bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost‐effectiveness analysis of solifenacin flexible dosing in patients with overactive bladder symptoms in four Nordic countries
Authors: MILSOM IAN , AXELSEN SUSANNE , KULSENG‐HANSEN SIGURD , MATTIASSON ANDERS , NILSSON CARL GUSTAF , WICKSTRØM JANNIE
Published: April 2009

Objective. The purpose of the present analysis was to analyze and compare the cost‐effectiveness of solifenacin flexible dosing (5–10 mg) with tolterodine 4 mg sustained release (SR) or placebo (assumed to be comparable to no treatment) for patients with overactive bladder (OAB) symptoms.Design. A decision‐analytic model was constructed.Methods. Costs and effects were evaluated for the three treatment options in a one‐year timeframe. Costs included were treatment costs, cost of pad use, and patients productivity loss based on data from the Nordic countries.Sample. Results from two randomized controlled trials were used as input data in the cost‐effectiveness analysis.Main outcome measures. Quality adjusted life years and incremental cost‐effectiveness ratio.Results. Solifenacin flexible dosing was more effective with respect to reducing OAB symptoms compared to both placebo and tolterodine 4 mg. Treatment with both solifenacin and tolterodine was more costly compared to placebo, but treatment with solifenacin was a less costly alternative compared to tolterodine 4 mg SR. Sensitivity analyses revealed that the conclusions were robust.Conclusion. Solifenacin flexible dosing was a cost‐effective treatment alternative compared to tolterodine 4 mg SR.
2008 Landis Award Lecture Inflammation and the Autodigestion Hypothesis
Authors: SCHMID‐SCHÖNBEIN GEERT W.
Published: April 2009

Although long recognized in microvascular research, an increasing body of evidence suggests that inflammatory markers are present in human diseases. Since the inflammatory cascade serves as a repair mechanism, the presence of inflammatory markers in patient groups has raised an important question about the mechanisms that initiate the inflammatory cascade (i.e., the mechanisms that cause tissue injury). Using a severe form of inflammation, shock, and multiorgan failure, for which there is no accepted injury mechanism, we summarize studies that suggest that the powerful pancreatic digestive enzymes play a central role in the destruction of the intestine and other tissues if their compartmentalization in the lumen of the intestine and in the pancreas is compromised. Further, we summarize evidence that uncontrolled degrading enzyme activity in plasma causes proteolytic cleavage of the extracellular domain of membrane receptors and loss of associated cell functions. For example, in a model of metabolic disease with type II diabetes, proteolytic cleavage of the insulin receptor causes the inability of insulin to signal glucose transport across membranes. The evidence suggests that uncontrolled proteolytic and lipolytic enzyme activity may trigger the mechanism for tissue injury. The significance of such mechanisms remain to be explored in human diseases.
Melioration behaviour in the Harvard game is reduced by simplifying decision outcomes
Authors: Stillwell David J. , Tunney Richard J.
Published: April 2009

Self-control experiments have previously been highlighted as examples of suboptimal decision making. In one such experiment, the Harvard game, participants make repeated choices between two alternatives. One alternative has a higher immediate pay-off than the other, but with repeated choices results in a lower overall pay-off. Preference for the alternative with the higher immediate pay-off seems to be impulsive and will result in a failure to maximize pay-offs. We report an experiment that modifies the Harvard game, dividing the pay-off from each choice into two separate consequences—the immediate and the historic components. Choosing the alternative with the higher immediate pay-off ends the session prematurely, leading to a loss of opportunities to earn further pay-offs and ultimately to a reduced overall pay-off. This makes it easier for participants to learn the outcomes of their actions. It also provides the opportunity for a further test of normative decision making by means of one of its most specific and paradoxical predictions—that the truly rational agent should switch from self-control to impulsivity toward the end of the experimental sessions. The finding that participants maximize their expected utility by both overcoming impulsivity and learning to switch implies that melioration behaviour is not due to the lure of impulsivity, but due to the difficulty of learning which components are included in the pay-off schedules.
Short article: Rapid extraction of mean identity from sets of faces
Authors: de Fockert Jan , Wolfenstein Cecilia
Published: April 2009

Recent evidence suggests that the notion that the visual system can rapidly extract summary statistics from complex scenes extends to representing sets of faces in terms of mean emotion or gender. Here we show that observers can also extract a mean identity from a set of faces with different identities. Observers first saw a set of four faces with different identities and were subsequently asked whether or not a single test face had been present in the preceding set. They were significantly more likely to respond that the test face had been present in the set if it was the morphed mean of all four set faces than when it was an actual set member. This finding suggests that representations based on summary statistics are available for face identity.
Where Media Turn During Crises: A Look at Information Subsidies and the Virginia Tech Shootings
Authors: Wigley Shelley , Fontenot Maria
Published: April 2009

This pilot study explored the use of official and nonofficial sources as information subsidies in coverage of the Virginia Tech shootings and introduced a new type of information subsidy—new technology sources. Results indicated that reporters used significantly more new technology sources as information subsidies during the first two days of the crisis compared to the latter stage of the crisis, and that nonofficial sources were used to a greater extent than official sources. This study advances the literature on information subsidies by introducing a new type of subsidy, new technology, and therefore provides a benchmark for future studies on the use of new technology as an information subsidy in news coverage.
Peter Friedl: Painting a picture of cancer immunology
Authors: Sedwick Caitlin
Published: April 2009

Friedl uses confocal and intravital microscopy to investigate the movement of T cells and cancer cells.
Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis
Authors: Hotulainen Pirta , Llano Olaya , Smirnov Sergei , Tanhuanpää Kimmo , Faix Jan , Rivera Claudio , Lappalainen Pekka
Published: April 2009

Dendritic spines are small protrusions along dendrites where the postsynaptic components of most excitatory synapses reside in the mature brain. Morphological changes in these actin-rich structures are associated with learning and memory formation. Despite the pivotal role of the actin cytoskeleton in spine morphogenesis, little is known about the mechanisms regulating actin filament polymerization and depolymerization in dendritic spines. We show that the filopodia-like precursors of dendritic spines elongate through actin polymerization at both the filopodia tip and root. The small GTPase Rif and its effector mDia2 formin play a central role in regulating actin dynamics during filopodia elongation. Actin filament nucleation through the Arp2/3 complex subsequently promotes spine head expansion, and ADF/cofilin-induced actin filament disassembly is required to maintain proper spine length and morphology. Finally, we show that perturbation of these key steps in actin dynamics results in altered synaptic transmission.
The circuitry of cargo flux in the ESCRT pathway
Authors: Hurley James H. , Ren Xuefeng
Published: April 2009

The endosomal sorting complex required for transport (ESCRT) complexes sort ubiquitinated membrane proteins into multivesicular bodies, which is a key step in the lysosomal degradation pathway. Shields et al. (Shields, S.B., A.J. Oestreich, S. Winistorfer, D. Nguyen, J.A. Payne, D.J. Katzmann, and R. Piper. 2009. J. Cell Biol. 185:213–224) identify a new ubiquitin-binding site in ESCRT-I and provide evidence that the upstream ESCRT-I and -II complexes sort cargo in parallel rather than in series.
For Reasons of State: Political Executions, Republicanism, and the Medici in Florence, 1480–1560
Authors: Baker Nicholas Scott
Published: April 2009

Prior to the late fifteenth century in Florence, the losers of political conflicts routinely faced exile as punishment for their perceived crimes. Following the Pazzi conspiracy of 1478, however, such political criminals increasingly received death sentences rather than banishment. This article explores how the changing nature of punishment for political crimes in Renaissance Florence from the fifteenth to the sixteenth centuries can be read as a barometer of political change in the city. It examines the relationship between the growing number of political executions and the long transformation of Florence from a republic to a principality, with reference to the broader context of fifteenth- and sixteenth-century Italy.
Baseline factors associated with congestive heart failure in patients receiving etoricoxib or diclofenac: multivariate analysis of the MEDAL program
Authors: Krum Henry , Curtis Sean P. , Kaur Amarjot , Wang Hongwei , Smugar Steven S. , Weir Matthew R. , Laine Loren , Brater D. Craig , Cannon Christopher P.
Published: April 2009

Aims

Non‐steroidal anti‐inflammatory drugs have been associated with increased risk of congestive heart failure (CHF). We aimed to assess the impact of treatment with etoricoxib or diclofenac on risk of CHF relative to baseline risk factors.

Methods and results

We performed a multivariate analysis of 34 701 patients with arthritis receiving etoricoxib 60 or 90 mg, or diclofenac 150 mg, daily for a mean of 18 months, to assess the incidence of confirmed, adjudicated CHF events resulting in emergency room visit or hospitalization. Analyses were performed using a Cox proportional hazard model to evaluate the hazard ratio (HR) between the levels of each risk marker for the incidence of CHF. Significant risk markers included history of CHF (HR: 6.69, 95% CI 3.59–12.47; P <0.0001), age ≥65 years (2.56, 1.65–3.98; P <0.0001), and history of hypertension (1.83, 1.16–2.89; P = 0.0094) or diabetes (1.83, 1.15–2.94; P = 0.0116). Etoricoxib vs. diclofenac was a significant risk factor only when pooling the etoricoxib 90 mg cohorts (1.88; 1.13–3.10; P = 0.0143). Etoricoxib 60 mg did not significantly increase risk vs. diclofenac.

Conclusion

History of CHF was highly associated with risk for CHF hospitalization. Hypertension, diabetes, and older age also increased risk modestly. There appeared to be a dose‐related increase in CHF with etoricoxib compared with diclofenac, which reached statistical significance when the etoricoxib 90 mg groups (osteoarthritis and rheumatoid arthritis) were pooled.

(Clinicaltrials.gov: NCT00092703, NCT00092742, NCT00250445).
Combining multibeam-sonar and multifrequency-echosounder data: examples of the analysis and imaging of large euphausiid schools
Authors: Korneliussen Rolf J. , Heggelund Yngve , Eliassen Inge K. , Øye Ola K. , Knutsen Tor , Dalen John
Published: April 2009

Korneliussen, R. J., Heggelund, Y., Eliassen, I. K., Øye, O. K., Knutsen, T., and Dalen, J. 2009. Combining multibeam-sonar and multifrequency-echosounder data: examples of the analysis and imaging of large euphausiid schools. – ICES Journal of Marine Science, 66: 991–997. The first high-resolution, quantitative, multibeam sonar (Simrad MS70) ever developed was mounted in a keel of RV “G. O. Sars” with port-orientated beams. Each ping samples a volume of 60° horizontally × 45° vertically with 500 beams, which is often enough to insonify a complete school of fish or zooplankton. The large amount of resulting data is efficiently preprocessed with automatic, real-time detections of school candidates; these are accepted or rejected during post-processing. The system was used on the continental shelf near the Subantarctic island of South Georgia to study Antarctic krill (Euphausia superba), and some of the detected schools were immediately sampled with a six-frequency echosounder (Simrad EK60), then trawled with various nets to verify the target species and their size composition. For schools acoustically categorized as euphausiids, data from the two acoustic systems were used to estimate the school morphometrics and the krill size distributions. The principal objectives of this study were to explore the potential of combining data from a multibeam sonar, multifrequency echosounders, and nets, and to describe the efficient processing methods and software that facilitate the multi-instrument analyses. Three-dimensional morphometrics based on the MS70 data were consistent with corresponding two-dimensional morphometrics based on the echosounder data and could be used to improve the acoustic classifications of taxa or species. Additionally, automatic preprocessing and integration of data from different sources into the same user interface allowed efficient exploration and interpretation of all the acoustic data.
On the effect of the North Atlantic Oscillation on temperature and salinity of the subpolar North Atlantic intermediate and deep waters
Authors: Sarafanov Artem
Published: April 2009

Sarafanov, A. 2009. On the effect of the North Atlantic Oscillation on temperature and salinity of the subpolar North Atlantic intermediate and deep waters. – ICES Journal of Marine Science, 66: 1448–1454. The close relationship between the observed water mass properties and the winter North Atlantic Oscillation (NAO) index (1950–2000s; r2 ≈ 0.65) implies that changes in the NAO-related atmospheric forcing may account for up to two-thirds of thermohaline changes at the intermediate and deep levels in the subpolar North Atlantic on a decadal time-scale. Persistent NAO decline (amplification) results in increase (decrease) in temperature and salinity in the intermediate–deep water column. A general mechanism explaining the close link between the NAO and coherent decadal changes in the intermediate and deep-water temperature and salinity in the region is inferred from the observed changes in the regional circulation and water mass properties. Two factors dominate this link: (i) intensity of convection in the Labrador Sea controlling injection of relatively cold freshwater into the intermediate layer, and (ii) zonal extension of the Subpolar Gyre that regulates the relative contribution of cold fresh subpolar water and warm saline subtropical water to the deep-water formation.
Empirical analyses of the length, weight, and condition of adult Atlantic salmon on return to the Scottish coast between 1963 and 2006
Authors: Bacon P. J. , Palmer S. C. F. , MacLean J. C. , Smith G. W. , Whyte B. D. M. , Gurney W. S. C. , Youngson A. F.
Published: April 2009

Bacon, P. J., Palmer, S. C. F., MacLean, J. C., Smith, G. W., Whyte, B. D. M., Gurney, W. S. C., and Youngson, A. F. 2009. Empirical analyses of the length, weight, and condition of adult Atlantic salmon on return to the Scottish coast between 1963 and 2006. – ICES Journal of Marine Science, 66: 844–859. Sea age, size, and condition of adult Atlantic salmon (Salmo salar) are prime determinants of individual, and hence population, productivity. To elucidate potential mechanisms, 151 000 records of salmon returning to six Scottish coastal sites over 44 years were analysed for length, weight, and condition, by site, sex, sea age, and river age. After correcting for capture effort biases, all sites showed seasonal increases in length and weight for both 1 sea winter (1SW) and 2SW fish. However, whereas condition increased slightly with season for 2SW, it decreased notably for 1SW. Sites showed common decadal trends in length, weight, and condition. Within years, length and weight residuals from trends were coherent across sites, but residuals from condition trends were not. Rates of seasonal condition change also showed decadal trends, dramatically different between sea ages, but common across sites within sea-age groups. Longer salmon were disproportionately heavy in all seasons. 1SW condition was markedly lower in 2006. Detrended correlations with oceanic environmental variables were generally not significant, and always weak. A published correlation between the condition of 1SW salmon caught at a single site and sea surface temperatures in the Northeast Atlantic could not be substantiated for any of the six fisheries over the wider time-scales examined.
Application of a generalized additive model (GAM) to reveal relationships between environmental factors and distributions of pelagic fish and krill: a case study in Sendai Bay, Japan
Authors: Murase Hiroto , Nagashima Hiroshi , Yonezaki Shiroh , Matsukura Ryuichi , Kitakado Toshihide
Published: April 2009

Murase, H., Nagashima, H., Yonezaki, S., Matsukura, R., and Kitakado, T. 2009. Application of a generalized additive model (GAM) to reveal relationships between environmental factors and distributions of pelagic fish and krill: a case study in Sendai Bay, Japan. – ICES Journal of Marine Science, 66: 1417–1424. A generalized additive model (GAM) was applied to fishery-survey data to reveal the influences of environmental factors on the distribution patterns of Japanese anchovy (Engraulis japonicus), sand lance (Ammodytes personatus), and krill (Euphausia pacifica). Echosounder and physical-oceanographic data were collected in Sendai Bay, Japan, in spring 2005. A hierarchical model was used with two spatial strata: (i) presence and absence of each species; and (ii) biomass density of each species, given its presence; and six environmental covariates (surface water temperature, salinity, and chlorophyll, and near-seabed water temperature, salinity, and depth). The results indicate non-linear responses of the two indices to the environmental covariates. In addition, the biomasses estimated by the GAMs were comparable with estimates based on conventional, stratified-random sampling for each species. GAMs are very useful for (i) investigating the effects of environmental factors on the distributions of biological organisms, and (ii) predicting the distributions of animal densities in unsurveyed areas.
Extinction circuits for fear and addiction overlap in prefrontal cortex
Authors: Peters Jamie , Kalivas Peter W. , Quirk Gregory J.
Published: April 2009

Extinction is a form of inhibitory learning that suppresses a previously conditioned response. Both fear and drug seeking are conditioned responses that can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders and addiction, respectively. Recent evidence indicates that the medial prefrontal cortex (mPFC) is critical for the extinction of both fear and drug-seeking behaviors. Moreover, a dorsal-ventral distinction is apparent within the mPFC, such that the prelimbic (PL-mPFC) cortex drives the expression of fear and drug seeking, whereas the infralimbic (IL-mPFC) cortex suppresses these behaviors after extinction. For conditioned fear, the dorsal-ventral dichotomy is accomplished via divergent projections to different subregions of the amygdala, whereas for drug seeking, it is accomplished via divergent projections to the subregions of the nucleus accumbens. Given that the mPFC represents a common node in the extinction circuit for these behaviors, treatments that target this region may help alleviate symptoms of both anxiety and addictive disorders by enhancing extinction memory.
Identifying New Components Participating in the Secondary Cell Wall Formation of Vessel Elements in Zinnia and Arabidopsis
Authors: Endo Satoshi , Pesquet Edouard , Yamaguchi Masatoshi , Tashiro Gen , Sato Mayuko , Toyooka Kiminori , Nishikubo Nobuyuki , Udagawa-Motose Makiko , Kubo Minoru , Fukuda Hiroo , Demura Taku
Published: April 2009

Xylem vessel elements are hollow cellular units that assemble end-to-end to form a continuous vessel throughout the plant body; the xylem vessel is strengthened by the xylem elements' reinforced secondary cell walls (SCWs). This work aims to unravel the contribution of unknown actors in xylem vessel differentiation using the model in vitro cell culture system of Zinnia elegans differentiating cell cultures and the model in vivo system of Arabidopsis thaliana plants. Tracheary Element  Differentiation-Related6 (TED6) and TED7 were selected based on an RNA interference (RNAi) screen in the Zinnia system. RNAi reduction of TED6 and 7 delayed tracheary element (TE) differentiation and co-overexpression of TED6 and 7 increased TE differentiation in cultured Zinnia cells. Arabidopsis TED6 and 7 were expressed preferentially in differentiating vessel elements in seedlings. Aberrant SCW formation of root vessel elements was induced by transient RNAi of At TED7 alone and enhanced by inhibition of both TED6 and 7. Protein–protein interactions were demonstrated between TED6 and a subunit of the SCW-related cellulose synthase complex. Our strategy has succeeded in finding two novel components in SCW formation and has opened the door for in-depth analysis of their molecular functions.
The WD40 Repeat Protein NEDD1 Functions in Microtubule Organization during Cell Division inArabidopsis thaliana
Authors: Zeng C.J. Tracy , Lee Y.-R. Julie , Liu Bo
Published: April 2009

Although cells of flowering plants lack a structurally defined microtubule-organizing center like the centrosome, organization of the spindles and phragmoplasts in mitosis is known to involve the evolutionarily conserved γ-tubulin complex. We have investigated the function of Arabidopsis thaliana NEDD1, a WD40 repeat protein related to the animal NEDD1/GCP-WD protein, which interacts with the γ-tubulin complex. The NEDD1 protein decorates spindle microtubules (MTs) preferentially toward spindle poles and phragmoplast MTs toward their minus ends. A T-DNA insertional allele of the single NEDD1 gene was isolated and maintained in heterozygous sporophytes, and NEDD1's function in cell division was analyzed in haploid microspores produced by the heterozygote. In approximately half of the dividing microspores exhibiting aberrant MT organization, spindles were no longer restricted to the cell periphery and became abnormally elongated. After mitosis, MTs aggregated between reforming nuclei but failed to appear in a bipolar configuration. Consequently, defective microspores did not form a continuous cell plate, and two identical nuclei were produced with no differentiation into generative and vegetative cells. Our results support the notion that the plant NEDD1 homolog plays a critical role in MT organization during mitosis, and its function is likely linked to that of the γ-tubulin complex.
Management of Elevated Intracranial Pressure
Authors: Vanderheyden Beth A. , Buck Brian D.
Published: April 2009

Elevated intracranial pressure (ICP) is a primary cause of morbidity and mortality for many neurologic disorders. The relationship between ICP and brain volume is influenced by autoregulatory processes that can become dysfunctional. As a result, neurologic damage can occur by systemic and intracranial insults such as ischemia and excitatory amino acids. Therefore, survival is dependent on optimizing ICP and cerebral perfusion pressure. Treatment of intracranial hypertension requires intensive monitoring and aggressive therapy. Intracranial pressure monitoring techniques such as intraventricular catheters are useful for determining ICP elevations before changes in vital signs and neurologic status. Therapeutic modalities, generally aimed at reducing cerebral blood volume, brain tissue, and cerebrospinal fluid (CSF) volume, include nonpharmacologic (CSF removal, controlled hyperventilation, and elevating the patient’s head) and pharmacologic management. Mannitol and sedation are first-line agents used to lower ICP. Barbiturate coma may be beneficial in patients with elevated ICP refractory to conventional treatment. The use of prophylactic antiseizure therapy and optimal nutrition prevents significant complication. Currently, investigations are directed at discovering useful neuroprotective agents that prevent secondary neurologic injury.
Update on Vasopressors and Inotropes in Septic Shock
Authors: Rudis Maria I. , Chant Clarence
Published: April 2009

Vasopressors and inotropes are used in septic shock in patients who remain hypotensive despite adequate fluid resuscitation. The goal is to increase blood pressure to optimize perfusion to organs. Generally, goal-directed therapy to supra-normal oxygen transport variables cannot be recommended due to lack of benefit. Traditionally, vasopressors and inotropes in septic shock have been started in a step-wise fashion starting with dopamine. Recent data suggest that there may be true differences among vasopressors and inotropes on local tissue perfusion as measured by regional hemodynamic and oxygen transport. When started early in septic shock, norepinephrine decreases mortality, optimizes hemodynamic variables, and improves systemic and regional (eg, renal, gastric mucosal, splanchnic) perfusion. Epinephrine causes a greater increase in cardiac index (CI) and oxygen delivery (DO2 ) and increases gastric mucosal flow, but increases lactic acid and may not adequately preserve splanchnic circulation owing to its predominant vasoconstrictive alpha (α ) effects. Epinephrine may be particularly useful when used earlier in the course of septic shock in young patients and those who do not have any known cardiac abnormalities. Unlike epinephrine, dopamine does not preferentially increase the proportion of CI that preferentially goes to the splanchnic circulation. Dopamine is further limited because it cannot increase CI by more than 35% and is accompanied by tachycardia or tachydysrhythmias. Dopamine, as opposed to norepinephrine, may worsen splanchnic oxygen consumption (VO2 ) and oxygen extraction ratio (O2 ER). Low-dose dopamine has not been shown to consistently increase the glomerular filtration rate or prevent renal failure, and, indeed, worsens splanchnic tissue oxygen use. Routine use of concurrently administered dopamine with vasopressors is not recommended. Phenylephrine should be used when a pure vasoconstrictor is desired in patients who may not require or do not tolerate the beta (β ) effects of dopamine or norepinephrine with or without dobutamine. Patients with high filling pressure and hypotension may benefit from the combination of phenylephrine and dobutamine. Investigational approaches to vasopressor-refractory hypotension in septic shock include the use of vasopressin and corticosteroids.
Treatment of Common Childhood Malignancies
Authors: Bickert Betsy M.
Published: April 2009

Malignancy is the fourth leading cause of death in persons aged 1 to 19 years. The success of the pediatric oncology cooperative group clinical trials has allowed a systematic approach to the treatment of relatively rare malignancies. Each trial builds on previous results in terms of both survival and toxicity. This article will discuss the current treatment regimens for several of the more common pediatric malignancies and their long-term complications developed through this process.
Review of the Current ACS Practice Guideline to Develop an Ischemic Chest Pain Protocol
Authors: Cohen Victor , Murphy Daniel G. , Williams Janet
Published: April 2009

This review covers the major recommendations to the 2000 American College of Cardiology/American Heart Association (ACC/AHA) Acute Coronary Syndromes (ACS) Practice Guidelines. This review describes the evidence-based medicine that rationalizes the recommended pharmacotherapy for ST elevation myocardial infarction (STEMI) and non- STEMI (NSTEMI) ACS. To ensure conformity, an Ischemic Chest Pain Protocol (ICPP) order form was developed. The ICPP is like a menu that includes orders for all the recommended therapies in an easy-to-use checklist format. The ICPP has facilitated the implementation, acceptance, and understanding of the 2002 ACC/AHA ACS practice guidelines. Hence with improved conformity, it is hoped that the improved outcomes that were intended will result. A description of the ICPP and a mechanism for implementation is provided in this article.
Extended-Spectrum β-Lactamase Resistance in the ICU
Authors: Sahloff Eric G. , Martin Steven J.
Published: April 2009

Despite the recent focus on gram-positive infections in the intensive care unit (ICU), gram-negative resistance mechanisms continue to challenge the critical care practitioner. A recent national surveillance study of United States ICUs found Escherichia coli, Enterbacter species, Klebsiella species, and Pseudomonas aeruginosa represented 72% of all gram-negative bacilli recovered. E coli, Klebsiella pneumoniae, and Enterobacter species are significant producers of a β -lactamase that inactivates almost all β -lactam antibiotics, so-called extended-spectrum β -lactamases or ESBLs. Many clinical laboratories may not test for ESBL-production in these organisms, thus clinicians may be unaware of the rising incidence of this plasmid-mediated resistance mechanism. Since initial reports of ESBLs in the 1980s, investigators have found an association with ESBL-producing organisms and the critically ill population. Risk factors for ESBL-related infection in the ICU include arterial, central-venous, and urinary-catheters; mechanical ventilation; abdominal surgery; prior antibiotic therapy with ceftazidime or other extended spectrum cephalosporins; length of time in the ICU; and overall acuity of illness. This article reviews the emergence and epidemiology of the ESBL evolution, describes the clinical implications of ESBL production in the ICU, and outlines a strategy for management of infection in patients at risk for ESBL-producing organisms.
Discovery, characterization and validation of single nucleotide polymorphisms within 206 bovine genes that may be considered as candidate genes for beef production and quality
Authors: Williams J. L. , Dunner S. , Valentini A. , Mazza R. , Amarger V. , Checa M. L. , Crisà A. , Razzaq N. , Delourme D. , Grandjean F. , Marchitelli C. , García D. , Pérez Gomez R. , Negrini R. , Ajmone Marsan P. , Levéziel H.
Published: April 2009

A large number of putative single nucleotide polymorphisms (SNPs) have been identified from the bovine genome‐sequencing project. However, few of these have been validated and many will turn out to be sequencing artefacts or have low minor allele frequencies. In addition, there is little information available on SNPs within coding regions, which are likely to be responsible for phenotypic variation. Therefore, additional SNP discovery is necessary to identify and validate polymorphisms both in specific genes and genome‐wide. Sequence‐tagged sites within 286 genes were resequenced from a panel of animals representing a wide range of European cattle breeds. For 80 genes, no polymorphisms were identified, and 672 putative SNPs were identified within 206 genes. Fifteen European cattle breeds (436 individuals plus available parents) were genotyped with these putative SNPs, and 389 SNPs were confirmed to have minor allele frequencies above 10%. The genes containing SNPs were localized on chromosomes by radiation hybrid mapping and on the bovine genome sequence by Blast. Flanking microsatellite loci were identified, to facilitate the alignment of the genes containing the SNPs in relation to mapped quantitative trait loci. Of the 672 putative SNPs discovered in this work, only 11 were found among the validated SNPs and 100 were found among the approximately 2.3 million putative SNPs currently in dbSNP. The genes studied in this work could be considered as candidates for traits associated with beef production and the SNPs reported will help to assess the role of the genes in the genetic control of muscle development and meat quality. The allele frequency data presented allows the general utility of the SNPs to be assessed.
CMC‐544 (inotuzumab ozogamicin) shows less effect on multidrug resistant cells: analyses in cell lines and cells from patients with B‐cell chronic lymphocytic leukaemia and lymphoma
Authors: Takeshita Akihiro , Shinjo Kaori , Yamakage Nozomi , Ono Takaaki , Hirano Isao , Matsui Hirotaka , Shigeno Kazuyuki , Nakamura Satoki , Tobita Tadasu , Maekawa Masato , Ohnishi Kazunori , Sugimoto Yoshikazu , Kiyoi Hitoshi , Naoe Tomoki , Ohno Ryuzo
Published: April 2009

The effect of CMC‐544, a calicheamicin‐conjugated anti‐CD22 monoclonal antibody, was analysed in relation to CD22 and P‐glycoprotein (P‐gp) in B‐cell chronic lymphocytic leukaemia (CLL) and non‐Hodgkin lymphoma (NHL) in vitro. The cell lines used were CD22‐positive parental Daudi and Raji, and their P‐gp positive sublines, Daudi/MDR and Raji/MDR. Cells obtained from 19 patients with B‐cell CLL or NHL were also used. The effect of CMC‐544 was analysed by viable cell count, morphology, annexin‐V staining, and cell cycle distribution. A dose‐dependent, selective cytotoxic effect of CMC‐544 was observed in cell lines that expressed CD22. CMC‐544 was not effective on Daudi/MDR and Raji/MDR cells compared with their parental cells. The MDR modifiers, PSC833 and MS209, restored the cytotoxic effect of CMC‐544 in P‐gp‐expressing sublines. In clinical samples, the cytotoxic effect of CMC‐544 was inversely related to the amount of P‐gp (P = 0·003), and to intracellular rhodamine‐123 accumulation (P < 0·001). On the other hand, the effect positively correlated with the amount of CD22 (P = 0·010). The effect of CMC‐544 depends on the levels of CD22 and P‐gp. Our findings will help to predict the clinical effectiveness of this drug on these B‐cell malignancies, suggesting a beneficial effect with combined use of CMC‐544 and MDR modifiers.
Transforming growth factor‐β in allergic inflammatory disease of the upper airways: friend or foe?
Authors: Salib R. J. , Howarth P. H.
Published: April 2009

TGF‐β is a multi‐functional cytokine with a huge array of effects on a variety of cell types. It is rapidly emerging as a key major player in the way the airway epithelium behaves and its ability to repair itself. This is not only of relevance to allergic airway diseases such as asthma and allergic rhinitis, which are increasing in prevalence worldwide, but in many other diseases. The full impact any disruption of TGF‐β signalling may have in the development and persistence of allergic inflammatory airway diseases is yet to be fully realized and remains the subject of ongoing research. There has been a recent revival of interest in the role of regulatory T cells in controlling allergic inflammation. Evidence is emerging of a significant contribution by TGF‐β to this regulatory process. This review aims to summarize current knowledge relating to TGF‐β in relation to allergic inflammatory upper airways disease, and attempts to clarify some of the discrepancies and inconsistencies in this area. It also considers the therapeutic implications of novel TGF‐β therapy, including potential future applications in the treatment of nasal polyposis and reduction of post‐operative scar tissue formation following endoscopic sinus surgery.
Non‐atopic intrinsic asthma and the ‘family tree’ of chronic respiratory disease syndromes
Authors: Holt P. G. , Sly P. D.
Published: April 2009

We present a scheme below in which the most common forms of inflammatory diseases of the respiratory tract, notably atopic and non‐atopic asthma and COPD, are depicted as separate offshoots from a common ‘at‐risk’ pathway underpinned by genotypes related to aberrations in control of host defence and tissue repair mechanisms. We propose that entrance into this pathway is initially programmed by environmental experience during infancy and early childhood, in particular by severe lower respiratory tract infection, and that further progression towards expression of specific disease phenotype(s) is determined by the nature, timing and frequency of additional environmental insults subsequently encountered. At the one extreme, early sensitization of at‐risk subjects to aeroallergens can potentially drive rapid progression towards expression of the atopic asthmatic phenotype under the dual onslaught of inflammatory responses to allergens/pathogens. At the opposite end of the spectrum the drip‐feed effects of occasional infections on respiratory function(s) are amplified over a longer time frame by inflammation resulting from exposure to tobacco smoke and/or related chemical pollutants. Non‐atopic asthma is envisaged to fit between these two extremes, being driven essentially by the downstream effects of respiratory infections alone in at‐risk subjects. An important common factor in all three disease phenotypes is that acute exacerbations are typically driven by infections, the host responses to which display a characteristic T‐helper type 2‐like footprint, which in our view points to underlying genotype(s) which result in unbalanced host responses to respiratory pathogens.
γ‐aminobutyric acid nurtures allergic asthma
Authors: Lu W.‐Y. , Inman M. D.
Published: April 2009

Asthma often occurs as a result of immune‐based inflammatory responses, which consequently cause pathological changes in airway structural cells. However, the underlying mechanisms of airway pathology in asthma are still not fully understood. Our recent studies revealed a critical role of γ‐aminobutyric acid (GABA) signalling pathway in the airway epithelium of allergic asthma through its ability to stimulate mucus production. This review briefly describes the GABAergic signalling system and its role in the regulation of mucus protein production in bronchial airway epithelial cells.
Phenotypic and functional markers for 1α,25-dihydroxyvitamin D3-modified regulatory dendritic cells
Authors: Pedersen A W , Holmstrøm K , Jensen S S , Fuchs D , Rasmussen S , Kvistborg P , Claesson M H , Zocca M-B
Published: April 2009

The clinical use of dendritic cells (DCs) to induce antigen-specific immune tolerance has been hampered by the lack of a widely acknowledged method for generating human regulatory DCs but even more so by the non-existence of reliable markers. Thus, we set out to find reliable markers that can be measured with simple methods to identify regulatory DCs that are applicable for future clinical studies. Human DCs were generated from peripheral blood monocytes in the presence of 1α,25-dihydroxyvitamin D3 (VD3), which gave rise to a phenotype that resembles immature DCs, with the exception of high CD14 and reduced CD1a on the cell surface. These VD3-treated DCs exert a long-lasting inefficient T cell stimulation and induce T cell hyporesponsiveness with regulatory potential. Importantly, such VD3-treated DCs were readily distinguishable from untreated DCs by low levels of interleukin-23 secretion and low expression of miR-155 upon exposure to maturation stimuli. Furthermore, VD3-treated DCs showed over-expression of miR-378. All these features can be used as robust markers for quality control of VD3-treated regulatory DCs in future clinical studies.
The effect of surface–solute interactions on the transport of solutes through porous materials
Authors: Rose D. A. , Abbas F. , Adey M. A.
Published: April 2009

We have investigated the effect of differences in surface charge, valency of ion, solute concentration, solution flux and physical structure on the leaching and uptake of individual ions from simple solutions flowing through porous materials. We studied the miscible displacement of solutions of four salts (KBr, K2SO4, CaBr2 and CaSO4) having different cation : anion ratios separately through three inert materials (ballotini, pumice and ceramic) and two sizes of a reactive material (sepiolite) over several ranges of concentration (c) and at many pore‐water velocities (v) under steady vertical saturated flow. Breakthrough curves of individual effluent ions (K+, Br−, Ca2+ and SO42−) were analysed by CXTFIT 2.0 to optimize transport parameters (retardation factor, R; dispersion coefficient, K) assuming that transport was governed by the convective–dispersion equation. In the inert materials, R did not differ significantly from 1 irrespective of c. In sepiolite, R was < 1 for anions and > 1 for cations, and became more extreme as c decreased. R varied with the valency of the anions, as predicted by diffuse double layer theory, and with that of the cations by a simple charge balance. Freundlich isotherms, reconstructed from R values, described the sorption of the cations and exclusion of the anions. For the inert materials, K did not depend on the ion or c and increased monotonically with v. For sepiolite, K also increased with v and with small but non‐significant differences between ions and concentrations. The K(v) functions were consistent with Passioura’s theory of dispersion in aggregated media, and the transport was reversible as R and K values did not depend on whether the media were being leached or resalinized. The effective dispersion coefficient of an ion is K* = K/R so, although K(v) appears to be unaffected by ion or concentration of solute in sepiolite, K*(v) will be affected. Thus, the controlling factor of these surface–solute interactions is R.
Impact of stone content on water movement in water‐repellent sand
Authors: Urbanek E. , Shakesby R. A.
Published: April 2009

Soils are commonly stony, especially in steep upland or heavily degraded sites. The hydrological effect of large stone contents has been previously investigated in wettable but not in water‐repellent soils. For the latter, the focus has instead been on the impact of other soil characteristics (e.g. cracks and macropores) likely to promote water percolation. This paper investigates stone effects on water flow in water‐repellent sand under laboratory conditions. Seventy‐five experiments were performed on a water‐repellent sand mixed with a range of quantities of different‐sized wettable and water‐repellent stones. The time taken for water to pass through each sand–stone mix, the percolated water volumes and numbers of dry and wet stones following each 60‐minute experiment were recorded. At large stone contents (> 55% or > 65% by weight, depending on stone wettability), percolation occurred relatively quickly and in comparatively large quantities. At intermediate stone contents (45–65%) percolation response was variable and at stone contents < 45% for wettable and < 55% for water‐repellent soils no water percolation occurred. We argue that with large stone contents flow pathways develop along sand–stone interfaces and a continuous preferential flow path can form provided there are sufficient stone‐to‐stone connections. The distribution and alignment of the stones, especially at intermediate stone contents, are important for promoting water movement. Water repellency determinations based only on the fine sediment component in stony soils could therefore be misleading as regards determining their hydrological response: the influence of the clastic component must also be considered.
High concentrations of blue crab (Callinectes sapidus) larvae along the offshore edge of a coastal current: effects of convergent circulation
Authors: TILBURG CHARLES E. , DITTEL ANA I. , EPIFANIO CHARLES E.
Published: April 2009

Using a combination of observations and numerical modeling, we examined the distribution of blue crab (Callinectes sapidus) larvae along the edge of the buoyant plume emanating from the mouth of Delaware Bay along the east coast of the USA. Our observations consisted of larval sampling and hydrographic measurements taken along a series of transects that spanned the plume, the plume edge, and the coastal ocean. The numerical model is a realistic circulation model of Delaware Bay and the adjoining coastal ocean that includes daily wind forcing, daily river discharge, and tides. We tested the hypothesis that the offshore edges of coastal currents are regions of convergence and retention for larvae of estuary dependent species. Collected data showed a marked difference between the distribution of early and late stage larvae. Patches of early stage larvae occurred within lower salinities typical of the estuarine plume and higher salinities associated with the offshore edge of the plume. Late‐stage larvae occurred almost entirely in salinities characteristic of the offshore edge. The field study was followed by a modeling component that simulated larval distributions over the spawning season of 2005. Output from the model showed simulated larval distributions that were similar to the observations. This study provides new insight into the distribution of larvae and larval patches in Delaware Bay and any region with extensive buoyancy and tidally driven flow. Results indicate that larvae tend to congregate along the edges of plumes emanating from estuaries due solely to physical mechanisms, regardless of the initial spawning location.
Seismic data reconstruction using multidimensional prediction filters
Authors: Naghizadeh M. , Sacchi M.D.
Published: April 2009

In this paper we discuss a beyond‐alias multidimensional implementation of the multi‐step autoregressive reconstruction algorithm for data with missing spatial samples. The multi‐step autoregressive method is summarized as follows: vital low‐frequency information is first regularized adopting a Fourier based method (minimum weighted norm interpolation); the reconstructed data are then used to estimate prediction filters that are used to interpolate higher frequencies. This article discusses the implementation of the multi‐step autoregressive method to data with more than one spatial dimension. Synthetic and real data examples are used to examine the performance of the proposed method. Field data are used to illustrate the applicability of multidimensional multi‐step autoregressive operators for regularization of seismic data.
Intercomparison, interpretation, and assessment of spring phenology in North America estimated from remote sensing for 1982–2006
Authors: WHITE MICHAEL A. , De BEURS KIRSTEN M. , DIDAN KAMEL , INOUYE DAVID W. , RICHARDSON ANDREW D. , JENSEN OLAF P. , O'KEEFE JOHN , ZHANG GONG , NEMANI RAMAKRISHNA R. , Van LEEUWEN WILLEM J. D. , BROWN JESSLYN F. , De WIT ALLARD , SCHAEPMAN MICHAEL , LIN XIOAMAO , DETTINGER MICHAEL , BAILEY AMEY S. , KIMBALL JOHN , SCHWARTZ MARK D. , BALDOCCHI DENNIS D. , LEE JOHN T. , LAUENROTH WILLIAM K.
Published: April 2009

Shifts in the timing of spring phenology are a central feature of global change research. Long‐term observations of plant phenology have been used to track vegetation responses to climate variability but are often limited to particular species and locations and may not represent synoptic patterns. Satellite remote sensing is instead used for continental to global monitoring. Although numerous methods exist to extract phenological timing, in particular start‐of‐spring (SOS), from time series of reflectance data, a comprehensive intercomparison and interpretation of SOS methods has not been conducted. Here, we assess 10 SOS methods for North America between 1982 and 2006. The techniques include consistent inputs from the 8 km Global Inventory Modeling and Mapping Studies Advanced Very High Resolution Radiometer NDVIg dataset, independent data for snow cover, soil thaw, lake ice dynamics, spring streamflow timing, over 16 000 individual measurements of ground‐based phenology, and two temperature‐driven models of spring phenology. Compared with an ensemble of the 10 SOS methods, we found that individual methods differed in average day‐of‐year estimates by ±60 days and in standard deviation by ±20 days. The ability of the satellite methods to retrieve SOS estimates was highest in northern latitudes and lowest in arid, tropical, and Mediterranean ecoregions. The ordinal rank of SOS methods varied geographically, as did the relationships between SOS estimates and the cryospheric/hydrologic metrics. Compared with ground observations, SOS estimates were more related to the first leaf and first flowers expanding phenological stages. We found no evidence for time trends in spring arrival from ground‐ or model‐based data; using an ensemble estimate from two methods that were more closely related to ground observations than other methods, SOS trends could be detected for only 12% of North America and were divided between trends towards both earlier and later spring.