bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial communication and virulence: lessons from evolutionary theory
Authors: Diggle Stephen P.
Published: October 2010

At the heart of tackling the huge challenge posed by infectious micro-organisms is the overwhelming need to understand their nature. A major question is, why do some species of bacteria rapidly kill their host whilst others are relatively benign? For example,Yersinia pestis, the causative organism of plague, is a highly virulent human pathogen whilst the closely relatedYersinia pseudotuberculosiscauses a much less severe disease. Using molecular techniques such as mutating certain genes, microbiologists have made significant advances over recent decades in elucidating the mechanisms that govern the production of virulence factors involved in causing disease in many bacterial species. There are also evolutionary and ecological factors which will influence virulence. Many of these ideas have arisen through the development of evolutionary theory and yet there is strikingly little empirical evidence testing them. By applying both mechanistic and adaptive approaches to microbial behaviours we can begin to address questions such as, what factors influence cooperation and the evolution of virulence in microbes and can we exploit these factors to develop new antimicrobial strategies?
Effect of total alkaloids from Commelina communis L. on lung damage by influenza virus infection
Authors: Zhang Guo‐Bin , Bing Fei‐Hong , Liu Jun , Li Zhi , Liao Yi‐Fan , Li Jing , Dong Chang‐Yuan
Published: October 2010

Whether administration of total alkaloids from Commelina communis L. (TAC) reduces lung damage in influenza virus‐infected mice was investigated. Compared with untreated mice, significantly less severe damage was found in the lungs of mice administered TAC at 8 mg/kg per day for 6 days. TAC significantly decreased viral loads in the lungs. The concentrations of IFN‐γ in the serum of TAC‐treated mice were significantly lower than those of virus control mice at 4 and 6 days post‐infection. The results indicate that TAC imparted partial protection to the mice by reducing pulmonary viral loads and limiting lesions in the lungs.
The idiotype (Id) cascade in mice elicited the production of anti‐R24 Id and anti‐anti‐Id monoclonal antibodies with antitumor and protective activity against human melanoma
Authors: Ramos Angelita S. , Parise Carolina B. , Travassos Luiz R. , Han Sang W. , de Campos‐Lima Pedro O. , de Moraes Jane Z.
Published: October 2010

Gangliosides have been considered as potential targets for immunotherapy because they are overexpressed on the surface of melanoma cells. However, immunization with purified gangliosides results in a very poor immune response, usually mediated by IgM antibodies. To overcome this limitation, we immunized mice with R24, a monoclonal antibody (mAb) that recognizes the most tumor‐restricted ganglioside (GD3); our goal was to obtain anti‐idiotype (Id) antibodies bearing the internal image of GD3. Animals produced anti‐Id and anti‐anti‐Id antibodies. Both anti‐Id and anti‐anti‐Id antibodies were able to inhibit mAb R24 binding to GD3. In addition, the anti‐anti‐Id antibodies were shown to recognize GD3 directly. Anti‐Id and anti‐anti‐Id mAb were then selected from two fusion experiments for evaluation. The most interesting finding emerged from the characterization of the anti‐anti‐Id mAb 5.G8. It was shown to recognize two different GD3‐expressing human melanoma cell lines in vitro and to mediate tumor cell cytotoxicity by complement activation and antibody‐dependent cellular cytotoxicity. The biological activity of the anti‐anti‐Id mAb was also tested in a mouse tumor model, in which it was shown to be a powerful growth inhibitor of melanoma cells. Thus, activity of the anti‐anti‐Id mAb 5.G8 matched that of the prototypic anti‐GD3 mAb R24 both in vitro and in vivo. Altogether, our results indicate that the idiotype approach might produce high affinity, specific and very efficient antitumor immune responses. (Cancer Sci 2011; 102: 64–70)
Comparison of balloon vs. straight catheter for the measurement of portal hypertension
Authors: Zipprich A. , Winkler M. , Seufferlein T. , Dollinger M. M.
Published: October 2010

Aliment Pharmacol Ther 2010; 32: 1351–1356

Background  The hepatic venous pressure gradient (HVPG) is used as an estimation of portal pressure (PP) in the management of patients with cirrhosis. Two methods are available using either a straight or a balloon catheter, but have never been compared head‐to‐head.

Aim  To compare the two methods of determining HVPG, straight and balloon catheter, regarding reproducibility and reliability.

Methods  In 47 patients with liver cirrhosis, HVPG was assessed using both catheters in sequence. In another 29 patients, the wedged hepatic venous pressure (WHVP) determined either with straight or balloon catheter was correlated with a direct measurement of PP. Variation coefficient and intraclass correlation coefficient were calculated.

Results  Variation coefficients for balloon catheter were 0.07 (HVPG), 0.02 (WHVP) and 0.06 [free hepatic venous pressure (FHVP)]. Variation coefficients for straight catheter were 0.17 (HVPG), 0.06 (WHVP) and 0.07 (FHVP), demonstrating a significantly wider variation of the HVPG and WHVP measurements (P < 0.001). Comparison of WHVP with PP revealed a correlation coefficient of 0.72 (P = 0.004) using balloon catheter and 0.58 (P = 0.011) using straight catheter.

Conclusions  Measurements with the balloon catheter currently represent the most reliable and reproducible method to assess HVPG. The results are of particular clinical relevance if repeated measurements are required for therapeutic adjustments.
Measuring whole‐body neutrophil redistribution using a dedicated whole‐body counter and ultra‐low doses of 111Indium
Authors: Szczepura Katherine R. , Ruparelia Prina , Solanki Chandra K. , Balan Kottekkattu , Newbold Paul , Summers Charlotte , Chilvers Edwin R. , Peters A. Michael
Published: October 2010

Eur J Clin Invest 2010; 41 (1): 77–83

Background  There is increasing interest in the ‘homing’ of neutrophils to bone marrow. The aim of this study was to measure the whole‐body redistribution of 111In using a whole‐body counter following the administration of ultra‐small activities of 111In‐labelled neutrophils.

Methods  The detectors of a dedicated whole‐body counter were fitted with lead collimators. Whole‐body 111In distribution was recorded at 45 min, 24 h, and 2, 4, 7 and 10 days after administration of 111In‐labelled neutrophils (0·29–0·74 MBq) in eight healthy non‐smokers, five healthy smokers, eight patients with inactive bronchiectasis, three with asthma and nine with chronic obstructive pulmonary disease (COPD).

Results  Intravascular 45‐min 111In‐labelled neutrophil recovery was not significantly different between groups, ranging from 33 (SD 8%) in healthy smokers to 45 (14%) in healthy non‐smokers (P > 0·05). Peaks were identified on the whole body count profile corresponding to the chest, upper abdomen (liver/spleen) and pelvis (bone marrow). 111In distribution changed between 45 min and 24 h and then remained stable thereafter. Peak chest counts increased ∼1·5‐fold between 45 min and 24 h, whereas upper abdominal peak counts decreased by ∼25% with no significant inter‐group differences. The increment in pelvic counts (∼2·7‐fold) was similar between groups, except COPD patients, in whom it was 2·04 (0·35; P < 0·02 vs. healthy participants).

Conclusions  Assuming neutrophils are distributed only between blood, liver, spleen and bone marrow, the data suggest that marrow pools 25% and destroys 67% of circulating neutrophils, rising in COPD to 40% and 80%, respectively, possibly as a result of the effects on marrow of chronic hypoxaemia.
Linking ecological immunology and evolutionary medicine: the case for apolipoprotein E
Authors: Trotter Justin H. , Liebl Andrea L. , Weeber Edwin J. , Martin Lynn B.
Published: October 2010

1. Evolutionary medicine seeks to understand whether and to what extent aspects of human disease are adaptations for coping with infections or injuries, or the consequence of mismatches between modern and ancestral environments. Ecological immunology by comparison focuses largely on how organisms balance investments in immune defences against other traits (e.g., cognitive and reproductive functions) to maximize fitness.

2. Here we address the potential benefit of merging these two young disciplines by reviewing the biomedical literature involving variation at the human apolipoprotein epsilon (apoE) locus. Allelic variants at this locus are differentially susceptible to certain parasites [e.g. herpes‐simplex virus‐1 (HSV‐1) and Chlamydia pneumoniae], as well as Alzheimer’s and coronary artery disease, although susceptibility is impacted by environmental factors such as exercise and diet. ApoE variants also exhibit extensive physiological differences, particularly in immune and cognitive traits.

3. Considered altogether, we suggest that apoe‐associated diseases are maladaptive plastic responses to conditions in modern environments, and predict that allelic variation at the apoE locus arose as both a consequence of genetic accommodation of historically adaptive environmental responses and because of the particular susceptibility of lipid transport molecules as infection pathways for certain parasites.

4. The goal of this paper is not to support unequivocally this hypothesis because relevant data remain scarce. We intend instead to provide a framework whereby existing hypotheses, which tend to emphasize faulty signalling via one allele (apoE4), can be evaluated through ecologically‐informed experiments.
Escape from the pond: stress and developmental responses to ranavirus infection in wood frog tadpoles
Authors: Warne Robin W. , Crespi Erica J. , Brunner Jesse L.
Published: October 2010

1. Animal populations exhibit considerable variation in their susceptibility to infection by emerging diseases, yet it is poorly understood how environmental and intrinsic factors contribute to these patterns. Considering that intrinsic factors (e.g. life history stage, nutritional state) can impact immune function, knowledge of the physiological mechanisms that mediate susceptibility to infection may improve our understanding of the emergence of disease in natural populations.

2. Ranavirus outbreaks have been associated with die‐offs of amphibians worldwide. While the ecological factors associated with epidemics have been widely studied, little is known about how physiological factors mediate amphibian responses to ranavirus infection.

3. The neuroendocrine hypothalamus‐pituitary‐interrenal axis (HPI) is a physiological system central to coordinating energy balance and development. It is known to both stimulate and inhibit immune function in vertebrates in different contexts. We hypothesized that the HPI axis would also mediate responses to ranavirus infection. We used wood frog (Rana sylvatica) larvae and ranavirus isolated from recent die‐offs of local wood frog populations to examine the physiological responses to infection.

4. In addition to increasing odds of death with increasing doses of virus in an LD50 study, we saw a 1·7‐fold increase in the odds of death with each increase in Gosner stage at the time of infection.

5. We then examined the HPI stress response of prometamorphic tadpoles exposed to a lethal dose of ranavirus. Infected tadpoles exhibited significantly elevated corticosterone levels, more rapid developmental changes, and a greater decrease in body weight relative to controls over 6 days after exposure.

6. Although elevated corticosterone mobilizes resources and enhances immunity, its acceleration of metamorphosis may be maladaptive in response to ranavirus infection, because it can draw energy away from expensive immune responses. These findings provide insight into how the balance of energy between development and immune function may contribute to patterns of ranavirus infection in pre‐metamorphic amphibians.
Community care assessment of exacerbations of chronic obstructive pulmonary disease
Authors: Hutchinson Anastasia F. , Thompson Michelle A. , Brand Caroline A. , Black Jim , Anderson Gary P. , Irving Louis B.
Published: October 2010

hutchinson a.f., thompson m.a., brand c.a., black j., anderson g.p. & irving l.b. (2010)Community care assessment of exacerbations of chronic obstructive pulmonary disease.Journal of Advanced Nursing66(11), 2490–2499.

Aim. The aim of this study was to develop a clinical algorithm to assess chronic obstructive pulmonary disease exacerbation severity in a community setting.

Background. An important aspect of community management of exacerbations is assessing patient safety. Although researchers have investigated risk factors for rapid deterioration, there is a lack of evidence validating clinical measures of exacerbation severity.

Methods. This was a prospective, community‐based cohort study of patients enrolled in the Melbourne Longitudinal Chronic Obstructive Pulmonary Disease Cohort. The outreach team collected data on symptom severity at baseline and exacerbation onset using the Medical Research Council Dyspnoea Scale, St George Quality‐of‐Life Questionnaire and Symptom Severity Index.

Results. Ninety‐two patients were monitored from 2003 to 2005. There were 148 exacerbations: 121 (82%) were treated at home and 27 (17·5%) required hospitalization. An ordinal logistic regression model demonstrated that a combination of chronic obstructive pulmonary disease severity with dyspnoea and wheeze severity at exacerbation onset could differentiate severe from milder episodes [(OR 7·69, 95%CI: 3·9–11·5,P < 0·01), area under the receiver operating characteristics curve 0·75 (95%CI: 0·65–0·86)].

Conclusion. The majority of chronic obstructive pulmonary disease exacerbations can be safely managed in a community setting, but clinical assessment alone may not be sufficient to identify all patients who will develop complications such as respiratory failure. Further research is needed to validate clinical assessment and decision‐making algorithms for community‐management of chronic obstructive pulmonary disease exacerbations.
The optimal cut‐off for predicting large oesophageal varices using transient elastography is disease specific
Authors: Pritchett S. , Cardenas A. , Manning D. , Curry M. , Afdhal N. H.
Published: October 2010

Summary.  The diagnosis of cirrhosis requires screening for oesophageal varices by upper gastrointestinal endoscopy. In many countries, serological tests and elastography are replacing liver biopsy for diagnosing cirrhosis. The aims of this study were to see whether there was an optimal cut‐off of liver stiffness that could predict the presence of large (>F2) oesophageal varices and whether this was disease specific. A total of two hundred and twenty‐two patients with all cause cirrhosis (Child class A) were screened, and 211 had successful elastography and are included in the analysis. Of the patients studied, one hundred and thirty‐two patients had no or small F1 varices and 79 had large varices. Liver stiffness of 19.8 kPa had a negative predictive value of 91% and a positive predictive value of 55% with an area under the curve (AUC) on receiver operating characteristics (ROC) of 0.73 in differentiating between small and large varices. Seven patients with large varices would have been incorrectly classified. In the 157 patients with hepatitis C as the aetiology of cirrhosis, the negative predictive value was 98% and only one patient was misclassified. Liver stiffness was superior in diagnostic accuracy to platelet count in all patients. A liver stiffness of >19.8 kPa could be utilized as a cut‐off for endoscopy and beta blocker utilization, particularly in patients with hepatitis C.
Resource Defence or Exploded Lek? – A Question of Perspective
Authors: Kotrschal Alexander , Taborsky Barbara
Published: October 2010

It becomes increasingly obvious that animal mating systems cannot be classified into distinct categories, but transitions between mating system classes are continuous. Positioning a certain mating system at this continuum is often not straightforward, however. Depending on which characteristic is considered, a mating system may end up at very different positions on this gradient. Here, we explore the potential conflict between mating system classifications that may arise when they are based on different criteria by investigating the mating system of the cichlid fish Simochromis pleurospilus in which males defend small patches of homogeneously distributed food resources (turf algae) vigorously against food competitors, but they allow specific females to use them. We hypothesized that male defence may generate high‐quality feeding patches serving to attract females, and hence male territoriality constitutes a form of courtship. Our field data show that males selectively allow approximately one‐third of the visiting females to feed on their territory and that females preferentially feed in male territories and usually sample several territories successively. As males protect food patches against other algae grazers and guard females from harassment by food competitors, females gain nutritional benefits from visiting male territories. Hence, males appear to generate essential resources for females, which is the key feature of resource‐defence mating systems, although the distributions of resources and of males and females are characteristics of an exploded lek.
A rapid infusion protocol is safe for total dose iron polymaltose: time for change
Authors: Garg M. , Morrison G. , Friedman A. , Lau A. , Lau D. , Gibson P. R.
Published: October 2010

Background:  Intravenous correction of iron deficiency by total dose iron polymaltose is inexpensive and safe, but current protocols entail prolonged administration over more than 4 h. This results in reduced patient acceptance, and hospital resource strain. We aimed to assess prospectively the safety of a rapid intravenous protocol and compare this with historical controls.

Methods:  Consecutive patients in whom intravenous iron replacement was indicated were invited to have up to 1.5 g iron polymaltose by a 58‐min infusion protocol after an initial 15‐min test dose without pre‐medication. Infusion‐related adverse events (AE) and delayed AE over the ensuing 5 days were also prospectively documented and graded as mild, moderate or severe.

Results:  One hundred patients, 63 female, mean age 54 (range 18–85) years were studied. Thirty‐four infusion‐related AE to iron polymaltose occurred in a total of 24 patients – 25 mild, 8 moderate and 1 severe; higher than previously reported for a slow protocol iron infusion. Thirty‐one delayed AE occurred in 26 patients – 26 mild, 3 moderate and 2 severe; similar to previously reported. All but five patients reported they would prefer iron replacement through the rapid protocol again. The presence of inflammatory bowel disease (IBD) predicted infusion‐related reactions (54% vs 14% without IBD, P < 0.001) and the serum C‐reactive protein was higher in those with reactions (P= 0.043).

Conclusion:  Iron polymaltose can be successfully administered using a rapid total dose infusion protocol and was well accepted by patients. It offers significant cost, resource utilization and time benefits for the patient and hospital system.
Analysis of distinct short and prolonged components in rebound spiking of deep cerebellar nucleus neurons
Authors: Sangrey Thomas , Jaeger Dieter
Published: October 2010

Deep cerebellar nucleus (DCN) neurons show pronounced post‐hyperpolarization rebound burst behavior, which may contribute significantly to responses to strong inhibitory inputs from cerebellar cortical Purkinje cells. Thus, rebound behavior could importantly shape the output from the cerebellum. We used whole‐cell recordings in brain slices to characterize DCN rebound properties and their dependence on hyperpolarization duration and depth. We found that DCN rebounds showed distinct fast and prolonged components, with different stimulus dependence and different underlying currents. The initial depolarization leading into rebound spiking was carried by hyperpolarization‐activated cyclic nucleotide‐gated current, and variable expression of this current could lead to a control of rebound latency. The ensuing fast rebound burst was due to T‐type calcium current, as previously described. It was highly variable between cells in strength, and could be expressed fully after short periods of hyperpolarization. In contrast, a subsequent prolonged rebound component required longer and deeper periods of hyperpolarization before it was fully established. We found using voltage‐clamp and dynamic‐clamp analyses that a slowly inactivating persistent sodium current fits the conductance underlying this prolonged rebound component, resulting in spike rate increases over several seconds. Overall, our results demonstrate that multiphasic DCN rebound properties could be elicited differentially by different levels of Purkinje cell activation, and thus create a rich repertoire of potential rebound dynamics in the cerebellar control of motor timing.
Temporal dynamics of sinusoidal and non‐sinusoidal amplitude modulation
Authors: Prendergast Garreth , Johnson Sam R. , Green Gary G. R.
Published: October 2010

Previous behavioural studies in human subjects have demonstrated the importance of amplitude modulations to the process of intelligible speech perception. In functional neuroimaging studies of amplitude modulation processing, the inherent assumption is that all sounds are decomposed into simple building blocks, i.e. sinusoidal modulations. The encoding of complex and dynamic stimuli is often modelled to be the linear addition of a number of sinusoidal modulations and so, by investigating the response of the cortex to sinusoidal modulation, an experimenter can probe the same mechanisms used to encode speech. The experiment described in this paper used magnetoencephalography to measure the auditory steady‐state response produced by six sounds, all modulated in amplitude at the same frequency but which formed a continuum from sinusoidal to pulsatile modulation. Analysis of the evoked response shows that the magnitude of the envelope‐following response is highly non‐linear, with sinusoidal amplitude modulation producing the weakest steady‐state response. Conversely, the phase of the steady‐state response was related to the shape of the modulation waveform, with the sinusoidal amplitude modulation producing the shortest latency relative to the other stimuli. It is shown that a point in auditory cortex produces a strong envelope following response to all stimuli on the continuum, but the timing of this response is related to the shape of the modulation waveform. The results suggest that steady‐state response characteristics are determined by features of the waveform outside of the modulation domain and that the use of purely sinusoidal amplitude modulations may be misleading, especially in the context of speech encoding.
CAN TRADE REALLY HURT? AN EMPIRICAL FOLLOW‐UP ON SAMUELSON'S CONTROVERSIAL PAPER
Authors: BITZER JÜRGEN , GÖRG HOLGER , SCHRÖDER PHILIPP J.H.
Published: October 2010

This paper investigates Samuelson's [Samuelson, P. A. “Where Ricardo and Mill Rebut and Confirm Arguments of Mainstream Economists Supporting Globalization.” Journal of Economic Perspectives, 18(3), 2004, 135–46] argument that technical progress of the trade partner may hurt the home country. We illustrate this prospect in a simple Ricardian model for situations with outward knowledge spillovers. Within this framework Samuelson's Act II effects may occur. Based on industry level panel data for 17 OECD countries for the period 1973–2000 we show econometrically that the outflow of domestic knowledge via exports or foreign direct investment (FDI) to the rest of the world may have a negative impact on industry output in the home country. This is particularly so when exporting to technologically less advanced countries and, more specifically, China. (JEL F10, F11, F14, O30)
AN EXPERIMENTAL ANALYSIS OF DYNAMIC INCENTIVES TO SHARE KNOWLEDGE
Authors: DECK CARY , ERKAL NISVAN
Published: October 2010

Knowledge‐sharing arrangements are an important part of the innovation process as they help firms acquire technological capabilities, shorten development time, and spread risk and cost. A question central to the study of knowledge‐sharing arrangements is the impact of competition on cooperation. While cooperation has the benefit of avoiding duplication, it may have an adverse effect on the competitive advantage of a leading firm. Hence, firms face a difficult challenge during the innovation process while deciding which components of it, if any, to carry out in collaboration with other firms. This paper reports the results of controlled laboratory experiments which identify how the decision to form research joint ventures changes with both relative progress during the R&D process and the intensity of product market competition. The design is based on a modified version of Erkal and Minehart “Optimal Sharing Strategies in Dynamic Games of Research and Development.” Research Paper 1038, University of Melbourne, Department of Economics, 2008. The results indicate that if expected profits are such that the lagging firms always stay in the race, cooperation unravels as firms move forward in the discovery process and as monopoly profits become more attractive. These results are generally consistent with the theoretical predictions. (JEL C91, L24, O30, D81)
WHAT DETERMINES FAMILY STRUCTURE?
Authors: BLAU DAVID M. , van der KLAAUW WILBERT
Published: October 2010

We use data from the 1979 cohort of the National Longitudinal Survey of Youth to estimate the effects of policy and labor market variables on the demographic behaviors that determine children's family structure experiences: union formation and dissolution, and fertility. Male and female wages have substantial effects on family structure for children of black and Hispanic mothers. The tax treatment of children also affects family structure. Welfare reform, welfare benefits, and unilateral divorce had much smaller effects on family structure for the children of this cohort of women. Trends in wages and tax rates explain only a small share of the observed changes in family structure in recent decades. (JEL J12)
The Shc locus regulates insulin signaling and adiposity in mammals
Authors: Tomilov Alexey A. , Ramsey Jon J. , Hagopian Kevork , Giorgio Marco , Kim Kyoungmi M. , Lam Adam , Migliaccio Enrica , Lloyd Kent C. , Berniakovich Ina , Prolla Tomas A. , Pelicci PierGiuseppe , Cortopassi Gino A.
Published: October 2010

Longevity of a p66Shc knockout strain (ShcP) was previously attributed to increased stress resistance and altered mitochondria. Microarrays of ShcP tissues indicated alterations in insulin signaling. Consistent with this observation, ShcP mice were more insulin sensitive and glucose tolerant at organismal and tissue levels, as was a novel p66Shc knockout (ShcL). Increasing and decreasing Shc expression in cell lines decreased and increased insulin sensitivity, respectively – consistent with p66Shc’s function as a repressor of insulin signaling. However, differences between the two p66Shc knockout strains were also observed. ShcL mice were fatter and susceptible to fatty diets, and their fat was more insulin sensitive than controls. On the other hand, ShcP mice were leaner and resisted fatty diets, and their adipose was less insulin sensitive than controls. ShcL and ShcP strains are both highly inbred on the C57Bl/6 background, so we investigated gene expression at the Shc locus, which encodes three isoforms, p66, p52, and p46. Isoform p66 is absent in both strains; thus, the remaining difference to which to attribute the ‘lean’ phenotype is expression of the other two isoforms. ShcL mice have a precise deletion of p66Shc and normal expression of p52 and p46Shc isoforms in all tissues; thus, a simple deletion of p66Shc results in a ‘fat’ phenotype. However, ShcP mice in addition to p66Shc deletion have a fourfold increase in p46Shc expression in white fat. Thus, p46Shc overexpression in fat, rather than p66Shc deletion, is the likely cause of decreased adiposity and reduced insulin sensitivity in the fat of ShcP mice, which has implications for the longevity of the strain.
Extubation in intensive care units in the UK: an online survey
Authors: Hodd Jack , Doyle Alex , Carter Joseph , Albarran John , Young Peter
Published: October 2010

Aim: To determine the current practice among critical care nurses in the UK with regard to airway management during cuff deflation and extubation.

Background: There are a number of techniques used by clinicians to prevent aspiration during cuff deflation and extubation of patients. There are no published clinical studies comparing the different manoeuvres available to clinicians at the time of extubation nor any data to suggest which technique is most commonly used.

Methods: All members of the British Association of Critical Care Nurses with an email address were invited to participate in an online survey.

Results: A total of 533 (29%) nurses from 184 (84%) intensive care unit (ICUs) in the UK completed the survey. Just under half of the sample (n = 258, 48·4%) had more than 10 years of critical care experience and the vast majority (n = 427, 80·1%) worked in general ICUs. The majority of respondents (n = 461, 86·5%) suction the trachea during cuff deflation and extubation. A further 304 (57%) respondents ask patients to cough as part of extubation. Respondents increase the positive end expiratory pressure setting on the ventilator infrequently as part of routine procedure for extubation (n = 7, 1·3%).

Conclusion: The majority of UK critical care nurses either suction the trachea during cuff deflation and extubation of patients and/or simply ask the patient to cough. Further clinical trials are required to identify the most appropriate and safe technique for critically ill patients.
Footwall dip of a core complex detachment fault: thermobarometric constraints from the northern Snake Range (Basin and Range, USA)
Authors: COOPER F. J. , PLATT J. P. , ANCZKIEWICZ R. , WHITEHOUSE M. J.
Published: October 2010

Low‐angle detachment faults are common features in areas of large‐scale continental extension and are typically associated with metamorphic core complexes, where they separate upper plate brittle extension from lower plate ductile stretching and metamorphism. In many core complexes, the footwall rocks have been exhumed from middle to lower crustal depths, leading to considerable debate about the relationship between hangingwall and footwall rocks, and the role that detachment faults play in footwall exhumation. Here, garnet–biotite thermometry and garnet–muscovite–biotite–plagioclase barometry results are presented, together with garnet and zircon geochronology data, from seven locations within metapelitic rocks in the footwall of the northern Snake Range décollement (NSRD). These locations lie both parallel and normal to the direction of footwall transport to constrain the pre‐exhumation geometry of the footwall. To determine P–T gradients precisely within the footwall, the ΔPT method of Worley & Powell (2000) has been employed, which minimizes the contribution of systematic uncertainties to thermobarometric calculations. The results show that footwall rocks reached pressures of 6–8 kbar and temperatures of 500–650 °C, equivalent to burial depths of 23–30 km. Burial depth remains constant in the WNW–ESE direction of footwall transport, but increases from south to north. The lack of a burial gradient in the direction of footwall transport implies that the footwall rocks, which today define a sub‐horizontal datum in the direction of fault transport, also defined a sub‐horizontal datum at depth in Late Cretaceous time. This suggests that the footwall was not tilted about the normal to the fault transport direction during exhumation, and hence that the NSRD did not form as a low‐angle normal fault cutting down through the lower crust. Instead, the following evolution for the northern Snake Range footwall is proposed. (i) Mesozoic contraction caused substantial crustal thickening by duplication and folding of the miogeoclinal sequence, accompanied by upper greenschist to amphibolite facies metamorphism. (ii) About half of the total exhumation was accomplished by roughly coaxial stretching and thinning in Late Cretaceous to Early Tertiary time, accompanied by retrogression and mylonitic deformation. (iii) The footwall rocks were then ‘captured’ from the middle crust along a moderately dipping NSRD that soled into the middle crust with a rolling‐hinge geometry at both upper and lower terminations.
Cone beam imaging: is this the ultimate imaging modality?
Authors: Koong Bernard
Published: October 2010

Abstract:This review article provides an overview of cone beam (CB) imaging technology and its role in orofacial imaging, including comparison with two‐dimensional (2D) radiography and multislice computed tomography (MCT). The radiation dose levels of CB systems are discussed, with reference to those delivered by MCT and common dental 2D views. The large variation in dose levels delivered by CB systems and the importance of using ultra low‐dose CB units are emphasized. Low‐dose MCT protocols can be used. CB and MCT image quality are compared. CB is an essential technique that all dental and orofacial clinicians must be familiar with. Where ultra low‐dose systems and protocols are used, CB imaging should be considered in day‐to‐day clinical practice. However, CB imaging is not the technique of choice in many clinical scenarios. Rather than replacing other modalities, CB imaging complements intraoral 2D radiography, panoramic radiography, MCT and other techniques including magnetic resonance imaging, ultrasound and nuclear medicine. MCT is a much more powerful and flexible modality and presently remains the technique of choice over CB imaging in many clinical scenarios. All radiologic examinations, including CB and MCT, should be comprehensively evaluated in entirety. The responsibilities and the radiological skill levels of clinicians involved in imaging as well as the associated ethical and medico‐legal implications require consideration.

To cite this article: Koong B. Cone beam imaging: is this the ultimate imaging modality?. Clin. Oral Impl. Res.21, 2010; 1201–1208. doi: 10.1111/j.1600‐0501.2010.01996.x
Is There a COPII‐Mediated Membrane Traffic in Chloroplasts?
Authors: Brandizzi Federica
Published: October 2010

COPII proteins facilitate membrane transport from the endoplasmic reticulum (ER) to the Golgi. They are highly conserved, although there are variations in their subcellular localization across plant, animal and yeast cells. Such variations may be needed to suit the unique organization of the ER and Golgi in the different cell systems. Earlier bioinformatics analyses have indicated that the Arabidopsis nuclear genome may encode chloroplast isoforms of the cytosolic trafficking protein machineries, including COPI and COPII, for vesicular transport within chloroplasts. These analyses suggest the intriguing possibility that plants may have evolved or adapted COP‐like proteins to suit membrane trafficking events within specialized organelles. Here, we discuss recent data on the distribution and activity of the product of the At5g18570 locus, which encodes a putative chloroplast isoform of Sar1, the GTPase that regulates COPII assembly on the surface of the ER. Evidence is accumulating that the protein is targeted to the chloroplasts, that it has GTPase activity and that it may have a role in thylakoid membrane development, supporting the possibility that COPII‐like trafficking machinery may be active in chloroplasts.
Uplifting Unbelief
Authors: McLennan Gregor
Published: October 2010

This article analyses three of Taylor's principal theoretical moves: his basic account of secularity and related rejection of secularist ‘subtraction stories’; his comprehension of historico-empirical realities in the light of a sort of philosophy of history; and his presentation of the transcendental quality of the experience of ‘fullness’. Motivated to contest Taylor's framing of the ‘unbeliever’ as spirituality deprived and intellectually complacent, the coherence, content and rhetorical overkill of his argumentation in each of these areas is questioned.
Care staff attitudes and experiences of working with older people with dementia
Authors: Moyle Wendy , Murfield Jenny E , Griffiths Susan G , Venturato Lorraine
Published: October 2010

Aim:  To determine care staff attitudes to dementia, assess levels of job satisfaction and explore how these attitudes and experience may relate to each other.

Methods:  Forty‐nine staff from four long‐term care facilities were surveyed using the Approaches to Dementia Questionnaire and the Staff Experience of Working with Demented Residents Questionnaire.

Results:  Attitudes were positive, focusing most on ‘person‐centred’ care (4.35) as opposed to ‘hopefulness’ (3.66). Job satisfaction was also good, being highest in terms of ‘resident contact’ (2.92) but lowest for work ‘environment’ (2.12). Care staff attitudes to dementia were positively correlated with job satisfaction (r= 0.366, n= 48, P= 0.011), particularly for attitudes focused on ‘person‐centred’ care (r= 0.393, n= 48, P= 0.006).

Conclusions:  Findings suggest an important relationship between care staff attitudes and levels of job satisfaction. More work is needed to specify this relationship.
Powder Synthesis, Sintering Kinetics, and Nickel‐Activated Pressureless Sintering of Ti3AlC2
Authors: Panigrahi Bharat Bhooshan , Gracio Jose J. , Chu Min‐Cheol , Cho Seong‐Jai , Reddy N. Subba
Published: October 2010

This work aims to produce Ti3AlC2 powder via a new route that consists of two‐step processes, and studies the sintering kinetics and effect of nickel addition on the pressureless sintering behavior of Ti3AlC2 powder. Ti3AlC2 powder of about 5 μm was produced using TiCx and Al powder. Relative density of about 97.6% was achieved using 1 wt% nickel as a sintering aid. Ti3AlC2 powder shows two different activation energies (AE) of sintering, 347 ± 4 and 183 ± 8 kJ/mol at lower and higher temperature ranges, respectively. These AE were found to be matching closely with the AE of Al diffusion in the Ti–Al binary system reported in the literature, indicating that the sintering of ternary Ti3AlC2 ceramic was controlled by the diffusion of Al atoms. When nickel is added, Ni reacts with Ti3AlC2, tends to decompose it, and forms Ni‐based compounds and liquid phase. Nickel was found to suppress the grain growth of Ti3AlC2 significantly. Sintered sample exhibited a Vickers hardness of 3.2 GPa at a load of 10 N.
Propagation of a partial incomplete ossification of the humeral condyle in an American cocker spaniel
Authors: Witte P. G. , Bush M. A. , Scott H. W.
Published: October 2010

A hypoattenuating lesion in the left humeral condyle of an American cocker spaniel consistent with partial incomplete ossification of the humeral condyle was observed on computed tomography. Left forelimb lameness developed over the following three weeks at which time repeat computed tomography examination confirmed propagation of the lesion. Lameness resolved following placement of a transcondylar positional screw, suggesting that lameness was secondary to condylar instability. To the authors' knowledge this is the first report of propagation of an intracondylar lesion in a dog.
Total hip arthroplasty in the horse: Overview, technical considerations and case report
Authors: Huggons N. , Andrea R. , Grant B. , Duncan C.
Published: October 2010

A total hip arthroplasty was performed in a small equine patient with a history of traumatic subluxation of the coxofemoral joint during infancy resulting in severe degenerative changes to the femoral head and acetabulum. The transtrochanteric surgical approach used to expose the joint, as well as the technique and technology to replace the joint, is described. The patient was weightbearing within 24 h of surgery and walking successfully without sling support 4 days post operatively. On the fifth post operative day, the patient abruptly deteriorated and succumbed to multiple pulmonary thromboemboli and a jejunal infarction. Despite the systemic complications in this case, the initial short‐term success of this treatment option indicate its potential to be considered in the management of equine coxofemoral joint disease/lesions.
Penile and preputial tumours in the horse: Literature review and proposal of a standardised approach
Authors: Van Den TOP J. G. B. , ENSINK J. M. , GRÖNE A. , KLEIN W. R. , BARNEVELD A. , Van WEEREN P. R.
Published: October 2010

Penile and preputial tumours are not uncommon in the horse, but can cause discomfort and lead to serious complications. Several types of tumour of the male external genitalia have been described. The most common type is the squamous cell carcinoma (SCC), which is found mainly in older horses. Reports of a breed predilection for penile tumour formation are equivocal, but castration, coat colour, poor hygiene and various infectious agents have all been suggested to predispose to the development of some types of tumour (e.g. SCC, papilloma and melanoma).

Careful assessment of the primary tumour is an important first step in the design of an optimal treatment protocol. Invasiveness, differentiation grade, tumour size and presence of metastases are all relevant to the decision to pursue additional diagnostic procedures or specific treatment options.

To date, no standard protocol has been reported for the approach to penile tumours in the horse and treatments range from minimally invasive therapies (e.g. topical use of 5‐fluorouracil) to radical surgical interventions (e.g.en bloc penile and preputial resection with penile retroversion). Completeness of removal of the neoplasm and therefore risk of recurrence is highly dependant on the type of therapy chosen. However, the size and histopathological features of the primary tumour are also important factors with respect to the likelihood of recurrence.

This review describes the most common penile and preputial neoplasms in the horse, and outlines a standard protocol aimed at arriving at a specific diagnosis and tailoring the therapeutic approach accordingly.
Mcl-1 Is Essential for Germinal Center Formation and B Cell Memory
Authors: Vikstrom Ingela , Carotta Sebastian , Lüthje Katja , Peperzak Victor , Jost Philipp J. , Glaser Stefan , Busslinger Meinrad , Bouillet Philippe , Strasser Andreas , Nutt Stephen L. , Tarlinton David M.
Published: October 2010

Germinal Center Survival

The humoral immune response, which comprises antibodies secreted by B lymphocytes, is critical for protection against pathogens. In response to infection, B lymphocytes proliferate and differentiate into antibody-producing effector cells. After an infection clears, a small number of cells persist as memory B cells; however, the survival signals that regulate effector and memory B lymphocyte generation are not well understood. To probe this question,

Vikstrom
et al.

(p.
1095
, published online 7 October) deleted prosurvival genes in activated, antigen-specific B cells during a T lymphocyte–dependent immune response in mice. They found that a specific programmed cell death inhibitor, known as Mcl1, was required for the formation of germinal-center B cells (an effector cell population) and memory B cells but not for their maintenance. Dysregulation of the B cell responses mediated by Mcl1 may be a trigger for lymphomagenesis.
Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists
Authors: Wu Beili , Chien Ellen Y. T. , Mol Clifford D. , Fenalti Gustavo , Liu Wei , Katritch Vsevolod , Abagyan Ruben , Brooun Alexei , Wells Peter , Bi F. Christopher , Hamel Damon J. , Kuhn Peter , Handel Tracy M. , Cherezov Vadim , Stevens Raymond C.
Published: October 2010

Regulating Migration

The migration of cells around the body is an important factor in cancer development and the establishment of infection. Movement is induced by small proteins called chemokines, and so for a specific function, migration is controlled by a relevant chemokine binding to its respective receptor. This family of receptors is known as guanine (G) protein–coupled receptors, which span cell membranes to mediate between external signals from chemokines and internal mechanisms. The chemokine receptor CXCR4 is implicated in many types of cancer and in infection, and

Wu
et al.

(p.
1066
, published online 7 October; see the Report by

Chien
et al.

) report on a series of crystal structures obtained for CXCR4 bound to small molecules. In every case, the same homodimer structure was observed, suggesting that the interface is functionally relevant. These structures offer insights into the interactions between CXCR4 and its natural chemokine, as well as with the virus HIV-1.
γ-Secretase Gene Mutations in Familial Acne Inversa
Authors: Wang Baoxi , Yang Wei , Wen Wen , Sun Jing , Su Bin , Liu Bo , Ma Donglai , Lv Dan , Wen Yaran , Qu Tao , Chen Min , Sun Miao , Shen Yan , Zhang Xue
Published: October 2010

Mutations causing a rare skin disease reveal a signaling pathway that is a drug target for Alzheimer’s disease.
Retrospective study of clinical complications occurring after arterial punctures in 111 dogs
Authors: Shiroshita Y. , Tanaka R. , Shibazaki A. , Yamane Y.
Published: October 2010

The clinical complications occurring after 111 dogs had undergone arterial punctures were reviewed in relation to the dogs' breed, bodyweight, age, sex and underlying diseases. Seven of the dogs had moderate to extensive ecchymoses, which were significantly more common in dogs under 3‐5 kg in bodyweight and in dogs with disorders of the cardiovascular system.
Clinical, pathological and epidemiological findings in three outbreaks of ovine protozoan myeloencephalitis
Authors: Caldow G. L. , Gidlow J. R. , Schock A.
Published: October 2010

Ovine protozoan myeloencephalitis is a disease of sheep associated with the apicomplexan protozoan Sarcocystis tenella. This paper describes the clinical, pathological and epidemiological findings in three affected flocks from a well‐defined geographical area. Clinical signs were restricted to sheep under one year old in their first winter and were first observed at least 42 days after they had been moved off the hill grazing areas to low ground pasture, or after they were given conserved forage. The findings are discussed in relation to the timescale of the life cycle of S tenella and it is suggested that clinical disease was precipitated by the change from a low level of exposure to infection on the hill to a high level of exposure through contaminated pasture or forage. Possible preventive strategies are discussed.
Self‐selection of the analgesic drug carprofen by lame broiler chickens
Authors: Danbury T. C. , Weeks C. A. , Waterman‐Pearson A. E. , Kestin S. C. , Chambers J. P.
Published: October 2010

Lame and sound broilers, selected from commercial flocks, were trained to discriminate between different coloured feeds, one of which contained carprofen. The two feeds were then offered simultaneously and the birds were allowed to select their own diet from the two feeds. In an initial study to assess the most appropriate concentration of drug, the plasma concentrations of carprofen were linearly related to the birds' dietary intake. The walking ability of lame birds was also significantly improved in a dose‐dependent manner and lame birds tended to consume more analgesic than sound birds. In a second study, in which only one concentration of analgesic was used, lame birds selected significantly more drugged feed than sound birds, and that as the severity of the lameness increased, lame birds consumed a significantly higher proportion of the drugged feed.