bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidermal growth factor receptor lacking C‐terminal autophosphorylation sites retains signal transduction and high sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor
Authors: Maegawa Mari , Arao Tokuzo , Yokote Hideyuki , Matsumoto Kazuko , Kudo Kanae , Tanaka Kaoru , Kaneda Hiroyasu , Fujita Yoshihiko , Ito Fumiaki , Nishio Kazuto
Published: January 2009

Constitutively active mutations of epidermal growth factor receptor (EGFR) (delE746_A750) activate downstream signals, such as ERK and Akt, through the phosphorylation of tyrosine residues in the C‐terminal region of EGFR. These pathways are thought to be important for cellular sensitivity to EGFR tyrosine kinase inhibitors (TKI). To examine the correlation between phosphorylation of the tyrosine residues in the C‐terminal region of EGFR and cellular sensitivity to EGFR TKI, we used wild‐type (wt) EGFR, as well as the following constructs: delE746_A750 EGFR; delE746_A750 EGFR with substitution of seven tyrosine residues to phenylalanine in the C‐terminal region; and delE746_A750 EGFR with a C‐terminal truncation at amino acid 980. These constructs were transfected stably into HEK293 cells and designated HEK293/Wt, HEK293/D, HEK293/D7F, and HEK293/D‐Tr, respectively. The HEK293/D cells were found to be 100‐fold more sensitive to EGFR TKI (AG1478) than HEK293/Wt. Surprisingly, the HEK293/D7F and HEK293/D‐Tr cells, transfected with EGFR lacking the C‐terminal autophosphorylation sites, retained high sensitivity to EGFR TKI. In these three high‐sensitivity cells, the ERK pathway was activated without ligand stimulation, which was inhibited by EGFR TKI. In addition, although EGFR in the HEK293/D7F and HEK293/D‐Tr cells lacked significant tyrosine residues for EGFR signal transduction, phosphorylation of Src homology and collagen homology (Shc) was spontaneously activated in these cells. Our results indicate that tyrosine residues in the C‐terminal region of EGFR are not required for cellular sensitivity to EGFR TKI, and that an as‐yet‐unknown signaling pathway of EGFR may exist that is independent of the C‐terminal region of EGFR. (Cancer Sci 2009; 100: 552–557)
Human Nei‐like protein NEIL3 has AP lyase activity specific for single‐stranded DNA and confers oxidative stress resistance in Escherichia coli mutant
Authors: Takao Masashi , Oohata Yoshitsugu , Kitadokoro Kengo , Kobayashi Kumiko , Iwai Shigenori , Yasui Akira , Yonei Shuji , Zhang Qiu‐Mei
Published: January 2009

Oxidative base damage leads to alteration of genomic information and is implicated as a cause of aging and carcinogenesis. To combat oxidative damage to DNA, cells contain several DNA glycosylases including OGG1, NTH1 and the Nei‐like proteins, NEIL1 and NEIL2. A third Nei‐like protein, NEIL3, is composed of an amino‐terminal Nei‐like domain and an unknown carboxy‐terminal domain. In contrast to the other well‐described DNA glycosylases, the DNA glycosylase activity and in vivo repair function of NEIL3 remains unclear. We show here that the structural modeling of the putative NEIL3 glycosylase domain (1–290) fits well to the known Escherichia coli Fpg crystal structure. In spite of the structural similarity, the recombinant NEIL3 and NEIL3(1–290) proteins do not cleave any of several test oligonucleotides containing a single modified base. Within the substrates, we detected AP lyase activity for single‐stranded (ss) DNA but double‐stranded (ds) DNA. The activity is abrogated completely in mutants with an amino‐terminal deletion and at the zinc‐finger motif. Surprisingly, NEIL3 partially rescues an E. coli nth nei mutant from hydrogen peroxide sensitivity. Taken together, repair of certain base damage including base loss in ssDNA may be mediated by NEIL3.
A new preparation method to study fresh plant structures with X‐ray computed tomography
Authors: LEROUX O. , LEROUX F. , BELLEFROID E. , CLAEYS M. , COUVREUR M. , BORGONIE G. , VAN HOOREBEKE L. , MASSCHAELE B. , VIANE R.
Published: January 2009

Since the development of X‐ray computed tomography as a medical diagnostic tool, it was adapted and extended for many scientific applications, including plant structure research. As for many biological studies, sample preparation is of major importance to obtain good‐quality images. Therefore, we present a new preparation method for fresh material which includes critical point drying and heavy metal staining. This technique enhances the contrast of fresh tissues, prevents artefacts such as tissue compression, and requires no embedding.
Views on nurse prescribing: a survey of community mental health nurses in the Republic of Ireland
Authors: WELLS J. , BERGIN M. , GOONEY M. , JONES A.
Published: January 2009

A nurse prescribing scheme has recently been implemented within the Republic of Ireland. This paper reports on the views of community mental health nurses on nurse prescribing just prior to the implementation of the scheme. Data were gathered through a 13‐item questionnaire administered to 103 members of the Association of Community Mental Health Nurses in Ireland. Results indicated a distinct difference of view between male and female community mental health nurses, with female nurses having greater reservations towards the desirability of nurse prescribing in relation to educational preparation and impact on professional relationships. Overall, only 17% of respondents favoured being supervised in their prescribing practice by their consultant psychiatrist. The paper concludes that there is ambivalence towards prescribing in this important group of nurses which may need to be taken into account if nurse prescribing is to be successfully implemented within the Irish mental health service context.
Associations between birthweight and weight change during infancy and later childhood, and systolic blood pressure at age 15 years: the COMPASS study
Authors: Kark Malin , Tynelius Per , Rasmussen Finn
Published: January 2009

Inconsistent findings have been reported on associations between postnatal weight change with later blood pressure. This study analysed the impact of weight change during fetal life, infancy and later childhood on systolic blood pressure (SBP) in adolescence. A longitudinal population‐based study was conducted in Stockholm, Sweden. Weight, length at birth and gestational age were extracted from the Medical Birth Register, weight and height in childhood was collected from child health records, and body size and SBP were measured during a health examination at 15 years of age. Complete data on 2438 individuals were analysed using linear regression.

In fully adjusted models SBP increased 0.99 mmHg [95% confidence interval (CI), 0.27, 1.71] in girls and 1.02 mmHg [0.31, 1.73] in boys per 1 SD increase in weight during the first year of life. The effect on SBP of weight change from 10 to 15 years among boys was 3.70 mmHg [2.67, 4.73] and among girls 1.30 mmHg [0.38, 2.22] per 1 SD increase in weight. Weight gain in infancy and later childhood was positively associated with SBP at age 15 years, while birthweight showed a weaker inverse association with SBP. No apparent effect of weight gain from 1 to 10 years of age was seen. Degree of weight change in infancy was equally important for SBP in both boys and girls, while growth during puberty showed a stronger association with SBP among boys than among girls.
Immunopathogenesis of human schistosomiasis
Authors: BURKE M. L. , JONES M. K. , GOBERT G. N. , LI Y. S. , ELLIS M. K. , McMANUS D. P.
Published: January 2009

Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4+Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL‐4 and IL‐13 drive this response, whereas IL‐10, IL13Rα2, IFN‐γ and a subset of regulatory T‐cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T‐cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti‐pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.
Contact allergies in haemodialysis patients: a prospective study of 75 patients
Authors: Gaudy‐Marqueste C. , Jouhet C. , Castelain M. , Brunet P. , Berland Y. , Grob J. J. , Richard M. A.
Published: January 2009

Background:  Haemodialysis exposes patients to many potentially sensitizing allergens.

Objectives:  The primary objective of this study was to evaluate the prevalence of delayed hypersensitivity in a population of haemodialysis patients. Secondary objectives were to identify the possible risk factors for contact sensitization and to propose a series of skin tests adapted to haemodialysis patients.

Methods:  A prospective monocentric study was carried out in a nonselected population of haemodialysis patients. For each patient, medical history of atopy and allergic contact dermatitis, ongoing treatments (including topical ones), presence of eczema at the site of vascular access for haemodialysis were recorded. Allergological investigation included delayed hypersensitivity tests (European Environmental and Contact Dermatitis Research Group battery, tests GERDA, additional list and a battery of antiseptics and other dialysis‐specific allergens) and latex skin prick test.

Results:  Seventy‐five patients (41 men, 34 women, mean age of 65 years old), with a mean 3.8 years under dialysis, were included. Nineteen patients (25%) had at least one positive skin test and 13 (17%) a positive patch test to at least one allergen relative to dialysis process including eight tests to lidocaine–prilocaine cream and three to povidone–iodine. Tests results seemed clinically relevant since nine patients had localized pruritus at the fistula site and six patients active eczema around it.

Conclusion:  Contact sensitizations are frequent in haemodialysis patients and are linked to vascular access conditioning especially the use of lidocaine–prilocaine cream. Designing a specific test battery could help to diagnose the potential allergens and subsequently to give advice to avoid contact with sensitizing agents.
Population pharmacokinetics of sevoflurane in conjunction with the AnaConDa®: toward target‐controlled infusion of volatiles into the breathing system
Authors: ENLUND M. , KIETZMANN D. , BOUILLON T. , ZÜCHNER K. , MEINEKE I.
Published: January 2009

Background: The Anesthetic Conserving Device (AnaConDa®) uncouples delivery of a volatile anesthetic (VA) from fresh gas flow (FGF) using a continuous infusion of liquid volatile into a modified heat–moisture exchanger capable of adsorbing VA during expiration and releasing adsorbed VA during inspiration. It combines the simplicity and responsiveness of high FGF with low agent expenditures. We performed in vitro characterization of the device before developing a population pharmacokinetic model for sevoflurane administration with the AnaConDa®, and retrospectively testing its performance (internal validation).

Materials and methods: Eighteen females and 20 males, aged 31–87, BMI 20‐38, were included. The end‐tidal concentrations were varied and recorded together with the VA infusion rates into the device, ventilation and demographic data. The concentration–time course of sevoflurane was described using linear differential equations, and the most suitable structural model and typical parameter values were identified. The individual pharmacokinetic parameters were obtained and tested for covariate relationships. Prediction errors were calculated.

Results: In vitro studies assessed the contribution of the device to the pharmacokinetic model. In vivo, the sevoflurane concentration–time courses on the patient side of the AnaConDa® were adequately described with a two‐compartment model. The population median absolute prediction error was 27% (interquartile range 13–45%).

Conclusion: The predictive performance of the two‐compartment model was similar to that of models accepted for TCI administration of intravenous anesthetics, supporting open‐loop administration of sevoflurane with the AnaConDa®. Further studies will focus on prospective testing and external validation of the model implemented in a target‐controlled infusion device.
Effects of PEEP levels following repeated recruitment maneuvers on ventilator‐induced lung injury
Authors: KO S.‐C. , ZHANG H. , HAITSMA J. J. , CHENG K.‐C. , LI C.‐F. , SLUTSKY A. S.
Published: January 2009

Background: Different levels of positive end‐expiratory pressure (PEEP) with and without a recruitment maneuver (RM) may have a significant impact on ventilator‐induced lung injury but this issue has not been well addressed.

Methods: Anesthetized rats received hydrochloric acid (HCl, pH 1.5) aspiration, followed by mechanical ventilation with a tidal volume of 6 ml/kg. The animals were randomized into four groups of 10 each: (1) high PEEP at 6 cm H2O with an RM by applying peak airway pressure at 30 cm H2O for 10 s every 15 min; (2) low PEEP at 2 cm H2O with RM; (3) high PEEP alone; and (4) low PEEP alone.

Results: The mean arterial pressure and the amounts of fluid infused were similar in the four groups. Application of the higher PEEP improved oxygenation compared with the lower PEEP groups (P<0.05). The lung compliance was better reserved, and the systemic cytokine responses and lung wet to dry ratio were lower in the high PEEP than in the low PEEP group for a given RM (P<0.05).

Conclusions: The use of a combination of periodic RM and the higher PEEP had an additive effect in improving oxygenation and pulmonary mechanics and attenuation of inflammation.
Iatrogenic systemic air embolism treated with hyperbaric oxygen therapy
Authors: JØRGENSEN T. B. , SØRENSEN A. M. , JANSEN E. C.
Published: January 2009

Air embolism is a rare and potentially severe complication of surgical and invasive procedures. Emboli large enough to produce symptoms require immediate treatment because of the risk of ‘gas lock’ in the right side of the heart and subsequent circulatory failure. If air is transmitted to the arterial circulation through a shunt, it may cause cerebral emboli with neurological symptoms. We present two cases with venous air emboli and concurrent cerebral arterial emboli. Both patients were successfully treated with hyperbaric oxygen therapy.
Variation of Acoustic Courtship Signals in Insects and Amphibians: No Evidence for Bimodality, but Identical Dependence on Duration
Authors: Reinhold Klaus
Published: January 2009

In an influential review, acoustic courtship traits of frogs were classified into the two categories, static and dynamic traits, based on their coefficients of variation and female preference functions. As stabilizing selection can be expected to diminish phenotypic variation, static traits showing comparatively low variation were assumed to be mainly influenced by stabilizing selection through female choice. The more variable dynamic traits on the other hand were proposed to be under directional or less severe selection. Such bimodality in variation would be very valuable, as the pattern of selection could be predicted from signal variability. To examine whether a bimodal pattern of signal variation is generally found in acoustic advertisement signals, I reviewed the literature for available and reliable data for insects and anurans. I found no evidence of bimodality, but detected that coefficients of variation increased with signal duration in accordance with a power law. This relationship between duration and variability seems to be virtually identical in both insects and amphibians. Moreover, such a dependence of the extent of variation on the examined time window seems to be a general pattern, since temporal variation in action potential density, stock market prices and time perception also show a similar pattern.
A Statistical Modelling Approach to the Occurrence and Timing of Reconciliation in Wild Japanese Macaques
Authors: Majolo Bonaventura , Ventura Raffaella , Koyama Nicola F.
Published: January 2009

In various social species, animals have been observed to share friendly relationships with some group members and to resolve conflicts through reconciliation, the exchange of affiliative behaviour soon after a conflict that functions to restore the relationship between the former opponents. The valuable relationship hypothesis predicts that reconciliation should be observed more often after conflicts between friends. Friendly relationships can be described by three dimensions (i.e. value, security and compatibility); however, research into the relative importance of these dimensions for the occurrence of reconciliation is sparse. Moreover, reconciliation may depend on factors other than the social relationship between opponents including, for example, their social status or the context of the conflict. Our study aimed at analysing which factors are important determinants of reconciliation and at testing the valuable relationship hypothesis, by analysing the relative effects of relationship value, security and compatibility on the occurrence and timing of reconciliation. We collected data on two troops of wild Japanese macaques living on Yakushima Island, Japan, and selected the best predicting variables of reconciliation using linear mixed models. Our results show that reconciliation occurs more frequently, and earlier, after conflicts between opponents who exchange a higher percentage of grooming. Two additional variables related to relationship security and value were selected in the best models: frequency of aggression and of approaches resulting in tolerated co‐feeding. Among the variables not related to relationship quality, distance between opponents at the end of the conflict, kinship, sex of the opponents and context of conflict (i.e. during feeding or social time) were included in our models. Our findings support the valuable relationship hypothesis and, in particular, highlight that the fitness‐related benefits of social relationships (i.e. the relationship value) are important determinants of the evolution of friendly relationships and reconciliation.
Calls in the Forest: A Comparative Approach to How Bats Find Tree Cavities
Authors: Ruczyński Ireneusz , Kalko Elisabeth K. V. , Siemers Björn M.
Published: January 2009

Although tree cavities are a particularly critical resource for forest bats, how bats search for and find new roosts is still poorly known. Building on a recent study on the sensory basis of roost finding in the noctule (Ruczynski et al. 2007), here we take a comparative approach to how bats find roosts. We tested the hypothesis that species’ flight abilities and echolocation call characteristics play important roles in how well and by which cues bats find new tree roosts. We used the very manoeuvrable, faintly echolocating brown long‐eared bat (Plecotus auritus) and the less manoeuvrable, louder Daubenton’s bat (Myotis daubentonii) as study species. The species are sympatric in European temperate forests and both roost in tree cavities. We trained bats in short‐term captivity to find entrances to tree cavities and experimentally manipulated the sensory cues available to them. In both species, cue type influenced the search time for successful cavity detection. Visual, olfactory and temperature cues did not improve the bats’ performance over the performance by echolocation alone. Eavesdropping on conspecific echolocation calls played back from inside the cavity decreased search time in Daubenton’s bat (M. daubentonii), underlining the double function of echolocation signals – orientation and communication. This was not so in the brown long‐eared bat (P. auritus) that has low call amplitudes. The highly manoeuvrable P. auritus found cavities typically from flight and the less manoeuvrable M. daubentonii found more entrances during crawling. Comparison with the noctule data from Ruczyński et al. (2007) indicates that manoeuvrability predicts the mode of cavity search. It further highlights the importance of call amplitude for eavesdropping and cavity detection in bats.
Use of questionnaire infeasibility in order to detect cognitive disorders: Example of the Center for Epidemiologic Studies Depression Scale in psychiatry settings
Authors: Nishiyama Takeshi , Ozaki Norio , Iwata Nakao
Published: January 2009

Aim:  To examine the extent to which cognitive disorders influenced the feasibility and accuracy of both the 20‐item and the 10‐item Center for Epidemiologic Studies Depression Scale (CES‐D).

Methods:  Cross‐sectional analyses of 223 first‐visit patients in a psychiatric clinic and 108 patients in a psychiatric department in a general hospital were conducted. To assess the influence of age, gender, and the presence of cognitive disorders on the feasibility of both versions of the CES‐D, multiple logistic regression was performed with feasibility per se as the dummy dependent variable. In order to assess the accuracy of the CES‐D, receiver operating characteristic (ROC) analysis was performed.

Results:  The infeasibility of both types of CES‐D were so strongly associated with the presence of cognitive disorders that it can be used as an indicator of cognitive impairment. Moreover, the 10‐item CES‐D had almost as acceptable an internal consistency reliability as the 20‐item CES‐D in the study settings.

Conclusions:  Information obtained from both versions of the CES‐D could be utilized fully, using infeasibility as an indicator of cognitive disorders, in psychiatry settings. Other screening instruments with as heavy a cognitive load as the CES‐D can also be used in the same manner as an indicator of cognitive disorders to save the need for instruments specifically designed for dementia. Such usage can decrease the burden on both the respondent and the clinician in clinical practice.
Neurostructural imaging findings in children with post‐traumatic stress disorder: Brief review
Authors: Jackowski Andrea Parolin , De Araújo Celia Maria , De Lacerda Acioly Luiz Tavares , De Jesus Mari Jair , Kaufman Joan
Published: January 2009

Child maltreatment has been associated with different psychiatric disorders. Studies on both animals and humans have suggested that some brain areas would be directly affected by severe psychological trauma. The pathophsysiology of post‐traumatic stress disorder (PTSD) appears to be related to a complex interaction involving genetic and environmental factors. Advanced neuroimaging techniques have been used to investigate neurofunctional and neurostructural abnormalities in children, adolescents, and adults with PTSD. This review examined structural brain imaging studies that were performed in abused and traumatized children, and discusses the possible biological mechanisms involved in the pathophysiology of PTSD, the implications and future directions for magnetic resonance imaging (MRI) studies. Published reports in refereed journals were reviewed by searching Medline and examining references of the articles related to structural neuroimaging of PTSD. Structural MRI studies have been performed in adults and children to evaluate the volumetric brain alterations in the PTSD population. In contrast with studies involving adults, in which hippocampus volumetric reduction was the most consistent finding, studies involving children and adolescents with PTSD have demonstrated smaller medial and posterior portions of the corpus callosum.
Maintaining network activity in submerged hippocampal slices: importance of oxygen supply
Authors: Hájos Norbert , Ellender Tommas J. , Zemankovics Rita , Mann Edward O. , Exley Richard , Cragg Stephanie J. , Freund Tamás F. , Paulsen Ole
Published: January 2009

Studies in brain slices have provided a wealth of data on the basic features of neurons and synapses. In the intact brain, these properties may be strongly influenced by ongoing network activity. Although physiologically realistic patterns of network activity have been successfully induced in brain slices maintained in interface‐type recording chambers, they have been harder to obtain in submerged‐type chambers, which offer significant experimental advantages, including fast exchange of pharmacological agents, visually guided patch‐clamp recordings, and imaging techniques. Here, we investigated conditions for the emergence of network oscillations in submerged slices prepared from the hippocampus of rats and mice. We found that the local oxygen level is critical for generation and propagation of both spontaneously occurring sharp wave–ripple oscillations and cholinergically induced fast oscillations. We suggest three ways to improve the oxygen supply to slices under submerged conditions: (i) optimizing chamber design for laminar flow of superfusion fluid; (ii) increasing the flow rate of superfusion fluid; and (iii) superfusing both surfaces of the slice. These improvements to the recording conditions enable detailed studies of neurons under more realistic conditions of network activity, which are essential for a better understanding of neuronal network operation.
Motion direction tuning in human visual cortex
Authors: Mercier Manuel , Schwartz Sophie , Michel Christoph M. , Blanke Olaf
Published: January 2009

A number of electrophysiological studies have been conducted in recent years in order to clarify the dynamics of visual motion processing in the human brain. Using a variety of event‐related potential (ERP) measures, several parameters such as onset, offset, contrast and velocity have been investigated, while a critical aspect of visual motion, that of direction, has received less attention. Here we used multichannel electroencephalography and distributed source localization to study brain activity for different directions of visual motion using random dot stimuli. Our data reveal differential extrastriate activation at 164–226 ms after motion onset that coded for motion direction with different ERP maps and underlying electrical generators for each tested direction. This activation was paralleled initially (164–186 ms) by a distinct extrastriate activation encoding whether the motion stimulus consisted of directed motion stimuli (as above) or contained undirected incoherent motion (control stimulus). Application of a linear inverse solution localized the brain activity for each tested motion direction to distinct brain regions within the same larger network of extrastriate brain regions. These regions included bilateral temporo‐occipital and bilateral parieto‐occipital cortex. The present data in healthy subjects are compatible with extrastriate activity that is tuned to different directions of visual motion. This extends previous clinical data and suggests the presence of distributed macroscopic motion direction tuning in primate extrastriate cortex that may complement the classical microscopic motion tuning at the columnar level.
The development of melanopsin‐containing retinal ganglion cells in mice with early retinal degeneration
Authors: Ruggiero Linda , Allen Charles N. , Lane Brown R. , Robinson David W.
Published: January 2009

In mammals, the neuronal pathways by which rod and cone photoreceptors mediate vision have been well documented. The roles that classical photoreceptors play in photoentrainment, however, have been less clear. In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin project directly to the suprachiasmatic nucleus of the hypothalamus, the site of the circadian clock, and thereby contribute to non‐image‐forming responses to light. Classical photoreceptors are not necessary for photoentrainment as loss of rods and cones does not eliminate light entrainment. Conflicting evidence arose, however, when attenuated phase‐shifting responses were observed in the retinal‐degenerate CBA/J mouse. In this study, we examined the time course of retinal degeneration in CBA/J mice and used these animals to determine if maturation of the outer retina regulates the morphology, number and distribution of ipRGCs. We also examined whether degeneration during the early development of the outer retina can alter the function of the adult circadian system. We report that dendritic stratification and distribution of ipRGCs was unaltered in mice with early retinal degeneration, suggesting that normal development of the outer retina was not necessary for these processes. We found, however, that adult CBA/J mice have greater numbers of ipRGCs than controls, implicating a role for the outer retinal photoreceptors in regulating developmental cell death of ipRGCs.
Individual variations of serum testosterone in patients with prostate cancer receiving androgen deprivation therapy
Authors: Morote Juan , Planas Jacques , Salvador Carlos , Raventós Carles X. , Catalán Roberto , Reventós Jaume
Published: January 2009

OBJECTIVE

To analyse individual variations in serum testosterone level, the cumulative rate of ‘breakthrough’ increases over castrate levels, and to evaluate whether the increases can be predicted.

PATIENTS AND METHODS

Serum testosterone levels were determined every 6 months over 3 years in 73 consecutive patients with prostate cancer who were medically castrated, prospectively enrolled in a single tertiary academic centre. Patients recruited for this study were being treated with a 3‐monthly depot of luteinizing hormone‐releasing hormone agonist over 6–48 months. Serum testosterone was measured using a chemiluminescent assay with a lower sensitivity level of 15 ng/dL and interassay coefficient of variation of 25% at low testosterone concentrations.

RESULTS

Individual variations could not be explained by the interassay variation coefficient in 26% of the patients. The rate of breakthrough increases >50 ng/dL increased from 12.3% at the first determination to 24.7% at the third, then remaining stable. The rate of breakthrough increases of 20–50 ng/dL increased from 27.4% at the first determination to 31.5% at the second, and then remained stable. A first determination of <20 ng/dL provided an 11.4% probability for future increases of >50 ng/dL, with a 5.7% probability if two consecutive determinations were <20 ng/dL and a null probability when three consecutive determinations were <20 ng/dL.

CONCLUSIONS

Individual variations in serum testosterone level cannot be explained by the coefficient of variation of the assay in a quarter of patients who are medically castrated. Breakthrough increases over castrate levels increase over time and those of >50 ng/dL can be predicted from the previous levels.
Chemosensitization of gemcitabine‐resistant human bladder cancer cell line both in vitro and in vivo using antisense oligonucleotide targeting the anti‐apoptotic gene, clusterin
Authors: Muramaki Mototsugu , So Alan , Hayashi Norihiro , Sowery Richard , Miyake Hideaki , Fujisawa Masato , Gleave Martin E.
Published: January 2009

OBJECTIVE

To characterize changes in clusterin (sCLU‐2) expression in bladder cancer cells after continuous treatment with gemcitabine and to determine whether knockdown of sCLU‐2 can re‐introduce sensitivity of gemcitabine‐resistant cells to treatment with gemcitabine.

MATERIALS AND METHODS

A human bladder cancer cell line, UM‐UC‐3, was continuously exposed to increasing doses of gemcitabine in vitro, and a gemcitabine‐resistant cell line UM‐UC‐3R was developed. The role of sCLU‐2 in chemoresistant phenotype acquired in both in vitro and in vivo was then analysed using antisense oligonucleotide targeting the sCLU‐2 gene (OGX‐011).

RESULTS

Treatment of parental UM‐UC‐3 cells (UM‐UC‐3P) with gemcitabine induced transient up‐regulation of sCLU‐2 protein. There was a sustained increase in sCLU‐2 expression levels in UM‐UC‐3R compared with UM‐UC‐3P cells (6.4‐fold). Treatment of UM‐UC‐3R cells with OGX‐011 resulted in a dose‐dependent and sequence‐ specific inhibition in sCLU‐2 expression. Furthermore, OGX‐011 chemo‐sensitized UM‐UC‐3R cells to gemcitabine in vitro with a reduction in the concentration that reduces the effect by 50% (IC50) from 100 nm to 10 nm. Tumour volume and the incidence of metastasis in nude mice injected with UM‐UC‐3R cells was significantly greater than those of nude mice injected with UM‐UC‐3P cells; however, systemic administration of OGX‐011 plus a low dose of gemcitabine significantly suppressed tumour volume and the incidence of metastasis in both groups.

CONCLUSION

These findings suggest that sCLU‐2 plays a significant role in the acquisition of chemoresistant phenotype in bladder cancer cells and the knockdown of sCLU‐2 using OGX‐011 combined with a chemotherapeutic agent could be an attractive approach for advanced bladder cancer through the enhancement of chemosensitivity.
Introduction of non‐native freshwater fish can certainly be bad
Authors: Vitule Jean Ricardo Simões , Freire Carolina Arruda , Simberloff Daniel
Published: January 2009

In this paper, we respond to Gozlan’s views of the introduction of freshwater fish, as we strongly disagree with his view and approach. We demonstrate that many real‐world examples of freshwater fish introductions have catastrophic ecological consequences. We detail a few noteworthy examples, such as those of the Nile perch, carp, tilapias, catfishes, and the zebra mussel. We discuss within‐nation introductions, and we explore several related problems, such as hybridization and spread of pathogens and parasites. We propose that Gozlan’s analysis is biased, as more reliable data on impacts that are already widespread are urgently needed, mainly in the biologically richest areas of the world. Thus, we continue to advocate the precautionary principle, because species introductions, once established, are largely irreversible.
Preserved visual representations despite change blindness in infants
Authors: Wang Su‐hua , Mitroff Stephen R.
Published: January 2009

Combining theoretical hypotheses of infant cognition and adult perception, we present evidence that infants can maintain visual representations despite their failure to detect a change. Infants under 12 months typically fail to notice a change to an object's height in a covering event. The present experiments demonstrated that 11‐month‐old infants can nevertheless maintain a viable representation of both the pre‐ and post‐change heights despite their ‘change blindness’. These results suggest that infants, like adults, can simultaneously maintain multiple representations, even if they do not optimally use them.
Why Some Countries Trade More Than Others: The Effect of the Governance Environment on Trade Flows
Authors: Li Shaomin , Samsell Darryl P.
Published: January 2009

Manuscript Type: Empirical

Research Question/Issue: We study why some countries trade more than others by examining the effect of governance environment on trade flows between countries. We argue that countries with highly rule‐based governance environments are relatively easy to trade with their transparent regulations and fair rules. In contrast, countries with highly relation‐based governance environments are more difficult and/or more costly to trade with and therefore tend to have smaller trade flows.

Research Findings/Results: Examining trade patterns among 44 countries representing 89 per cent of world trade, we find that overall, rule‐based countries trade more than relation‐based countries. Countries with a large gap in governance environments tend to trade less. A positive effect on trade flows exist between two highly rule‐based countries, but not between two highly relation‐based countries. Any trade relationship involving a relation‐based country negatively affects trade flows.

Theoretical Implications: This study refines and extends institutional theory and contributes to both governance and trade literatures by distinguishing two governance environments and how they affect trade flows between countries.

Practical Implications: In addition to trade policies, governments must pay attention to the governance environment to evaluate their own and their trading partners' trading environment. When selecting trading partners, a firm needs to consider the prospective trading partner's characteristics (such as reputation, resources, and so forth), the trade policies of the partner's country, and the governance environment of that country.
The Central Role of Group‐Based Hatred as an Emotional Antecedent of Political Intolerance: Evidence from Israel
Authors: Halperin Eran , Canetti‐Nisim Daphna , Hirsch‐Hoefler Sivan
Published: January 2009

In recent years, political scientists have shifted the focus of explaining political phenomena from the purely cognitive perspective to an integrated emotion‐cognition one. Yet most studies which examine antecedents of political intolerance ignore the potential role played by “gut feelings” or group‐based negative emotions in endorsing those attitudes. Moreover, even the few studies that deal with emotions and intolerance concentrate exclusively on the role of groups of emotions (positive vs. negative, dispositional vs. surveillance) or on basic emotions (anger or fear) and ignore the potential influence of more complex discrete emotions like hatred on political intolerance. Hence, the main goal of this study was to create a deeper understanding regarding the role of discrete negative emotions in increasing political intolerance among different groups of individuals in different contexts. In order to do so, the relations between political intolerance and three group‐based negative emotions (hatred, anger, and fear) were tested by means of four large‐scale nationwide surveys. Within the surveys, various intolerance measurement methods were used in various contexts (wartime vs. no‐war/routine periods) and among individuals with different levels of political sophistication. Results, obtained via multiple regression analysis and structural equation modeling, show that: (1) Group‐based hatred is the most important antecedent of political intolerance even when controlling for important intolerance inducers such as perceived threat. (2) Other group‐based negative emotions like anger or fear influence political intolerance wholly through the mediation of hatred or perceived threat. (3) The role of group‐based hatred in inducing political intolerance is more substantial in the face of heightened existential threat and among unsophisticated individuals than among sophisticated ones.
Dynamic Voluntary Provision of Public Goods: A Generalization
Authors: FUJIWARA KENJI , MATSUEDA NORIMICHI
Published: January 2009

In this note we examine if the proposition offered by Fershtman and Nitzan (1991) and Wirl (1996) in the context of a dynamic voluntary provision model with a linear production function can be generalized to a more general CES formulation. By comparing the steady‐state stocks of a public good in open‐loop and feedback Nash equilibria with that under the cooperative solution, we demonstrate that their ranking among the steady‐state stocks is indeed preserved under the CES framework.
THE REVOLUTIONARY VISION OF WILLIAM BLAKE
Authors: Altizer Thomas J. J.
Published: January 2009

It was William Blake's insight that the Christian churches, by inverting the Incarnation and the dialectical vision of Paul, have repressed the body, divided God from creation, substituted judgment for grace, and repudiated imagination, compassion, and the original apocalyptic faith of early Christianity. Blake's prophetic poetry thus contributes to the renewal of Christian ethics by a process of subversion and negation of Christian moral, ecclesiastical, and theological traditions, which are recognized precisely as inversions of Jesus, and therefore as instances of the forms of evil that God‐in‐Christ overcomes through Incarnation, reversing the Fall. Blake's great epic poems, particularly Milton (1804–08) and Jerusalem (1804–20), embody his heterodox representation of the final coincidence of Christ and Satan through which, at last, all things are made new.
Femoral nerve involvement in diabetics
Authors: Kurt S. , Kaplan Y. , Karaer H. , Erkorkmaz U.
Published: January 2009

Background and purpose:  In this study, the conduction of the femoral nerve has been evaluated in diabetic patients without clinical signs of femoral nerve involvement and in a group of healthy subjects.

Methods:  Forty‐eight patients have been included in the study. Patients have been examined in terms of neuropathy and their neuropathy scores have been calculated. In addition to the nerve conduction studies have been performed. The findings of the diabetic patients have been compared with those of the 26 healthy volunteers.

Results:  There has been a statistically significant difference between diabetics and the healthy volunteers in the control group in terms of both femoral nerve motor latency and amplitude. The femoral latencies of patients have significantly been related to the total neuropathy score. A significant difference between diabetic patients without polyneuropathy and the controls was observed with respect to their femoral latencies.

Conclusion:  In our study, femoral nerve conduction abnormalities have been determined in diabetics who clinically did not have femoral nerve involvement. It has been observed that these abnormalities become more evident as the polyneuropathy of the patients becomes more serious. Our study has shown that femoral nerve conductions may increase the sensitivity of the diagnosis of polyneuropathy.
Translating Research into Practice Intervention Improves Management of Acute Pain in Older Hip Fracture Patients
Authors: Titler Marita G. , Herr Keela , Brooks John M. , Xie Xian‐Jin , Ardery Gail , Schilling Margo L. , Marsh J. Lawrence , Everett Linda Q. , Clarke William R.
Published: January 2009

Objective.To test an interdisciplinary, multifaceted, translating research into practice (TRIP) intervention to (a) promote adoption, by physicians and nurses, of evidence‐based (EB) acute pain management practices in hospitalized older adults, (b) decrease barriers to use of EB acute pain management practices, and (c) decrease pain intensity of older hospitalized adults.

Study Design.Experimental design with the hospital as the unit of randomization.

Study Setting.Twelve acute care hospitals in the Midwest.

Data Sources.(a) Medical records (MRs) of patients ≥65 years or older with a hip fracture admitted before and following implementation of the TRIP intervention and (b) physicians and nurses who care for those patients.

Data Collection.Data were abstracted from MRs and questions distributed to nurses and physicians.

Principal Findings.The Summative Index for Quality of Acute Pain Care (0–18 scale) was significantly higher for the experimental (10.1) than comparison group (8.4) at the end of the TRIP implementation phase. At the end of the TRIP implementation phase, patients in the experimental group had a lower mean pain intensity rating than those in the comparison group ( p<.0001).

Conclusion.The TRIP intervention improved quality of acute pain management of older adults hospitalized with a hip fracture.
Identification of Nonadaptive MBA Writers Through the Use of Linguistic Analysis
Authors: Divoky James J. , Rothermel Mary Anne
Published: January 2009

Samples of formal business reports and business memos were obtained from MBA students in multiple disciplines. The samples were analyzed in terms of their relative cohesion, concreteness of wording, causal relationships, intentional referencing, and readability. A classification function based on these measures was then used to identify entering MBA students as using either a memo or report style of writing, based on their personal statements and GMAT analytical writing essays. Documents for these students from the beginning and end of their academic programs were similarly analyzed. We found that students who are initially classified as report writers consistently produce documents of that quality throughout their programs. Moreover, we also found that, if memo writers do not quickly adapt their style of writing, they tend to produce documents using a memo style without regard to the type of document being requested.
Acute Effect of Circumferential Pulmonary Vein Isolation on Left Atrial Substrate
Authors: UDYAVAR AMEYA R. , HUANG SUNG‐HAO , CHANG SHIH‐LIN , LIN YENN‐JIANG , TAI CHING‐TAI , LO LI‐WEI , TUAN TA‐CHUAN , HU YU‐FENG , WONGCHAROEN WANWARANG , TSAO HSUAN‐MING , HIGA SATOSHI , CHEN SHIH‐ANN
Published: January 2009

Introduction:
The left atrial (LA) substrate plays an important role in the maintenance of atrial fibrillation (AF). However, little is known about the acute effect of circumferential pulmonary vein isolation (CPVI). This study was to investigate the acute change of LA activation, voltage and P wave in surface electrocardiogram (ECG) after CPVI.

Methods and Results:
Electroanatomic mapping (NavX) was performed in 50 patients with AF (mean age = 54 ± 10 years, 36 males) who underwent only CPVI. The mean peak‐to‐peak bipolar voltage and total activation time of LA were obtained during sinus rhythm before and immediately after CPVI. The average duration and amplitude of P waves in 12‐lead ECG were also analyzed before and after CPVI. Change in the earliest LA breakthrough sites could cause decreased LA total activation time. Downward shift in the breakthrough site was inversely proportional to the proximity of the breakthrough site to the radiofrequency lesions. A shortening of P‐wave duration and decrease in voltage after CPVI were observed after CPVI. Patients with recurrent AF had less voltage reduction in the atrial wall 1 cm from the circumferential PV lesions compared with those without recurrent AF (60.1 ± 11.7% vs 74.1 ± 6.6%, P = 0.002). Reduction of voltage ≤64.4% in this area after CPVI is related with recurrent AF.

Conclusion:
CPVI could result in acute change of LA substrate, involving LA activation and voltage. Less reduction of voltage in the atrial wall adjacent to the circumferential PV lesions after CPVI may be associated to the recurrence of AF.
Z‐Score for Benchmarking Reader Competence in a Central ECG Laboratory
Authors: Panicker Gopi Krishna , Karnad Dilip R. , Joshi Rajesh , Shetty Sheetal , Vyas Niraj , Kothari Snehal , Narula Dhiraj
Published: January 2009

Background: ECGs from thorough QT studies must be read in a central laboratory by trained experts. Standards of expertise are not presently defined. We, therefore, studied the use of Z‐scores to define reader competence.

Methods: Two hundred ECGs were read by 24 experts and the mean and standard deviation (SD) of QT measurements calculated for each ECG. Z‐scores ([QTreader– mean QTexperts]/ SDexperts) for each ECG and mean of absolute Z‐scores of all ECGs read by a reader were calculated. The highest mean absolute Z‐score of experts was considered the cutoff to define competence. Hundred of these standardized ECGs were used to assess performance of readers from the central laboratory.

Results: All experts had mean absolute Z‐scores ≤ 1.5. Using this cutoff, one of 28 experienced readers and 7 of 15 trainees had unacceptable Z‐scores. After re‐training, all achieved Z‐scores <1.5. Comparing histograms of actual Z‐scores of the 100 ECGs of readers with unacceptable scores with that of the reader with the best Z‐score showed two patterns. Readers with histograms having a peak and tails similar to that of the best reader, but with leftward or rightward shift, consistently made shorter or longer QT measurements, respectively. A histogram with a flatter peak and wider tails, suggested that measurements were long in some ECGs and short in others.

Conclusion: Mean absolute Z‐score is useful to assess competence for measuring the QT interval on ECGs. Analysis of histograms can pinpoint problems in QT measurements.