bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer‐specific survival after radical cystectomy and standardized extended lymphadenectomy for node‐positive bladder cancer: prediction by lymph node positivity and density
Authors: Wiesner Christoph , Salzer Alice , Thomas Christian , Gellermann‐Schultes Claudia , Gillitzer Rolf , Hampel Christian , Thüroff Joachim W. 
Published: February 2009

OBJECTIVETo investigate the associations between different overall or topographically restricted lymph node (LN) variables and cancer‐specific survival (CSS) after radical cystectomy (RC) and extended LN dissection (LND) with curative intent in patients with LN‐positive bladder cancer.PATIENTS AND METHODSBetween 2001 and 2006, 152 patients had RC with standardized extended LND for bladder cancer with curative intent. Patients with positive LNs were stratified according to the median of the LN variables (LNs removed, number of positive LNs, LN density). CSS was related to overall and topographically restricted LN variables, e.g. different levels of LND, and relationships were tested by univariate and multivariate analyses. Level 1 LND comprised the regions of the external and internal iliac LNs and of the obturator LNs, level 2 the templates of common iliac and presacral LNs, and level 3 the para‐aortic and paracaval LNs up to the inferior mesenteric artery. The mean (range) follow‐up was 22 (1–84) months.RESULTSLN metastases were diagnosed in 46 of the 152 patients (30%) with extended LND. In these 46 patients, the median number of removed LNs was 33 (level 1, 15.5; level 2, 9.0; level 3, 7.0), the median number of positive LNs was 3 (1.5, 0.5 and 0.0, respectively) and the median LN density was 0.11 (0.10, 0.02 and 0.0, respectively). The CSS was 76% at 1 year and 23% at 3 years. There were significant correlations between the 3‐year CSS and the overall LN density (≤0.11 vs >0.11; 34% vs 8%, P = 0.008), and the total number of positive LNs (≤3 vs >3; 33% vs 8%; P = 0.05). Overall LN density (hazard ratio 0.33, 95% confidence interval 0.15–0.72; P = 0.006) was an independent predictor for CSS in multivariate analysis.CONCLUSIONSOverall LN density is an independent predictor of survival after RC and extended LND with curative intent. Evaluation of topographically restricted LN positivity and density for different regions and levels of LND does not improve the prediction of CSS compared with overall LN positivity and density. A low incidence of level 3 LN positivity questions the clinical relevance of removing para‐aortic and paracaval LNs. However, our data need to be confirmed by a prospective randomized trial.
Magnetic resonance imaging in the prediction of biochemical recurrence of prostate cancer after radical prostatectomy
Authors: Fuchsjäger Michael H. , Shukla‐Dave Amita , Hricak Hedvig , Wang Liang , Touijer Karim , Donohue John F. , Eastham James A. , Kattan Michael W. 
Published: February 2009

OBJECTIVETo investigate whether magnetic resonance imaging (MRI) findings, when converted into a scoring system, can predict the biochemical recurrence of prostate cancer after radical prostatectomy (RP).PATIENTS AND METHODSBetween January 2000 and October 2004, 610 patients with biopsy‐confirmed prostate cancer had MRI before RP, with whole‐mount step‐sectioning of the pathology sample. MRI findings were retrospectively scored on a seven‐point scale based on Tumour‐Node‐Mestastasis staging (1, no tumour seen, to 7, lymph node metastasis). MRI scores were added to published 5‐ and 10‐year clinical preoperative nomograms for predicting recurrence. The predictive accuracy of MRI was quantified as the differences in bootstrap‐corrected concordance indices of the models with and without MRI.RESULTSAs of August 2007, 64 (10.5%) patients had a biochemical recurrence. MRI scores were associated with recurrence (P < 0.001) with hazard ratios of 1.76 and 1.81 in the 5‐ and 10‐year models, respectively. Actual recurrence rates by MRI score were: 1, 0%; 2, 4.5%; 3, 9%; 4, 24.1%; 5, 33.3%; 6, 69.2%; 7, 100%. When MRI was added, the concordance indices of the 5‐ and 10‐year models increased, from 0.762 to 0.776 (P = 0.081) and 0.773 to 0.788 (P = 0.107), respectively; the improvement was not significant.CONCLUSIONThe MRI scoring system devised was a strong predictor of biochemical recurrence after RP. Although MRI did not provide added prognostic value to standard clinical nomograms, in centres where MRI is used routinely, it might increase the confidence of the clinician in assessing the risk of recurrence by contributing supporting data.
Bridging gaps in risk discourse: home care case management and client choices
Authors: Ceci Christine , Purkis Mary Ellen 
Published: February 2009

AbstractThis paper examines, and problematises, a well‐entrenched conceptualisation of how home care case management practice works – that is, that case managers offer alternatives, and clients make choices. This understanding of practice is reinforced by organisational policy that states that clients have the right to live at risk if that is their choice. Analysis of data from a field study of home care practice in a western Canadian city, drawing predominantly on case managers’ accounts of actual practice situations, underscores the limitations of such a view, and suggests that conceptualising such practices as ongoing and fragile negotiations between freedom and security offers a more useful frame for thinking through the distance and difference between current home care policy and practice and what people might actually need.
Economic inequality and population health: looking beyond aggregate indicators
Authors: Böckerman Petri , Johansson Edvard , Helakorpi Satu , Uutela Antti 
Published: February 2009

AbstractThis paper studies the sensitivity of various health indicators to income inequality as measured by regional Gini coefficients, using individual microdata from Finland over the period 1993–2005. There is no overall association between income and health at the regional level. We discovered that, among men, there are no significant associations between income inequality and several measures of health status. Among women or among both sexes combined, there are some indications of associations in the predicted direction between income inequality and physical health, disability retirement, sick leave, and consumption of medicines, but none are robust to different model specifications. Only among the population aged less than 30 there is some indication that mental health is associated with inequality. Our findings confirm that income inequality in small populations (not large enough to measure the overall class pyramid of the society) is often immaterial for health outcomes.
‘Futureless persons’: shifting life expectancies and the vicissitudes of progressive illness
Authors: Gibson Barbara E. , Zitzelsberger Hilde , McKeever Patricia 
Published: February 2009

AbstractMedical technological advances can have profound effects on people's lives by extending the life course and creating uncertain futures. This is the case for a number of persons with ‘diseases of childhood’ who can now survive well into adulthood with technological support. This paper draws on a Canadian qualitative study of young men with Duchenne muscular dystrophy (DMD) which examined the effects of a shifting life expectancy on personal identities. Engaging with Pierre Bourdieu's central concept of habitus, we discuss the temporal dimensions of social exclusion and marginalised identities. Participants’ narrative accounts revealed how their dispositions were orientated to a shortened lifespan that exerted damaging effects regardless of actual lifespan. Compounding their material, social and symbolic isolation was a temporal isolation whereby the men had lived every day anticipating that it could be their last for as much as a decade. The findings suggest a need to re‐orient medical and social discourses to serve and include adults with DMD and other conditions previously limited to childhood in their communities.
The effects of natalizumab on inflammatory mediators in multiple sclerosis: prospects for treatment‐sensitive biomarkers
Authors: Khademi M. , Bornsen L. , Rafatnia F. , Andersson M. , Brundin L. , Piehl F. , Sellebjerg F. , Olsson T. 
Published: February 2009

Background:  Natalizumab affects systemic cytokine expressions and clinical course in relapsing–remitting multiple sclerosis (RRMS). We analyzed levels of inflammatory cytokines in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs), levels of matrix metalloproteinase (MMP)‐9 and osteopontin (OPN) in CSF, and clinical outcome measures in 22 natalizumab‐treated RRMS patients.Methods:  mRNA levels of cytokines in cells were detected with real‐time RT‐PCR. Protein levels of OPN and MMP‐9 were measured by ELISA.Results:  Natalizumab reduced CSF cell counts (P < 0.0001). Tumor necrosis factor (TNF) and interferon‐γ (IFN‐γ) mRNAs were significantly increased in PBMCs. In contrast, expressions of IFN‐γ and interleukin (IL)‐23 were decreased but IL‐10 increased in the CSF cells. OPN and MMP‐9 were reduced in the CSF. Patients being in remission at baseline showed the same deviations of mediators as those in relapse after natalizumab treatment. The open label clinical outcome measures were either stable or improved during therapy.Conclusions:  Natalizumab attenuates pro‐inflammatory mediators intrathecally and the reduced pro‐inflammatory milieu may allow increased production of the anti‐inflammatory mediator IL‐10. The increased systemic cytokines may impede the improvement of certain clinical measures like fatigue. The affected mediators seem to be sensitive to an immune‐modifying treatment which could be used as biomarkers for this therapy.
Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources
Authors: Dryden C , Young D , Hepburn M , Mactier H 
Published: February 2009

Objectives  The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug‐misusing women.Design  Retrospective cohort study from 1 January 2004 to 31 December 2006.Setting  Inner‐city maternity hospital providing dedicated multidisciplinary care to drug‐misusing women.Population  Four hundred and fifty singleton pregnancies of drug‐misusing women prescribed substitute methadone in pregnancy.Methods  Case note review.Main outcome measures  Development of NAS and duration of infant hospital stay.Results  45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34–0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7–17 days). Infants born to methadone‐prescribed drug‐misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days.Conclusions  Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug‐misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources.
Tissue plasminogen activator promotes axonal outgrowth on CNS myelin after conditioned injury
Authors: Minor Kenneth , Phillips Jacob , Seeds Nicholas W. 
Published: February 2009

J. Neurochem. (2009) 109, 706–715.AbstractFollowing CNS injury, myelin‐associated inhibitors represent major obstacles to axonal regeneration and functional recovery. The following study suggests that the proteolytic enzyme tissue plasminogen activator (tPA) plays a major function in ‘conditioning‐injury induced’ axon regeneration. In this paradigm, prior peripheral nerve injury leads to an enhanced ability of sensory neurons to regenerate their central axons in the presence of the CNS inhibitory microenvironment. tPA is widely expressed by CNS and PNS neurons and plays major roles in synaptic reorganization and plasticity. This study shows that cultured neurons from mice deficient in tPA, in contrast to wild‐type mice, fail to undergo conditioning‐injury induced axonal regeneration in the presence of purified myelin membranes. Interestingly, neurons from mice deficient in plasminogen, the best known substrate for tPA, showed active axon regeneration. These results suggest a novel plasminogen‐independent role for tPA in promoting axonal regeneration on CNS myelin.
Cerebral inflammation contributes to encephalopathy and brain edema in acute liver failure: protective effect of minocycline
Authors: Jiang Wenlei , Desjardins Paul , Butterworth Roger F. 
Published: February 2009

AbstractEncephalopathy and brain edema are serious complications of acute liver failure (ALF). The precise pathophysiologic mechanisms responsible have not been fully elucidated but it has been recently proposed that microglia‐derived proinflammatory cytokines are involved. In the present study we evaluated the role of microglial activation and the protective effect of the anti‐inflammatory drug minocycline in the pathogenesis of hepatic encephalopathy and brain edema in rats with ALF resulting from hepatic devascularisation. ALF rats were killed 6 h after hepatic artery ligation before the onset of neurological symptoms and at coma stages of encephalopathy along with their appropriate sham‐operated controls and in parallel with minocycline‐treated ALF rats. Increased OX‐42 and OX‐6 immunoreactivities confirming microglial activation were accompanied by increased expression of interleukins (IL‐1β, IL‐6) and tumor necrosis factor‐alpha (TNF‐α) in the frontal cortex at coma stage of encephalopathy in ALF rats compared with sham‐operated controls. Minocycline treatment prevented both microglial activation as well as the up‐regulation of IL‐1β, ΙL‐6 and TNF‐α mRNA and protein expression with a concomitant attenuation of the progression of encephalopathy and brain edema. These results offer the first direct evidence for central proinflammatory mechanisms in the pathogenesis of brain edema and its complications in ALF and suggest that anti‐inflammatory agents may be beneficial in these patients.
Stability of international environmental agreements: an illustration with asymmetrical countries
Authors: Bahn Olivier , Breton Michèle , Sbragia Lucia , Zaccour Georges 
Published: February 2009

AbstractIn this paper we use a dynamic model to analyze the composition and stability of international environmental agreements (IEAs) in an asymmetrical framework. Signatory countries are assumed to optimize the total welfare of the international agreement's members, while non‐signatory countries optimize their own individual welfare, taking into account the dynamics of the pollution stock. Our model is calibrated using data from the MERGE climate policy assessment model. We briefly review two contrasting approaches to define stability of IEAs, and provide a numerical illustration in each case.
Applying path‐counting methods for measuring the robustness of the network‐structured system
Authors: Kobayashi Kazuhiro , Morohosi Hozumi , Oyama Tatsuo 
Published: February 2009

AbstractWe consider the path‐counting problem that asks how many paths exist between any two different nodes in a network after deleting an arbitrary number of edges or nodes from the original network. Using path‐counting methods, we propose a quantitative method for measuring the robustness of the network‐structured system. First we define the connectivity function and attempt to obtain the expected connectivity function for the network. Applying the Monte Carlo method, we estimate expected edge deletion and node deletion connectivity functions when an arbitrary number of edges or nodes are deleted from the original network. We attempt to approximate the expected edge deletion connectivity function using an appropriate nonlinear function with two parameters. We also show the numerical results of applying the path‐counting method with their analysis in order to quantitatively evaluate the connectivity for some special types of networks.
Mild Head Trauma and Chronic Headaches in Returning US Soldiers
Authors: Theeler Brett J. , Erickson Jay C. 
Published: February 2009

Objective.— To determine the incidence and types of head or neck trauma and headache characteristics among US Army soldiers evaluated for chronic headaches at a military neurology clinic following a combat tour in Iraq.Background.— Head or neck trauma and headaches are common in US soldiers deployed to Iraq. The temporal association between mild head trauma and headaches, as well as the clinical characteristics of headaches associated with mild head trauma, has not been systematically studied in US soldiers returning from Iraq.Methods.— A retrospective cohort study was conducted with 81 US Army soldiers from the same brigade who were evaluated at a single military neurology clinic for recurrent headaches after a 1‐year combat tour in Iraq. All subjects underwent a standardized interview and evaluation to determine the occurrence of head or neck trauma during deployment, mechanism and type of trauma, headache type, and headache characteristics.Results.— In total, 33 of 81 (41%) soldiers evaluated for headaches reported a history of head or neck trauma while deployed to Iraq. A total of 18 (22%) subjects had concussion without loss of consciousness and 15 (19%) had concussion with loss of consciousness. Ten subjects also had an accompanying traumatic neck injury. No subjects had moderate or severe traumatic brain injury. Exposure to blasts was the most common cause of trauma, accounting for 67% of head and neck injuries. Headaches began within one week after trauma in 12 of 33 (36%) soldiers with head or neck injury. Another 12 (36%) reported worsening of pre‐existing headaches after trauma. Headaches were classified as migraine type in 78% of soldiers with head or neck trauma. Headache types, frequency, severity, duration, and disability were similar for soldiers with and without a history of head or neck trauma.Conclusion.— A history of mild head trauma, usually caused by exposure to blasts, is found in almost half of returning US combat troops who receive specialized care for headaches. In many cases, head trauma was temporally associated with either the onset of headaches or the worsening of pre‐existing headaches, implicating trauma as a precipitating or exacerbating factor, respectively. Headaches in head trauma‐exposed soldiers are usually migraine type and are similar to nontraumatic headaches encountered at a military specialty clinic.
Igf1r+/CD34+immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast‐like ICC in Ws/Ws rat colon
Authors: Wang X.Y. , Albertí E. , White E.J. , Mikkelsen H.B. , Larsen J.O. , Jiménez M. , Huizinga J.D. 
Published: February 2009

AbstractThe colon of Ws/Ws mutant rats shows impairment of pacemaker activity and altered inhibitory neurotransmission. The present study set out to find structural correlates to these findings to resolve mechanisms. In the colon of Ws/Ws rats, interstitial cells of Cajal associated with Auerbach’s plexus (ICC‐AP) were significantly decreased and ICC located at the submuscular plexus and intramuscular ICC were rarely observed based on immunohistochemistry and electron microscopy. Ultrastructural investigations revealed that there was no overall loss of all types of interstitial cells combined. Where loss of ICC was observed, a marked increase in fibroblast‐like ICC (FL‐ICC) was found at the level of AP. Immunoelectron microscopy proved FL‐ICC to be c‐Kit–but gap junction coupled to each other and to c‐Kit+ICC; they were associated with enteric nerves and occupied space normally occupied by ICC in the wild‐type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin‐like growth factor 1 receptor (Igf1r) occurred, co‐localized with CD34 but not with c‐Kit. A significantly higher number of Igf1r+/CD34+cells were found in Ws/Ws compared to wild‐type rat colons. These CD34+/Igf1r+cells in the Ws/Ws colon occupied the same space as FL‐ICC. Hence we propose that a subset of immature ICC (FL‐ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase. The functional capabilities of the immature ICC and the regenerative capabilities of the adult progenitor cells need further study. The morphological features described here show that the loss of pacemaker activity is not associated with failure to develop a network of interstitial cells around AP but a failure to develop this network into fully functional pacemaker cells. The reduction in nitrergic innervation associated with the Ws mutation may be the result of a reduction in nitrergic neurons.
The R439C mutation in LMNA causes lamin oligomerization and susceptibility to oxidative stress
Authors: Verstraeten Valerie L.R.M. , Caputo Sandrine , Van Steensel Maurice A.M. , Duband‐Goulet Isabelle , Zinn‐Justin Sophie , Kamps Miriam , Kuijpers Helma J.H. , Östlund Cecilia , Worman Howard J. , Briedé Jacob J. , Le Dour Caroline , Marcelis Carlo L.M. , Van Geel Michel , Steijlen Peter M. , Van Den Wijngaard Arthur , Ramaekers Frans C.S. , Broers Jos L.V. 
Published: February 2009

AbstractDunnigan‐type familial partial lipodystrophy (FPLD) is a laminopathy characterized by an aberrant fat distribution and a metabolic syndrome for which oxidative stress has recently been suggested as one of the disease‐causing mechanisms. In a family affected with FPLD, we identified a heterozygous missense mutation c.1315C>T in the LMNA gene leading to the p.R439C substitution. Cultured patient fibroblasts do not show any prelamin A accumulation and reveal honeycomb‐like lamin A/C formations in a significant percentage of nuclei. The mutation affects a region in the C‐terminal globular domain of lamins A and C, different from the FPLD‐related hot spot. Here, the introduction of an extra cysteine allows for the formation of disulphide‐mediated lamin A/C oligomers. This oligomerization affects the interaction properties of the C‐terminal domain with DNA as shown by gel retardation assays and causes a DNA‐interaction pattern that is distinct from the classical R482W FPLD mutant. Particularly, whereas the R482W mutation decreases the binding efficiency of the C‐terminal domain to DNA, the R439C mutation increases it. Electron spin resonance spectroscopy studies show significantly higher levels of reactive oxygen species (ROS) upon induction of oxidative stress in R439C patient fibroblasts compared to healthy controls. This increased sensitivity to oxidative stress seems independent of the oligomerization and enhanced DNA binding typical for R439C, as both the R439C and R482W mutants show a similar and significant increase in ROS upon induction of oxidative stress by H2O2.