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Showing papers by "University of Bologna published in 2011"


Journal ArticleDOI
TL;DR: Everolimus, as compared with placebo, significantly prolonged progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumors and was associated with a low rate of severe adverse events.
Abstract: A B S T R AC T BACKGROUND Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. METHODS We randomly assigned 410 patients who had advanced, low-grade or intermediategrade pancreatic neuroendocrine tumors with radiologic progression within the previous 12 months to receive everolimus, at a dose of 10 mg once daily (207 patients), or placebo (203 patients), both in conjunction with best supportive care. The primary end point was progression-free survival in an intention-to-treat analysis. In the case of patients in whom radiologic progression occurred during the study, the treatment assignments could be revealed, and patients who had been randomly assigned to placebo were offered open-label everolimus. Results The median progression-free survival was 11.0 months with everolimus as compared with 4.6 months with placebo (hazard ratio for disease progression or death from any cause with everolimus, 0.35; 95% confidence interval [CI], 0.27 to 0.45; P<0.001), representing a 65% reduction in the estimated risk of progression or death. Estimates of the proportion of patients who were alive and progression-free at 18 months were 34% (95% CI, 26 to 43) with everolimus as compared with 9% (95% CI, 4 to 16) with placebo. Drug-related adverse events were mostly grade 1 or 2 and included stomatitis (in 64% of patients in the everolimus group vs. 17% in the placebo group), rash (49% vs. 10%), diarrhea (34% vs. 10%), fatigue (31% vs. 14%), and infections (23% vs. 6%), which were primarily upper respiratory. Grade 3 or 4 events that were more frequent with everolimus than with placebo included anemia (6% vs. 0%) and hyperglycemia (5% vs. 2%). The median exposure to everolimus was longer than exposure to placebo by a factor of 2.3 (38 weeks vs. 16 weeks). Conclusions Everolimus, as compared with placebo, significantly prolonged progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumors and was associated with a low rate of severe adverse events. (Funded by Novartis Oncology; RADIANT-3 ClinicalTrials.gov number, NCT00510068.)

2,357 citations


Journal ArticleDOI
Paul Hollingworth1, Denise Harold1, Rebecca Sims1, Amy Gerrish1  +174 moreInstitutions (59)
TL;DR: Meta-analyses of all data provided compelling evidence that ABCA7 and the MS4A gene cluster are new Alzheimer's disease susceptibility loci and independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance.
Abstract: We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10).

1,771 citations


Journal ArticleDOI
12 May 2011-Blood
TL;DR: The criteria and significance of early or precursor lesions and the identification of certain lymphoid neoplasms largely associated with particular age groups, such as children and the elderly are addressed, and the issue of borderline categories having overlapping features with large B-cell lymphomas is reviewed.

1,735 citations


Journal ArticleDOI
TL;DR: Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, regardless of whether there was a lead-in phase.
Abstract: Methods In this randomized, phase 3 trial, we evaluated the addition of telaprevir to peginter feron alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response. A total of 663 patients were assigned to one of three groups: the T12PR48 group, which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks; the lead-in T12PR48 group, which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks; and the control group (PR48), which received peginterferon plus ribavirin for 48 weeks. The primary end point was the rate of sustained virologic response, which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug. Results Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse (83% in the T12PR48 group, 88% in the lead-in T12PR48 group, and 24% in the PR48 group), a partial response (59%, 54%, and 15%, respectively), and no response (29%, 33%, and 5%, respectively) (P<0.001 for all comparisons). Grade 3 adverse events (mainly anemia, neutropenia, and leukopenia) were more frequent in the telaprevir groups than in the control group (37% vs. 22%). Conclusions Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection, re gardless of whether there was a lead-in phase. (Funded by Tibotec and Vertex Phar maceuticals; REALIZE ClinicalTrials.gov number, NCT00703118.)

1,558 citations


Journal ArticleDOI
TL;DR: A survey of the major documents and events in the area of fractional calculus that took place since 1974 up to the present date can be found in this article, where the authors report some of the most important documents and major events.

1,267 citations


Journal ArticleDOI
TL;DR: Benefit of TAVI with the CoreValve Revalving System is maintained over time up to 1 year, with acceptable mortality rates at various time points, although procedural complications are strongly associated with early mortality at 30 days.
Abstract: Background—There is a lack of information on the incidence and predictors of early mortality at 30 days and late mortality between 30 days and 1 year after transcatheter aortic valve implantation (TAVI) with the self-expanding CoreValve Revalving prosthesis. Methods and Results—A total of 663 consecutive patients (mean age 81.0±7.3 years) underwent TAVI with the third generation 18-Fr CoreValve device in 14 centers. Procedural success and intraprocedural mortality were 98% and 0.9%, respectively. The cumulative incidences of mortality were 5.4% at 30 days, 12.2% at 6 months, and 15.0% at 1 year. The incidence density of mortality was 12.3 per 100 person-year of observation. Clinical and hemodynamic benefits observed acutely after TAVI were sustained at 1 year. Paravalvular leakages were trace to mild in the majority of cases. Conversion to open heart surgery (odds ratio [OR] 38.68), cardiac tamponade (OR 10.97), major access site complications (OR 8.47), left ventricular ejection fraction <40% (OR 3.51), ...

1,069 citations


Journal ArticleDOI
TL;DR: The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors.
Abstract: Background Human immunodeficiency virus (HIV)‐infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects Methods We performed a case-control study involving antiretroviral therapy (ART)‐experienced HIVinfected patients treated at Modena University, Italy, from 2002 through 2009 These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure Polypathology (Pp) was defined as the concurrent presence of $2 NICMs Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp Results There were 2854 patients and 8562 control subjects The mean age was 46 years, and 37% were women Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P ,001) Pp prevalence among patients aged 41‐50 years was similar to that among controls aged 51‐60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P , 001) age (odds ratio [OR], 111), male sex (OR, 177), nadir CD4 cell count ,200 cells/lL (OR, 446), and ART exposure (OR, 101) Conclusions Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors These data support the need for earlier screening for NICMs in HIV-infected patients

1,045 citations


Journal ArticleDOI
TL;DR: Preliminary evidence suggesting that MMPs could enhance cognitive functions is provided, but available evidence should be considered with caution and further high quality studies investigating more standardized mindfulness meditation programs are needed.

1,017 citations


Journal ArticleDOI
TL;DR: Authors F. Piscaglia, C. Nolsøe, M. M. Gilja, and H. P. Weskott review the manuscript and suggest ways in which the manuscript could have been improved.
Abstract: Authors F. Piscaglia1, C. Nolsøe2, C. F. Dietrich3, D. O. Cosgrove4, O. H. Gilja5, M. Bachmann Nielsen6, T. Albrecht7, L. Barozzi8, M. Bertolotto9, O. Catalano10, M. Claudon11, D. A. Clevert12, J. M. Correas13, M. D’Onofrio14, F. M. Drudi15, J. Eyding16, M. Giovannini17, M. Hocke18, A. Ignee19, E. M. Jung20, A. S. Klauser21, N. Lassau22, E. Leen23, G. Mathis24, A. Saftoiu25, G. Seidel26, P. S. Sidhu27, G. ter. Haar28, D. Timmerman29, H. P. Weskott30

975 citations


Journal ArticleDOI
TL;DR: In this article, the relative contribution of star formation rate (SFR)-driven and starburst-driven galaxies to the global SFR density in the redshift interval 1.5 1000 M ☉ yr-1 was quantified.
Abstract: Two main modes of star formation are know to control the growth of galaxies: a relatively steady one in disk-like galaxies, defining a tight star formation rate (SFR)-stellar mass sequence, and a starburst mode in outliers to such a sequence which is generally interpreted as driven by merging. Such starburst galaxies are rare but have much higher SFRs, and it is of interest to establish the relative importance of these two modes. PACS/Herschel observations over the whole COSMOS and GOODS-South fields, in conjunction with previous optical/near-IR data, have allowed us to accurately quantify for the first time the relative contribution of the two modes to the global SFR density in the redshift interval 1.5 1000 M ☉ yr-1, off-sequence sources significantly contribute to the SFR density (46% ± 20%). We conclude that merger-driven starbursts play a relatively minor role in the formation of stars in galaxies, whereas they may represent a critical phase toward the quenching of star formation and morphological transformation in galaxies.

927 citations


Journal ArticleDOI
TL;DR: The BRAF V600E mutation was present in all patients with HCL who were evaluated, and may have implications for the pathogenesis, diagnosis, and targeted therapy of HCL.
Abstract: Background Hairy-cell leukemia (HCL) is a well-defined clinicopathological entity whose underlying genetic lesion is still obscure. Methods We searched for HCL-associated mutations by performing massively parallel sequencing of the whole exome of leukemic and matched normal cells purified from the peripheral blood of an index patient with HCL. Findings were validated by Sanger sequencing in 47 additional patients with HCL. Results Whole-exome sequencing identified five missense somatic clonal mutations that were confirmed on Sanger sequencing, including a heterozygous mutation in BRAF that results in the BRAF V600E variant protein. Since BRAF V600E is oncogenic in other tumors, further analyses were focused on this genetic lesion. The same BRAF mutation was noted in all the other 47 patients with HCL who were evaluated by means of Sanger sequencing. None of the 195 patients with other peripheral B-cell lymphomas or leukemias who were evaluated carried the BRAF V600E variant, including 38 patients with spl...

Book
26 Jul 2011
TL;DR: This article estimated glomerular filtration rate of the human glomerus and showed that the estimated rate can be improved by using the enzyme GFR-BPBP-DBPDBPdiastolic blood pressure
Abstract: ACEangiotensin-converting enzymeBPblood pressureDBPdiastolic blood pressureeGFRestimated glomerular filtration rateESCEuropean Society of CardiologyESHEuropean Society of HypertensionETendothelinIM...

Journal ArticleDOI
TL;DR: The XENON100 detector, installed underground at the Laboratori Nazionali del Gran Sasso of INFN, Italy, finds no evidence for dark matter, leading to the most stringent limit on dark matter interactions today.
Abstract: We present results from the direct search for dark matter with the XENON100 detector, installed underground at the Laboratori Nazionali del Gran Sasso of INFN, Italy. XENON100 is a two-phase time-projection chamber with a 62 kg liquid xenon target. Interaction vertex reconstruction in three dimensions with millimeter precision allows the selection of only the innermost 48 kg as the ultralow background fiducial target. In 100.9 live days of data, acquired between January and June 2010, no evidence for dark matter is found. Three candidate events were observed in the signal region with an expected background of (1.8{+-}0.6) events. This leads to the most stringent limit on dark matter interactions today, excluding spin-independent elastic weakly interacting massive particle (WIMP) nucleon scattering cross sections above 7.0x10{sup -45} cm{sup 2} for a WIMP mass of 50 GeV/c{sup 2} at 90% confidence level.

Journal ArticleDOI
S. Chatrchyan, Vardan Khachatryan, Albert M. Sirunyan, A. Tumasyan  +2268 moreInstitutions (158)
TL;DR: In this article, the transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transversal momentum resolution.
Abstract: Measurements of the jet energy calibration and transverse momentum resolution in CMS are presented, performed with a data sample collected in proton-proton collisions at a centre-of-mass energy of 7TeV, corresponding to an integrated luminosity of 36pb−1. The transverse momentum balance in dijet and γ/Z+jets events is used to measure the jet energy response in the CMS detector, as well as the transverse momentum resolution. The results are presented for three different methods to reconstruct jets: a calorimeter-based approach, the ``Jet-Plus-Track'' approach, which improves the measurement of calorimeter jets by exploiting the associated tracks, and the ``Particle Flow'' approach, which attempts to reconstruct individually each particle in the event, prior to the jet clustering, based on information from all relevant subdetectors

Journal ArticleDOI
TL;DR: In this article, the dependence of galaxy structure (size and Sersic index) and mode of star formation (ΣSFR and SFRIR/SFRUV) on the position of galaxies in the star formation rate (SFR) versus mass diagram is analyzed.
Abstract: We analyze the dependence of galaxy structure (size and Sersic index) and mode of star formation (ΣSFR and SFRIR/SFRUV) on the position of galaxies in the star formation rate (SFR) versus mass diagram. Our sample comprises roughly 640,000 galaxies at z ~ 0.1, 130,000 galaxies at z ~ 1, and 36,000 galaxies at z ~ 2. Structural measurements for all but the z ~ 0.1 galaxies are based on Hubble Space Telescope imaging, and SFRs are derived using a Herschel-calibrated ladder of SFR indicators. We find that a correlation between the structure and stellar population of galaxies (i.e., a "Hubble sequence") is already in place since at least z ~ 2.5. At all epochs, typical star-forming galaxies on the main sequence are well approximated by exponential disks, while the profiles of quiescent galaxies are better described by de Vaucouleurs profiles. In the upper envelope of the main sequence, the relation between the SFR and Sersic index reverses, suggesting a rapid buildup of the central mass concentration in these starbursting outliers. We observe quiescent, moderately and highly star-forming systems to co-exist over an order of magnitude or more in stellar mass. At each mass and redshift, galaxies on the main sequence have the largest size. The rate of size growth correlates with specific SFR, and so does ΣSFR at each redshift. A simple model using an empirically determined star formation law and metallicity scaling, in combination with an assumed geometry for dust and stars, is able to relate the observed ΣSFR and SFRIR/SFRUV, provided a more patchy dust geometry is assumed for high-redshift galaxies.

Journal ArticleDOI
TL;DR: In this article, the authors presented a source catalog for the 4Ms Chandra Deep Field-South (CDF-S) survey, which is the deepest Chandra survey to date and covers an area of 464.5 arcmin2.
Abstract: We present source catalogs for the 4 Ms Chandra Deep Field-South (CDF-S), which is the deepest Chandra survey to date and covers an area of 464.5 arcmin2. We provide a main Chandra source catalog, which contains 740 X-ray sources that are detected with WAVDETECT at a false-positive probability threshold of 10–5 in at least one of three X-ray bands (0.5-8 keV, full band; 0.5-2 keV, soft band; and 2-8 keV, hard band) and also satisfy a binomial-probability source-selection criterion of P 75% of the main-catalog sources are active galactic nuclei (AGNs); of the 300 new main-catalog sources, about 35% are likely normal and starburst galaxies, reflecting the rise of normal and starburst galaxies at the very faint flux levels uniquely accessible to the 4 Ms CDF-S. Near the center of the 4 Ms CDF-S (i.e., within an off-axis angle of 3'), the observed AGN and galaxy source densities have reached 9800+1300 – 1100 deg–2 and 6900+1100 – 900 deg–2, respectively. Simulations show that our main catalog is highly reliable and is reasonably complete. The mean backgrounds (corrected for vignetting and exposure-time variations) are 0.063 and 0.178 counts Ms–1 pixel–1 (for a pixel size of 0492) for the soft and hard bands, respectively; the majority of the pixels have zero background counts. The 4 Ms CDF-S reaches on-axis flux limits of 3.2 × 10–17, 9.1 × 10–18, and 5.5 × 10–17 erg cm–2 s–1 for the full, soft, and hard bands, respectively. An increase in the CDF-S exposure time by a factor of 2-2.5 would provide further significant gains and probe key unexplored discovery space.

Journal ArticleDOI
TL;DR: There is little doubt that power production by renewable energies, energy storage by hydrogen, and electric power transportation and distribution by smart electric grids will play an essential role in phasing out fossil fuels.
Abstract: Hydrogen is often proposed as the fuel of the future, but the transformation from the present fossil fuel economy to a hydrogen economy will need the solution of numerous complex scientific and technological issues, which will require several decades to be accomplished. Hydrogen is not an alternative fuel, but an energy carrier that has to be produced by using energy, starting from hydrogen-rich compounds. Production from gasoline or natural gas does not offer any advantage over the direct use of such fuels. Production from coal by gasification techniques with capture and sequestration of CO₂ could be an interim solution. Water splitting by artificial photosynthesis, photobiological methods based on algae, and high temperatures obtained by nuclear or concentrated solar power plants are promising approaches, but still far from practical applications. In the next decades, the development of the hydrogen economy will most likely rely on water electrolysis by using enormous amounts of electric power, which in its turn has to be generated. Producing electricity by burning fossil fuels, of course, cannot be a rational solution. Hydroelectric power can give but a very modest contribution. Therefore, it will be necessary to generate large amounts of electric power by nuclear energy of by renewable energies. A hydrogen economy based on nuclear electricity would imply the construction of thousands of fission reactors, thereby magnifying all the problems related to the use of nuclear energy (e.g., safe disposal of radioactive waste, nuclear proliferation, plant decommissioning, uranium shortage). In principle, wind, photovoltaic, and concentrated solar power have the potential to produce enormous amounts of electric power, but, except for wind, such technologies are too underdeveloped and expensive to tackle such a big task in a short period of time. A full development of a hydrogen economy needs also improvement in hydrogen storage, transportation and distribution. Hydrogen and electricity can be easily interconverted by electrolysis and fuel cells, and which of these two energy carriers will prevail, particularly in the crucial field of road vehicle powering, will depend on the solutions found for their peculiar drawbacks, namely storage for electricity and transportation and distribution for hydrogen. There is little doubt that power production by renewable energies, energy storage by hydrogen, and electric power transportation and distribution by smart electric grids will play an essential role in phasing out fossil fuels.

Journal ArticleDOI
01 Sep 2011
TL;DR: A survey of some of the most important lines of hybridization of metaheuristics with other techniques for optimization, which includes, for example, the combination of exact algorithms and meta heuristics.
Abstract: Research in metaheuristics for combinatorial optimization problems has lately experienced a noteworthy shift towards the hybridization of metaheuristics with other techniques for optimization. At the same time, the focus of research has changed from being rather algorithm-oriented to being more problem-oriented. Nowadays the focus is on solving the problem at hand in the best way possible, rather than promoting a certain metaheuristic. This has led to an enormously fruitful cross-fertilization of different areas of optimization. This cross-fertilization is documented by a multitude of powerful hybrid algorithms that were obtained by combining components from several different optimization techniques. Hereby, hybridization is not restricted to the combination of different metaheuristics but includes, for example, the combination of exact algorithms and metaheuristics. In this work we provide a survey of some of the most important lines of hybridization. The literature review is accompanied by the presentation of illustrative examples.

Journal ArticleDOI
TL;DR: On the 30th anniversary of enactment of the Bayh-Dole Act in the U.S., this paper considered the rationale for academic entrepreneurship and described the evolving role of universities in the commercialization of research.
Abstract: On the 30th anniversary of enactment of the Bayh-Dole Act in the U.S., we consider the rationale for academic entrepreneurship and describe the evolving role of universities in the commercialization of research. We also discuss and appraise the effects of legislative reform in several OECD countries relating to academic entrepreneurship. The article synthesizes papers from the special section and outlines an agenda for additional research on various aspects of academic entrepreneurship in terms of system, university and individual levels. We also consider measurement and methodological issues that must be addressed in additional research.

Journal ArticleDOI
TL;DR: In this article, the authors studied the effect of collision centrality on the transverse momentum of PbPb collisions at the LHC with a data sample of 6.7 inverse microbarns.
Abstract: Jet production in PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76 TeV was studied with the CMS detector at the LHC, using a data sample corresponding to an integrated luminosity of 6.7 inverse microbarns. Jets are reconstructed using the energy deposited in the CMS calorimeters and studied as a function of collision centrality. With increasing collision centrality, a striking imbalance in dijet transverse momentum is observed, consistent with jet quenching. The observed effect extends from the lower cut-off used in this study (jet transverse momentum = 120 GeV/c) up to the statistical limit of the available data sample (jet transverse momentum approximately 210 GeV/c). Correlations of charged particle tracks with jets indicate that the momentum imbalance is accompanied by a softening of the fragmentation pattern of the second most energetic, away-side jet. The dijet momentum balance is recovered when integrating low transverse momentum particles distributed over a wide angular range relative to the direction of the away-side jet.

Journal ArticleDOI
20 Oct 2011-Neuron
TL;DR: A high-dimensional model of the representational space in human ventral temporal (VT) cortex in which dimensions are response-tuning functions that are common across individuals and patterns of response are modeled as weighted sums of basis patterns associated with these response tunings is presented.

Journal ArticleDOI
TL;DR: On the 30th anniversary of enactment of the Bayh-Dole Act in the U.S., this paper considered the rationale for academic entrepreneurship and described the evolving role of universities in the commercialization of research.

Journal ArticleDOI
TL;DR: A meta-analysis of the current findings about the efficacy of MBCT for psychiatric patients found it was significantly better than usual care alone for reducing major depression relapses in patients with three or more prior depressive episodes.
Abstract: Mindfulness- based Cognitive Therapy (MBCT) is a meditation program based on an integration of Cognitive behavioural therapy and Mindfulness-based stress reduction. The aim of the present work is to review and conduct a meta-analysis of the current findings about the efficacy of MBCT for psychiatric patients. A literature search was undertaken using five electronic databases and references of retrieved articles. Main findings included the following: 1) MBCT in adjunct to usual care was significantly better than usual care alone for reducing major depression (MD) relapses in patients with three or more prior depressive episodes (4 studies), 2) MBCT plus gradual discontinuation of maintenance ADs was associated to similar relapse rates at 1 year as compared with continuation of maintenance antidepressants (1 study), 3) the augmentation of MBCT could be useful for reducing residual depressive symptoms in patients with MD (2 studies) and for reducing anxiety symptoms in patients with bipolar disorder in remission (1 study) and in patients with some anxiety disorders (2 studies). However, several methodological shortcomings including small sample sizes, non-randomized design of some studies and the absence of studies comparing MBCT to control groups designed to distinguish specific from non-specific effects of such practice underscore the necessity for further research.

Journal ArticleDOI
10 Mar 2011
TL;DR: The functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli are discussed and the recently described roles of these pathways in cancer stem cells, cellular senescence and aging are evaluated.
Abstract: Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.

Journal ArticleDOI
M. Ageron1, Juanan Aguilar2, I. Al Samarai1, Arnauld Albert  +284 moreInstitutions (21)
TL;DR: The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational neutrino telescope in the Mediterranean Sea as mentioned in this paper, where the main purpose of the detector is to perform neutrinos astronomy and the apparatus also offers facilities for marine and Earth sciences.
Abstract: The ANTARES Neutrino Telescope was completed in May 2008 and is the first operational Neutrino Telescope in the Mediterranean Sea. The main purpose of the detector is to perform neutrino astronomy and the apparatus also offers facilities for marine and Earth sciences. This paper describes the design, the construction and the installation of the telescope in the deep sea, offshore from Toulon in France. An illustration of the detector performance is given.

Journal ArticleDOI
TL;DR: Five experimental strategies developed by different research groups for extending the longevity of resin-dentin bonds are examined, finding a combination of several of these strategies should result in overcoming the critical barriers to progress currently encountered in dentin bonding.
Abstract: The limited durability of resin-dentin bonds severely compromises the lifetime of tooth-colored restorations Bond degradation occurs via hydrolysis of suboptimally polymerized hydrophilic resin components and degradation of water-rich, resin-sparse collagen matrices by matrix metalloproteinases (MMPs) and cysteine cathepsins This review examined data generated over the past three years on five experimental strategies developed by different research groups for extending the longevity of resin-dentin bonds They include: (1) increasing the degree of conversion and esterase resistance of hydrophilic adhesives; (2) the use of broad-spectrum inhibitors of collagenolytic enzymes, including novel inhibitor functional groups grafted to methacrylate resins monomers to produce anti-MMP adhesives; (3) the use of cross-linking agents for silencing the activities of MMP and cathepsins that irreversibly alter the 3-D structures of their catalytic/allosteric domains; (4) ethanol wet-bonding with hydrophobic resins to completely replace water from the extrafibrillar and intrafibrillar collagen compartments and immobilize the collagenolytic enzymes; and (5) biomimetic remineralization of the water-filled collagen matrix using analogs of matrix proteins to progressively replace water with intrafibrillar and extrafibrillar apatites to exclude exogenous collagenolytic enzymes and fossilize endogenous collagenolytic enzymes A combination of several of these strategies should result in overcoming the critical barriers to progress currently encountered in dentin bonding

Journal ArticleDOI
TL;DR: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options, and the most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden, international normalized ratio >1.2, and extrahepatic disease.

Journal ArticleDOI
Devin P. Locke1, LaDeana W. Hillier1, Wesley C. Warren1, Kim C. Worley2, Lynne V. Nazareth2, Donna M. Muzny2, Shiaw-Pyng Yang1, Zhengyuan Wang1, Asif T. Chinwalla1, Patrick Minx1, Makedonka Mitreva1, Lisa Cook1, Kim D. Delehaunty1, Catrina Fronick1, Heather Schmidt1, Lucinda Fulton1, Robert S. Fulton1, Joanne O. Nelson1, Vincent Magrini1, Craig Pohl1, Tina Graves1, Chris Markovic1, Andy Cree2, Huyen Dinh2, Jennifer Hume2, Christie Kovar2, Gerald R. Fowler2, Gerton Lunter3, Gerton Lunter4, Stephen Meader3, Andreas Heger3, Chris P. Ponting3, Tomas Marques-Bonet5, Tomas Marques-Bonet6, Can Alkan5, Lin Chen5, Ze Cheng5, Jeffrey M. Kidd5, Evan E. Eichler5, Evan E. Eichler7, Simon D. M. White8, Stephen M. J. Searle8, Albert J. Vilella9, Yuan Chen9, Paul Flicek9, Jian Ma10, Jian Ma11, Brian J. Raney11, Bernard B. Suh11, Richard Burhans12, Javier Herrero9, David Haussler11, Rui Faria6, Rui Faria13, Olga Fernando6, Olga Fernando14, Fleur Darré6, Domènec Farré6, Elodie Gazave6, Meritxell Oliva6, Arcadi Navarro6, Roberta Roberto15, Oronzo Capozzi15, Nicoletta Archidiacono15, Giuliano Della Valle16, Stefania Purgato16, Mariano Rocchi15, Miriam K. Konkel17, Jerilyn A. Walker17, Brygg Ullmer17, Mark A. Batzer17, Arian F.A. Smit18, Robert Hubley18, Claudio Casola19, Daniel R. Schrider19, Matthew W. Hahn19, Víctor Quesada20, Xose S. Puente20, Gonzalo R. Ordóñez20, Carlos López-Otín20, Tomas Vinar21, Brona Brejova21, Aakrosh Ratan12, Robert S. Harris12, Webb Miller12, Carolin Kosiol, Heather A. Lawson1, Vikas Taliwal22, André L. Martins22, Adam Siepel22, Arindam RoyChoudhury23, Xin Ma22, Jeremiah D. Degenhardt22, Carlos Bustamante24, Ryan N. Gutenkunst25, Thomas Mailund26, Julien Y. Dutheil26, Asger Hobolth26, Mikkel H. Schierup26, Oliver A. Ryder, Yuko Yoshinaga27, Pieter J. de Jong27, George M. Weinstock1, Jeffrey Rogers2, Elaine R. Mardis1, Richard A. Gibbs2, Richard K. Wilson1 
27 Jan 2011-Nature
TL;DR: The orang-utan species, Pongo abelii and Pongo pygmaeus, are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution and a primate polymorphic neocentromere, found in both Pongo species are described.
Abstract: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.

Journal ArticleDOI
TL;DR: In this paper, the centrality dependence of the chargedparticle multiplicity density at midrapidity in Pb-Pb collisions at root s(NN) = 2: 76 TeV is presented.
Abstract: The centrality dependence of the charged-particle multiplicity density at midrapidity in Pb-Pb collisions at root s(NN) = 2: 76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor of 2 from peripheral (70%-80%) to central (0%-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions.

Journal ArticleDOI
TL;DR: Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks as mentioned in this paper.
Abstract: Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.