposed. This forecasting method is compared with the functional Nadaraya–Watson method and with finite‐dimensional nonparametric predictors for several real‐time series. Prediction intervals based on the bootstrap and conditional distribution estimation for those nonparametric methods are also compared. Copyright © 2010 John Wiley & Sons, Ltd.
Contribution of different kinematic models and a complex Jurassic stratigraphy in the construction of a forward model for the Montagna dei Fiori fault‐related fold (Central Apennines, Italy)
Authors: Di Francesco L. , Fabbi S. , Santantonio M. , Bigi S. , Poblet J.
Published: January 2010

The Montagna dei Fiori has received attention from geologists over the past decades because of both its Jurassic stratigraphy and its complex present‐day structure. The latter is the result of multiple phases of deformation, from the Early Jurassic, during the opening of the Tethyan Ocean, to Neogene evolution of the Apennines fold‐and‐thrust belt. In this paper, we present a new stratigraphic interpretation of the Jurassic palaeogeography, based on a new geological mapping project in the area. Using this new stratigraphy, we constructed two forward models, using a combination of different fault/fold interactions, in order to unravel the kinematic evolution of the Montagna dei Fiori fault‐related fold. The first model was constructed manually using the fault‐bend and fault‐propagation theories from an initial configuration which included previous extensional features, whereas the second model was constructed using the software 2DMove (Midland Valley) using the fault‐bend and trishear fault‐propagation folding theories and starting from a layer‐cake stratigraphy. Both forward models involved the same main steps and provided a reasonable geological simulation of the geometry of the Montagna dei Fiori structure. Copyright © 2010 John Wiley & Sons, Ltd.
Suicide in later life: public health and practitioner perspectives
Authors: Manthorpe Jill , Iliffe Steve
Published: January 2010

Objectives

Suicide in later life is a public health concern. Given the need for practical guidance and policy implementation, this paper aims to provide a critical interpretive synthesis approach to prioritize the likely relevance of publications and the contribution that they make to understanding of the problem.

Methods

A selective review of the English language literature focusing on the epidemiology of suicide among older people was conducted; the search strategy built on that of a previous review. Papers were selected for their ability to shed light on the potential for prevention and practice from public health perspectives.

Results

Whilst the majority of older people who commit suicide have major depression, suicide seems to be due to a combination of personality factors and co‐morbidities, including chronic pain and disablement. Complex multi‐component public health studies are underway and are likely to provide useful knowledge to guide practice more precisely, but there is remarkably little information about the involvement of older people in risk reduction or about harm minimization approaches at patient and public participation levels.

Conclusions

For lack of sufficient evidence from intervention trials that are specific to older people, practitioners need to extrapolate from studies of younger adults and be aware of risk factors for suicide in later life. Public health approaches combined with practitioners' experiences of older people at risk may help minimize the risks of suicide in later life. These are fruitful areas for collaborative practice development, service initiatives, evaluation, and research. Copyright © 2010 John Wiley & Sons, Ltd.
An index of fatal toxicity for drugs of misuse
Authors: King Leslie A. , Corkery John M.
Published: January 2010

Objective

To determine the lethal toxicity of five commonly‐used illicit substances by relating the number of associated deaths to their availability.

Methods

An index of toxicity was calculated for each of five drugs [heroin, cocaine/crack, ecstasy (MDMA), amphetamine and cannabis] as the ratio of the number of deaths associated with that substance to its availability in the period 2003–2007. Three separate proxy measures of availability were used (number of users as determined by household surveys, number of seizures by law enforcement agencies and estimates of the market size). All data are related to England and Wales only.

Results

There was a broad correlation between all three denominators of availability. Not unexpectedly, heroin and cannabis showed, respectively, the highest and lowest toxicities. The index of fatal toxicity of MDMA was close to that of amphetamine and cocaine/crack. There was a rank correlation between this index and other measures of lethal toxicity based on safety ratios.

Conclusions

These results are contrary to widely‐held public views of the relative fatal toxicity of MDMA. Copyright © 2010 John Wiley & Sons, Ltd.
Hydraulic evolution and total suspended solids capture of an infiltration trench
Authors: Emerson Clay H. , Wadzuk Bridget M. , Traver Robert G.
Published: January 2010

Stormwater best management practice (BMP) design must incorporate the expected long‐term performance from both a water quantity and water quality perspective to sustainably mitigate hydrologic and water quality impacts of development. Infiltration trench structures are one of many infiltration BMPs that reduce runoff volume and capture pollutants. Research on the longevity of these structures is sparse, leading to concerns about their long‐term value and impeding implementation. In the present study, an infiltration trench was monitored from its inception to determine its hydrologic performance over time and total suspended solids (TSS) capture efficiency. The infiltration trench was intentionally undersized to accelerate longevity‐related processes. The infiltration trench provided a 36% TSS removal rate and displayed a distinct decrease in its ability to infiltrate stormwater runoff over the first three years of operation. Results indicate that infiltration through the bottom of the BMP became negligible, while infiltration through the sides of the BMP remained active over the 3‐year study period. The results lead to recommendations for BMP design. Copyright © 2010 John Wiley & Sons, Ltd.
Identification of best predictors for forecasting seasonal rainfall and runoff in Australia
Authors: Kirono Dewi G. C. , Chiew Francis H. S. , Kent David M.
Published: January 2010

The first step towards developing a reliable seasonal runoff forecast is identifying the key predictors that drive rainfall and runoff. This paper investigates the lag relationships between rainfall across Australia and runoff across southeast Australia versus 12 atmospheric‐oceanic predictors, and how the relationships change over time. The analysis of rainfall data indicates that the relationship is greatest in spring and summer in northeast Australia and in spring in southeast Australia. The best predictors for spring rainfall in eastern Australia are NINO4 [sea surface temperature (SST) in western Pacific] and thermocline (20 °C isotherm of the Pacific) and those for summer rainfall in northeast Australia are NINO4 and Southern Oscillation Index (SOI) (pressure difference between Tahiti and Darwin). The relationship in northern Australia is greatest in spring and autumn with NINO4 being the best predictor. In western Australia, the relationship is significant in summer, where SST2 (SST over the Indian Ocean) and II (SST over the Indonesian region) is the best predictor in the southwest and northwest, respectively.

The analysis of runoff across southeast Australia indicates that the runoff predictability in the southern parts is greatest in winter and spring, with antecedent runoff being the best predictor. The relationship between spring runoff and NINO4, thermocline and SOI is also relatively high and can be used together with antecedent runoff to forecast spring runoff. In the northern parts of southeast Australia, the atmospheric‐oceanic variables are better predictors of runoff than antecedent runoff, and have significant correlation with winter, spring and summer runoff. For longer lead times, the runoff serial correlation is reduced, especially over the northern parts, and the atmospheric‐oceanic variables are likely to be better predictors for forecasting runoff. The correlations between runoff versus the predictors vary with time, and this has implications for the development of forecast relationship that assumes stationarity in the historical data. Copyright © 2010 John Wiley & Sons, Ltd.
Spatial interpolation of snow water equivalency using surface observations and remotely sensed images of snow‐covered area
Authors: Harshburger Brian J. , Humes Karen S. , Walden Von P. , Blandford Troy R. , Moore Brandon C. , Dezzani Raymond J.
Published: January 2010

As demand for water continues to escalate in the western Unites States, so does the need for accurate monitoring of the snowpack in mountainous areas. In this study, we describe a simple methodology for generating gridded‐estimates of snow water equivalency (SWE) using both surface observations of SWE and remotely sensed estimates of snow‐covered area (SCA). Multiple regression was used to quantify the relationship between physiographic variables (elevation, slope, aspect, clear‐sky solar radiation, etc.) and SWE as measured at a number of sites in a mountainous basin in south‐central Idaho (Big Wood River Basin). The elevation of the snowline, obtained from the SCA estimates, was used to constrain the predicted SWE values. The results from the analysis are encouraging and compare well to those found in previous studies, which often utilized more sophisticated spatial interpolation techniques. Cross‐validation results indicate that the spatial interpolation method produces accurate SWE estimates [mean R2 = 0·82, mean mean absolute error (MAE) = 4·34 cm, mean root mean squared error (RMSE) = 5·29 cm]. The basin examined in this study is typical of many mid‐elevation mountainous basins throughout the western United States, in terms of the distribution of topographic variables, as well as the number and characteristics of sites at which the necessary ground data are available. Thus, there is high potential for this methodology to be successfully applied to other mountainous basins. Copyright © 2010 John Wiley & Sons, Ltd.
Inhibition of Met/HGF receptor and angiogenesis by NK4 leads to suppression of tumor growth and migration in malignant pleural mesothelioma
Authors: Suzuki Yoshinori , Sakai Katsuya , Ueki Junko , Xu Qing , Nakamura Takahiro , Shimada Hideaki , Nakamura Toshikazu , Matsumoto Kunio
Published: January 2010

NK4 exhibits two distinct biological actions: antagonistic inhibition of hepatocyte growth factor (HGF) through binding to the Met/HGF receptor, and antiangiogenic action through binding to perlecan. Here, the anti‐tumor effect of NK4 on malignant pleural mesothelioma was investigated. Of the 7 human malignant mesothelioma cell lines (ACC‐Meso‐1, ACC‐Meso‐4, EHMES‐1, EHMES‐10, H28, H2052 and JMN‐1B), only EHMES‐10 cells formed subcutaneous tumors when implanted into mice. For EHMES‐10 cells, HGF facilitated invasion of the cells in collagen gel, whereas NK4 and neutralizing anti‐HGF antibody suppressed the HGF‐induced invasion. In addition, NK4 but not anti‐HGF antibody suppressed proliferation of EHMES‐10 cells in collagen, suggesting that the suppression by NK4 was independent of the HGF‐Met pathway. In the subcutaneous tumor model, recombinant adenovirus‐mediated intratumoral expression of NK4 inhibited tumor growth, while the invasive characteristic of tumor cells was not observed. Analysis of Met receptor tyrosine phosphorylation, proliferation, apoptosis and blood vessels in the tumor tissues indicated that the inhibitory effect of NK4 expression might be primarily caused by the inhibition of tumor angiogenesis. In all the 7 mesothelioma lines, HGF stimulated Met tyrosine phosphorylation, and this was associated with enhanced cell migration. HGF‐dependent Met activation and migration were inhibited by NK4. Since malignant pleural mesothelioma represents an aggressive neoplasm characterized by extensive invasive growth, suppression of invasive growth has therapeutic value. Thus, the simultaneous inhibition of the HGF‐Met pathway and angiogenesis by NK4 for treatment of malignant pleural mesothelioma is significant, particularly to attenuate migration and invasive growth.
Incidence of cancers, ischemic cardiovascular diseases and mortality during 5‐year follow‐up after stopping antioxidant vitamins and minerals supplements: A postintervention follow‐up in the SU.VI.MAX Study
Authors: Hercberg Serge , Kesse‐Guyot Emmanuelle , Druesne‐Pecollo Nathalie , Touvier Mathilde , Favier Alain , Latino‐Martel Paule , Briançon Serge , Galan Pilar
Published: January 2010

The Supplementation in Vitamins and Mineral Antioxidants Study was a double‐blind, placebo‐controlled, randomized trial, in which 12,741 French adults (7,713 women aged 35–60 years and 5,028 men aged 45–60 years) received a combination of ascorbic acid (120 mg), vitamin E (30 mg), β‐carotene (6 mg), selenium (100 μg) and zinc (20 mg), or placebo daily for a median follow‐up time of 7.5 years [October 1994 to September 2002]. Antioxidant supplementation decreased total cancer incidence and total mortality in men. Postintervention follow‐up assessment of total cancer incidence, ischemic cardiovascular disease incidence and total mortality was carried out for 5 years [September 1, 2002, to September 1, 2007]. No late effect of antioxidant supplementation was revealed 5 years after ending the intervention neither on ischemic cardiovascular disease incidence and mortality in both genders nor on cancer incidence in women. Regarding duration of intervention effects in men, the reduced risk of total cancer incidence and total mortality was no longer evident after the 5‐year postintervention follow‐up. During the postsupplementation period, the relative risk (RR) for total cancer incidence (n = 126) was 0.98 (95% confidence interval [CI], 0.75–1.27) among antioxidant recipients compared to nonrecipients. For total mortality (n = 90), the RR was 0.98 (95% CI, 0.75–1.26) for men receiving antioxidants compared to nonrecipients. In conclusion, beneficial effects of antioxidant supplementation in men disappeared during postintervention follow‐up.
Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer
Authors: Delage Barbara , Fennell Dean A. , Nicholson Linda , McNeish Iain , Lemoine Nicholas R. , Crook Tim , Szlosarek Peter W.
Published: January 2010

Arginine, a semi‐essential amino acid in humans, is critical for the growth of human cancers, particularly those marked by de novo chemoresistance and a poor clinical outcome. In addition to protein synthesis, arginine is involved in diverse aspects of tumour metabolism, including the synthesis of nitric oxide, polyamines, nucleotides, proline and glutamate. Tumoural downregulation of the enzyme argininosuccinate synthetase (ASS1), a recognised rate‐limiting step in arginine synthesis, results in an intrinsic dependence on extracellular arginine due to an inability to synthesise arginine for growth. This dependence on extracellular arginine is known as arginine auxotrophy. Several tumours are arginine auxotrophic, due to variable loss of ASS1, including hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer. Importantly, targeting extracellular arginine for degradation in the absence of ASS1 triggers apoptosis in arginine auxotrophs. Several phase I/II clinical trials of the arginine‐lowering drug, pegylated arginine deiminase, have shown encouraging evidence of clinical benefit and low toxicity in patients with ASS1‐negative tumours. In part, ASS1 loss is due to epigenetic silencing of the ASS1 promoter in various human cancer cell lines and tumours, and it is this silencing that confers arginine auxotrophy. In relapsed ovarian cancer, this is associated with platinum refractoriness. In contrast, several platinum sensitive tumours, including primary ovarian, stomach and colorectal cancer, are characterised by ASS1 overexpression, which is regulated by proinflammatory cytokines. This review examines the prospects for novel approaches in the prevention, diagnosis and treatment of malignant disease based on ASS1 pathophysiology and its rate‐limiting product, arginine.
Citrus consumption and cancer incidence: the Ohsaki cohort study
Authors: Li Wen‐Qing , Kuriyama Shinichi , Li Qiang , Nagai Masato , Hozawa Atsushi , Nishino Yoshikazu , Tsuji Ichiro
Published: January 2010

Basic research and case–control studies have suggested that citrus consumption may protect against cancer. However, the protective effect has been observed from few prospective studies. This study investigated the association of citrus consumption with cancer incidence among 42,470 Japanese adults in the Ohsaki National Health Insurance Cohort, which covered an age range of 40–79 years, and was followed up from 1995 to 2003 for all‐cancer and individual cancer incidence. Citrus consumption was assessed using a self‐administered questionnaire. The Cox proportional hazard model was applied to estimate relative risks (RRs) and 95% CIs. During the 323,204 person‐years of follow‐up, 3,398 cases were identified totally. Citrus consumption, especially daily consumption, was correlated with reduced all‐cancer incidence, the RRs were 0.89 (95% CI = 0.80–0.98) for total participants, 0.86 (0.76–0.98) for males and 0.93 (0.79–1.09) for females, as well as multiple cancers at individual sites, especially pancreatic (RR = 0.62, 95% CI = 0.38–1.00) and prostate cancer (RR = 0.63, 95% CI = 0.41–0.97). Joint effect analysis showed a reduced risk of overall cancer existed only for subjects who consumed ≥1 cup green tea/day (RR = 0.83, 95% CI = 0.73–0.93) as well as for males (RR = 0.83, 95% CI = 0.71–0.97) or females (RR = 0.82, 95% CI = 0.68–0.99). These findings suggest that citrus consumption is associated with reduced all‐cancer incidence, especially for subjects having simultaneously high green tea consumption. Further work on the specific citrus constituents is warranted, and clinical trials are ultimately necessary to confirm the protective effect.
Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms
Authors: Yue Wei , Wang Ji‐Ping , Li Yuebai , Fan Ping , Liu Guijian , Zhang Nan , Conaway Mark , Wang Hongkun , Korach Kenneth S. , Bocchinfuso Wayne , Santen Richard
Published: January 2010

Development of breast cancer involves genetic factors as well as lifetime exposure to estrogen. The precise molecular mechanisms whereby estrogens influence breast tumor formation are poorly understood. While estrogen receptor α (ERα) is certainly involved, nonreceptor mediated effects of estradiol (E2) may also play an important role in facilitating breast tumor development. A “reductionist” strategy allowed us to examine the role of ERα independent effects of E2 on mammary tumor development in ERα knockout (ERKO) mice bearing the Wnt‐1 oncogene. Exogenous E2 “clamped” at early follicular and midluteal phase levels (i.e., 80 and 240 pg/ml) accelerated tumor formation in a dose‐related fashion in ERKO/Wnt‐1 animals (p = 0.0002). Reduction of endogenous E2 by oophorectomy (p < 0.001) or an aromatase inhibitor (AI) (p = 0.055) in intact ERKO/Wnt‐1 animals delayed tumorigenesis as further evidence for an ER‐independent effect. The effects of residual ERα or β were not involved since enhancement of tumor formation could not be blocked by the antiestrogen fulvestrant. 17α‐OH‐E2, a metabolizable but ER‐impeded analogue of E2 stimulated tumor development without measurable uterine stimulatory effects. Taken together, our results suggest that ER‐independent actions of E2 can influence breast tumor development in concert with ER dependent effects. These observations suggest 1 mechanism whereby AIs, which block E2 synthesis, would be more effective for breast cancer prevention than use of antiestrogens, which only block ER‐mediated effects.
Intake of fatty acids and antioxidants and pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area
Authors: Gong Zhihong , Holly Elizabeth A. , Wang Furong , Chan June M. , Bracci Paige M.
Published: January 2010

There are no well‐established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population‐based case‐control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all ptrend < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2–2.1) and 1.4 (95% CI: 1.1–1.9); both ptrend < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1–2.0); ptrend = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50–0.92); ptrend = 0.007] and omega‐3 fatty acids [≥0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25–0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51–0.94); ptrend = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49–0.92); ptrend = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both ptrend < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega‐3 fatty acids, vitamins C and E may reduce the risk.
Path homomorphisms, graph colorings, and boolean matrices
Authors: Nešetřil Jaroslav , Tardif Claude
Published: January 2010

We investigate bounds on the chromatic number of a graph G derived from the nonexistence of homomorphisms from some path \documentclass{article}\footskip=0pc\pagestyle{empty}\begin{document}\begin{eqnarray*}\vec{P}\end{eqnarray*}\end{document} into some orientation \documentclass{article}\footskip=0pc\pagestyle{empty}\begin{document}\begin{eqnarray*}\vec{G}\end{eqnarray*}\end{document} of G. The condition is often efficiently verifiable using boolean matrix multiplications. However, the bound associated to a path \documentclass{article}\footskip=0pc\pagestyle{empty}\begin{document}\begin{eqnarray*}\vec{P}\end{eqnarray*}\end{document} depends on the relation between the “algebraic length” and “derived algebraic length” of \documentclass{article}\footskip=0pc\pagestyle{empty}\begin{document}\begin{eqnarray*}\vec{P}\end{eqnarray*}\end{document}. This suggests that paths yielding efficient bounds may be exponentially large with respect to G, and the corresponding heuristic may not be constructive. © 2009 Wiley Periodicals, Inc. J Graph Theory 63: 198–209, 2010
Evaluation, management, and outcome of focal bacterial infections (FBIs) in nontoxic infants under two months of age
Authors: Vidwan Gurpreet , Geis Gary L.
Published: January 2010

BACKGROUND:

Well‐appearing young infants with focal bacterial infections present to the emergency department (ED) and are often admitted for a sepsis evaluation of blood, urine, and spinal fluid. However, the risk of concomitant systemic infections (CSI) in this population is not well reported, specifically comparing febrile to afebrile infants. We hypothesized that afebrile, well‐appearing infants under two months of age with a defined focal bacterial infection on exam have a very low risk of CSI.

METHODS:

This retrospective study was conducted at an urban, academic, tertiary care pediatric hospital ED on patients seen from January 2000‐December 2005. Eligible infants were less than 60 days of age, well‐appearing on exam, and with normal‐for‐age vital signs who presented with a focal bacterial infection on exam. Exclusion criteria included immunodeficiency, indwelling catheter, previous admission for bacterial infection, or current use of systemic antibiotics. Main study outcome was risk of CSI in febrile and afebrile groups.

RESULTS:

One hundred ninety seven patients were included in the study population. Of these, 39 were febrile and 158 were afebrile. Four patients had a documented CSI: one case of S. pneumoniae bacteremia and three cases of E. coli urinary tract infection. Of these 4 infants, 3 were febrile (7.7% CSI risk) and 1 was afebrile (0.6%). Febrile infants had a significantly higher risk of CSI (OR 13.1, 95% CI 1.3, 129.5).

CONCLUSIONS:

CSI is very uncommon in afebrile, well‐appearing infants under 60 days of age with a focal bacterial infection. Journal of Hospital Medicine 2010;5:76–82. © 2010 Society of Hospital Medicine.
A hospitalist postgraduate training program for physician assistants
Authors: Will Kristen K. , Budavari Adriane I. , Wilkens James A. , Mishark Kenneth , Hartsell Zachary C.
Published: January 2010

Many hospitalist groups are hiring physician assistants (PAs) to augment their physician services. Finding PAs with hospitalist experience is difficult. Employers often have to recruit PAs from other specialties or hire new graduates who have limited hospital experience. Furthermore, entry‐level PA training focuses on primary care, with more clinical rotations centered in the outpatient setting. In light of these challenges, our institution created a 12‐month postgraduate training program in Hospital Medicine for 1 PA per year. It is the first reported postgraduate PA hospitalist fellowship to offer a certificate of completion. The program's curriculum is based on the Society of Hospital Medicine (SHM) “Core Competencies,” and is comprised of 12 one‐month rotations in different aspects of hospital medicine supplemented by formal didactic instruction. In addition, the PA fellow completes “teaching modules” on various topics not directly covered in their rotations. Furthermore, this postgraduate physician assistant training program represents a model that can be utilized at almost any institution, academic or community‐based. As the need for hospitalists increases, so will the need for trained physician assistants in hospital medicine. Journal of Hospital Medicine 2010;5:94–98. © 2010 Society of Hospital Medicine.
Examining guideline‐concordant care for acute myocardial infarction (AMI): The case of hospitalized post‐acute and long‐term care (PAC/LTC) residents
Authors: Radcliff Tiffany A. , Levy Cari R.
Published: January 2010

BACKGROUND:

Previous studies have examined differences in care for acute myocardial infarction (AMI) according to patient characteristics such as age, gender, or insurance, but little attention has been given to whether admission source is related to guideline adherence.

OBJECTIVE:

To investigate: (1) the use of aspirin and reperfusion in the care of post‐acute/long‐term care (PAC/LTC) patients who are hospitalized for AMI, and (2) 30‐day mortality associated with these treatments.

DESIGN:

Secondary examination of data from the Cooperative Cardiovascular Project (CCP) national baseline data.

SETTING:

A total of 4013 U.S. hospitals.

SUBJECTS:

Patients hospitalized with a confirmed AMI admitted from PAC/LTC (n = 8151) or community‐dwelling (n = 120,032) settings.

MEASUREMENTS:

Early administration of aspirin and reperfusion via either thrombolysis or percutaneous intervention.

RESULTS:

PAC/LTC patients were less likely to receive treatment for AMI, even after adjustment for multiple variables associated with treatment choice. Differences persisted with additional econometric adjustment using seemingly‐unrelated regression. Multivariable logistic regression results indicated that aspirin was related to improved 30‐day survival for both PAC/LTC and community admissions (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.43‐0.58 for PAC/LTC, and OR, 0.57; 95% CI, 0.54‐0.60 for community). Reperfusion was associated with higher ORs for mortality for eligible patients admitted from community setting (OR, 1.24; 95% CI, 1.13‐1.35), but ideally‐eligible candidates had lower ORs for mortality (OR, 0.58; 95% CI, 0.35‐0.95 for PAC/LTC, and OR, 0.74; 95% CI, 0.68‐0.81 for community).

CONCLUSIONS:

Patients transferred from PAC/LTC settings were less likely to receive early treatment for AMI than other patients. Future trials should inform which guidelines are applicable to PAC/LTC patients. Journal of Hospital Medicine 2010;5:E3–E10. © 2010 Society of Hospital Medicine.
Recent trends of mean and extreme precipitation in Korea
Authors: Jung Il‐Won , Bae Deg‐Hyo , Kim Gwangseob
Published: January 2010

The spatial and temporal variability of precipitation in Korea were investigated using 183 weather station data for 1973–2005. A set of 16 indices that represent mean and extreme values of precipitation data were estimated using daily precipitation data, linear and spatial trend relationships of the indices were analysed using the Mann–Kendall test and Moran's I test statistic, respectively. Results demonstrate that annual precipitation data have a significant positive trend and there is a strong spatial relationship in their variability. The increase of annual precipitation is mainly associated with the increase of frequency and intensity of heavy precipitation during summer season. However, precipitation during spring and winter seasons had a decreasing trend. This variation of precipitation is likely to increase flood and drought risk. It means that the increase of annual precipitation should not be helpful for water resources management but could be a burden to river management and dam operation in Korea. Copyright © 2010 Royal Meteorological Society
Wind direction‐dependent statistical downscaling of precipitation applied to the Upper Danube catchment
Authors: Schipper Janus Willem , Frueh Barbara , Pfeiffer Andreas , Zaengl Guenther
Published: January 2010

Simulating regional climate has become increasingly important during the last decade. Although general circulation models reproduce today's global‐scale climate reasonably well, regional and even local effects need to be simulated by regional‐scale climate models, which provide substantially higher resolutions.

The study presented here was aimed at statistically downscaling precipitation simulations of a regional climate model onto a 1 km grid for hydrological modeling of a catchment of roughly 75,000 sq km. The area of interest is the upper Danube catchment, which is located in southern Germany and partly in Austria, Switzerland, and Italy (Alpine area). Simulating regional climate of such a large area (approx. 450 × 450 km) at this high resolution over many years is limited by the computer resources available. An approach to gain 1 km precipitation simulations over climatological periods of time is to apply a statistical downscaling method. The downscaling method applied was used in a regional climate model, which was in turn nested in a global circulation model. The time period for verification was 1991–2001.

Two types of the same downscaling method based on the climatological relationship between the observed and simulated precipitation patterns are used. The first type is based on precipitation patterns only. The second type additionally uses the wind direction and wind speed dependence of precipitation patterns in the Alpine area.

It will be shown that both downscaling types improve the simulation results significantly for the complete verification period. Although both types are limited by the performance of the course grid model output, the wind‐dependent type improves the results even more, especially on days with a distinct wind‐dependent precipitation pattern. Copyright © 2011 Royal Meteorological Society
Harmonic analysis of climatological temperature over Antarctica: present day and greenhouse warming perspectives
Authors: Justino F. , Setzer A. , Bracegirdle T. J. , Mendes D. , Grimm A. , Dechiche G. , Schaefer C. E. G. R.
Published: January 2010

On the basis of ERA40 and NCEP/NCAR Reanalysis (NNR) and simulations from CCCma, CCSM, CSIRO, HadCM3, MIROC‐MEDRES and GFDL, which support the Intergovernmental Panel on Climate Change (IPCC) 4th Assessment Report (AR4), we demonstrated that the amplitude of the annual and the semi‐annual harmonics delivered by the ERA40 and NNR is dominated by distinct seasonal variability. The maximum first harmonic amplitude of near surface temperature 2‐metre air temperature (t2m) according the NNR is located over the Plateau of East Antarctica, whereas analyses for ERA40 show maximum amplitude over the west Antarctic ice sheet. The spatial pattern of the first harmonic of t2m in NNR more closely corresponds to station observations, suggesting that the seasonal cycle of t2m over Antarctica may be biased in ERA‐40. A comparison between the global climate models (GCMs) and NNR demonstrates that the models satisfactorily simulate the amplitude of the first and second harmonics; however, the modelling results differ among themselves in terms of the amplitude values. Larger seasonal variability is identified for CCCma, HadCM3 and MIROC‐MEDRES with values as high as 20 °C over the Antarctic plateau. We have further identified that the CSIRO GCM does not reproduce the seasonal amplitude of t2m as compared to other models, which is primarily due to its overestimation of the cloud cover and weak seasonal changes of precipitation. Calculations of the harmonic analysis based upon greenhouse warming (GW) conditions reveal that there is no substantial seasonal difference between the amplitude of the first harmonic as projected by GW and present day (PD) simulations over the Antarctic continent. Over the polar ocean, however, the amplitude of the first harmonic is reduced in all climate models under future conditions. In order to narrow down the uncertainties on future climate projections, analyses of the cloud forcing which include the short‐ and long‐wave radiation and the surface mass balance (SMB) may provide substantial information on the cause of the discrepancies as simulated by climate models over the Antarctic region. Copyright © 2010 Royal Meteorological Society