bluuebunny/crossref_metadata_2025 huggingface dataset:
Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings
Authors: Piessevaux H. , De Winter B. , Louis E. , Muls V. , De Looze D. , Pelckmans P. , Deltenre M. , Urbain D. , Tack J.
Published: February 2009

Abstract  Both dyspeptic and gastro‐oesophageal reflux‐like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in factors associated with pathophysiological mechanisms. The aims of this study were: (i) to assess the prevalence of dyspeptic symptoms with and without overlapping reflux symptoms in the general population and their impact on daily life and on healthcare utilization; and (ii) to compare symptom groupings in the general population to FD patients. A total of 2025 subjects, representative of the Belgian general population, were used in this study. The subjects were submitted to a questionnaire with validated questions on their dyspeptic and reflux symptoms and with evaluators of impact on daily life and use of healthcare resources. Significant dyspeptic symptoms were found in 417 (20.6%). Overlapping reflux symptoms were present in 141 (33.8%). In this group, symptoms were more frequent and more severe. Dyspeptic symptoms induced weight loss (12.7%) and absenteeism (12.4%), affected daily life (61.2%) and generated use of healthcare resources, such as medical consultations (61.4%) and medication (70.9%). Factor analysis revealed a three‐component structure with factor 1 including fullness, bloating and early satiety, factor 2 including nausea and vomiting and factor 3 including discomfort, pain, belching and reflux. If forced in a four‐factor model, the analysis separates belching as independent factor. Dyspeptic symptoms are frequent in the general population, with overlapping reflux symptoms and increased symptom burden in about a third.
B‐cell activation in patients with irritable bowel syndrome (IBS)
Authors: öhman L. , Lindmark A.‐c. , Isaksson S. , Posserud I. , Strid H. , Sjövall H. , Simrén M.
Published: February 2009

Abstract  Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B‐cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV‐light inactivated bacterial cocktail consisting of the probiotic Gram‐positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19+ B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA‐DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B‐cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells.
Lower‐crust S‐wave velocity beneath western Yunnan Province from waveform inversion of dense seismic observations
Authors: Gao Xing , Su Youliang , Wang Weimin , Pei Shunping , Guo Zhi
Published: February 2009

We use teleseismic body waveforms to explore S‐wave layered velocity structures beneath 30 portable digital seismic stations deployed around western Yunnan Province. Results show that the Moho depth in this region is ∼40 km and decreases in general from north to south, consistent with previous geophysical studies. Associated with this lateral variation of the Moho depth, the lower crust above the Moho discontinuity has a 15–25 km thick zone with an S‐wave velocity lower than that of the upper crust. This lower velocity zone might be interpreted as a lower crust weak channel, which may mechanically partially decouple the upper‐crust deformation from the underlying mantle. Thus, the inverted S‐wave velocity structure could provide new evidence for the lateral flow of lower crust in the build‐up of the south‐eastern Tibetan plateau.
Assessing the marginal error in diagnosis and cure of Schistosoma mansoni in areas of low endemicity using Percoll and PCR techniques
Authors: Allam Amal Farahat , Kader Ola , Zaki Adel , Youssef Shehab Amel , Farag Hoda Fahmy
Published: February 2009

Objective  The Kato–Katz technique misses a proportion of low‐intensity schistosomiasis cases. We set out to estimate the rate of false negative results after Kato–Katz.

Method  Comparison with the more sensitive Percoll technique and polymerase chain reaction (PCR).

Results  Amongst Kato–Katz negative Schistosoma mansoni specimens in a hypoendemic area, Percoll detected 11% positive cases and PCR detected 23%. After treatment, the cure rate was 97% by Kato–Katz, 90% by Percoll and 71% by PCR. Results of Kato–Katz and Percoll showed moderate agreement, all cases positive by Kato–Katz were positive by Percoll. However, PCR showed some negative results amongst cases considered sure positives.

Conclusion  The Percoll technique seems to be the technique of choice for diagnosis of S. mansoni in low intensity areas and after treatment.
Domestic smoke exposure is associated with alveolar macrophage particulate load
Authors: Fullerton Duncan G. , Jere Khuzwayo , Jambo Kondwani , Kulkarni Neeta S. , Zijlstra Eduard E. , Grigg Jonathan , French Neil , Molyneux Malcolm E. , Gordon Stephen B.
Published: February 2009

Objectives  Indoor air pollution is associated with impaired respiratory health. The pre‐dominant indoor air pollutant to which two billion of the world’s population is exposed is biomass fuel smoke. We tested the hypothesis that reported smoke exposure in men and women is associated with increased alveolar macrophage uptake of biomass smoke particulates.

Methods  Healthy volunteers attending for research bronchoscopy in Malawi completed a questionnaire assessment of smoke exposure. Particulate matter visible in alveolar macrophages (AM) was quantified using digital image analysis. The geometric mean of the percentage area of the cytoplasm occupied by particulates in 50 cover‐slip adherent AM was calculated and termed particulate load.

Results  In 57 subjects (40 men and 17 women) there was a significant difference between the particulate load in groups divided according to pre‐dominant lighting form used at home (anovaP = 0.0009) and type of cooking fuel (P = 0.0078).

Conclusions  Particulate load observed in macrophages is associated with the reported type of biomass fuel exposure. Macrophage function in relation to respiratory health should now be investigated in biomass smoke exposed subjects.
Impact of intense, longitudinal retreatment with praziquantel on cure rates of schistosomiasis mansoni in a cohort of occupationally exposed adults in western Kenya
Authors: Black Carla L. , Steinauer Michelle L. , Mwinzi Pauline N. M. , Evan Secor W. , Karanja Diana M. S. , Colley Daniel G.
Published: February 2009

Objective  To investigate trends in the efficacy of praziquantel (PZQ) suggestive of the emergence of drug resistance against Schistosoma mansoni infection after 12.5 years of intense, repeated use in a small geographic area along the shores of Lake Victoria.

Methods  As part of a longitudinal study, 178 men occupationally exposed to schistosomes were repeatedly tested for S. mansoni infection at 4‐ to 6‐week intervals and treated with PZQ at each reinfection. We compared cure rates by year of study and examined factors associated with cure failure in a multivariate logistic regression model.

Results  Overall, the cure rate after a single dose of PZQ was 66%, ranging annually from 36% to 82%. In multivariate analysis, failure to cure after 1 PZQ dose was significantly associated with high intensity of infection and having fewer previous exposures to dying worms. Even after adjustment for these factors, treatments administered in 2006 were significantly more likely to result in cure failures than treatments administered in 2004, the year in which PZQ efficacy was highest. While cure rates varied over the course of 12 years, there was no consistent downward trend towards decreased efficacy over time. In years for which malacological data were available, periods of low PZQ efficacy coincide with high rates of S. mansoni infection in nearby snail populations.

Conclusion  We did not find a pattern of cure failures consistent with development of clinical resistance to PZQ in our intensely treated cohort.
PCR diagnosis of visceral leishmaniasis in an endemic region, Mymensingh district, Bangladesh
Authors: Alam Mohammad Zahangir , Shamsuzzaman Abul Khair M. , Kuhls Katrin , Schönian Gabriele
Published: February 2009

Detection of Leishmania parasites in a clinical sample is necessary to confirm a suspected case of leishmaniasis. We compared the sensitivity of internal transcribed spacer 1‐PCR (ITS 1‐PCR) assay for parasite diagnosis with that of microscopic detection in clinical samples from kala‐azar (KA) or post‐kala‐azar dermal leishmaniasis (PKDL) suspects in Mymensingh. Of 39 specimens collected from 35 KA and four PKDL suspects, 26 were positive by microscopic examination of smears from bone marrow and skin exudates; 38 specimens spotted on filter paper and 27 of the 28 Giemsa‐stained slides tested by PCR proved positive by ITS1‐PCR.
CMV‐specific T‐cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients: a pilot study
Authors: Sund Fredrik , Lidehäll Anna‐Karin , Claesson Kerstin , Foss Aksel , Tötterman Thomas H. , Korsgren Olle , Eriksson Britt‐Marie
Published: February 2009

Sund F, Lidehäll A‐K, Claesson K, Foss A, Tötterman TH, Korsgren O, Eriksson B‐M. CMV‐specific T‐cell immunity, viral load, and clinical outcome in seropositive renal transplant recipients: a pilot study. Clin Transplant 2010: 24: 401–409. © 2009 Wiley Periodicals, Inc.

Abstract: Background:  Cytomegalovirus (CMV) infection is still the leading opportunistic infection following solid organ transplantation. The aim of this prospective study of renal transplant recipients was to evaluate the dynamics of CMV‐specific T‐cells, viral load, and clinical symptoms of CMV infection.

Methods:  Levels of tetramer‐selected CD8+ T‐cells (TetraCD8), CMV‐specific interferon‐γ producing CD8+ T‐cells (IFNγCD8), and CD4+ T‐cells (IFNγCD4), measured using major histocompatibility complex‐tetramer and cytokine flow cytometry techniques, and CMV DNA were monitored monthly in 17 CMV‐seropositive patients up to one yr (median 12 months, range 3–12) after transplantation and correlated to clinical outcome.

Results:  CMV DNAemia was detected in 94% of the patients, but only one patient developed CMV disease. CMV DNAemia >1 million copies/mL was seen in asymptomatic patients. CMV‐specific T‐cells decreased rapidly after transplantation. TetraCD8 and IFNγCD8 regenerated within three months, whereas IFNγCD4 recovery was impaired up to one yr after transplantation. The proportion of IFNγCD4 at two months post‐transplantation as compared with baseline, correlated strongly with the magnitude of the CMV DNAemia.

Conclusions:  Monitoring the reduction of IFNγCD4 compared with baseline during the first months after transplantation could be considered in predicting risk for high‐grade CMV DNAemia and in deciding strategic approaches for pre‐emptive and prophylactic therapy.
Does the use of pulmonary artery catheters increase the number of organs available for transplantation?
Authors: Hadjizacharia Pantelis , Salim Ali , Brown Carlos , Inaba Kenji , Chan Linda S. , Mascarenhas Angela , Margulies Daniel R.
Published: February 2009

Hadjizacharia P, Salim A, Brown C, Inaba K, Chan LS, Mascarenhas A, Margulies DR. Does the use of pulmonary artery catheters increase the number of organs available for transplantation? Clin Transplant 2010: 24: 62–66. © 2009 John Wiley & Sons A/S.

Abstract:  Aggressive donor management, including the placement of a pulmonary artery catheter (PAC) to monitor hemodynamic status and tissue perfusion, has been associated with a significant increase in the number of organs recovered for transplantation. Nonetheless, there has been growing scrutiny over the use of PACs because of their known complications and lack of therapeutic effect. The purpose of this study is to evaluate the use of PACs in the management of organ donors. The records of all patients who successfully donated organs between January 1, 2002 and December 31, 2005 were reviewed. A total of 96 patients underwent successful organ donation during the four‐yr study period. Of these, 49 (51.0%) were managed with a PAC. Compared with donors managed without a PAC, there were significantly more hearts recovered from donors managed with a PAC (71.4% vs. 44.7%; p = 0.0079) with no difference in the daily administration of fluids and vasopressors between the two groups. The management of organ donors with a PAC can help maximize cardiac procurement.
Mountain birch under multiple stressors – heavy metal‐resistant populations co‐resistant to biotic stress but maladapted to abiotic stress
Authors: ERÄNEN J. K. , NILSEN J. , ZVEREV V. E. , KOZLOV M. V.
Published: February 2009

Stress adaptations often include a trade‐off of weakened performance in nonlocal conditions, resulting in divergent selection, and potentially, genetic differentiation and evolutionary adaptation. Results of a two‐phase (greenhouse and field) common garden experiment demonstrated adaptation of mountain birch (Betula pubescenssubsp.czerepanovii) populations from industrially polluted areas of the Kola Peninsula, north‐western Russia, to heavy metals (HM), whereas no adaptations to wind or drought stress were detected in populations from wind‐exposed sites. HM‐adapted seedlings were maladapted to drought but less palatable (co‐resistant) to insect herbivores, even under background HM concentrations. The absence of adaptations to harsh microclimate and the generally high adaptive potential of mountain birch, a critical forest forming tree in subarctic Europe, need to be accounted for in models predicting consequences of human‐driven environmental changes, including the projected climate change.
The fitness costs of developmental canalization and plasticity
Authors: VAN BUSKIRK J. , STEINER U. K.
Published: February 2009

Organisms are capable of an astonishing repertoire of phenotypic responses to the environment, and these often define important adaptive solutions to heterogeneous and unpredictable conditions. The terms ‘phenotypic plasticity’ and ‘canalization’ indicate whether environmental variation has a large or small effect on the phenotype. The evolution of canalization and plasticity is influenced by optimizing selection‐targeting traits within environments, but inherent fitness costs of plasticity may also be important. We present a meta‐analysis of 27 studies (of 16 species of plant and 7 animals) that have measured selection on the degree of plasticity independent of the characters expressed within environments. Costs of plasticity and canalization were equally frequent and usually mild; large costs were observed only in studies with low sample size. We tested the importance of several covariates, but only the degree of environmental stress was marginally positively related to the cost of plasticity. These findings suggest that costs of plasticity are often weak, and may influence phenotypic evolution only under stressful conditions.
Lacustrine radiations in AfricanSynodontiscatfish
Authors: DAY J. J. , BILLS R. , FRIEL J. P.
Published: February 2009

Synodontiscatfish are a species‐rich, tropical pan‐African genus that predominately occur in fluviatile environments, but which also form a small radiation within Lake Tanganyika (LT). Here we estimateSynodontisrelationships, based on mitochondrial and nuclear DNA, greatly expanding previous sampling. Data were analysed using different methods of phylogenetic inference: Bayesian (also testing compositional heterogeneity), likelihood and parsimony, in order to investigate biogeographic history and the extent of intralacustrine speciation within this group. Bayesian‐relaxed clock analyses were used to estimate timings of radiations. Our analyses reveal a single origin of the LT flock with the inclusion of the nonendemicS. victoriae, and that these taxa evolved relatively recently (5.5 Ma), considerably later than the formation of LT (9–12 Ma). Two internal endemic clades diversified at a similar time (2–2.5 Ma), corresponding to a period of climate change, when lake levels dropped. We find evidence for a further species flock, composed of riverine southern African taxa, the diversification of which is very rapid, 0.8 Ma (95% HPD: 0.4–1.5) and infer a similar scenario for the diversification of this flock to southern African serrachromine cichlids in that they radiated in the now extinct lake Makgadikgadi. We also reveal that the biogeographic history ofSynodontiscatfish is more complex than previously thought, with nonmonophyletic geographic species groupings.
Applying the genetic theories of ageing to the cytoplasm: cytoplasmic genetic covariation for fitness and lifespan
Authors: DOWLING D. K. , MAKLAKOV A. A. , FRIBERG U. , HAILER F.
Published: February 2009

Two genetic models exist to explain the evolution of ageing – mutation accumulation (MA) and antagonistic pleiotropy (AP). Under MA, a reduced intensity of selection with age results in accumulation of late‐acting deleterious mutations. Under AP, late‐acting deleterious mutations accumulate because they confer beneficial effects early in life. Recent studies suggest that the mitochondrial genome is a major player in ageing. It therefore seems plausible that the MA and AP models will be relevant to genomes within the cytoplasm. This possibility has not been considered previously. We explore whether patterns of covariation between fitness and ageing across 25 cytoplasmic lines, sampled from a population of Drosophila melanogaster, are consistent with the genetic associations predicted under MA or AP. We find negative covariation for fitness and the rate of ageing, and positive covariation for fitness and lifespan. Notably, the direction of these associations is opposite to that typically predicted under AP.
Release of lipoxygenase products and monoterpenes by tomato plants as an indicator of Botrytis cinerea‐induced stress
Authors: Jansen R. M. C. , Miebach M. , Kleist E. , Van Henten E. J. , Wildt J.
Published: February 2009

Changes in emission of volatile organic compounds (VOCs) from tomato induced by the fungus Botrytis cinerea were studied in plants inoculated by spraying with suspensions containing B. cinerea spores. VOC emissions were analysed using on‐line gas chromatography–mass spectrometry, with a time resolution of about 1 h, for up to 2 days after spraying. Four phases were delimited according to the starting point and the applied day/night rhythm of the experiments. These phases were used to demonstrate changes in VOC flux caused by B. cinerea infestation. Tomato plants inoculated with B. cinerea emitted a different number and amount of VOCs after inoculation compared to control plants that had been sprayed with a suspension without B. cinerea spores. The changes in emissions were dependent on time after inoculation as well as on the severity of infection. The predominant VOCs emitted after inoculation were volatile products from the lipoxygenase pathway (LOX products). The increased emission of LOX products proved to be a strong indicator of a stress response, indicating that VOC emissions can be used to detect plant stress at an early stage. Besides emission of LOX products, there were also increases in monoterpene emissions. However, neither increased emission of LOX products nor of monoterpenes is specific for B. cinerea attack. The emission of LOX products is also induced by other stresses, and increased emission of monoterpenes seems to be the result of mechanical damage induced by secondary stress impacts on leaves.
Efficacy of entecavir treatment for lamivudine‐resistant hepatitis B over 3 years: Histological improvement or entecavir resistance?
Authors: Suzuki Yoshiyuki , Suzuki Fumitaka , Kawamura Yusuke , Yatsuji Hiromi , Sezaki Hitomi , Hosaka Tetsuya , Akuta Norio , Kobayashi Masahiro , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kobayashi Mariko , Miyakawa Yuzo , Kumada Hiromitsu
Published: February 2009

Background and Aims:  Long‐term lamivudine therapy is required for patients with chronic hepatitis B, because hepatitis reappears frequently after it has withdrawn. However, hepatitis B virus (HBV) mutants resistant to lamivudine emerge frequently accompanied by breakthrough hepatitis.

Methods:  Effects of entecavir were evaluated in 19 patients who had developed breakthrough hepatitis during lamivudine therapy for longer than 5 years. This study is a subgroup analysis of a previously reported study. Entecavir, in either 0.5 or 1.0 mg/day doses, was given to 10 and nine patients for 52 weeks, respectively, and then all received 1.0 mg/day entecavir for an additional 68–92 weeks.

Results:  There were no differences in biochemical and virological responses in the two groups of patients with respect to the two different initial doses of entecavir. Serum levels of alanine aminotransferase were normalized in 17 (90%) patients, and hepatitis B e antigen (HBeAg) disappeared from the serum in two (14%) of the 14 patients who were HBeAg‐positive before. Furthermore, a decrease in histological activity index score greater than 2 points was achieved in nine of the 11 (82%) patients in whom annual liver biopsies were performed during 3 years while they received entecavir. HBV mutants resistant to entecavir emerged in five of the 19 (26%) patients, and hepatitis flare occurred in two of them (40%).

Conclusion:  Entecavir in the long term would be useful for histological improvement of breakthrough hepatitis induced by lamivudine‐resistant HBV mutants in patients with chronic hepatitis B. However, the relatively high rate of entecavir resistance is a concern, and other strategies need to be considered when available.
Relationship between Helicobacter pylori hopQ genotype and clinical outcome in Asian and Western populations
Authors: Ohno Tomoyuki , Sugimoto Mitsushige , Nagashima Aiko , Ogiwara Hiroaki , Vilaichone Ratha‐Korn , Mahachai Varocha , Graham David Y , Yamaoka Yoshio
Published: February 2009

Background and Aims:  Outer membrane proteins of Helicobacter pylori mediate important pathogen–host interactions such as colonization, adhesion and the inflammatory response. hopQ genotypes have been suggested to be associated with increased risk of peptic ulcer. The aim of this study was to test the relation of hopQ genotype to H. pylori‐related disease and histological changes in Asian and Western countries.

Methods:  hopQ genotype, cagA status and vacA genotype of H. pylori isolated from patients from Asian and Western countries were determined and the results were compared with the clinical presentation and gastric histology.

Results:  Most Asian strains possessed virulent genotypes (hopQ type I, vacA s1‐m1 and cagA‐positive). In Western countries, hopQ type I genotype was significantly linked with vacA s1 and m1 genotypes and cagA‐positive status. Inflammatory cell infiltration and atrophy scores were significantly higher in patients with hopQ type I strains than those with type II in Western patients. However, the hopQ type I genotype was not associated with an increased risk for peptic ulcer or gastric cancer, and had no additive effects to vacA genotypes or cagA‐positive status.

Conclusion:  The expression of multiple putative virulence factors in Asian strains likely explains the relatively high incidence of clinical outcomes including gastric cancer compared with other parts of the world. Although hopQ genotype did not improve the predictive value above other genotyping for development of H. pylori‐related gastroduodenal diseases, the hopQ genotype might be able to add a useful virulence marker for gastroduodenal diseases.
Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression
Authors: Farrell Geoffrey C , Larter Claire Z , Hou Jing Yun , Zhang Rena H , Yeh Matthew M , Williams Jacqueline , Dela Peňa Aileen , Francisco Rona , Osvath Sarah R , Brooling John , Teoh Narcissus , Sedger Lisa M
Published: February 2009

Background and Aims:  We examined extrinsic and intrinsic (endogenous) mitochondrial apoptosis pathways in experimental non‐alcoholic steatohepatitis (NASH).

Methods:  To assess extrinsic pathways, we measured hepatic expression of death‐inducing cytokine receptors (tumor necrosis factor‐α‐receptor (TNF‐R)1, TNF‐R2, Fas, and TNFα‐related apoptosis‐inducing ligand‐receptor (TRAIL‐R) mRNA, TUNEL, caspase 3 activation, liver injury and liver pathology in mice fed a methionine and choline deficient (MCD) diet. For endogenous stress pathways, we determined serum insulin‐like growth factor‐1 (IGF‐1), hepatic p53, Bcl‐XL, tBid and p21 expression.

Results:  Methionine and choline deficient feeding increased alanine aminotransferase (ALT) and apoptosis from day 10, without increases in TNF‐R1, TNF‐R2, and Fas. However, murine TRAIL receptors, particularly decoyTRAIL‐R1/TNFRSFH23 and Killer/DR5 mRNA increased. MCD feeding enhanced hepatic p53 expression, corresponding to ∼50% fall in serum IGF‐1, decreased Bcl‐XL, enhanced Bid cleavage to tBid, and up‐regulation of p21. Nutritional restitution experiments showed that correcting either methionine or choline deficiency suppressed liver inflammation (extrinsic pathway), but failed to correct apoptosis, IGF‐1 or p53.

Conclusions:  Methionine and choline deficiency lower IGF‐1 to de‐repress p53 during induction of steatohepatitis. The p53 induced by nutritional stress is biologically active in mediating mitochondrial cell death pathways, but may also be responsible for TRAIL receptor expression, thereby linking intrinsic and exogenous apoptosis pathways in NASH.
X chromosome number causes sex differences in gene expression in adult mouse striatum
Authors: Chen Xuqi , Grisham William , Arnold Arthur P.
Published: February 2009

Previous research suggests that sex differences in the nigrostriatal system are created by direct effects of the sex chromosomes (XX vs. XY), independent of the action of gonadal hormones. Here we tested for sex chromosome effects on expression of three mRNAs in the striatum and nucleus accumbens of adult mice of the four core genotypes model (XX and XY gonadal males, XX and XY gonadal females). Mice were gonadectomized (GDX) at 47–51 days old to eliminate group differences in the levels of gonadal steroids. Three weeks later, mice were killed and brains collected for in situ hybridization of the striatum, or the striatum was dissected out for quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Expression in XX and XY mice was measured by in situ hybridization using riboprobes encoding the dynorphin precursor Pdyn (prodynorphin), the substance P precursor Tac1 (preprotachykinin) or dopamine D2 receptor. XX mice had higher expression, relative to XY mice of the same gonadal sex, of Pdyn and Tac1 mRNA in specific striatal regions. Quantitative PCR confirmed that GDX XX mice have higher Pdyn expression in striatum than XY mice, regardless of their gonadal sex. XX had higher Pdyn expression than XY or XO mice, indicating that the sex chromosome effect is the result of XX vs. XY differences in the number of X chromosomes, probably because of sex differences in the expression of X gene(s) that escape inactivation. We detected no sex chromosome effect on D2 receptor mRNA.
Main olfactory system mediates social buffering of conditioned fear responses in male rats
Authors: Kiyokawa Yasushi , Takeuchi Yukari , Nishihara Masugi , Mori Yuji
Published: February 2009

We previously reported that the presence of a conspecific animal blocked freezing of a male rat in response to an auditory conditioned stimulus that had been paired with foot shocks, as well as associated Fos expression in the paraventricular nucleus. Here we investigated how this ‘social buffering’ is mediated by examining the contributions of both physical contact and the main olfactory system. Fear‐conditioned rats exposed to the conditioned stimulus alone responded by freezing and increased Fos expression in the paraventricular nucleus. However, the presence of another rat, but not a guinea pig, dramatically mitigated these responses, even if the dyad was separated by a wire mesh or a pair of wire meshes 5 cm apart. In contrast, social buffering was absent when a transparent acrylic board was inserted between the double wire mesh. Lesioning of the main olfactory epithelium by injection of ZnSO4 intranasally also abolished social buffering. Thus, we conclude that the main olfactory system is essential for the social buffering but does not require physical contact between the dyad.
Rapid cortical reorganisation and improved sensitivity of the hand following cutaneous anaesthesia of the forearm
Authors: Björkman Anders , Weibull Andreas , Rosén Birgitta , Svensson Jonas , Lundborg Göran
Published: February 2009

The cortical representation of various body parts constantly changes based on the pattern of afferent nerve impulses. As peripheral nerve injury results in a cortical and subcortical reorganisation this has been suggested as one explanation for the poor clinical outcome seen after peripheral nerve repair in humans. Cutaneous anaesthesia of the forearm in healthy subjects and in patients with nerve injuries results in rapid improvement of hand sensitivity. The mechanism behind the improvement is probably based on a rapid cortical and subcortical reorganisation. The aim of this work was to study cortical changes following temporary cutaneous forearm anaesthesia. Ten healthy volunteers participated in the study. Twenty grams of a local anaesthetic cream (EMLA®) was applied to the volar aspect of the right forearm. Functional magnetic resonance imaging was performed during sensory stimulation of all fingers of the right hand before and during cutaneous forearm anaesthesia. Sensitivity was also clinically assessed before and during forearm anaesthesia. A group analysis of functional magnetic resonance image data showed that, during anaesthesia, the hand area in the contralateral primary somatosensory cortex expanded cranially over the anaesthetised forearm area. Clinically right hand sensitivity in the volunteers improved during forearm anaesthesia. No significant changes were seen in the left hand. The clinically improved hand sensitivity following forearm anaesthesia is probably based on a rapid expansion of the hand area in the primary somatosensory cortex which presumably results in more nerve cells being made available for the hand in the primary somatosensory cortex.
Genetic, immunological and biochemical evidence for a Rnf complex in the acetogen Acetobacterium woodii
Authors: Biegel Eva , Schmidt Silke , Müller Volker
Published: February 2009

Acetogenic bacteria grow by the oxidation of various substrates coupled to the reduction of carbon dioxide (acetogenesis) or other electron acceptors but the mechanisms of energy conservation are still enigmatic. Here, we report the presence of a rnf gene cluster rnfCDGEAB in Acetobacterium woodii that is speculated to encode a novel, energy‐conserving ferredoxin:NAD+‐oxidoreductase complex composed of at least six different subunits. Transcriptional analysis revealed that the genes constitute an operon. RnfC and RnfG were heterologously produced and antibodies were generated. Western blot analyses demonstrated that these subunits were produced and are associated with the cytoplasmic membrane. The subunits were present in cells respiring with either carbon dioxide or caffeate. A preparation with NADH dehydrogenase activity was obtained from detergent solubilized membranes that contained RnfC and RnfG.
Suprapubic catheter insertion is an outpatient procedure: cost savings resultant on closing an audit loop
Authors: Khan Azhar , Abrams Paul
Published: February 2009

OBJECTIVE

To explore, by an audit, the regional practice of inserting a suprapubic catheter (SPC), and to prospectively determine the proportion of patients that can be successfully managed on an outpatient basis in one department.

METHODS

Both local and regional practice were determined by a retrospective analysis of the hospital database for all cases of SPC insertion between April 2005 and March 2006. In addition, a questionnaire was e‐mailed to each of 11 urology departments. Locally, from August 2006 onwards, all patients scheduled for SPC insertion were referred to a new clinic, where the SPC was inserted using a new SPC kit and the Seldinger technique.

RESULTS

Locally, 66 patients (mean age 70 years, range 26–93) had a SPC inserted between April 2005 and March 2006; 49 had an elective procedure while 17 were emergency admissions. The median (range) hospital stay was 3.5 (1–85) days. Within the region, 480 SPCs were inserted in theatre during the same period, of which 52% (249) were inserted as elective inpatients, 11% (52) were inserted as a day case, and 37% (179) had SPCs as emergency admissions. A nurse‐led outpatient service was available in two hospitals, where 89% of patients seen in the clinic had successful insertion under local anaesthesia, and only 11% were referred for insertion under general anasthesia. Between August 2006 and July 2007, 50 of 54 patients had a SPC inserted successfully in the new SPC clinic. There were no major complications. The cost benefits of adopting an outpatient management strategy were significant, at ≈£GB 100 000/year in our hospital, £790 000/year in the region and £9 500 000/year for the UK.

CONCLUSION

An outpatient procedure for a SPC is safe and feasible in most patients, and its widespread use would produce considerable cost savings.
Predicting the outcome of prostate biopsy: comparison of a novel logistic regression‐based model, the prostate cancer risk calculator, and prostate‐specific antigen level alone
Authors: Hernandez David J. , Han Misop , Humphreys Elizabeth B. , Mangold Leslie A. , Taneja Samir S. , Childs Stacy J. , Bartsch Georg , Partin Alan W.
Published: February 2009

OBJECTIVES

To develop a logistic regression‐based model to predict prostate cancer biopsy at, and compare its performance to the risk calculator developed by the Prostate Cancer Prevention Trial (PCPT), which was based on age, race, prostate‐specific antigen (PSA) level, a digital rectal examination (DRE), family history, and history of a previous negative biopsy, and to PSA level alone.

PATIENTS AND METHODS

We retrospectively analysed the data of 1280 men who had a biopsy while enrolled in a prospective, multicentre clinical trial. Of these, 1108 had all relevant clinical and pathological data available, and no previous diagnosis of prostate cancer. Using the PCPT risk calculator, we calculated the risks of prostate cancer and of high‐grade disease (Gleason score ≥7) for each man. Receiver operating characteristic (ROC) curves for the risk calculator, PSA level and the novel regression‐based model were compared.

RESULTS

Prostate cancer was detected in 394 (35.6%) men, and 155 (14.0%) had Gleason ≥7 disease. For cancer prediction, the area under the ROC curve (AUC) for the risk calculator was 66.7%, statistically greater than the AUC for PSA level of 61.9% (P < 0.001). For predicting high‐grade disease, the AUCs were 74.1% and 70.7% for the risk calculator and PSA level, respectively (P = 0.024). The AUCs increased to 71.2% (P < 0.001) and 78.7% (P = 0.001) for detection and high‐grade disease, respectively, with our novel regression‐based models.

CONCLUSIONS

ROC analyses show that the PCPT risk calculator modestly improves the performance of PSA level alone in predicting an individual’s risk of prostate cancer or high‐grade disease on biopsy. This predictive tool might be enhanced by including percentage free PSA and the number of biopsy cores.
Can dutasteride delay or prevent the progression of prostate cancer in patients with biochemical failure after radical therapy? Rationale and design of the Avodart after Radical Therapy for Prostate Cancer Study
Authors: Schröder Fritz H. , Bangma Chris H. , Wolff Johannes M. , Alcaraz Antonio , Montorsi Francesco , Mongiat‐Artus Pierre , Abrahamsson Per‐Anders , McNicholas Tom A. , Castro Ramiro S. , Nandy Indrani M.
Published: February 2009

OBJECTIVE

To describe the Avodart after Radical Therapy for prostate cancer Study (ARTS), investigating the use of dutasteride (a dual 5α‐reductase inhibitor that suppresses intraprostatic dihydrotestosterone, reduces tumour volume and improves other markers of tumour regression in prostate cancer) to prevent or delay disease progression in patients with biochemical recurrence after therapy with curative intent.

PATIENTS AND METHODS

An increasing serum prostate‐specific antigen (PSA) level after radical prostatectomy (RP) or radiotherapy (RT) is indicative of recurrent prostate cancer and typically pre‐dates clinically detectable metastatic disease by several years. ARTS is an ongoing European multicentre trial in which patients are stratified by previous therapy (RP with or without salvage RT vs primary RT) and randomized to double‐blind treatment with dutasteride 0.5 mg or placebo once daily for 2 years. Eligible patients will have a PSA doubling time (DT) of 3–24 months. Biochemical recurrence is defined as three increases in PSA level from the nadir, with each increase ≥4 weeks apart and each PSA level ≥0.2 ng/mL, and a final PSA level of ≥0.4 ng/mL (after RP) or ≥2 ng/mL (after primary RT). Study endpoints include time to PSA doubling, time to disease progression, treatment response (PSA decrease or an increase of ≤15% from baseline), changes in PSA and PSADT, and changes in anxiety (Memorial Anxiety Scale for Prostate Cancer).

CONCLUSIONS

ARTS will be the first study to evaluate the effects of dutasteride on PSADT, disease progression and treatment response in patients with biochemical failure after RP or RT, and should help to elucidate the potential role of dual 5α‐reductase inhibition in prostate cancer.
Qualitative modelling and indicators of exploited ecosystems
Authors: Dambacher Jeffrey M. , Gaughan Daniel J. , Rochet Marie‐Joëlle , Rossignol Philippe A. , Trenkel Verena M.
Published: February 2009

Implementing ecosystem‐based fisheries management requires indicators and models that address the impacts of fishing across entire ecological communities. However, the complexity of many ecosystems presents a challenge to analysis, especially if reliant on quantification because of the onerous task of precisely measuring or estimating numerous parameters. We present qualitative modelling as a complementary approach to quantitative methods. Qualitative modelling clarifies how community structure alone affects dynamics, here of exploited populations. We build an array of models that describe different ecosystems with different harvesting practices, and analyse them to predict responses to various perturbations. This approach demonstrates the utility of qualitative modelling as a means to identify and interpret community‐level indicators for systems that are at or near equilibrium, and for those that are frequently perturbed away from equilibrium. Examining the interaction of ecological and socio‐economic variables associated with commercial fisheries provides an understanding of the main feedbacks that drive and regulate exploited ecosystems. The method is particularly useful for systems where the basic relationships between variables are understood but where precise or detailed data are lacking.
THE EQUAL ABSOLUTE SACRIFICE PRINCIPLE REVISITED
Authors: Lambert Peter J. , Naughton Helen T.
Published: February 2009

Abstract We summarize the literature on equal absolute sacrifice income taxes, and make some extensions. We adapt the utilitarian equal sacrifice criterion to a wide class of rank‐dependent social welfare functions, and find that liabilities depend on both income and position in the distribution. We investigate whether such taxes need be progressive, using a combination of analytics and simulation, and in the process uncover tax functions not previously recognized as equating sacrifices. Finally, out of horizontal equity considerations a new concept of ‘the equal treatment of equals’ by an income tax emerges, with implications for future work whose significance is discussed.
USING HAPPINESS DATA FOR ENVIRONMENTAL VALUATION: ISSUES AND APPLICATIONS
Authors: Welsch Heinz , Kühling Jan
Published: February 2009

Abstract In addition to standard methods of environmental valuation, a novel approach has recently emerged which models individuals' self‐rated happiness as a function of their incomes and the prevailing environmental conditions. The estimated relationship is used to calculate the trade‐off people would be willing to make between income and environmental conditions, i.e. the increase in income necessary to compensate individuals for any given decline in environmental quality. While the basic idea is simple, the theoretical and empirical details may be complex, and they may vary from application to application. This paper discusses the relevant conceptual and methodological issues and reviews applications to air and water pollution, noise nuisance, climate parameters, and natural hazards.
PROFITS AND PLAGIARISM: THE CASE OF MEDICAL GHOSTWRITING
Authors: ANEKWE TOBENNA D.
Published: February 2009

This paper focuses on medical ghostwriting in the United States. I argue that medical ghostwriting often involves plagiarism and, in those cases, can be treated as an act of research misconduct by both the federal government and research institutions. I also propose several anti‐ghostwriting measures, including: 1) journals should implement guarantor policies so that researchers may be better held accountable for their work; 2) research institutions and the federal government should explicitly prohibit medical ghostwriting and outline appropriate penalties; and 3) a publicly available database should be created to record researchers' ethics violations.
LIVING TO THE BITTER END? A PERSONALIST APPROACH TO EUTHANASIA IN PERSONS WITH SEVERE DEMENTIA
Authors: GASTMANS CHRIS , DE LEPELEIRE JAN
Published: February 2009

The number of people suffering from dementia will rise considerably in the years to come. This will have important implications for society. People suffering from dementia have to rely on relatives and professional caregivers when their disorder progresses. Some people want to determine for themselves their moment of death, if they should become demented. They think that the decline in personality caused by severe dementia is shocking and unacceptable. In this context, some people consider euthanasia as a way to avoid total deterioration. In this article, we discuss some practical and ethical dilemmas regarding euthanasia in persons with severe dementia based on an advance euthanasia directive. We are using a personalist approach in dealing with these ethical dilemmas.
AUTONOMY AND ETHICAL TREATMENT IN DEPRESSION
Authors: BIEGLER PAUL
Published: February 2009

Antidepressant medication and evidence‐based psychotherapy have largely equivalent efficacy in the management of the common, less severe grades of depression. As a result, several national guidelines recommend that either can be used in the treatment of this disorder. Psychotherapy, however, differs in that it assists insight into how the depressed person appraises and manages the stressors that frequently trigger depressive episodes. I argue that the self‐knowledge achieved through psychotherapy has moral value in that it promotes the autonomy of stressor‐related decisions. I further argue that such an effect comprises a compelling moral reason for doctors to see evidence‐based psychotherapy not as merely optional, but as a necessary treatment for their patients with depression.
A RIGHT TO REPRODUCE?
Authors: QUIGLEY MUIREANN
Published: February 2009

How should we conceive of a right to reproduce? And, morally speaking, what might be said to justify such a right? These are just two questions of interest that are raised by the technologies of assisted reproduction. This paper analyses the possible legitimate grounds for a right to reproduce within the two main theories of rights; interest theory and choice theory.
THE DUTY TO DIE AND THE BURDENSOMENESS OF LIVING
Authors: CHOLBI MICHAEL
Published: February 2009

This article addresses the question of whether the arguments for a duty to die given by John Hardwig, the most prominent philosophical advocate of such a duty, are sound. Hardwig believes that the duty to die is relatively widespread among those with burdensome illnesses, dependencies, or medical conditions. I argue that although there are rare circumstances in which individuals have a duty to die, the situations Hardwig describes are not among these.

After reconstructing Hardwig's argument for such a duty, highlighting his central premise that ill, dependent, or aged individuals can impose unfair burdens upon others by continuing to live, I clarify precisely what Hardwig intends by his thesis that many of us have a duty to die. I then show that an important disanalogy exists between an uncontroversial example in which an individual has a duty to die and the situations in which Hardwig proposes individuals have a duty to die. More specifically, in situations where a duty to die exists, an individual's having a duty to die logically implies that those she burdens have a right to kill that individual in self‐defense. I then suggest that the burdens that ill, dependent, or aged individuals impose on their families, loved ones, or caregivers do not constitute the kind of threat that warrants the latter killing the former in self‐defense. Hence, the duty to die is much rarer than Hardwig supposes.
PUBLICATION ETHICS AND THE GHOST MANAGEMENT OF MEDICAL PUBLICATION
Authors: SISMONDO SERGIO , DOUCET MATHIEU
Published: February 2009

It is by now no secret that some scientific articles are ghost authored – that is, written by someone other than the person whose name appears at the top of the article. Ghost authorship, however, is only one sort of ghosting. In this article, we present evidence that pharmaceutical companies engage in the ghost management of the scientific literature, by controlling or shaping several crucial steps in the research, writing, and publication of scientific articles. Ghost management allows the pharmaceutical industry to shape the literature in ways that serve its interests.

This article aims to reinforce and expand publication ethics as an important area of concern for bioethics. Since ghost‐managed research is primarily undertaken in the interests of marketing, large quantities of medical research violate not just publication norms but also research ethics. Much of this research involves human subjects, and yet is performed not primarily to increase knowledge for broad human benefit, but to disseminate results in the service of profits. Those who sponsor, manage, conduct, and publish such research therefore behave unethically, since they put patients at risk without justification. This leads us to a strong conclusion: if medical journals want to ensure that the research they publish is ethically sound, they should not publish articles that are commercially sponsored.