bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of programmable integrases
Authors: Gordley Russell M. , Gersbach Charles A. , Barbas Carlos F.
Published: March 2009

Accurate modification of the 3 billion-base-pair human genome requires tools with exceptional sequence specificity. Here, we describe a general strategy for the design of enzymes that target a single site within the genome. We generated chimeric zinc finger recombinases with cooperative DNA-binding and catalytic specificities that integrate transgenes with >98% accuracy into the human genome. These modular recombinases can be reprogrammed: New combinations of zinc finger domains and serine recombinase catalytic domains generate novel enzymes with distinct substrate sequence specificities. Because of their accuracy and versatility, the recombinases/integrases reported in this work are suitable for a wide variety of applications in biological research, medicine, and biotechnology where accurate delivery of DNA is desired.
Genome-wide discovery of functional transcription factor binding sites by comparative genomics: The case of Stat3
Authors: Vallania Francesco , Schiavone Davide , Dewilde Sarah , Pupo Emanuela , Garbay Serge , Calogero Raffaele , Pontoglio Marco , Provero Paolo , Poli Valeria
Published: March 2009

The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. However, the use of high throughput experimental methods, such as ChIP-chip and ChIP-sequencing, is limited by their high cost and strong dependence on cellular type and context. We developed a computational method for the genome-wide identification of functional transcription factor binding sites based on positional weight matrices, comparative genomics, and gene expression profiling. The method was applied to Stat3, a transcription factor playing crucial roles in inflammation, immunity and oncogenesis, and able to induce distinct subsets of target genes in different cell types or conditions. A newly generated positional weight matrix enabled us to assign affinity scores of high specificity, as measured by EMSA competition assays. Phylogenetic conservation with 7 vertebrate species was used to select the binding sites most likely to be functional. Validation was carried out on predicted sites within genes identified as differentially expressed in the presence or absence of Stat3 by microarray analysis. Twelve of the fourteen sites tested were bound by Stat3 in vivo, as assessed by Chromatin Immunoprecipitation, allowing us to identify 9 Stat3 transcriptional targets. Given its high validation rate, and the availability of large transcription factor-dependent gene expression datasets obtained under diverse experimental conditions, our approach appears to be a valid alternative to high-throughput experimental assays for the discovery of novel direct targets of transcription factors.
Baroreflex contribution to blood pressure and heart rate oscillations: time scales, time-variant characteristics and nonlinearities
Authors: Di Rienzo M , Parati G , Radaelli A , Castiglioni P
Published: March 2009

The aim of this paper is to highlight the aspects of the baroreflex control of the cardiovascular system that could be relevant to the analysis and modelling of cardiovascular oscillations and regulation. In particular, complex and/or controversial issues of the baroreflex control are addressed on the basis of results obtained in previous studies by others as well as by our group. Attention has been focused on time-variant and nonlinear characteristics of the baroreflex function and on the influence of this physiological mechanism on different frequency regions of blood pressure and heart rate spectra.
Assessing causality in normal and impaired short-term cardiovascular regulation via nonlinear prediction methods
Authors: Nollo Giandomenico , Faes Luca , Antolini Renzo , Porta Alberto
Published: March 2009

We investigated the ability of mutual nonlinear prediction methods to assess causal interactions in short-term cardiovascular variability during normal and impaired conditions. Directional interactions between heart period (RR interval of the ECG) and systolic arterial pressure (SAP) short-term variability series were quantified as the cross-predictability (CP) of one series given the other, and as the predictability improvement (PI) yielded by the inclusion of samples of one series into the prediction of the other series. Nonlinear prediction was performed through global approximation (GA), approximation with locally constant models (LA0) and approximation with locally linear models (LA1) of the nonlinear function linking the samples of the two series, on patients with neurally mediated syncope and control subjects. Causality measures were evaluated in the two directions (from SAP to RR and from RR to SAP) in the supine (SU) position, in the upright position after head-up tilt (early tilt, ET) and after prolonged upright posture (late tilt, LT). While the trends for the GA, LA0 and LA1 methods were substantially superimposable, PI elicited better than CP the prevalence of causal coupling from RR to SAP during SU. Both CP and PI noted a marked decrease in coupling in both causal directions in syncope subjects during LT, documenting the impairment of cardiovascular regulation in the minutes just preceding syncope.
Complexity of cardiovascular regulation in small animals
Authors: Aubert André E , Vandeput Steven , Beckers Frank , Liu Jiexin , Verheyden Bart , Van Huffel Sabine
Published: March 2009

Oscillations of heart rate and blood pressure are related to the activity of the underlying control mechanism. They have been investigated mostly with linear methods in the time and frequency domains. Also, in recent years, many different nonlinear analysis methods have been applied for the evaluation of cardiovascular variability. This review presents the most commonly used nonlinear methods. Physiological understanding is obtained from various results from small animals.
Testing foetal–maternal heart rate synchronization via model-based analyses
Authors: Riedl Maik , van Leeuwen Peter , Suhrbier Alexander , Malberg Hagen , Grönemeyer Dietrich , Kurths Jürgen , Wessel Niels
Published: March 2009

The investigation of foetal reaction to internal and external conditions and stimuli is an important tool in the characterization of the developing neural integration of the foetus. An interesting example of this is the study of the interrelationship between the foetal and the maternal heart rate. Recent studies have shown a certain likelihood of occasional heart rate synchronization between mother and foetus. In the case of respiratory-induced heart rate changes, the comparison with maternal surrogates suggests that the evidence for detected synchronization is largely statistical and does not result from physiological interaction. Rather, they simply reflect a stochastic, temporary stability of two independent oscillators with time-variant frequencies. We reanalysed three datasets from that study for a more local consideration. Epochs of assumed synchronization associated with short-term regulation of the foetal heart rate were selected and compared with synchronization resulting from white noise instead of the foetal signal. Using data-driven modelling analysis, it was possible to identify the consistent influence of the heartbeat duration of maternal beats preceding the foetal beats during epochs of synchronization. These maternal beats occurred approximately one maternal respiratory cycle prior to the affected foetal beat. A similar effect could not be found in the epochs without synchronization. Simulations based on the fitted models led to a higher likelihood of synchronization in the data segments with assumed foetal–maternal interaction than in the segment without such assumed interaction. We conclude that the data-driven model-based analysis can be a useful tool for the identification of synchronization.
Analysis of sympathetic neural discharge in rats and humans
Authors: Montano Nicola , Furlan Raffaello , Guzzetti Stefano , McAllen Robin M , Julien Claude
Published: March 2009

Neural signals convey information through two different modalities: intensity and discharge pattern. The intensity code is based on the number of action potentials per unit time, which is then easily translated into neurotransmitter release. This kind of information may be assessed simply by counting the number of spikes or bursts over a time unit. However, the discharge pattern is a further, efficient means of neural information transfer. Rhythmic patterns (i.e. oscillations) can support highly structured, temporal codes based on correlation and synchronization. It is therefore clear that applying frequency domain analysis to sympathetic activity recorded in animals and humans may provide additional information about the neural control of the circulation. Over the last century, data obtained by the analysis of sympathetic activity in experimental animals, and recently also in humans, have provided fundamental contributions to our understanding of the physiological mechanisms involved in the neural control of circulation, as well as how these are altered in cardiovascular and non-cardiovascular diseases. The aim of this paper is to address some aspects related to the recording, analysis and interpretation of sympathetic activity in rats and humans, with special emphasis on analysis in the frequency domain.
Clinical impact of evaluation of cardiovascular control by novel methods of heart rate dynamics
Authors: Huikuri Heikki V , Perkiömäki Juha S , Maestri Roberto , Pinna Gian Domenico
Published: March 2009

Heart rate variability (HRV) has been conventionally analysed with time- and frequency-domain methods, which measure the overall magnitude of RR interval fluctuations around its mean value or the magnitude of fluctuations in some predetermined frequencies. Analysis of heart rate dynamics by novel methods, such as heart rate turbulence after ventricular premature beats, deceleration capacity of heart rate and methods based on chaos theory and nonlinear system theory, have gained recent interest. Recent observational studies have suggested that some indices describing nonlinear heart rate dynamics, such as fractal scaling exponents, heart rate turbulence and deceleration capacity, may provide useful prognostic information in various clinical settings and their reproducibility may be better than that of traditional indices. For example, the short-term fractal scaling exponent measured by the detrended fluctuation analysis method has been shown to predict fatal cardiovascular events in various populations. Similarly, heart rate turbulence and deceleration capacity have performed better than traditional HRV measures in predicting mortality in post-infarction patients. Approximate entropy, a nonlinear index of heart rate dynamics, which describes the complexity of RR interval behaviour, has provided information on the vulnerability to atrial fibrillation. There are many other nonlinear indices which also give information on the characteristics of heart rate dynamics, but their clinical usefulness is not as well established. Although the concepts of nonlinear dynamics, fractal mathematics and complexity measures of heart rate behaviour, heart rate turbulence, deceleration capacity in relation to cardiovascular physiology or various cardiovascular events are still far away from clinical medicine, they are a fruitful area for research to expand our knowledge concerning the behaviour of cardiovascular oscillations in normal healthy conditions as well as in disease states.
Comparative X-ray diffraction study of the crystalline microstructure of tetragonal and monoclinic vanadium–zirconium dioxide solid solutions produced from gel precursors
Authors: Kojdecki Marek Andrzej , Ruiz de Sola Esther , Serrano Francisco Javier , Amigó José María , Alarcón Javier
Published: March 2009

The microstructural characteristics of solid solutions, prepared by heating dried gel precursors with nominal compositions VxZr1−xO2(0 ≤x≤ 0.1) at 723 and 1573 K, were determined from X-ray diffraction patterns. The crystalline microstructure of the resulting specimens, characterized by a prevalent crystallite shape, a volume-weighted crystallite size distribution and a second-order lattice strain distribution, was found to depend on the vanadium content. A characteristic feature of all size distributions was their bimodality, explained as a result of transformations between tetragonal and monoclinic phases during thermal treatment. A comparative study of the microstructure of both zirconia phases has been carried out, enabling reconstruction of a probable course of crystallization of both pure and vanadium-doped zirconias: on heating a sample, nucleation and the early growth stages involve crystallites of both phases; then on annealing and cooling, the crystallites of one phase transform into the other, depending on the thermal treatment temperature. Each logarithmic normal component of the crystallite size distribution of the resulting phase can be attributed to one of these processes. The limit of solubility of vanadium in tetragonal and monoclinic zirconia is estimated from the microstructural characteristics.
Tilt and twist grain boundaries
Authors: Morawiec A.
Published: March 2009

Grain boundaries are frequently classified into tilt, twist and mixed-type boundaries. However, the classification (into tilt and twist) is not a dichotomy; due to crystal symmetries, some boundaries may be concurrently tilt and twist boundaries. Formal conditions for a planar homophase boundary between crystals withm3msymmetry to be a tilt as well as a twist boundary are determined, and a procedure for verification of whether a boundary has such dual character is given.
Increasing hospital‐wide delivery of smoking cessation care for nicotine‐dependent in‐patients: a multi‐strategic intervention trial
Authors: Freund Megan , Campbell Elizabeth , Paul Christine , Sakrouge Rebecca , Lecathelinais Christophe , Knight Jenny , Wiggers John , Walsh Raoul A. , Jones Therese , Girgis Afaf , Nagle Amanda
Published: March 2009

Aims, design and intervention  Smoking care provision to in‐patients is important in assisting smoking cessation and for management of nicotine withdrawal. Limited studies have reported the effectiveness of interventions designed to increase the hospital‐wide provision of such care. A quasi‐experimental matched‐pair trial, involving two intervention and two control hospitals in NSW, Australia, investigated whether a multi‐strategic intervention increased hospital‐wide smoking care provision.

Participants and measurements  Patient surveys (n = 274–347 per experimental condition), medical notes audits (n = 181–228) and health professional surveys (n = 229–302) were used to collect outcome data at baseline and follow‐up.

Findings  Significantly greater increases in intervention hospitals compared to control hospitals were found for patient‐reported offer of nicotine replacement therapy (NRT) (intervention 34% versus control 12%), provision of NRT (16% versus 4%) and provision of written resources (11% versus 2%), and for the recording in medical notes of smoking management discussion (13% versus 3%), offer of NRT (24% versus 3%) and provision of NRT (21% versus 5%). Intervention group health professionals reported significantly greater increases in the mean estimate of patients who: had their smoking management discussed (30% versus 17%); were offered or provided with NRT (30% versus 18%); were asked their intention to smoke post‐discharge (22% versus 10%); and were provided with discharge NRT (21% versus 4%).

Conclusions  Implementation of a multi‐strategic intervention is effective in increasing hospital smoking care delivery, particularly the provision of NRT. Research is required to identify methods to increase further the delivery of this and other forms of smoking care.
Patterns of change in withdrawal symptoms, desire to smoke, reward motivation and response inhibition across 3 months of smoking abstinence
Authors: Dawkins Lynne , Powell Jane H. , Pickering Alan , Powell John , West Robert
Published: March 2009

Aims  We have demonstrated previously that acute smoking abstinence is associated with lowered reward motivation and impaired response inhibition. This prospective study explores whether these impairments, along with withdrawal‐related symptoms, recover over 3 months of sustained abstinence.

Design  Participants completed a 12‐hour abstinent baseline assessment and were then allocated randomly to quit unaided or continue smoking. All were re‐tested after 7 days, 1 month and 3 months. Successful quitters' scores were compared with those of continuing smokers, who were tested after ad libitum smoking.

Setting  Goldsmiths, University of London.

Participants  A total of 33 smokers who maintained abstinence to 3 months, and 31 continuing smokers.

Measurements  Indices demonstrated previously in this cohort of smokers to be sensitive to the effect of nicotine versus acute abstinence: reward motivation [Snaith–Hamilton pleasure scale (SHAPS), Card Arranging Reward Responsivity Objective Test (CARROT), Stroop], tasks of response inhibition [anti‐saccade task; Continuous Performance Task (CPT)], clinical indices of mood [Hospital Anxiety and Depression Scale (HADS)], withdrawal symptoms [Mood and Physical Symptoms Scale (MPSS)] and desire to smoke.

Findings  SHAPS anhedonia and reward responsivity (CARROT) showed significant improvement and plateaued after a month of abstinence, not differing from the scores of continuing smokers tested in a satiated state. Mood, other withdrawal symptoms and desire to smoke all declined from acute abstinence to 1 month of cessation and were equivalent to, or lower than, the levels reported by continuing, satiated smokers. Neither group showed a change in CPT errors over time while continuing smokers, but not abstainers, showed improved accuracy on the anti‐saccade task at 3 months.

Conclusion  Appetitive processes and related affective states appear to improve in smokers who remain nicotine‐free for 3 months, whereas response inhibition does not. Although in need of replication, the results suggest tentatively that poor inhibitory control may constitute a long‐term risk factor for relapse and could be a target for intervention.
Can cocaine use be evaluated through analysis of wastewater? A nation‐wide approach conducted in Belgium
Authors: Van Nuijs Alexander L. N. , Pecceu Bert , Theunis Laetitia , Dubois Nathalie , Charlier Corinne , Jorens Philippe G. , Bervoets Lieven , Blust Ronny , Meulemans Herman , Neels Hugo , Covaci Adrian
Published: March 2009

Aims  Cocaine is the second most‐used illicit drug world‐wide and its consumption is increasing significantly, especially in western Europe. Until now, the annual prevalence has been estimated indirectly by means of interviews. A recently introduced and direct nation‐wide approach based on measurements of the major urinary excreted metabolite of cocaine, benzoylecgonine, in wastewater is proposed.

Design  Wastewater samples from 41 wastewater treatment plants (WWTPs) in Belgium, covering approximately 3 700 000 residents, were collected. Each WWTP was sampled on Wednesdays and Sundays during two sampling campaigns in 2007–08. Samples were analysed for cocaine (COC) and its metabolites, benzoylecgonine (BE) and ecgonine methylester (EME) by a validated procedure based on liquid chromatography coupled with tandem mass spectrometry. Concentrations of BE were used to calculate cocaine consumption (g/day per 1000 inhabitants) for each WWTP region and for both sampling campaigns (g/year per 1000 inhabitants).

Findings  Weekend days showed significantly higher cocaine consumption compared with weekdays. The highest cocaine consumption was observed for WWTPs receiving wastewater from large cities, such as Antwerp, Brussels and Charleroi. Results were extrapolated for the total Belgian population and an estimation of a yearly prevalence of cocaine use was made based on various assumptions. An amount of 1.88 tonnes (t) per year [standard error (SE) 0.05 t] cocaine is consumed in Belgium, corresponding to a yearly prevalence of 0.80% (SE 0.02%) for the Belgian population aged 15–64 years. This result is in agreement with an earlier reported estimate of the Belgian prevalence of cocaine use conducted through socio‐epidemiological studies (0.9% for people aged 15–64 years).

Conclusions  Wastewater analysis is a promising tool to evaluate cocaine consumption at both local and national scale. This rapid and direct estimation of the prevalence of cocaine use in Belgium corresponds with socio‐epidemiological data. However, the strategy needs to be refined further to allow a more exact calculation of cocaine consumption from concentrations of BE in wastewater.
Twelve‐Step affiliation and 3‐year substance use outcomes among adolescents: social support and religious service attendance as potential mediators
Authors: Chi Felicia W. , Kaskutas Lee A. , Sterling Stacy , Campbell Cynthia I. , Weisner Constance
Published: March 2009

Aims  Twelve‐Step affiliation among adolescents is little understood. We examined 12‐Step affiliation and its association with substance use outcomes 3 years post‐treatment intake among adolescents seeking chemical dependency (CD) treatment in a private, managed‐care health plan. We also examined the effects of social support and religious service attendance on the relationship.

Design  We analyzed data for 357 adolescents, aged 13–18, who entered treatment at four Kaiser Permanente Northern California CD programs between March 2000 and May 2002 and completed both baseline and 3‐year follow‐up interviews.

Measures  Measures at follow‐up included alcohol and drug use, 12‐Step affiliation, social support and frequency of religious service attendance.

Findings  At 3 years, 68 adolescents (19%) reported attending any 12‐Step meetings, and 49 (14%) reported involvement in at least one of seven 12‐Step activities, in the previous 6 months. Multivariate logistic regression analyses indicated that after controlling individual and treatment factors, 12‐Step attendance at 1 year was marginally significant, while 12‐Step attendance at 3 years was associated with both alcohol and drug abstinence at 3 years [odds ratio (OR) 2.58, P < 0.05 and OR 2.53, P < 0.05, respectively]. Similarly, 12‐Step activity involvement was associated significantly with 30‐day alcohol and drug abstinence. There are possible mediating effects of social support and religious service attendance on the relationship between post‐treatment 12‐Step affiliation and 3‐year outcomes.

Conclusions  The findings suggest the importance of 12‐Step affiliation in maintaining long‐term recovery, and help to understand the mechanism through which it works among adolescents.
Results from two randomized clinical trials evaluating the impact of quarterly recovery management checkups with adult chronic substance users
Authors: Scott Christy K , Dennis Michael L.
Published: March 2009

Aims  Post‐discharge monitoring and early reintervention have become standard practice when managing numerous chronic conditions. These two experiments tested the effectiveness of recovery management checkup (RMC) protocols for adult chronic substance users.

Intervention  RMC included quarterly monitoring; motivational interviewing to provide personalized feedback and to resolve ambivalence about substance use; treatment linkage, engagement and retention protocols to increase the amount of treatment received.

Participants and setting  Recruited from sequential addiction treatment admissions, participants in the two experiments were, on average, 36 and 38 years of age, mainly female (59% versus 46%), African American (85% versus 80%) and met past‐year criteria for dependence (87% versus 76%).

Design  Participants in both experiments were assigned randomly to the RMC or control condition and interviewed quarterly for 2 years.

Measurement  The Global Appraisal of Individual Needs (GAIN) was the main assessment instrument.

Findings  RMC participant outcomes were better than control participants in both experiments. Effect sizes were larger in the second experiment in terms of reducing days to readmission (Cohen's d = 0.41 versus d = 0.22), successive quarters in the community using substances (d = −0.32 versus −0.19), past‐month symptoms of abuse/dependence (d = −0.23 versus −0.02) and increasing the days of abstinence over 2 years (d = +0.29 versus 0.04).

Conclusion  RMC, which provided ongoing monitoring and linkage, is feasible to conduct and is effective for adults with chronic substance dependence.
Individual trajectories of substance use in lesbian, gay and bisexual youth and heterosexual youth
Authors: Marshal Michael P. , Friedman Mark S. , Stall Ron , Thompson Amanda L.
Published: March 2009

Aims Several decades of research have shown that lesbian, gay and bisexual (LGB) adults are at high risk for substance use and substance use disorders, and a recent meta‐analysis shows that these disparities most probably begin in adolescence; however, no studies to date have examined longitudinal growth in substance use in LGB youth and heterosexual youth to determine if they follow different trajectories into young adulthood. The primary aims of this paper were to estimate individual trajectories of substance use in youth and examine differences between self‐identified LGB and heterosexual subsamples.

Method A school‐based, longitudinal study of health‐related behaviors of adolescents and their outcomes in young adulthood was used to test our hypotheses (The National Longitudinal Study of Adolescent Health). Participants were included if they were interviewed at all three waves and were not missing information regarding self‐identified sexual orientation (n = 10 670).

Results Latent curve models (LCMs) showed that LGB identity was associated significantly with individual variability in substance use intercepts and slopes, above and beyond age, race and gender. Self‐identified LGB youth reported higher initial rates of substance use and on average their substance use increased over time more rapidly than did substance use by heterosexual youth. Two other indicators of sexual orientation (same‐sex romantic attraction and same‐sex sexual behavior) were also associated with substance use trajectories, and differential results were found for youth who identified as ‘mostly heterosexual’ and bisexual compared with youth who identified as completely heterosexual or homosexual.

Conclusions Sexual orientation is an important risk marker for growth in adolescent substance use, and the disparity between LGB and heterosexual adolescents increases as they transition into young adulthood. More research is needed in order to examine: causal mechanisms, protective factors, important age‐related trends (using a cohort‐sequential design), the influence of gay‐related developmental milestones, curvilinear effects over time and long‐term health outcomes.
Pre‐oxygenation and apnoea in pregnancy: changes during labour and with obstetric morbidity in a computational simulation
Authors: McClelland S. H. , Bogod D. G. , Hardman J. G.
Published: March 2009

Using the Nottingham Physiology Simulator, we investigated the effects on pre‐oxygenation and apnoea during rapid sequence induction of labour, obesity, sepsis, pre‐eclampsia, maternal haemorrhage and multiple pregnancy in term pregnancy. Pre‐oxygenation with 100% oxygen was followed by simulated rapid sequence induction when end‐tidal nitrogen tension was less than 1 kPa, and apnoea. Labour, morbid obesity and sepsis accelerated pre‐oxygenation and de‐oxygenation during apnoea. Fastest pre‐oxygenation was in labour, with 95% of the maximum change in expired oxygen tension occurring in 47 s, compared to 97 s in a standard pregnant subject. The labouring subject with a body mass index of 50 kg.m−2 demonstrated the fastest desaturation, the time taken to fall to an arterial saturation < 90% being 98 s, compared to 292 s in a standard pregnant subject. Pre‐eclampsia prolonged pre‐oxygenation and tolerance to apnoea. Maternal haemorrhage and multiple pregnancy had minor effects. Our results inform the risk‐benefit comparison of the anaesthetic options for Caesarean section.
A meta‐analysis of the utility of C‐reactive protein in predicting early, intermediate‐term and long term mortality and major adverse cardiac events in vascular surgical patients
Authors: Padayachee L. , Rodseth R. N. , Biccard B. M.
Published: March 2009

We conducted a meta‐analysis of the utility of pre‐operative C reactive protein (CRP) in predicting early (< 30 days), intermediate (30–180 days) and long term (> 180 days) mortality and major adverse cardiac events (MACE; cardiac mortality and nonfatal myocardial infarction (MI) combined) following vascular surgery. Of 291 studies identified, ten prospective patient cohorts were identified. A pre‐operative CRP > 3 mg.l−1 was not associated with 30‐day all‐cause mortality, cardiac mortality, nonfatal myocardial infarction or MACE. Intermediate‐term all‐cause mortality, cardiac death and MACE showed a trend to a worse outcome (odds ratio (OR) 9.07, 95% confidence interval (CI) 0.86–96.28, p = 0.07; OR 8.71, 95% CI 0.5–153.1, p = 0.14 and OR 2.81, 95% CI 0.78–5.18, p = 0.15 respectively). Long term all cause mortality (OR 2.40, 95% CI 1.15–5.02, p = 0.02), cardiac death (OR 5.66, 95% CI 1.71–18.73, p = 0.005) and MACE (OR 2.76, 95% CI 1.38–5.55, p = 0.004) were significantly increased.
Comparison of central venous oxygen saturation and mixed venous oxygen saturation during liver transplantation
Authors: El Masry A. , Mukhtar A. M. , El Sherbeny A. M. , Fathy M. , El‐Meteini M.
Published: March 2009

Central venous catheterisation is commonly performed during major surgery and intensive care, and it would be useful if central venous oxygen saturation could function as a surrogate for mixed venous oxygen saturation. We studied 50 patients undergoing living related liver transplantation. Blood samples were taken simultaneously from central venous and pulmonary artery catheters at nine time points during the pre‐anhepatic, anhepatic, and postanhepatic phases. Four hundred and fifty sets of measurement were obtained. There was a good correlation between central venous oxygen saturation and mixed venous oxygen saturation. The mean (SD) difference (95% limit of agreement) was lowest at the first time point (1.06 (0.65)%, −1.94% to 2.7%) and then increased throughout the study but remained acceptable. The change in mixed venous oxygen and central venous oxygen saturations occurred mostly in parallel and as a result changes in mixed venous oxygen saturation were reflected adequately in the change in central venous oxygen saturation. The correlation between mixed venous oxygen saturation and cardiac output was poor.
A simple fibreoptic assisted laryngoscope for paediatric difficult intubation: a manikin study*
Authors: Komiya K. , Inagawa G. , Nakamura K. , Kikuchi T. , Fujimoto J. , Sugawara Y. , Goto T.
Published: March 2009

The fibreoptic assisted laryngoscope is a new airway device. We compared the fibreoptic assisted laryngoscope with the Bullard laryngoscope, Macintosh laryngoscope and fibreoptic bronchoscope in a manikin with a simulated Cormack and Lehane Grade 4 laryngoscopic view. Eighteen anaesthetists intubated the manikin’s trachea using these devices and the success rate of intubation was measured. They were then asked to rate the subjective difficulty of intubation. The success rate (95% confidence interval) was 100% (94.6–100) with the fibreoptic assisted laryngoscope, 88.9% (80.5–97.3) using the Bullard laryngoscope, 37.0% (24.1–49.9) with the Macintosh laryngoscope, and 22.2% (11.1–33.3) using the fibreoptic bronchoscope. Tracheal intubation using the fibreoptic assisted laryngoscope or Bullard laryngoscope is easier than that using the Macintosh laryngoscope or fibreoptic bronchoscope by subjective difficulty score. All of the intubations were successful with the fibreoptic assisted laryngoscope without practice. These results suggest that fibreoptic assisted laryngoscope may be a useful tool for paediatric difficult intubation.
Tracheal tube fixation: the effect on depth of insertion of midline fixation compared to the angle of the mouth*
Authors: Sharma K. , Varshney M. , Kumar R.
Published: March 2009

Following successful placement of a tracheal tube (TT), it is frequently moved from the midline to the angle of the mouth. This study investigates the tracheal tube tip position in the two fixation positions in 200 adult patients. Following tracheal intubation, a fibreoptic bronchoscope (FOB) was introduced through a swivel connector and the distances from the swivel connector to the lips, carina, tip of TT and the crico‐tracheal membrane were measured with the TT in the midline and at the right angle of the mouth. The mean (SD) TT tip to carinal distance decreased from 3.60 (1.50) cm to 2.28 (1.55) cm in female patients, and 5.04 (1.43) cm to 3.69 (1.65) cm in male patients on moving the tracheal tube to the angle of the mouth. We conclude that there is a significant movement of the tracheal tube towards the carina on moving the TT from midline to angle of mouth and the depth of insertion of the tube should be adjusted accordingly.
A new instrument for pain assessment in the immediate postoperative period*
Authors: Machata A. M. , Kabon B. , Willschke H. , Fäßler K. , Gustorff B. , Marhofer P. , Curatolo M.
Published: March 2009

Perceptual‐cognitive impairment after general anaesthesia may affect the ability to reliably report pain severity with the standard visual analog scale (VAS). To minimise these limitations, we developed ‘PAULA the PAIN‐METER®’ (PAULA): it has five coloured emoticon faces on the forefront, it is twice as long as a standard VAS scale, and patients use a slider to mark their pain experience. Forty‐eight postoperative patients rated descriptive pain terms on PAULA and on a standard VAS immediately after admission and before discharge from the postanaesthesia care unit. Visual acuity was determined before both assessments. The values obtained with PAULA showed less variance than those obtained with the standard VAS, even at the first assessment, where only 23% of the patients had regained their visual acuity. Furthermore, the deviations of the absolute VAS values in individual patients for each descriptive pain term were significantly smaller with PAULA than with the standard VAS.
Refractory thrombotic thrombocytopenic purpura following influenza vaccination
Authors: Dias P. J. , Gopal S.
Published: March 2009

Thrombotic thrombocytopenic purpura (TTP) is characterised by the systemic microvascular aggregation of platelets causing ischaemia of the brain and other organs. We describe the case of a 54 year‐old man who presented with neurological signs, fever, severe thrombocytopenia, microangiopathic haemolytic anaemia and renal failure 5 days after receiving an influenza vaccination. He was diagnosed with acute refractory TTP caused by autoantibody‐mediated ADAMTS‐13 deficiency. He required stabilisation on the critical care unit before being successfully treated with 3 l plasma exchanges for 21 days and rituximab (MabThera®) at a dose of 375 mg.m−2, given weekly for a total of 4 weeks. Vaccination is an important part of preventative medicine and reduces morbidity and mortality. Only in a few rare cases has vaccination been associated with autoimmune pathology. We could find only one similar case report of thrombotic thrombocytopenic purpura following influenza vaccination. In addition to plasma exchange, rituximab appears to be effective and well tolerated in the treatment of refractory thrombotic thrombocytopenic purpura.
Chronic transfusion practice for children with sickle cell anaemia and stroke
Authors: Aygun Banu , McMurray Marsha A. , Schultz William H. , Kwiatkowski Janet L. , Hilliard Lee , Alvarez Ofelia , Heeney Matthew , Kalinyak Karen , Lee Margaret T. , Miller Scott , Helms Ronald W. , Ware Russell E. ,   for the SWiTCH Trial Investigators
Published: March 2009

Chronic transfusions to maintain haemoglobin S (HbS) ≤30% are the mainstay of treatment for children with sickle cell anaemia (SCA) and previous stroke. This HbS target is often hard to maintain, however, and values achieved in current practice are unknown. In preparation for the Phase III Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial, we collected data on 295 children with SCA and stroke who received transfusions at 23 institutions. The overall average pre‐transfusion %HbS was 35 ± 11% (institutional range 22–51%). Receiving scheduled transfusions on time was the most predictive variable for maintaining HbS at the ≤30% goal.
NF‐κB promotes iNOS and VEGF expression in salivary gland adenoid cystic carcinoma cells and enhances endothelial cell motility in vitro
Authors: Zhang Jiali , Peng Bin
Published: March 2009

Tumour cell‐derived angiogenic‐related factors and endothelial cell mobility are essential for neovascularization and haematogenous metastasis of adenoid cystic carcinoma (ACC) of the human salivary glands. Our previous study demonstrated that vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), and nuclear factor kappaB (NF‐κB) staining correlated with ACC microvessel density. However, there still remains a lack of direct evidence to clarify the function of liposaccharide‐induced NF‐κB activity in ACC angiogenesis.

Objectives:  This study aimed to demonstrate the function of liposaccharide‐induced NF‐κB signalling pathway (which would be relevant to angiogenesis) of ACC cell lines.

Materials and methods: A PCMV‐IκBαM vector transfection assay was performed to inhibit NF‐κB activity. Constitutive and liposaccharide‐induced NF‐κB activity, along with VEGF and iNOS expression, was detected by electrophoretic mobility shift assays, reverse transcription–polymerase chain reaction and Western blot assay. Tumour cell‐derived NO2− was evaluated by a nitrite determination assay, and endothelial cell mobility was investigated by endothelial cell proliferation, migration and tube formation assays.

Results: We demonstrated that regulation of VEGF and iNOS expression utilized the NF‐κB signalling pathway in ACC cell lines. In the constitutive and liposaccharide‐induced condition, NF‐κB activity was blocked by phosphorylation‐defective IκBα. Accordingly, mRNA and protein expression of VEGF and iNOS were significantly decreased, with a great drop in endogenous NO2−. Furthermore, supernatant from ACC‐2/IkBaM and ACC‐M/IkBaM cells resulted in much lower endothelial cell mobility than that from ACC‐2 and ACC‐M cells.

Conclusions: Our results suggest that NF‐κB promotes iNOS and VEGF expression in salivary gland ACC cells and enhances endothelial cell motility in vitro.
Generation of mice by transplantation of an adult spermatogonial cell line after cryopreservation
Authors: Yuan Zhe , Hou Ruoyu , Wu Ji
Published: March 2009

Objectives: The key to fertility in adult males is production of mature spermatogenic cells. Spermatogonial stem cells (SSC) have the dual capacity of self‐renewal and of differentiation into mature sperm. SSC transplantation may provide potential treatment for specific male infertilities. However, until now, there has been no evidence of offspring produced by transplantation of adult SSC line cells in humans or other mammals.

Materials and methods: A new line of SSCs from adult C57BL/6 mouse was established by using magnetic‐activated cell sorting. The cell line was characterized by immunocytochemistry, karyotype analysis and telomeric repeat amplification protocol (TRAP) telomerase activity assay. Spermatogenic function was examined by allograft into germ cell‐ablated recipient mice.

Results: For more than 14 months with more than 65 maintenance passages, the cell line showed a normal karyotype (40, XY) and high telomerase activity. It represented a Thy‐1+, Oct4+, SSEA‐1‐, c‐kit‐ (99 ± 1%) cell subpopulation. We cryopreserved these SSCs and successfully produced normal offspring after transplanting them into testes of busulphan‐sterilized mice.

Conclusions: We established and long‐term maintained an adult SSC line with normal spermatogenic function, without the need of genetic modification; thus, this study provides a model system for basic research and clinical application.
Analysis of human mammary fibroadenoma by Ki‐67 index in the follicular and luteal phases of menstrual cycle
Authors: Rego M. F. , Navarrete M. A. L. H. , Facina G. , Falzoni R. , Silva R. , Baracat E. C. , Nazario A. C. P.
Published: March 2009

Objectives:  Fibroadenoma is the most common benign mammary condition among women aged 35 or younger. Expression of Ki‐67 antigen has been used to compare proliferative activity of mammary fibroadenoma epithelium in the follicular and luteal phases of the menstrual cycle.

Materials and methods:  Ninety eumenorrheic women were selected for tumour excision; they were assigned to either of the two groups, according to their phase of menstrual cycle. At the end of the study, 75 patients with 87 masses were evaluated by epithelial cell Ki‐67 expression, blind (no information given concerning group to which any lesion belonged).

Results:  Both groups were found to be homogeneous relative to age, menarche, body mass index, previous gestation, parity, breastfeeding, number of fibroadenomas, family history of breast cancer and tabagism. Median tumour size was 2.0 cm and no relationship between proliferative activity and nodule diameter was observed. No typical pattern was observed in the expression of Ki‐67 in distinct nodules of the same patient. Average values for expression of Ki‐67 (per 1000 epithelial cells) in follicular and luteal phases were 27.88 and 37.88, respectively (P = 0.116).

Conclusion:  Our findings revealed that proliferative activities in the mammary fibroadenoma epithelium did not present a statistically significant difference in the follicular and luteal phases. The present study contributes to clarifying that fibroadenoma is a neoplasm and does not undergo any change in the proliferative activity during the menstrual cycle.
Body size determines the outcome of competition for webs among alien and native sheetweb spiders (Araneae: Linyphiidae)
Authors: EICHENBERGER BEATA , SIEGENTHALER EVA , SCHMIDT‐ENTLING MARTIN H.
Published: March 2009

Abstract 1. Biotic invasions are one of the most important reasons for changes in biodiversity. The alien sheetweb spider Mermessus trilobatus (Araneae: Linyphiidae) has become abundant in large parts of Central Europe within the past three decades. Its invasion might negatively influence native spiders, for instance via competition for webs.

2. Laboratory experiments were developed to test if M. trilobatus is competitively superior to native spiders. The alien M. trilobatus and five native sheetweb spiders (Erigone dentipalpis, E. atra, Gnathonarium dentatum, Dicymbium nigrum and Micrargus herbigradus) were compared with respect to their success to take over occupied webs from E. dentipalpis.

3. The rate of web takeover or defence was determined by body size, whereby individuals with a wider thorax invaded webs more successfully. After taking body size into account, the frequency of defence or web takeover did not differ between species. In 13% of all confrontations, predation against generally smaller opponents was recorded. Contrary to the predictions, raising the web value with food resources did not raise the effort expended on web defence but reduced predation by the web owner.

4. The current study does not indicate that the invasion of the relatively small‐sized M. trilobatus is facilitated by strong competitiveness. Nevertheless, M. trilobatus may displace smaller‐sized immature specimens and thereby threaten native spiders. Still, other reasons are likely to underlie the success of M. trilobatus in Europe, such as rapid reproduction or release from natural enemies.
The double cloak of invisibility: phenotypic plasticity and larval decoration in a geometrid moth,Synchlora frondaria, across three diet treatments
Authors: CANFIELD MICHAEL R. , CHANG SUE , PIERCE NAOMI E.
Published: March 2009

Abstract1. Crypsis is one of the main defences that insects use to avoid predators, and both the juveniles and adults of many geometrid moths are remarkable in their ability to blend into different host backgrounds. The larvae ofSynchlora frondariahave two methods to achieve crypsis: phenotypic plasticity in colouration that enable them to hide more effectively on their host plants, and a self‐decorating behaviour whereby the larvae camouflage themselves with materials from their host plants.

2. Larvae ofSynchlora frondariareared on three different host plants showed systematic differences in relative growth rate, survivorship and larval colouration.

3. Larval colouration varied across diet treatments in a way that was consistent with diet‐induced phenotypic plasticity, and larvae also exhibited characteristic decorating behaviour on all three hosts.

4. Larvae showed highest survivorship onHeterotheca subaxillaris(Asteraceae), and had significantly higher relative growth rates onH. subaxillaris(Asteraceae) andLantana camara(Verbenaceae) than onBejaria racemosa(Ericaceae).

5. Synchlora frondariaprovides an example of a species where both decorating behaviour and phenotypic plasticity in larval colouration produce a cryptic form that is remarkably responsive to its background.
Extreme longevity in freshwater mussels revisited: sources of bias in age estimates derived from mark–recapture experiments
Authors: HAAG WENDELL R.
Published: March 2009

1. There may be bias associated with mark–recapture experiments used to estimate age and growth of freshwater mussels. Using subsets of a mark–recapture dataset for Quadrula pustulosa, I examined how age and growth parameter estimates are affected by (i) the range and skew of the data and (ii) growth reduction due to handling. I compared predictions from von Bertalanffy growth models based on mark–recapture data with direct observation of mussel age and growth inferred from validated shell rings.

2. Growth models based on a dataset that included observations from a wide range of length classes (spanning ≥ the upper 50% of the population length range) produced only slightly biased age estimates for small and medium‐sized individuals (overestimated by 1–2 years relative to estimates from validated shell rings) but estimates became increasingly biased for larger individuals. Growth models using data that included only observations of larger animals (< the upper 50% of length range) overestimated age for all length classes, and estimated maximum age was two to six times greater than the maximum age observed in the population (47 years). Similarly, growth models using a left‐skewed dataset overestimated age.

3. Reductions of growth due to repeated handling also resulted in overestimates of age. The estimated age of mussels that were handled in two consecutive years was as much as twice that of mussels that were handled only once over the same period. Assuming a constant reduction in the annual rate of growth, handling an individual for five consecutive years could result in an estimated age that is five times too high.

4. These findings show that mark–recapture methods have serious limitations for estimating mussel age and growth. A previous paper (Freshwater Biology, 46, 2001, 1349) presented longevity estimates for three mussel species that were an order of magnitude higher than estimates inferred from shell rings. Because those estimates of extreme longevity were based on mark–recapture methods and subject to multiple, additive sources of bias, they cannot be considered accurate representations of life span and cannot be used to conclude that traditional methods of bivalve ageing by interpretation of shell rings are flawed.