bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of orally active inhibitors of protein and cellular fucosylation
Authors: Okeley Nicole M. , Alley Stephen C. , Anderson Martha E. , Boursalian Tamar E. , Burke Patrick J. , Emmerton Kim M. , Jeffrey Scott C. , Klussman Kerry , Law Che-Leung , Sussman Django , Toki Brian E. , Westendorf Lori , Zeng Weiping , Zhang Xinqun , Benjamin Dennis R. , Senter Peter D.
Published: March 2013

The key role played by fucose in glycoprotein and cellular function has prompted significant research toward identifying recombinant and biochemical strategies for blocking its incorporation into proteins and membrane structures. Technologies surrounding engineered cell lines have evolved for the inhibition of in vitro fucosylation, but they are not applicable for in vivo use and drug development. To address this, we screened a panel of fucose analogues and identified 2-fluorofucose and 5-alkynylfucose derivatives that depleted cells of GDP-fucose, the substrate used by fucosyltransferases to incorporate fucose into protein and cellular glycans. The inhibitors were used in vitro to generate fucose-deficient antibodies with enhanced antibody-dependent cellular cytotoxicity activities. When given orally to mice, 2-fluorofucose inhibited fucosylation of endogenously produced antibodies, tumor xenograft membranes, and neutrophil adhesion glycans. We show that oral 2-fluorofucose treatment afforded complete protection from tumor engraftment in a syngeneic tumor vaccine model, inhibited neutrophil extravasation, and delayed the outgrowth of tumor xenografts in immune-deficient mice. The results point to several potential therapeutic applications for molecules that selectively block the endogenous generation of fucosylated glycan structures.
Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamily
Authors: Wallrapp Frank H. , Pan Jian-Jung , Ramamoorthy Gurusankar , Almonacid Daniel E. , Hillerich Brandan S. , Seidel Ronald , Patskovsky Yury , Babbitt Patricia C. , Almo Steven C. , Jacobson Matthew P. , Poulter C. Dale
Published: March 2013

Significance

This paper reports a large-scale collaborative study of an approach for predicting the function of chain elongation prenyltransferases from genetic data. A diverse set of genes for enzymes in the isoprenoid synthase superfamily was identified for cloning, expression, X-ray structural analysis, and prediction of function by docking to homology models. Blind predictions, later verified biochemically, were accurate to within one isoprene unit for all but a few of the 74 enzymes studied, an extraordinarily high level of prediction given that the enzymes often give products whose chain lengths vary by one isoprene unit.
RNA–protein analysis using a conditional CRISPR nuclease
Authors: Lee Ho Young , Haurwitz Rachel E. , Apffel Alex , Zhou Kaihong , Smart Brian , Wenger Craig D. , Laderman Stephen , Bruhn Laurakay , Doudna Jennifer A.
Published: March 2013

RNA-binding proteins control the fate and function of the transcriptome in all cells. Here we present technology for isolating RNA–protein partners efficiently and accurately using an engineered clustered regularly interspaced short palindromic repeats (CRISPR) endoribonuclease. An inactive version of the Csy4 nuclease binds irreversibly to transcripts engineered with a 16-nt hairpin sequence at their 5′ ends. Once immobilized by Csy4 on a solid support, contaminating proteins and other molecules can be removed by extensive washing. Upon addition of imidazole, Csy4 is activated to cleave the RNA, removing the hairpin tag and releasing the native transcript along with its specifically bound protein partners. This conditional Csy4 enzyme enables recovery of specific RNA-binding partners with minimal false-positive contamination. We use this method, coupled with quantitative MS, to identify cell type-specific human pre-microRNA-binding proteins. We also show that this technology is suitable for analyzing diverse size transcripts, and that it is suitable for adaptation to a high-throughput discovery format.
Causal Judgement from Information about Outcome Magnitude
Authors: White Peter A.
Published: March 2013

Information was presented in which a candidate cause was either present or absent, and the outcome variable (number of spots on a patient's skin) could take any of four nonzero values. It was found that cause-absent information carried greater weight than cause-present information. This is contrary to the usual finding for contingency information about binary outcome variables. Judgement was influenced more by extreme values of the outcome variable, and larger outcome values tended to have more effect on judgements than smaller outcome values. The hypothesis that participants compute linear correlation is disconfirmed by these results. Instead, the results show that participants focus disproportionate attention on some kinds of events and neglect others.
Peakr: simulating solid-state NMR spectra of proteins
Authors: Schneider Robert , Odronitz Florian , Hammesfahr Björn , Hellkamp Marcel , Kollmar Martin
Published: March 2013

Motivation: When analyzing solid-state nuclear magnetic resonance (NMR) spectra of proteins, assignment of resonances to nuclei and derivation of restraints for 3D structure calculations are challenging and time-consuming processes. Simulated spectra that have been calculated based on, for example, chemical shift predictions and structural models can be of considerable help. Existing solutions are typically limited in the type of experiment they can consider and difficult to adapt to different settings.

Results: Here, we present Peakr, a software to simulate solid-state NMR spectra of proteins. It can generate simulated spectra based on numerous common types of internuclear correlations relevant for assignment and structure elucidation, can compare simulated and experimental spectra and produces lists and visualizations useful for analyzing measured spectra. Compared with other solutions, it is fast, versatile and user friendly.

Availability and implementation: Peakr is maintained under the GPL license and can be accessed at http://www.peakr.org. The source code can be obtained on request from the authors.

Contact:  robert.schneider@ibs.fr or mako@nmr.mpibpc.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Identifying Lyman α emitters powered by AGNs
Authors: Baek Sunghye , Ferrara Andrea
Published: March 2013

Lyman α emitters (LAEs) are usually thought to be powered by star formation. It has been recently reported that a fraction of LAEs at redshift z ∼ 3–4 host an active galactic nuclei (AGNs). If an AGN is present, it could be obscured and undetectable in X-rays, but yet dominate the Lyα luminosity. We examine the properties of these AGN-powered LAEs at high redshift (z ≥ 6) using radiative transfer cosmological simulations and obtain a reliable criterion to identify them from their observed Lyα line and surface brightness. We find that these sources should have (a) negative line weighted skewness, Sw < 0, and (b) surface brightness profile full width at half-maximum ≥1.5 arcsec. This parameter space cannot be populated by starburst LAEs. Thus, LAEs satisfying this criterion would be strong candidates for the presence of a hidden AGN powering their luminosity.
Evaluation of an in-house ELISA using the intermediate species Leptospira fainei for diagnosis of leptospirosis
Authors: Bourhy Pascale , Vray Muriel , Picardeau Mathieu
Published: March 2013

Leptospirosis is recognized as an emerging zoonotic disease generally affecting urban slums in developing countries and tropical regions. A combination of non-specific symptoms, low awareness among the medical community and a lack of readily available diagnostic tests have made leptospirosis an underdiagnosed disease. In this study, we tested an in-house ELISA with formalin-treated and boiled bacteria from the intermediate species Leptospira fainei as an antigen to detect Leptospira-specific IgM antibodies. A total of 819 serum samples, tested by a microscopic agglutination test (MAT) as a reference test, were used to evaluate the ELISA. Compared with positive and negative sera, the ELISA showed 94 % sensitivity and 99 % specificity. Positive and negative likelihood ratios were 94 and 0.06, respectively. No cross-reactivity was observed in sera from subjects with dengue and syphilis infections. The kappa value was 0.92 (95 % confidence interval 0.88–0.96), which indicated excellent agreement between the MAT and ELISA. The overall performance of this in-house ELISA suggests applicability as a rapid screening test for the diagnosis of leptospirosis in resource-limited settings and in hospitals and laboratories where a MAT is not available.
Electron yield soft X-ray photoabsorption spectroscopy under normal ambient-pressure conditions
Authors: Tamenori Yusuke
Published: March 2013

Ambient-pressure soft X-ray photoabsorption spectroscopy (XAS) was demonstrated to be applicable to the chemical analysis of hydrated transition-metal compounds. For this purpose, even under ambient-pressure conditions, electron yield detection XAS (EY-XAS), based on a simple drain-current set-up, was used to overcome a weakness in fluorescence yield detection XAS (FY-XAS), which does not give a pure soft XAS. The feasibility of EY-XAS was investigated and it was clarified that the EY-XAS under ambient-pressure conditions corresponds to the mixed data of the total EY and conversion EY spectra. Normal ambient-pressure EY-XAS analysis was applied to anhydrous (CoCl2) and to hydrated (CoCl2·6H2O) cobalt chloride at the CoL23-edge. The present measurements demonstrated the ability to unambiguously distinguish the different chemical states of cobalt ions, relying upon spectral differences that indicate octahedral/quasi-octahedral structural changes as a result of hydration/dehydration reactions.
Effects of the Voltage and Current Waveforms and Discharge Power on Hydrogen Peroxide Formation in Water-Spray Gliding Arc Reactors
Authors: Burlica Radu , Finney Wright , Locke Bruce
Published: March 2013

This paper deals with the effects of discharge power and voltage and current waveforms on the formation of hydrogen peroxide (H2O2) from liquid water sprayed as a fine aerosol into a plasma formed by a gliding arc discharge. The formation rates of H2O2were determined for different values of the power injected into the reactor (1-7 W), as well as for different means of applying the power [pulsed, alternating current (ac), and direct current (dc)], with argon carrier. For the same power injected into the plasma, the pulsed power was more efficient than the ac power which was, in turn, more effective than the dc power for the generation of H2O2. Energy yield increased with water flow up to 10 mL/min and thereafter was constant with a maximum of about 6 g/kWh.
Specific and sensitive detection of Alcaligenes species from an agricultural environment
Authors: Nakano Miyo , Niwa Masumi , Nishimura Norihiro
Published: March 2013

A quantitative real‐time PCR assay to specifically detect and quantify the genus Alcaligenes in samples from the agricultural environment, such as vegetables and farming soils, was developed. The minimum detection sensitivity was 106 fg of pure culture DNA, corresponding to DNA extracted from two cells of Alcaligenes faecalis. To evaluate the detection limit of A. faecalis, serially diluted genomic DNA from this organism was mixed with DNA extracted from soil and vegetables and then a standard curve was constructed. It was found that Alcaligenes species are present in the plant phytosphere at levels 102–104 times lower than those in soil. The approach presented here will be useful for tracking or quantifying species of the genus Alcaligenes in the agricultural environment.
Simple method for differentiating measles vaccine from wild‐type strains using loop‐mediated isothermal amplification
Authors: Nakayama Tetsuo , Sawada Akihito , Kubo Hideyuki , Kaida Atsushi , Tanaka Toshimitsu , Shigemoto Naoki , Komase Katsuhiro , Takeda Makoto
Published: March 2013

Because of increasing measles vaccine coverage, the proportion of patients with modified measles has been increasing. Such patients have low‐grade fever with very mild eruptions similar to vaccine‐related adverse events. Differentiation between these two pathogenic conditions is required to improve the quality of laboratory‐based measles surveillance. In this study, vaccine‐specific and wild‐type specific primer sets were designed for loop‐mediated isothermal amplification in the N gene, and vaccine strains, C1, D3, D4, D5, D8, D9, G3 and H1 wild strains were examined. Three vaccine strains were efficiently amplified using a vaccine‐specific primer set with an approximately 10‐times higher sensitivity than wild‐type primer. Modified measles was differentiated from vaccine‐associated cases by this system, but limitations were encountered with the other genotypes.
Advancing our thinking in presence‐only and used‐available analysis
Authors: Warton David , Aarts Geert
Published: March 2013

1. The problems of analysing used‐available data and presence‐only data are equivalent, and this paper uses this equivalence as a platform for exploring opportunities for advancing analysis methodology.

2. We suggest some potential methodological advances in used‐available analysis, made possible via lessons learnt in the presence‐only literature, for example, using modern methods to improve predictive performance. We also consider the converse – potential advances in presence‐only analysis inspired by used‐available methodology.

3. Notwithstanding these potential advances in methodology, perhaps a greater opportunity is in advancing our thinking about how to apply a given method to a particular data set.

4. It is shown by example that strikingly different results can be achieved for a single data set by applying a given method of analysis in different ways – hence having chosen a method of analysis, the next step of working out how to apply it is critical to performance.

5. We review some key issues to consider in deciding how to apply an analysis method: apply the method in a manner that reflects the study design; consider data properties; and use diagnostic tools to assess how reasonable a given analysis is for the data at hand.
Policy Instability in a Comparative Perspective: The Context of Heresthetic
Authors: Rosenthal Maoz
Published: March 2013

This article studies the factors that affect the likelihood of radical policy changes. Radical policy changes are defined here as acts in which political leaders choose a policy that is contradictory to policies they have committed to during elections and on whose basis they have formed coalitions. The reason for such changes is that quandaries change the policy space that shapes elections and initial coalitions. This change creates incentives for political players to re-bargain over existing coalitions. As the bargaining process decreases the leaders' survival prospects, the likelihood of leaders to opt for the ‘wrong side’ of the policy space will increase. I validate this claim using a case study and a large-N quantitative analysis of 51 cases from 34 countries.
Economic vote instability: Endogeneity or restricted variance? Spanish panel evidence from 2008 and 2011
Authors: Fraile Marta , Lewis‐Beck Michael S.
Published: March 2013

While the economic vote exists in Western democracies, the question of its stability remains a subject of controversy. This article focuses on two possible factors behind the instability observed: the endogeneity problem and the restricted variance problem. The former concerns the influence of partisan thinking on economic perception, while the latter concerns the influence of economic crisis, when virtually all voters may perceive a bad economy. These problems are examined using panel data from the Spanish national elections of 2008 and 2011. After various causality tests, it is concluded that the economic vote was influential in both contests, but apparently less so in 2011. It is shown in the article that the initial 2011 result misleads because of the statistical artifact presented by the restricted variance problem. Thus, an alternative strategy for exogenising economic perceptions is developed using aggregate economic measures in a pooled cross‐sectional design whereby it is demonstrated that the economy mattered greatly under the economic crisis of 2011. This estimation strategy could be applicable to other Western democracies experiencing such economic crisis.
Economic vulnerability and economic voting in 14 OECD countries
Authors: Fossati Diego
Published: March 2013

The economic voting literature shows that good economic performance bolsters the electoral prospects of incumbents. However, disagreement persists as to whether voters in vulnerable economic conditions are more likely to engage in economic voting. It is argued in this article that a crucial factor in explaining individual‐level variation in economic voting is the degree of exposure to economic risks, because risk exposure affects the saliency of the economy in voting decisions. In particular, the focus is on job insecurity and employability as key determinants of economic voting patterns. The article hypothesises that the extent of economic voting is greater in voters who are more vulnerable to unemployment and less employable in case of job loss. Support for these hypotheses is found in a test with a dataset that combines survey data on incumbent support with occupational unemployment rates and other measures of exposure to economic risks.
Sequential loss of genetic variation in flea beetle Agasicles hygrophila (Coleoptera: Chrysomelidae) following introduction into China
Authors: Ma Rui‐Yan , Jia Xiao‐Yun , Liu Wen‐Zhong , Laushman Roger H. , Zhao Long‐Long , Jia Dong , Wang Ren
Published: March 2013

The flea beetle (Agasicles hygrophila) was imported to Florida, USA and then introduced from Florida into China in 1987 as a biological control agent for the invasive plant alligator weed (Alternanthera philoxeroides). The initial beetle population was subsequently used for sequential introductions in other areas of China, but little is known about the genetic consequences of the introductions. In this study, the genetic diversity and population structure of five beetle populations, the source Florida population, three intentionally introduced China populations and one accidentally dispersed China population, were examined using amplified fragment length polymorphisms. The results showed a clear pattern of decreasing genetic diversity with the sequential introductions. The diversity was highest in the Florida population followed by the first introduction to Chongqing and then in Kunming and Fuzhou. The lowest diversity was found in the accidentally dispersed Guangzhou population that was first recorded in 1996. Both loci parameters and Nei's genetic diversity showed a high variation among these populations. Genetic differentiation among populations was further verified by the GST statistic (0.136–0.432). Beetles in Kunming had the highest gene flow with those in Guangzhou, and therefore lowest differentiation and closest genetic distance. These data show that sequential introduction influenced the genetic diversity of populations in China. Genetic diversity should be considered in planning introduction and long‐term maintenance of populations.
Clean Indoor Air Policies and Smoking in Mexico
Authors: Andalón Mabel
Published: March 2013

This paper empirically tests the association between recently adopted state‐level clean indoor air laws and the smoking behaviour ofMexican men and women. To deal with the problem of highly correlated policies across venues,Iconstruct an index of clean indoor air policies that measures the degree of strictness of smoking restrictions in different locations and the level of enforcement of the laws. Matching policies to individual‐level data from theNationalHealthSurvey 2006,Ifind that more comprehensive laws are not associated with the decision to smoke, but are negatively related to daily consumption of cigarettes by men. More specifically, a one unit increase in the index is associated with 3.9 fewer cigarettes smoked a day. The results that test for policy endogeneity show that states with higher intensity of smoking were not more or less likely to pass more comprehensive laws, which suggests that restrictive clean indoor air policies might have been effective at reducing the number of cigarettes smoked byMexican men who smoke.
Varying effort in capture–recapture studies
Authors: Efford Murray G. , Borchers David L. , Mowat Garth
Published: March 2013

The standard spatial capture–recapture design for sampling animal populations uses a fixed array of detectors, each operated for the same time. However, methods are needed to deal with the unbalanced data that may result from unevenness of effort due to logistical constraints, partial equipment failure or pooling of data for analysis.

We describe adjustments for varying effort for three types of data each with a different probability distribution for the number of observations per individual per detector per sampling occasion. A linear adjustment to the expected count is appropriate for Poisson‐distributed counts (e.g. faeces per searched quadrat). A linear adjustment on the hazard scale is appropriate for binary (Bernoulli‐distributed) observations at either traps or binary proximity detectors (e.g. automatic cameras). Data pooled from varying numbers of binary detectors have a binomial distribution; adjustment is achieved by varying the size parameter of the binomial.

We compared a hazard‐based adjustment to a more conventional covariate approach in simulations of one temporal and one spatial scenario for varying effort. The hazard‐based approach was the more parsimonious and appeared more resistant to bias and confounding.

We analysed a dataset comprising DNA identifications of female grizzly bears Ursus arctos sampled asynchronously with hair snares in British Columbia in 2007. Adjustment for variation in sampling interval had negligible effect on density estimates, but unmasked an apparent decline in detection probability over the season. Duration‐dependent decay in sample quality is an alternative explanation for the decline that could be included in future models.

Allowing for known variation in effort ensures that estimates of detection probability relate to a consistent unit of effort and improves the fit of detection models. Failure to account for varying effort may result in confounding between effort and density variation in time or space. Adjustment for effort allows rigorous analysis of unbalanced data with little extra cost in terms of precision or processing time. We suggest it should become routine in capture–recapture analyses. The methods have been made available in the R package secr.
The disposable Ambu aScope vs. a conventional flexible videoscope for awake intubation – a randomised study
Authors: KRISTENSEN M. S. , FREDENSBORG B. B.
Published: March 2013

Background

A new disposable flexible videoscope, the Ambu® aScope, has several potential advantages compared with reusable devices, but it is a prerequisite for its widespread use that it functions sufficiently well in the management of patients in whom difficulty with airway management is anticipated and awake intubation is indicated.

Methods

In a pilot study, 20 patients with normal airways were intubated with the aScope. Subsequently, 40 patients with predicted difficult tracheal intubation were randomly assigned to be intubated awake with either the aScope or the reusable Olympus BF videobronchoscope.

Results

All patients were successfully intubated awake. The median total intubation time, including the administration of local anaesthesia, was 278 vs. 234 s in the aScope and Olympus groups, respectively (P = 0.03). In two cases in the aScope group, the image became blurred immediately after the first injection of lidocaine via the injection channel, and the time that it took to replace the scopes was included in the intubation times.

Conclusion

Both the disposable aScope and the reusable Olympus videoscope allowed safe awake intubation in our elective patients with severely difficult, but uncompromised, airways. The occasional need to employ a spare scope because of malfunctioning would make the disposable aScope less suitable in patients with acutely compromised airways.
Pre‐hospital airway management by non‐physicians in Northern Finland – a cross‐sectional survey
Authors: RAATINIEMI L. , LÄNKIMÄKI S. , MARTIKAINEN M.
Published: March 2013

Background

Airway management is an important skill in pre‐hospital emergency medicine. The most optimal method depends on the resources and experience of the emergency medical service (EMS) providers. We wanted to study the frequency of occurrence, equipment used, problems experienced and maintenance of skills in pre‐hospital airway management by non‐physicians.

Methods

A structured questionnaire consisting of 30 questions was distributed to 383 EMS providers in three hospital districts (population 597,521 and area 147,467 km2) in Northern Finland.

Results

The questionnaire was answered by 226 EMS providers and 58.5% (224/383) were included in the final analyses. In all, 82.6% (185/224) of the EMS providers were allowed to perform endotracheal intubation (ETI) and 44.2% (99/224) could perform ETI using sedative agents. The annual mean frequency of using a supraglottic airway device (SAD) was 1.0 (range 0–20, n = 224), for ETI it was 2.0 (range 0–16, n = 185) and for bag‐valve‐mask ventilation it was 4.3 (range 0–30, n = 223). The mean frequency of drug‐assisted ETI was 1.1 (range 0–13, n = 99). Unsuccessful ETI had been experienced by 65.7% (119/181) of the EMS providers. Airway management had been practised in an operating room by 25.9% (56/216) and with a manikin by 81.3% (182/224) of the EMS providers during the past 12 months.

Conclusion

Advanced airway management procedures are uncommon for most EMS providers in Northern Finland. Procedures, training in and maintenance of airway management skills should be re‐evaluated.
Interacting biocontrol programmes: invasive cane toads reduce rates of breakdown of cowpats by dung beetles
Authors: González‐Bernal Edna , Greenlees Matthew J. , Brown Gregory P. , Shine Richard
Published: March 2013

Ecological interactions among invasive species can affect not only the success of the invaders, but also their impact on ecosystems in the invaded range. In Australia, both dung beetles (subfamily Scarabaeinae) and cane toads (Rhinella marina) were introduced for biocontrol: the beetles to break down bovine faeces piles (cowpats) that otherwise accumulate and reduce pasture productivity, and the cane toad to consume scarab beetles that eat sugarcane and thus reduce sugar production. The dung beetles have been a success, whereas the toads have been a failure. Our experimental studies show that as well as impacting native fauna directly, cane toads reduce the rate of cowpat breakdown by consuming dung beetles. In the laboratory, dehydrated toads actively sought out cowpats based on scent cues, and in field enclosures, the presence of a cane toad significantly reduced rates of cowpat decomposition. Although toads have benefited from agricultural activities, their spread across Australia likely has reduced the effectiveness of one of the most successful biocontrol programmes ever conducted in that continent.
Black Politicians Are More Intrinsically Motivated to Advance Blacks’ Interests: A Field Experiment Manipulating Political Incentives
Authors: Broockman David E.
Published: March 2013

Why are politicians more likely to advance the interests of those of their race? I present a field experiment demonstrating that black politicians are more intrinsically motivated to advance blacks’ interests than are their counterparts. Guided by elite interviews, I emailed 6,928 U.S. state legislators from a putatively black alias asking for help signing up for state unemployment benefits. Crucially, I varied the legislators’ political incentive to respond by randomizing whether the sender purported to live within or far from each legislator's district. While nonblack legislators were markedly less likely to respond when their political incentives to do so were diminished, black legislators typically continued to respond even when doing so promised little political reward. Black legislators thus appear substantially more intrinsically motivated to advance blacks’ interests. As political decision making is often difficult for voters to observe, intrinsically motivated descriptive representatives play a crucial role in advancing minorities’ political interests.
Understanding communication between surgeon and patient in outpatient consultations
Authors: White Sarah J. , Stubbe Maria H. , Dew Kevin P. , Macdonald Lindsay M. , Dowell Anthony C. , Gardner Rod
Published: March 2013

Background

There is an assumption that there is a similarity between surgeon‐patient and primary care consultations. Yet, surgeon communication has had far less analytic attention than its primary care counterparts. Therefore, this assumption of similarity (and the proposition here of dissimilarity) has yet to be evidenced through detailed interactional analysis.

Methods

Conversation analysis (CA) is a methodology used to understand both mundane and institutional interactions. Using CA, we have developed an understanding of surgeon‐patient interactions in outpatient clinic settings in New Zealand. Rather than attempting to determine what ‘bad’ communication is, we describe and analyse what occurs routinely in surgeon‐patient consultations, particularly how these interactions are built up by both patient and doctor.

Results

This research shows that while surgeon‐patient consultations share some similarities to the overall structure of primary care consultations, there are two unique structures that occur in surgical consultations. These structures follow a logical progression of activities and are influenced by the type of visit (referred versus follow‐up).

Discussion

This article summarizes the first comprehensive description of the overall interactional structure of surgeon‐patient consultations. It demonstrates that surgeon‐patient consultations are structurally distinct from primary care consultations. This key finding has implications for surgeon‐specific research and education, highlighting the need to question current assumptions in communication training and in clinical practice.
Contrast Transthoracic Echocardiography and the Placement of a Bicaval Dual‐Lumen Catheter in a Swine Model of Venovenous Extracorporeal Membrane Oxygenation
Authors: Hayes Don , Preston Thomas J. , Davis Ian C. , Duffy Victoria L. , McConnell Patrick I. , Whitson Bryan A. , Duffy Joseph S. , Yates Andrew R.
Published: March 2013

Placement of a bicaval dual‐lumen (BCDL) catheter demands sophisticated visualization in patients to assure proper positioning in order to administer single‐site venovenous extracorporeal membrane oxygenation (VV ECMO). Large animal models are needed and thus appropriate procedures to assure anatomic and functional cannula placement would assist in experimental design and procedures. This report describes the use of agitated blood and saline transthoracic contrast echocardiography to confirm appropriate placement and function of the BCDL catheter in a swine model of VV ECMO. Five consecutive common crossbred piglets had confirmation using this technique with assurances of cannulation while not significantly altering experimental time and procedures. Researchers studying VV ECMO in large animal models may want to consider this method of confirmation of BCDL catheter placement.
Situated knowledge and the EU sugar reform: a Caribbean life history
Authors: Richardson‐Ngwenya Pamela
Published: March 2013

This paper draws inspiration from an elderly sugarcane farmer in Barbados, Mr Thompson, who took part in a participatory video (PV) project and informal life history interviews with the author in 2007. The author mobilises Mr Thompson's life history as a situated account of the influence of the European Union (EU) sugar regime, considering how this trade regime and the local state‐owned sugar industry have been implicated in his life. It is demonstrated how Europe's wide‐reaching trade agenda is embodied in both the life history and the living present of a particular individual. Tracing the story of Mr Thompson, the paper draws heavily on his own words and audio‐visual presentations. From these video‐based expressions, we glimpse relations between a personal history, a set of embodied encounters and a broader (post)colonial legacy. Mr Thompson evokes an alternative understanding of sugar in Barbados, acting as a counterpoint to claims that promote neoliberal reform. Charting the experiences of one person, the paper suggests, offers a useful and valid position from which to critique the EU sugar reform at large. Finally, the paper discusses how a methodological coupling of PV and life history interviewing provided a valuable tool for engaging with and expressing situated knowledges.
How public participation in river management improvements is affected by scale
Authors: Maynard Carly M
Published: March 2013

The importance of extending physically based approaches to catchment management to include social considerations has recently been highlighted alongside increasing legislative pressure to utilise public participation in river management processes. Nine water managers, operating at varying geographical scales, from the UK and north‐west Europe were interviewed to determine their approach to, opinion of, and success in utilising public participation for decisionmaking. The results indicate that despite variations in approaches to, and perceptions of, participation, one dominant factor constrained the use of higher level participation: scale. The results demonstrate that the degree of participation and influence for ‘non‐certified’ experts was inversely proportional to the scale of the project. This was attributed to issues of practicality in communicating between a large number of individuals, but also to underlying factors such as availability of financial support and governing regulations that differ between organisations of different sizes. The findings were used to consider the role of Callon's public education, public debate and co‐production of knowledge models of scientific knowledge production (Callon 1990). It is suggested that, for practical application, traditional models be developed into more reflexive approaches that account for the complexity of real‐world situations.
Fentanyl Pharmacokinetics is not Dependent on Hepatic Uptake by Organic Anion‐Transporting Polypeptide 1B1 in Human Beings
Authors: Ziesenitz Victoria C. , König Sonja K. , Mahlke Nina , Jantos Ricarda , Skopp Gisela , Weiss Johanna , Haefeli Walter E. , Mikus Gerd
Published: March 2013

A recent study investigating the pharmacokinetics of fentanyl in Sprague–Dawley rats suggested fentanyl to be a substrate of rat organic anion‐transporting polypeptide Oatp. In human beings, the most important OATP for the pharmacokinetics of many drugs is OATP1B1. Therefore, genetic variants of OATP1B1 (SLCO1B1) might modulate fentanyl pharmacokinetics and efficacy in human beings. Sixteen healthy male and female volunteers, homozygous for SLCO1B1*1a (genetic wild‐type) (n = 11) or *15 (deficient haplotype carrying the single‐nucleotide polymorphisms rs2306283 and rs4149056 and exhibiting altered transport activity; n = 5), were included in this randomized crossover study. The participants received fentanyl (5 μg/kg) intravenously alone or with the OATP inhibitor rifampicin (600 mg single oral dose). The pharmacokinetics of fentanyl and norfentanyl were determined by liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS). In addition, fentanyl uptake in vitro was evaluated in OATP1B1 overexpressing HEK293 cells and compared to a mock‐transfected cell line. In the clinical trial, fentanyl clearance was 18.8 ± 8.2 mL/min. kg in SLCO1B1*1a and 19.5 ± 1.8 mL/min/kg in SLCO1B1*15 carriers and not significantly different between the genotypes. During rifampicin, fentanyl clearance was 15.0 ± 4.4 mL/min/kg in SLCO1B1*1a and 16.7 ± 5.9 mL/min/kg in SLCO1B1*15 carriers (p > 0.5). In addition, in vitro data also indicate that fentanyl is not transported by OATP1B1. In conclusion, our data indicate that OATP1B1 has no impact on fentanyl pharmacokinetics in human beings.
Effects of Antihypertensive and Triglyceride Lowering Agents on Splenocyte Apoptosis in Rats with Fatty Liver
Authors: Ackerman Zvi , Grozovski Maria , Oron‐Herman Mor , Rosenthal Talma , Sela Ben‐Ami , Amir Gail
Published: March 2013

Individuals with the metabolic syndrome (MS) and non‐alcoholic fatty liver disease (NAFLD) have an increased incidence of infection and infection‐related mortality. Rats given fructose‐enriched diet (FED) develop the MS including NAFLD. In this study, we characterized changes in splenocyte apoptosis in FED rats given medications to treat various components of the MS. Apoptosis of splenocytes may induce immunosuppression. Splenocyte apoptosis was evaluated by activated caspase‐3 immunohistochemistry in the periarterial sheath (PALS), (a T cell area), follicles (B cell area), marginal (B cell area) and in the red pulp zones. FED administration caused an enormous increase in splenocyte apoptosis in all of the spleen zones: PALS (+2966%), follicles (+3025%), marginal (+5228%) and red pulp (+7000%). Administration of captopril to the FED rats was associated with a further increase in the splenocyte apoptosis only in the marginal (150%), PALS (+105%) and red pulp (+67%) zones. Bezafibrate administration to the FED rats was associated with no further increase in apoptosis rates. Amlodipine administration to the FED rats was associated with almost complete amelioration of the splenocyte apoptosis that was induced by the FED diet. These pharmacological manipulations were also associated with changes in the hepatic lipids composition, and oxidative milieu that did not correlate to the changes in splenocyte apoptosis. NAFLD in FED rats is associated with an increase in splenic apoptosis. Agents administered to treat components of the MS in FED rats may lead to divergent changes in the splenic histology and splenocyte apoptosis.
A Bayesian Goodness of Fit Test and Semiparametric Generalization of Logistic Regression with Measurement Data
Authors: Schörgendorfer Angela , Branscum Adam J. , Hanson Timothy E.
Published: March 2013

Logistic regression is a popular tool for risk analysis in medical and population health science. With continuous response data, it is common to create a dichotomous outcome for logistic regression analysis by specifying a threshold for positivity. Fitting a linear regression to the nondichotomized response variable assuming a logistic sampling model for the data has been empirically shown to yield more efficient estimates of odds ratios than ordinary logistic regression of the dichotomized endpoint. We illustrate that risk inference is not robust to departures from the parametric logistic distribution. Moreover, the model assumption of proportional odds is generally not satisfied when the condition of a logistic distribution for the data is violated, leading to biased inference from a parametric logistic analysis. We develop novel Bayesian semiparametric methodology for testing goodness of fit of parametric logistic regression with continuous measurement data. The testing procedures hold for any cutoff threshold and our approach simultaneously provides the ability to perform semiparametric risk estimation. Bayes factors are calculated using the Savage–Dickey ratio for testing the null hypothesis of logistic regression versus a semiparametric generalization. We propose a fully Bayesian and a computationally efficient empirical Bayesian approach to testing, and we present methods for semiparametric estimation of risks, relative risks, and odds ratios when parametric logistic regression fails. Theoretical results establish the consistency of the empirical Bayes test. Results from simulated data show that the proposed approach provides accurate inference irrespective of whether parametric assumptions hold or not. Evaluation of risk factors for obesity shows that different inferences are derived from an analysis of a real data set when deviations from a logistic distribution are permissible in a flexible semiparametric framework.
Transurethral resection of the prostate in kidney transplant recipients: urological and renal functional outcomes at long‐term follow‐up
Authors: Volpe Alessandro , Billia Michele , Quaglia Marco , Vidali Matteo , Marchioro Giansilvo , Ceratti Giovanni , Sogni Filippo , De Lorenzis Elisa , De Angelis Paolo , Airoldi Andrea , Stratta Piero , Terrone Carlo
Published: March 2013

Objectives

To assess prospectively the safety and efficacy of transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) in patients who have undergone renal transplantation (RT).

To assess the impact of TURP on renal graft function.

Patients and Methods

Urological and renal functional outcomes of TURP performed in RT recipients for treatment of lower urinary tract obstruction attributable to BPH were prospectively assessed in a series of 32 consecutive patients with follow‐up of ≥48 months.

Maximum urinary flow rate (Qmax) at uroflowmetry, International Prostate Symptom Score (IPSS), post‐void residual urine volume (PVR), haemoglobin and serum creatinine (sCr) levels were recorded before TURP and 1, 6, 24 and 48 months after the procedure. The trends in these variables after TURP were evaluated.

Early and delayed complications were assessed and graded according to the Clavien classification system.

Results

TURP was performed at a mean of 6 months after RT.

No intraoperative complications occurred. Seven postoperative complications were observed (21.9%): two Clavien grade II and five Clavien grade IIIa.

Qmax, IPSS and PVR improved significantly after surgery and the improvement was maintained until 48 months. No patient required a repeat TURP during follow‐up.

SCr levels significantly decreased 1 and 6 months after TURP and did not significantly increase at long‐term follow‐up.

Conclusions

TURP for lower urinary tract obstruction attributable to BPH in RT recipients is safe and effective since it improves urinary flow, bladder emptying and related urinary symptoms.

TURP allows an early significant improvement of graft function that is maintained at a follow‐up of 48 months.
Survival after radical prostatectomy for clinically localised prostate cancer: a population‐based study
Authors: Røder Martin Andreas , Brasso Klaus , Christensen Ib Jarle , Johansen Jørgen , Langkilde Niels Christian , Hvarness Helle , Carlsson Steen , Jakobsen Henrik , Borre Michael , Iversen Peter
Published: March 2013

Objectives

To describe survival and cause of death in a nationwide cohort of Danish patients with prostate cancer undergoing radical prostatectomy (RP).

To describe risk factors associated with prostate cancer mortality.

Patients and Methods

Observational study of 6489 men with localised prostate cancer treated with RP at six different hospitals in Denmark between 1995 and 2011.

Survival was described using Kaplan–Meier estimates. Causes of death were obtained from the national registry and cross‐checked with patient files.

Cumulative incidence of death, any cause and prostate cancer‐specific, was described using Nelson–Aalen estimates.

Risk for prostate cancer death was analysed in a Cox multivariate regression model using the covariates: age, cT‐category, PSA level and biopsy Gleason score.

Results

The median follow‐up was 4 years. During follow‐up, 328 patients died, 109 (33.2%) from prostate cancer and 219 (66.8%) from other causes. Six patients (0.09%) died ≤30 days of RP.

In multivariate analysis, cT‐category was a predictor of prostate cancer death (P < 0.001). Compared with T1 disease, both cT2c (hazard ratio [HR] 2.2) and cT3 (HR 7.2) significantly increased the risk of prostate cancer death. For every doubling of PSA level the risk of prostate cancer death was increased by 34.8% (P < 0.001). Biopsy Gleason score 4 + 3 and ≥8 were associated with an increased risk of prostate cancer death compared with biopsy Gleason score ≤ 6 of 2.3 and 2.7 (P = 0.003), respectively.

The cumulative hazard of all‐cause and prostate cancer‐specific mortality after 10 years was 15.4% (95% confide3nce interval [CI] 13.2–17.7) and 6.6% (95% CI 4.9–8.2) respectively.

Conclusions

We present the first survival analysis of a complete, nationwide cohort of men undergoing RP for localised prostate cancer.

The main limitation of the study was the relatively short follow‐up.

Interestingly, our national results are comparable to high‐volume, single institution, single surgeon series.
Regulatory T cells, interleukin (IL)‐6, IL‐8, Vascular endothelial growth factor (VEGF), CXCL10, CXCL11, epidermal growth factor (EGF) and hepatocyte growth factor (HGF) as surrogate markers of host immunity in patients with renal cell carcinoma
Authors: Polimeno Marianeve , Napolitano Maria , Costantini Susan , Portella Luigi , Esposito Arianna , Capone Francesca , Guerriero Eliana , Trotta AnnaMaria , Zanotta Serena , Pucci Luigi , Longo Nicola , Perdonà Sisto , Pignata Sandro , Castello Giuseppe , Scala Stefania
Published: March 2013

Objective

To identify a phenotype that could be informative and prognostic in patients with renal cell carcinoma (RCC) peripheral blood was evaluated for TH1, TH2, regulatory T cells (Tregs), natural killer (NK) and NKT cells and for cytokines/chemokines.

Patients and Methods

Peripheral blood from 77 patients with RCC and 40 healthy controls was evaluated by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RA, CD45RO, CD152, CD184, CD279, CD3, CD16, CD56, CD161, CD158a, CD4, CD26, CD30, CD183 and CD184.

A concomitant evaluation of 38 molecules was conducted in patients’ serum using a multiplex biometric ELISA‐based immunoassay.

Results

The number of NK cells CD3−/CD16+, CD3−/CD16+/CD161+ (NK) and CD3−/CD16+/CD161+/CD158a+ (NK‐ Kir 2+) was greater in the patients with RCC (P < 0.05); and the number of Treg cells CD4+/CD25high+/FOXP3+ and the subset CD4+/CD25high+/FOXP3+/CD45RA+ (naïve) and CD45R0+(memory) cells, were greater in the patients with RCC (P < 0.001).

An increase in the following was observed in the serum of patients with RCC compared with healthy controls: interleukin (IL)‐4, IL‐6, IL‐8, IL‐10, G‐CSF, CXCL10, CXCL11, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). According to Ingenuity Pathway Analysis (IPA), CXCL10, IL‐6, IL‐8, epidermal growth factor (EGF), HGF and VEGF were associated with a network that controls cellular movement, tissue development and cellular growth.

Kaplan–Meier analysis for disease‐free survival showed that high numbers of CD4+/CD25high+/FOXP3+/CD45RA+ (Treg naïve) and low numbers of CD3−/CD16+/CD161+/CD158a+ (NK‐Kir+) cells predict short disease‐free survival in patients with RCC.

Conclusion

Concomitant evaluation of Treg (CD4+/CD25high+/FOXP3+ and CD4+/CD25high+/FOXP3+/CD45RA+) and of six soluble factors (IL‐6, IL‐8 ,VEGF, CXCL10, CXCL11, EGF, HGF) might be a surrogate marker of host immunity in patients with RCC.
ADHD and functional somatic symptoms: structural equations of a conceptual model
Authors: Giacobo Rodrigo Serra , Jané Maria Claustre , Bonillo Albert , Arrufat Francisco Javier , Araujo Eva
Published: March 2013

Aims

To examine the effect of anxiety and parental overprotection on functional somatic symptoms (FSS) in children with attention deficit hyperactivity disorder (ADHD).

Method

Seventy‐six children and adolescents (aged 6–17) with ADHD and their parents completed a clinical interview about psychiatric and somatic symptoms. Parents also reported about parenting styles. Structural equation modeling (SEM) was used.

Results

The generalized anxiety, overprotection, and specific phobia variables each had a direct effect on FSS.

Conclusions

Anxiety symptoms and parental overprotection may play a role in the development of FSS in children with ADHD. Further research is necessary to corroborate our findings.