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Showing papers by "University of Barcelona published in 2004"


Journal ArticleDOI
TL;DR: Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
Abstract: background The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results. methods In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation. results The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors. conclusions Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.

2,436 citations


Journal ArticleDOI
TL;DR: In this paper, the degradation of chlorophenols (CPs) by means of advanced oxidation processes (AOPs) was evaluated during the period 1995-2002 and different mechanistic degradation pathways were taken into account.
Abstract: Advanced oxidation processes (AOPs) constitute a promising technology for the treatment of wastewaters containing non-easily removable organic compounds. Chlorophenols (CPs) are a group of special interest due to their high toxicity and low biodegradability. Data concerning the degradation of CPs by means of AOPs reported during the period 1995–2002 are evaluated in this work. Among the AOPs, the following techniques are studied: processes based on hydrogen peroxide (H2O2+UV, Fenton, photo-Fenton and Fenton-like processes), photolysis, photocatalysis and processes based on ozone (O3, O3+UV and O3+catalyst). Half-life times and kinetic constants for CP degradation are reviewed and the different mechanistic degradation pathways are taken into account.

2,024 citations


Journal ArticleDOI
TL;DR: To describe the 12‐month and lifetime prevalence rates of mood, anxiety and alcohol disorders in six European countries, a large number of countries with high prevalence of these disorders have been surveyed.
Abstract: Objective: To describe the 12-month and lifetime prevalence rates of mood, anxiety and alcohol disorders in six European countries. Method: A representative random sample of non-institutionalized inhabitants from Belgium, France, Germany, Italy, the Netherlands and Spain aged 18 or older (n = 21425) were interviewed between January 2001 and August 2003. DSM-IV disorders were assessed by lay interviewers using a revised version of the Composite International Diagnostic Interview (WMH-CIDI). Results: Fourteen per cent reported a lifetime history of any mood disorder, 13.6% any anxiety disorder and 5.2% a lifetime history of any alcohol disorder. More than 6% reported any anxiety disorder, 4.2% any mood disorder, and 1.0% any alcohol disorder in the last year. Major depression and specific phobia were the most common single mental disorders. Women were twice as likely to suffer 12-month mood and anxiety disorders as men, while men were more likely to suffer alcohol abuse disorders. Conclusion: ESEMeD is the first study to highlight the magnitude of mental disorders in the six European countries studied. Mental disorders were frequent, more common in female, unemployed, disabled persons, or persons who were never married or previously married. Younger persons were also more likely to have mental disorders, indicating an early age of onset for mood, anxiety and alcohol disorders.

1,780 citations


Journal ArticleDOI
TL;DR: An international panel of neurologists interested in PNS recommended new criteria for those in whom no clinical consensus was reached in the past and defined “classical” syndrome and onconeural antibody as “well characterised”.
Abstract: Background: Paraneoplastic neurological syndromes (PNS) are defined by the presence of cancer and exclusion of other known causes of the neurological symptoms, but this criterion does not separate “true” PNS from neurological syndromes that are coincidental with a cancer. Objective: To provide more rigorous diagnostic criteria for PNS. Methods: An international panel of neurologists interested in PNS identified those defined as “classical” in previous studies. The panel reviewed the existing diagnostic criteria and recommended new criteria for those in whom no clinical consensus was reached in the past. The panel reviewed all reported onconeural antibodies and established the conditions to identify those that would be labelled as “well characterised”. The antibody information was obtained from published work and from unpublished data from the different laboratories involved in the study. Results: The panel suggest two levels of evidence to define a neurological syndrome as paraneoplastic: “definite” and “possible” . Each level can be reached combining a set of criteria based on the presence or absence of cancer and the definitions of “classical” syndrome and “well characterised” onconeural antibody. Conclusions: The proposed criteria should help clinicians in the classification of their patients and the prospective and retrospective analysis of PNS cases.

1,358 citations


Journal ArticleDOI
TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Abstract: background Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. methods Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. results Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. conclusions The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

1,336 citations


Journal ArticleDOI
TL;DR: The value of the biopsychosocial model has not been in the discovery of new scientific laws, as the term “new paradigm” would suggest, but rather in guiding parsimonious application of medical knowledge to the needs of each patient.
Abstract: The biopsychosocial model is both a philosophy of clinical care and a practical clinical guide. Philosophically, it is a way of understanding how suffering, disease, and illness are affected by multiple levels of organization, from the societal to the molecular. At the practical level, it is a way of understanding the patient’s subjective experience as an essential contributor to accurate diagnosis, health outcomes, and humane care. In this article, we defend the biopsychosocial model as a necessary contribution to the scientific clinical method, while suggesting 3 clarifications: (1) the relationship between mental and physical aspects of health is complex—subjective experience depends on but is not reducible to laws of physiology; (2) models of circular causality must be tempered by linear approximations when considering treatment options; and (3) promoting a more participatory clinician-patient relationship is in keeping with current Western cultural tendencies, but may not be universally accepted. We propose a biopsychosocial-oriented clinical practice whose pillars include (1) self-awareness; (2) active cultivation of trust; (3) an emotional style characterized by empathic curiosity; (4) self-calibration as a way to reduce bias; (5) educating the emotions to assist with diagnosis and forming therapeutic relationships; (6) using informed intuition; and (7) communicating clinical evidence to foster dialogue, not just the mechanical application of protocol. In conclusion, the value of the biopsychosocial model has not been in the discovery of new scientific laws, as the term “new paradigm” would suggest, but rather in guiding parsimonious application of medical knowledge to the needs of each patient.

1,207 citations


Journal ArticleDOI
TL;DR: In this paper, it is suggested that there may be several effects contributing to the catalytic properties of supported nanosized gold particles, and that it is useful to order them in a hierarchy.

1,109 citations


Journal ArticleDOI
TL;DR: It is proposed that the FKBP5 variant–dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals.
Abstract: The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

903 citations


Journal ArticleDOI
TL;DR: The KIDMED index, the first to evaluate the adequacy of Mediterranean dietary patterns in children and youth, confirms that this collective is undergoing important changes, which makes them a priority target for nutrition interventions.
Abstract: Objective To evaluate dietary habits in Spanish children and adolescents based on a Mediterranean Diet Quality Index tool, which considers certain principles sustaining and challenging traditional healthy Mediterranean dietary patterns. Design Observational population-based cross-sectional study. A 16-item Mediterranean Diet Quality Index was included in data gathered for the EnKid study (in which two 24-hour recalls, a quantitative 169-item food-frequency questionnaire and a general questionnaire about socio-economic, demographic and lifestyle items were administered). Setting Spain. Subjects In total, 3850 children and youths aged 2-24 years residing in Spain. Results Of the sample, 4.2% showed very low KIDMED index results, 49.4% had intermediate values and 46.4% had high index results. Important geographical differences were seen, with subjects from the Northeast showing the most favourable outcomes (52% with elevated scores vs. 37.5% of those from the North). Lower percentages of high diet quality were observed in low socio-economic groups, compared with middle and upper income cohorts (42.8%, 47.6% and 54.9%, respectively). Large cities had more positive results and only slight variations were seen for gender and age. Conclusions The KIDMED index, the first to evaluate the adequacy of Mediterranean dietary patterns in children and youth, confirms that this collective is undergoing important changes, which makes them a priority target for nutrition interventions. Results challenge certain commonly perceived notions tied to income level, population size and diet quality.

888 citations



Journal ArticleDOI
TL;DR: In this paper, Spanish learners of Catalan and Korean learners of Spanish were asked to perform a switching task between their first and dominant languages (L1, Spanish or Korean) and their second language (L2, Catalan or Spanish).


Journal ArticleDOI
TL;DR: Analytical results are derived, showing that the proposed class of models of social network formation reproduces the main statistical characteristics of real social networks: large clustering coefficient, positive degree correlations, and the emergence of a hierarchy of communities.
Abstract: We propose a class of models of social network formation based on a mathematical abstraction of the concept of social distance. Social distance attachment is represented by the tendency of peers to establish acquaintances via a decreasing function of the relative distance in a representative social space. We derive analytical results (corroborated by extensive numerical simulations), showing that the model reproduces the main statistical characteristics of real social networks: large clustering coefficient, positive degree correlations, and the emergence of a hierarchy of communities. The model is confronted with the social network formed by people that shares confidential information using the Pretty Good Privacy (PGP) encryption algorithm, the so-called web of trust of PGP.

Journal ArticleDOI
TL;DR: The authors describe measures for the control of ascites as well as strategies for its management and for the prevention of major complications, including gastrointestinal bleeding, spontaneous bacterial peritonitis, and the hepatorenal syndrome.
Abstract: This review summarizes current knowledge about the pathophysiology of ascites and explains the appropriate approach to clinical evaluation. The authors describe measures for the control of ascites as well as strategies for its management and for the prevention of major complications, including gastrointestinal bleeding, spontaneous bacterial peritonitis, and the hepatorenal syndrome.

Journal ArticleDOI
TL;DR: A number of alterations, both directly and indirectly related to hepatic injury and portal hypertension, result in the production or release of mediators into the venous circulation, where they influence the pulmonary microcirculation in experimental hepatopulmonary syndrome.
Abstract: ⇓“The tantalizing problem of the connective link in cirrhotic patients between oxygen unsaturation and possible arteriovenous shunting in the lungs remains unsolved, and any relation between arterial unsaturation and pulmonary vasodilation remains obscure.” Fig. 1.— Working model of molecular alterations in the pulmonary microcirculation in experimental hepatopulmonary syndrome (HPS). a) In the normal microvasculature, a balance of vasoconstrictive and vasodilatory factors, including paracrine endothelin (ET)-1-mediated vasoconstriction through the ETA receptor (▪) on smooth muscle cells (SMCs) and ET-1-mediated vasodilatation mediated through the ETB receptor (□) linked to endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs), maintain tone. b) During the development of HPS, a number of alterations, both directly and indirectly related to hepatic injury and portal hypertension, result in the production or release of mediators into the venous circulation, where they influence the pulmonary microcirculation. Increased expression of pulmonary endothelial ETB receptors and increased hepatic production and release of ET-1 contribute to an increase in eNOS expression and enhanced nitric oxide (NO) production in the microvascular endothelium during the initiation of HPS. Tumour necrosis factor (TNF)-α-mediated accumulation of intravascular macrophage-like cells also occurs after chronic common bile duct ligation. Haem oxygenase (HO)-1 and inducible nitric oxide synthase (iNOS) expression increase in these cells and contribute to the progression of HPS. CO: carbon monoxide. Fig. 2.— Algorithm for screening and therapeutic decisions in hepatopulmonary syndrome (HPS). OLT: orthotopic liver transplantation; P a,O2: arterial oxygen tension; P A–a,O2: alveolar–arterial oxygen tension difference; CEE: contrast-enhanced echocardiography; PFT: pulmonary function test; MAA: macroaggregated albumin. #: high-resolution thoracic computed tomographic scanning is highly recommended in order to exclude chronic respiratory comorbid conditions; ¶: high risk for post-operative OLT mortality. 1 mmHg=0.133 kPa. Fig. 3.— Plot demonstrating the relationship between cardiac output ( Q ') and transpulmonary pressure gradient (TPG; mean pulmonary arterial …

Journal ArticleDOI
TL;DR: Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates and may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS).
Abstract: The SLC7 family is divided into two subgroups, the cationic amino acid transporters (the CAT family, SLC7A1–4) and the glycoprotein-associated amino acid transporters (the gpaAT family, SLC7A5–11), also called light chains or catalytic chains of the hetero(di)meric amino acid transporters (HAT). The associated glycoproteins (heavy chains) 4F2hc (CD98) or rBAT (D2, NBAT) form the SLC3 family. Members of the CAT family transport essentially cationic amino acids by facilitated diffusion with differential trans-stimulation by intracellular substrates. In some cells, they may regulate the rate of NO synthesis by controlling the uptake of l-arginine as the substrate for nitric oxide synthase (NOS). The heterodimeric amino acid transporters are, in contrast, quite diverse in terms of substrate selectivity and function (mostly) as obligatory exchangers. Their selectivity ranges from large neutral amino acids (system L) to small neutral amino acids (ala, ser, cys-preferring, system asc), negatively charged amino acid (system xc−) and cationic amino acids plus neutral amino acids (system y+L and b0,+-like). Cotransport of Na+ is observed only for the y+L transporters when they carry neutral amino acids. Mutations in b0,+-like and y+L transporters lead to the hereditary diseases cystinuria and lysinuric protein intolerance (LPI), respectively.

Journal ArticleDOI
TL;DR: The present manuscript depicts the Barcelona‐Clínic Liver Cancer Group diagnostic and treatment strategy, based on the analysis of several cohort and randomized controlled studies that have allowed the continuous refinement of treatment indication and application.

Journal ArticleDOI
TL;DR: The role of leaf senescence in field-grown plants as a response to adverse climatic conditions and, more specifically, on how it contributes to plant survival under drought stress is focused on.
Abstract: Leaf senescence is a highly regulated physiological process that leads to leaf death and is, as such, the last developmental stage of the leaf. Plant aging and environmental stresses may induce the process of senescence. Here we will focus on the role of leaf senescence in field-grown plants as a response to adverse climatic conditions and, more specifically, on how it contributes to plant survival under drought stress. Drought induces several responses in plants including leaf senescence, which plays a major role in the survival of several species. Drought-induced leaf senescence contributes to nutrient remobilisation during stress, thus allowing the rest of the plant (i.e. the youngest leaves, fruits or flowers) to benefit from the nutrients accumulated during the life span of the leaf. In addition, drought-induced leaf senescence, especially when accompanied by leaf abscission, avoids large losses through transpiration, thus contributing to the maintenance of a favourable water balance of the whole plant. Drought-induced leaf senescence occurs gradually and is characterised by specific macroscopic, cellular, biochemical and molecular changes. Leaf yellowing (i.e. chlorophyll degradation) and specific changes in cell ultrastructure (e.g. chromatin condensation, thylakoid swelling, plastoglobuli accumulation), metabolism (e.g.protein degradation, lipid peroxidation) and gene expression occur during leaf senescence in drought-stressed plants. Cytokinins and ABA have been shown to be involved in the regulation of drought-induced leaf senescence, although the possible role of other plant hormones should not be excluded. Reactive oxygen species, whose concentrations increase during drought-induced leaf senescence, are also known to be regulators of this process. The complex mechanisms of regulation of leaf senescence in drought-stressed plants are discussed, and attention is drawn to those aspects that still require investigation.

Journal ArticleDOI
TL;DR: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.
Abstract: Objective: The HepatAssist liver support system is an extracorpo-real porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective. random-ized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL Versus 59% for control (it = 147; P= 0.12). When Survival was analyzed accounting for confounding factors. in the entire patient Population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio 0.56: P = 0.048). Conclusions: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Journal ArticleDOI
TL;DR: Evidence of neuropsychological impairment in euthymic bipolar patients is provided, after controlling for the effect of subsyndromal depressive symptoms, suggesting verbal memory and executive dysfunctions.
Abstract: Objective: Cognitive impairment in bipolar disorder may be a stable characteristic of the illness, although discrepancies have emerged with regard to what dysfunctions remain during remission periods. The aim of this study was to ascertain whether euthymic bipolar patients would show impairment in verbal learning and memory and in executive functions compared with healthy controls. Secondly, to establish if there was a relationship between clinical data and neuropsychological performance. Methods: Forty euthymic bipolar patients were compared with 30 healthy controls through a battery of neuropsychological tests assessing estimated premorbid IQ, attention, verbal learning and memory, and frontal executive functioning. The effect of subsyndromal symptomatology was controlled. Results: Remitted bipolar patients performed worse than controls in several measures of memory and executive function, after controlling for the effect of subclinical symptomatology, age and premorbid IQ. Verbal memory impairment was related to global assessment of function scores, as well as to a longer duration of illness, a higher number of manic episodes, and prior psychotic symptoms. Conclusions: Results provide evidence of neuropsychological impairment in euthymic bipolar patients, after controlling for the effect of subsyndromal depressive symptoms, suggesting verbal memory and executive dysfunctions. Cognitive impairment seems to be related to a worse clinical course and poor functional outcome.

Journal ArticleDOI
TL;DR: This manuscript examines the impact of mental health state and specific mental and physical disorders on work role disability and quality of life in six European countries.
Abstract: Objective: This manuscript examines the impact of mental health state and specific mental and physical disorders on work role disability and quality of life in six European countries. Method: The ESEMeD study was conducted in: Belgium, France, Germany, Italy, the Netherlands and Spain. Individuals aged 18 years and over who were not institutionalized were eligible for an in-home computer-assisted interview. Common mental disorders, work loss days (WLD) in the past month and quality of life (QoL) were assessed, using the WMH-2000 version of the CIDI, the WHODAS-II, and the mental and physical component scores (MCS, PCS) of the 12-item short form, respectively. The presence of five chronic physical disorders: arthritis, heart disease, lung disease, diabetes and neurological disease was also assessed. Multivariate regression techniques were used to identify the independent association of mental and physical disorders while controlling for gender, age and Country. Results: In each country, WLD and loss of QoL increased with the number of disorders. Most mental disorders had approximately 1.0 SD-unit lower mean MCS and lost three to four times more work days, compared with people without any 12-month mental disorder. The 10 disorders with the highest independent impact on WLD were: neurological disease, panic disorder, PTSD, major depressive episode, dysthymia, specific phobia, social phobia, arthritis, agoraphobia and heart disease. The impact of mental vs. physical disorders on QoL was specific, with mental disorders impacting more on MCS and physical disorders more on PCS. Compared to physical disorders, mental disorders had generally stronger 'cross-domain' effects. Conclusion: The results suggest that mental disorders are important determinants of work role disability and quality of life, often outnumbering the impact of common chronic physical disorders.

Journal ArticleDOI
TL;DR: The present neuropathological study reports the second case of menigoencephalitis following immunization with amyloid‐β peptide in AD, and focuses on exploring mechanisms underlying decreased tau pathology in relation to amyliod deposit regression, and possible molecular bases involved in the inflammatory response following Immunization.
Abstract: Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop beta-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non-treated transgenic animals. Immunization with amyloid-beta peptide has been initiated in a randomised pilot study in AD. Yet a minority of patients developed a neurological complication consistent with meningoencephalitis and one patient died; the trial has been stopped. Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads. The present neuropathological study reports the second case of meningoencephalitis following immunization with amyloid-beta peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation with amyloid deposit regression, and possible molecular bases involved in the inflammatory response following immunization. Inflammatory infiltrates were composed of CD8+, CD4+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. Characteristic neuropathological findings were focal depletion of diffuse and neuritic plaques, but not of amyloid angiopathy, and the presence of small numbers of extremely dense (collapsed) plaques surrounded by active microglia, and multinucleated giant cells filled with dense Abeta42 and Abeta40, in addition to severe small cerebral blood vessel disease and multiple cortical hemorrhages. Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1: SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau dependent on beta-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. Furthermore, amyloid reduction was accompanied by increased expression of the PA28a/beta inductor, and of LMP7, LMP2 and MECL1 subunits of the immunoproteasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells. Immunoproteasome subunit expression was accompanied by local presentation of MHC class I molecules. Release of antigenic peptides derived from beta-amyloid processing may enhance T-cell inflammatory responses accounting for the meningoencephalitis following amyloid-beta peptide immunization.

Journal ArticleDOI
TL;DR: Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features, and ECOG‐PS >1, ‘cutaneous variant’, stage I and chemotherapy use were independently associated with improved survival.
Abstract: Summary Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34‐90; male:female ratio 0AE9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin (‘cutaneous variant’; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve

Journal ArticleDOI
TL;DR: In this article, the authors integrate recent knowledge of the molecular inner workings of the prototype signaling cascades with their specific roles in intestinal epithelial homeostasis and in neoplastic transformation of the epithelium.
Abstract: The study of the epithelium of the adult mammalian intestine touches upon many modern aspects of biology. The epithelium is in a constant dialogue with the underlying mesenchyme to control stem cell activity, proliferation in transit-amplifying compartments, lineage commitment, terminal differentiation and, ultimately, cell death. There are spatially distinct compartments dedicated to each of these events. The Wnt, TGF-beta, BMP, Notch, and Par polarity pathways are the major players in homeostatic control of the adult epithelium. Several hereditary cancer syndromes deregulate these same signaling cascades through mutational (in)activation. Moreover, these mutations often also occur in sporadic tumors. Thus symmetry exists between the roles that these signaling pathways play in physiology and in cancer of the intestine. This is particularly evident for the Wnt/APC pathway, for which the mammalian intestine has become one of the most-studied paradigms. Here, we integrate recent knowledge of the molecular inner workings of the prototype signaling cascades with their specific roles in intestinal epithelial homeostasis and in neoplastic transformation of the epithelium.

Journal ArticleDOI
TL;DR: Chemoembolization, a technique combining intra-arterial chemotherapy and selected ischemia, has produced modest survival advantages in 2 RCTs and a meta-analysis, and is currently the mainstay of treatment for these stages.

Journal ArticleDOI
TL;DR: A microscopic calculation of ground state entanglement for the XY and Heisenberg models shows the emergence of universal scaling behavior at quantum phase transitions and a possible connection be-tween majorization and renormalization group irreversibility emerges from the numerical analysis.
Abstract: A microscopic calculation of ground state entanglement for the XY and Heisenbergmodels shows the emergence of universal scaling behavior at quantum phase transitions,Entanglement is thus controlled by conformal symmetry, Away from the critical point,entanglement gets saturated by a mass scale, Results borrowed from conformal fieldtheory imply irreversibility of entanglement loss along renormalization group trajecto-ries. Entanglement does not saturate in higher dimensions which appears to limit thesuccess of the density matrix renormalization group technique. A possible connection be-tween majorization and renormalization group irreversibility emerges from our numericalanalysis.

Journal ArticleDOI
TL;DR: The first results of the use of health services for mental disorders in six European countries as part of the ESEMeD project are presented.
Abstract: The ESEMeD ⁄ MHEDEA 2000 investigators. Use of mental health services in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand 2004: 109 (Suppl. 420): 47–54. a Blackwell Munksgaard 2004. Objective: Comprehensive information about access and patterns of use of mental health services in Europe is lacking. We present the first results of the use of health services for mental disorders in six European countries as part of the ESEMeD project. Method: The study was conducted in: Belgium, France, Germany, Italy, the Netherlands and Spain. Individuals aged 18 years and over who were not institutionalized were eligible for an computer-assisted interview done at home. The 21 425 participants were asked to report how frequently they consulted formal health services due to their emotions or mental health, the type of professional they consulted and the treatment they received as a result of their consultation in the previous year. Results: An average of 6.4% of the total sample had consulted formal health services in the previous 12months. Of the participants with a 12-month mental disorder, 25.7% had consulted a formal health service during that period. This proportion was higher for individuals with a mood disorder (36.5%, 95% CI 32.5–40.5) than for those with anxiety disorders (26.1%, 95% CI 23.1–29.1). Among individuals with a 12-month mental disorder who had contacted the health services 12months previously, approximately two-thirds had contacted a mental health professional. Among those with a 12-month mental disorder consulting formal health services, 21.2% received no treatment. Conclusion: The ESEMeD results suggest that the use of health services is limited among individuals with mental disorders in the European countries studied. The factors associated with this limited access and their implications deserve further research. The ESEMeD ⁄ MHEDEA 2000

Journal ArticleDOI
14 Jul 2004-JAMA
TL;DR: In this article, a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, and HIV patient care was designed to have broad US and international representation for areas with adequate access to antiretroviral management.
Abstract: ContextSubstantial changes in the field of human immunodeficiency virus (HIV) treatment have occurred in the last 2 years, prompting revision of the guidelines for antiretroviral management of adults with established HIV infection.ObjectiveTo update recommendations for physicians who provide HIV care regarding when to start antiretroviral therapy, what drugs to start with, when to change drug regimens, and what drug regimens to switch to after therapy fails.Data SourcesEvidence was identified and reviewed by a 16-member noncompensated panel of physicians with expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care. The panel was designed to have broad US and international representation for areas with adequate access to antiretroviral management.Study SelectionEvidence considered included published basic science, clinical research, and epidemiological data (identified by experts in the field or extracted through MEDLINE searches using terms relevant to antiretroviral therapy) and abstracts from HIV-oriented scientific conferences between July 2002 and May 2004.Data ExtractionData were reviewed to identify any information that might change previous guidelines. Based on panel discussion, guidelines were drafted by a writing committee and discussed by the panel until consensus was reached.Data SynthesisFour antiretroviral drugs recently have been made available and have broadened the options for initial and subsequent regimens. New data allow more definitive recommendations for specific drugs or regimens to include or avoid, particularly with regard to initial therapy. Recommendations are rated according to 7 evidence categories, ranging from I (data from prospective randomized clinical trials) to VII (expert opinion of the panel).ConclusionFurther insights into the roles of drug toxic effects, drug resistance, and pharmacological interactions have resulted in additional guidance for strategic approaches to antiretroviral management.

Journal ArticleDOI
TL;DR: Findings have major implications for the origin of Europeans, since they attest that the Franco-Cantabrian refuge area was indeed the source of late-glacial expansions of hunter-gatherers that repopulated much of Central and Northern Europe from ~15,000 years ago.
Abstract: Complete sequencing of 62 mitochondrial DNAs (mtDNAs) belonging (or very closely related) to haplogroup H revealed that this mtDNA haplogroup—by far the most common in Europe—is subdivided into numerous subhaplogroups, with at least 15 of them (H1–H15) identifiable by characteristic mutations. All the haplogroup H mtDNAs found in 5,743 subjects from 43 populations were then screened for diagnostic markers of subhaplogroups H1 and H3. This survey showed that both subhaplogroups display frequency peaks, centered in Iberia and surrounding areas, with distributions declining toward the northeast and southeast—a pattern extremely similar to that previously reported for mtDNA haplogroup V. Furthermore, the coalescence ages of H1 and H3 (∼11,000 years) are close to that previously reported for V. These findings have major implications for the origin of Europeans, since they attest that the Franco-Cantabrian refuge area was indeed the source of late-glacial expansions of hunter-gatherers that repopulated much of Central and Northern Europe from ∼15,000 years ago. This has also some implications for disease studies. For instance, the high occurrence of H1 and H3 in Iberia led us to re-evaluate the haplogroup distribution in 50 Spanish families affected by nonsyndromic sensorineural deafness due to the A1555G mutation. The survey revealed that the previously reported excess of H among these families is caused entirely by H3 and is due to a major, probably nonrecent, founder event.

Journal ArticleDOI
03 Dec 2004-Science
TL;DR: Climate during the whole period was predominantly maintained in interglacial-interstadial conditions, whereas the duration of stadials was much shorter.
Abstract: A continuous high-resolution Western Mediterranean sea surface temperature (SST) alkenone record spanning the past 250,000 years shows that abrupt changes were more common at warming than at cooling. During marine isotope stage (MIS) 6, SST oscillated following a stadial-interstadial pattern but at lower intensities and rates of change than in the Dansgaard/Oeschger events of MIS 3. Some of the most prominent events occurred over MISs 5 and 7, after prolonged warm periods of high stability. Climate during the whole period was predominantly maintained in interglacial-interstadial conditions, whereas the duration of stadials was much shorter.