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Showing papers by "University of Milano-Bicocca published in 2011"


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...

837 citations


Journal ArticleDOI
11 Nov 2011-Cell
TL;DR: It is reported that the plasma membrane localized Pattern Recognition Receptor (PRR) CD14 is required for the microbe-induced endocytosis of TLR4, and this innate immune trafficking cascade illustrates how pathogen detection systems operate to induce both membrane transport and signal transduction.

785 citations


Journal ArticleDOI
TL;DR: The complex genetic architecture of the risk regions of and refine the risk signals for celiac disease are defined, providing the next step toward uncovering the causal mechanisms of the disease.
Abstract: Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease.

715 citations



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.

551 citations


Journal ArticleDOI
15 Jan 2011-Cancer
TL;DR: There is an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL and debate on the optimal formulation and dosage of these agents continues.
Abstract: Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL.

486 citations


Journal ArticleDOI
TL;DR: Evidence is provided for a role of oncogenic K‐Ras in the metabolic reprogramming of cancer cells and chemical perturbation of enzymes along these pathways further supports the decoupling of glycolysis and TCA metabolism.
Abstract: Oncogenes such as K-ras mediate cellular and metabolic transformation during tumorigenesis. To analyze K-Ras-dependent metabolic alterations, we employed 13 C metabolic flux analysis (MFA), non-targeted tracer fate detection (NTFD) of 15 N-labeled glutamine, and transcriptomic profiling in mouse fibroblast and human carcinoma cell lines. Stable isotope-labeled glucose and glutamine tracers and computational determination of intracellular fluxes indicated that cells expressing oncogenic K-Ras exhibited enhanced glycolytic activity, decreased oxidative flux through the tricarboxylic acid (TCA) cycle, and increased utilization of glutamine for anabolic synthesis. Surprisingly, a non-canonical labeling of TCA cycle-associated metabolites was detected in both transformed cell lines. Transcriptional profiling detected elevated expression of several genes associated with glycolysis, glutamine metabolism, and nucleotide biosynthesis upon transformation with oncogenic K-Ras. Chemical perturbation of enzymes along these pathways further supports the decoupling of glycolysis and TCA metabolism, with glutamine supplying increased carbon to drive the TCA cycle. These results provide evidence for a role of oncogenic K-Ras in the metabolic reprogramming of cancer cells.

438 citations


Journal ArticleDOI
TL;DR: It is shown that pericytes, resident in small vessels of skeletal muscle, contribute to its growth and regeneration during postnatal life and increases significantly during acute injury or in chronically regenerating dystrophic muscle.
Abstract: Skeletal muscle fibres form by fusion of mesoderm progenitors called myoblasts. After birth, muscle fibres do not increase in number but continue to grow in size because of fusion of satellite cells, the postnatal myogenic cells, responsible for muscle growth and regeneration. Numerous studies suggest that, on transplantation, non-myogenic cells also may contribute to muscle regeneration. However, there is currently no evidence that such a contribution represents a natural developmental option of these non-myogenic cells, rather than a consequence of experimental manipulation resulting in cell fusion. Here we show that pericytes, transgenically labelled with an inducible Alkaline Phosphatase CreERT2, but not endothelial cells, fuse with developing myofibres and enter the satellite cell compartment during unperturbed postnatal development. This contribution increases significantly during acute injury or in chronically regenerating dystrophic muscle. These data show that pericytes, resident in small vessels of skeletal muscle, contribute to its growth and regeneration during postnatal life.

417 citations


Journal ArticleDOI
TL;DR: The Online Chemical Modeling Environment is a web-based platform that aims to automate and simplify the typical steps required for QSAR modeling and to invite the original authors to contribute their results, make them publicly available, share them with other users and to become members of the growing research community.
Abstract: The Online Chemical Modeling Environment is a web-based platform that aims to automate and simplify the typical steps required for QSAR modeling. The platform consists of two major subsystems: the database of experimental measurements and the modeling framework. A user-contributed database contains a set of tools for easy input, search and modification of thousands of records. The OCHEM database is based on the wiki principle and focuses primarily on the quality and verifiability of the data. The database is tightly integrated with the modeling framework, which supports all the steps required to create a predictive model: data search, calculation and selection of a vast variety of molecular descriptors, application of machine learning methods, validation, analysis of the model and assessment of the applicability domain. As compared to other similar systems, OCHEM is not intended to re-implement the existing tools or models but rather to invite the original authors to contribute their results, make them publicly available, share them with other users and to become members of the growing research community. Our intention is to make OCHEM a widely used platform to perform the QSPR/QSAR studies online and share it with other users on the Web. The ultimate goal of OCHEM is collecting all possible chemoinformatics tools within one simple, reliable and user-friendly resource. The OCHEM is free for web users and it is available online at http://www.ochem.eu.

416 citations



Journal ArticleDOI
TL;DR: A 2-layer symbolic network model based on the equilibrium equations of the Rescorla-Wagner model (Danks, 2003) is proposed, showing that for pseudo-derived words no special morpho-orthographic segmentation mechanism is required and predicting that productive affixes afford faster response latencies for new words.
Abstract: A 2-layer symbolic network model based on the equilibrium equations of the Rescorla-Wagner model (Danks, 2003) is proposed. The study first presents 2 experiments in Serbian, which reveal for sentential reading the inflectional paradigmatic effects previously observed by Milin, Filipovic Đurđevic, and Moscoso del Prado Martin (2009) for unprimed lexical decision. The empirical results are successfully modeled without having to assume separate representations for inflections or data structures such as inflectional paradigms. In the next step, the same naive discriminative learning approach is pitted against a wide range of effects documented in the morphological processing literature. Frequency effects for complex words as well as for phrases (Arnon & Snider, 2010) emerge in the model without the presence of whole-word or whole-phrase representations. Family size effects (Moscoso del Prado Martin, Bertram, Haikio, Schreuder, & Baayen, 2004; Schreuder & Baayen, 1997) emerge in the simulations across simple words, derived words, and compounds, without derived words or compounds being represented as such. It is shown that for pseudo-derived words no special morpho-orthographic segmentation mechanism, as posited by Rastle, Davis, and New (2004), is required. The model also replicates the finding of Plag and Baayen (2009) that, on average, words with more productive affixes elicit longer response latencies; at the same time, it predicts that productive affixes afford faster response latencies for new words. English phrasal paradigmatic effects modulating isolated word reading are reported and modeled, showing that the paradigmatic effects characterizing Serbian case inflection have crosslinguistic scope.


Journal ArticleDOI
TL;DR: The structure, robustness, and dynamics of ocean plankton ecosystems remain poorly understood due to sampling, analysis, and computational limitations, and the Tara Oceans consortium organizes expeditions to help fill this gap.
Abstract: With biology becoming quantitative, systems-level studies can now be performed at spatial scales ranging from molecules to ecosystems. Biological data generated consistently across scales can be integrated with physico-chemical contextual data for a truly holistic approach, with a profound impact on our understanding of life [1]–[5]. Marine ecosystems are crucial in the regulation of Earth's biogeochemical cycles and climate [6],[7]. Yet their organization, evolution, and dynamics remain poorly understood [8],[9]. The Tara Oceans project was launched in September 2009 for a 3-year study of the global ocean ecosystem aboard the ship Tara. A unique sampling programme encompassing optical and genomic methods to describe viruses, bacteria, archaea, protists, and metazoans in their physico-chemical environment has been implemented. Starting as a grassroots initiative of a few scientists, the project has grown into a global consortium of over 100 specialists from diverse disciplines, including oceanography, microbial ecology, genomics, molecular, cellular, and systems biology, taxonomy, bioinformatics, data management, and ecosystem modeling. This multidisciplinary community aims to generate systematic, open access datasets usable for probing the morphological and molecular makeup, diversity, evolution, ecology, and global impacts of plankton on the Earth system.

Journal ArticleDOI
13 Oct 2011-Blood
TL;DR: Recommendations represent the state-of-the-art management of CD30(+) LPDs and include definitions for clinical endpoints as well as response criteria for future clinical trials in CD30 (+) L PDs.

Journal ArticleDOI
TL;DR: The Discovery-690 shows very good PET physical performance for all the standard NEMA NU-2-2007 measurements and the new reconstruction algorithms available for PET data (TOF and PSF) allow further improvements of the D-690 image quality performance both qualitatively and quantitatively.
Abstract: Purpose The aim of this work was the assessment of the physical performance of the new hybrid PET∕CT system: Discovery-690. Methods The Discovery-690 combines a lutetium-yttrium-orthosilicate (LYSO) block detector designed PET tomograph with a 64-slice CT scanner. The system is further characterized by a dedicated powerful computing platform implementing fully 3D-PET iterative reconstruction algorithms. These algorithms can account for time of flight (TOF) information and∕or a 3D model of the PET point spread function (PSF). PET physical performance was measured following NEMA NU-2-2007 procedures. Furthermore, specific tests were used: (i) to measure the energy and timing resolution of the PET system and (ii) to evaluate image quality, by using phantoms representing different clinical conditions (e.g., brain and whole body). Data processing and reconstructions were performed as required by standard procedures. Further reconstructions were carried out to evaluate the performance of the new reconstruction algorithms. In particular, four algorithms were considered for the reconstruction of the PET data: (i) HD = standard configuration, without TOF and PSF, (ii) TOF = HD + TOF, (iii) PSF = HD + PSF, and (iv) TOFPSF = HD + TOF + PSF. Results The transverse (axial) spatial resolution values were 4.70 (4.74) mm and 5.06 (5.55) mm at 1 cm and 10 cm off axis, respectively. Sensitivity (average between 0 and 10 cm) was 7.5 cps∕kBq. The noise equivalent count rate (NECR) peak was 139.1 kcps at 29.0 kBq∕ml. The scatter fraction at the NECR peak was 37%. The correction accuracy for the dead time losses and random event counts had a maximum absolute error below the NECR peak of 2.09%. The average energy and timing resolution were 12.4% and 544.3 ps, respectively. PET image quality was evaluated with the NEMA IEC Body phantom by using four reconstruction algorithms (HD, TOF, PSF, and TOFPSF), as previously described. The hot contrast (after 3 iterations and for a lesion∕background activity ratio of 4:1) for the spheres of 10, 13, 17, and 22 mm was (HD) 29.8, 45.4, 55.4, and 68.1%; (TOF) 39.9, 53.5, 62.7, and 72.2%; (PSF) 28.3, 47.3, 60.4, and 71.8%; (TOFPSF) 43.8, 62.9, 70.6, and 76.4%. The cold contrast for the spheres of 28 and 37 mm was (HD) 62.4 and 65.2%; (TOF) 77.1 and 81.4%; (PSF) 62.0 and 65.2%; (TOFPSF) 77.3 and 81.6%. Similar hot and cold contrast trends were found during the analyses of other phantoms representing different clinical conditions (brain and whole body). Nevertheless, the authors observed a predominant role of either TOF or PSF, depending on the specific characteristics and dimensions of the phantoms. Conclusions Discovery-690 shows very good PET physical performance for all the standard NEMA NU-2-2007 measurements. Furthermore, the new reconstruction algorithms available for PET data (TOF and PSF) allow further improvements of the D-690 image quality performance both qualitatively and quantitatively.

Journal ArticleDOI
TL;DR: It is shown that autistic-like symptoms are rescued on administration of AVP and OT to young Oxtr(-/-) adult animals and that intracerebral administration of both OT and AVP lowers aggression and fully reverts social and learning defects by acting on V1a receptors and that seizure susceptibility is antagonized by peripherally administered OT.

Journal ArticleDOI
TL;DR: The authors found that participants were more interested in obtaining information about morality than about sociability when asked to form a global impression about others, while they looked for more symmetrical evidence on sociability or competence traits.
Abstract: Research on the two fundamental dimensions of social judgment, namely warmth and competence, has shown that warmth has a primary and a dominant role in information gathering about others. In two studies we examined whether the sociability and morality components of warmth play distinct roles in such a process. Study 1 (N=60) investigated which traits were mostly selected when forming impressions about others. The results showed that, regardless of the task goal, traits related to morality and sociability were differently processed. Furthermore, participants were more interested in obtaining information about morality than about sociability when asked to form a global impression about others. Study 2 (N=98) explored the adoption of asymmetric/symmetric strategies when asking questions to make inferences on others. As predicted, participants adopted an asymmetrically disconfirming strategy on morality traits, while they looked for more symmetrical evidence on sociability or competence traits. Overall, our findings indicated a distinct and a dominant role of the moral component of warmth in the information-gathering process. Copyright © 2010 John Wiley & Sons, Ltd.

Journal ArticleDOI
TL;DR: In this paper, the authors suggest that the hedonic attributes of a product perceived via one modality (such as touch) can "pull" (or bias) a person's estimates of the quality and pleasantness of the product derived from other sensory modalities into alignment, and by so doing, modulate a people's overall (multisensory) product experience.
Abstract: Touch plays an important, if often underacknowledged, role in our evaluation/appreciation of many different products. It is unsurprising, therefore, that there has been such a recent growth of interest in “tactile branding” and tactile marketing. This article reviews the evidence from the fields of marketing, psychology, and cognitive neuroscience, demonstrating just how important the feel of a product, not to mention the feel of its packaging, can be in determining people's overall product evaluation. Problems for tactile design associated with the growth of the aging population, and the growth of Internet-based shopping, are highlighted. The critical role that touch can play in multisensory product design, appreciation, and marketing is also discussed, as is the increasingly frequent use by marketers of synesthetic correspondences to evoke tactile sensations via the visual and auditory modalities. We put forward the argument that tactile stimulation may influence multisensory product evaluation by means of affective ventriloquism: Our suggestion is that the hedonic attributes of a product perceived via one modality (such as touch) can “pull” (or bias) a person's estimates of the quality and pleasantness of the product derived from other sensory modalities into alignment, and by so doing, modulate a person's overall (multisensory) product experience. What is more, powerful mathematical modeling approaches now exist to predict the magnitude of this kind of intersensory (or crossmodal) interaction effect, hence offering the promise of a more scientific approach to tactile design/marketing in the coming years. © 2011 Wiley Periodicals, Inc.

Journal ArticleDOI
TL;DR: Results suggest that {001} surfaces can be considered essentially as oxidation sites with a key role in the photoxidation, while {101} surfaces provide reductive sites which do not directly assist the oxidative processes.
Abstract: The promising properties of anatase TiO2 nanocrystals exposing specific surfaces have been investigated in depth both theoretically and experimentally. However, a clear assessment of the role of the crystal faces in photocatalytic processes is still under debate. In order to clarify this issue, we have comprehensively explored the properties of the photogenerated defects and in particular their dependence on the exposed crystal faces in shape-controlled anatase. Nanocrystals were synthesized by solvothermal reaction of titanium butoxide in the presence of oleic acid and oleylamine as morphology-directing agents, and their photocatalytic performances were evaluated in the phenol mineralization in aqueous media, using O2 as the oxidizing agent. The charge-trapping centers, Ti3+, O–, and O2–, formed by UV irradiation of the catalyst were detected by electron spin resonance, and their abundance and reactivity were related to the exposed crystal faces and to the photoefficiency of the nanocrystals. In vacuum c...

Journal ArticleDOI
TL;DR: The report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010 as discussed by the authors discusses the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of tools developed to meet the challenge of reconstructing and isolating these topologies.
Abstract: We present the report of the hadronic working group of the BOOST2010 workshop held at the University of Oxford in June 2010. The first part contains a review of the potential of hadronic decays of highly boosted particles as an aid for discovery at the LHC and a discussion of the status of tools developed to meet the challenge of reconstructing and isolating these topologies. In the second part, we present new results comparing the performance of jet grooming techniques and top tagging algorithms on a common set of benchmark channels. We also study the sensitivity of jet substructure observables to the uncertainties in Monte Carlo predictions.

Journal ArticleDOI
Roel Aaij, Bernardo Adeva1, Marco Adinolfi2, C. Adrover  +554 moreInstitutions (36)
TL;DR: In this paper, the production of J/psi mesons in proton-proton collisions at root s = 7 TeV is studied with the LHCb detector at the HetNets.
Abstract: The production of J/psi mesons in proton-proton collisions at root s = 7 TeV is studied with the LHCb detector at the LHC. The differential cross-section for prompt J/psi production is measured as a function of the J/psi transverse momentum p(T) and rapidity y in the fiducial region p(T) is an element of [0; 14] GeV/c and y is an element of [2.0; 4.5]. The differential cross-section and fraction of J/psi from b-hadron decays are also measured in the same p(T) and y ranges. The analysis is based on a data sample corresponding to an integrated luminosity of 5.2 pb(-1). The measured cross-sections integrated over the fiducial region are 10.52 +/- 0.04 +/- 1.40(-2.20)(+1.64) mu b for prompt J/psi production and 1.14 +/- 0.01 +/- 0.16 mu b for J/psi from b-hadron decays, where the first uncertainty is statistical and the second systematic. The prompt J/psi production cross-section is obtained assuming no J/psi polarisation and the third error indicates the acceptance uncertainty due to this assumption.

Journal ArticleDOI
TL;DR: The use of P1-type ATPases represents a M. tuberculosis strategy to neutralize the toxic effects of zinc in macrophages, suggesting that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race.

Journal ArticleDOI
TL;DR: In this paper, a combination of first-principles calculations and optical characterization experiments was employed to explain the mechanism by which Ga${}^{3+}$ doping prevents the trapping of free carriers due to shallow traps in RE${}_{3}$Al${} 5}$O${} 12}$ garnet scintillators (where RE represents a $3+$ rare-earth cation).
Abstract: We employ a combination of first-principles calculations and optical characterization experiments to explain the mechanism by which Ga${}^{3+}$ doping prevents the trapping of free carriers due to shallow traps in RE${}_{3}$Al${}_{5}$O${}_{12}$ garnet scintillators (where RE represents a $3+$ rare-earth cation). Specifically, we confirm that Ga${}^{3+}$ doping does not reduce the defect concentration (defect engineering), but rather leads to shifts in the valence and conduction bands such that the energy level of shallow defects is no longer in the forbidden gap where electrons can be trapped (band-gap engineering).

Journal ArticleDOI
TL;DR: In this paper, an implementation of the vector boson pair production processes ZZ, Wυγγγαγαβαβββγβαγ βαβ β βαγββ βα βββα β β ββ ββααβγ ββγγ β βγβγα βγ βγγβ βγ αβα αββ αβγ is presented.
Abstract: We present an implementation of the vector boson pair production processes ZZ, W + W − and WZ within the POWHEG framework, which is a method that allows the interfacing of NLO calculations to shower Monte Carlo programs. The implementation is built within the POWHEG BOX package. The Z/γ * interference, as well as singly resonant contributions, are properly included. We also considered interference terms arising from identical leptons in the final state. As a result, all contributions leading to the desired four-lepton system have been included in the calculation, with the sole exception of the interference between ZZ and W + W − in the production of a pair of same-flavour, oppositely charged fermions and a pair of neutrinos, which we show to be fully negligible. Anomalous trilinear couplings can be also set in the program, and we give some examples of their effect at the LHC. We have made the relevant code available at the POWHEG BOX web site.

Journal ArticleDOI
TL;DR: An overview of technical and analytical issues in exosome proteomics is offered, and the significance of proteomic studies in terms of biological and clinical usefulness is highlighted.
Abstract: Exosomes are membranous vesicles released by cells in extracellular fluids: they have been found and analyzed in blood, urine, amniotic fluid, breast milk, seminal fluid, saliva and malignant effusions, besides conditioned media from different cell lines. Several recent papers show that exosome proteomes of different origin include both a common set of membrane and cytosolic proteins, and specific subsets of proteins, likely correlated to cell-type associated functions. This is particularly interesting in relation to their possible involvement in human diseases. The knowledge of exosome proteomics can help not only in understanding their biological roles but also in supplying new biomarkers to be searched for in patients' fluids. This review offers an overview of technical and analytical issues in exosome proteomics, and it highlights the significance of proteomic studies in terms of biological and clinical usefulness.

Journal ArticleDOI
TL;DR: The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk, and are important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed.
Abstract: Summary Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of P arkinson’s disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab–Berber) from sites participating in the Genetic Epidemiology of Parkinson ’s Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identifi ed through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0·5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab–Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identifi ed for polymorphic variants in white individuals (M1646T, odds ratio 1·43, 95% CI 1·15–1·78; p=0·0012) and Asian individuals (A419V, 2·27, 1·35–3·83; p=0·0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar fi nding in the Arab–Berber series (combined odds ratio 0·82, 0·72–0·94; p=0·0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1·73, 1·20–2·49; p=0·0026), but no association was noted for R1628P (0·62, 0·36–1·07; p=0·087). In the Arab–Berber series, Y2189C showed potential evidence of risk association with PD (4·48, 1·33–15·09; p=0·012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent eff ects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefi t most from therapies targeted at LRRK2 pathogenic activity.

Journal ArticleDOI
TL;DR: Bihemispheric tDCS may achieve the training-induced recovery of motor functions and foster greater functional recovery and CIMT alone appears effective in modulating local excitability but not in removing the imbalance in transcallosal inhibition.
Abstract: Background. Recovery of motor function after stroke may depend on a balance of activity in the neural network involving the affected and the unaffected motor cortices. Objective. To assess whether ...

Journal ArticleDOI
TL;DR: In this article, direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive, however, whether this phenomenon r...
Abstract: Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon r...

Journal ArticleDOI
TL;DR: In the real life setting, fulfillment compliance with antihypertensive medications is effective in the primary prevention of cardiovascular outcomes.
Abstract: ObjectiveThe effect of compliance with antihypertensive medications on the risk of cardiovascular outcomes in a population without a known history of cardiovascular disease has been addressed by a large population-based prospective, cohort study carried out by linking Italian administrative database

Journal ArticleDOI
TL;DR: Harmony among staff (a good working climate) seems to be more useful in preventing aggression than some of the other strategies used in psychiatric wards, such as the presence of male nurses.
Abstract: Although fairly frequent in psychiatric in-patient, episodes of aggression/violence are mainly limited to verbal aggression, but the level of general health is significantly lower in nurses who report 'frequent' exposure to violent incidents, and there is disagreement between patients and staff concerning predictors of these episodes. We searched the Pubmed, Embase and PsychInfo databases for English, Italian, French or German language papers published between 1 January 1990 and 31 March 2010 using the key words "aggress*" (aggression or aggressive) "violen*" (violence or violent) and "in-patient" or "psychiatric wards", and the inclusion criterion of an adult population (excluding all studies of selected samples such as a specific psychiatric diagnosis other than psychosis, adolescents or the elderly, men/women only, personality disorders and mental retardation). The variables that were most frequently associated with aggression or violence in the 66 identified studies of unselected psychiatric populations were the existence of previous episodes, the presence of impulsiveness/hostility, a longer period of hospitalisation, non-voluntary admission, and aggressor and victim of the same gender; weaker evidence indicated alcohol/drug misuse, a diagnosis of psychosis, a younger age and the risk of suicide. Alcohol/drug misuse, hostility, paranoid thoughts and acute psychosis were the factors most frequently involved in 12 studies of psychotic patients. Harmony among staff (a good working climate) seems to be more useful in preventing aggression than some of the other strategies used in psychiatric wards, such as the presence of male nurses.