Showing papers by "University of Milano-Bicocca published in 2016"
TL;DR: The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe, and the lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension.
Abstract: Background:
People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU.
Methods and Findings:
We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence.
Conclusions:
1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes.
792 citations
TL;DR: Clinical, research, and policy recommendations to improve mental health care in prisons are presented and it is shown that opiate substitution treatments reduce substance misuse relapse and possibly reoffending.
553 citations
TL;DR: In the absolute rigidity range ∼60 to ∼500 GV, the antiproton p[over ¯], proton p, and positron e^{+} fluxes are found to have nearly identical rigidity dependence and the electron e^{-} flux exhibits a different rigidity dependent.
Abstract: A precision measurement by AMS of the antiproton flux and the antiproton-to-proton flux ratio in
primary cosmic rays in the absolute rigidity range from 1 to 450 GV is presented based on 3.49 × 105
antiproton events and 2.42 × 109 proton events. The fluxes and flux ratios of charged elementary particles
in cosmic rays are also presented. In the absolute rigidity range ∼60 to ∼500 GV, the antiproton ¯p, proton
p, and positron eþ fluxes are found to have nearly identical rigidity dependence and the electron e− flux
exhibits a different rigidity dependence. Below 60 GV, the ( ¯ p=p), ( ¯ p=eþ), and (p=eþ) flux ratios each
reaches a maximum. From ∼60 to ∼500 GV, the ( ¯ p=p), ( ¯ p=eþ), and (p=eþ) flux ratios show no rigidity
dependence. These are new observations of the properties of elementary particles in the cosmos.
464 citations
TL;DR: In conclusion, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis and are defined as potential targets for tumor immunotherapy.
451 citations
Charité1, Amgen2, University of Tübingen3, Goethe University Frankfurt4, Boston Children's Hospital5, University of Düsseldorf6, University of Pavia7, University of Milano-Bicocca8, University of Padua9, Erasmus University Rotterdam10, University of Pennsylvania11, Cincinnati Children's Hospital Medical Center12, Children's Hospital Los Angeles13, Children's Hospital of Philadelphia14, Seattle Children's15, Primary Children's Hospital16, Harvard University17, University of Colorado Denver18, University of Toronto19
TL;DR: This trial, which to the best of the authors' knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL.
Abstract: Purpose Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Methods This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II). Results We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures. Conclusion This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.
446 citations
TL;DR: The data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α andIL-1β.
Abstract: Anterior cruciate ligament (ACL) reconstruction restores knee stability but does not reduce the incidence of posttraumatic osteoarthritis induced by inflammatory cytokines. The aim of this research was to longitudinally measure IL-1β, IL-6, IL-8, IL-10, and TNF-α levels in patients subjected to ACL reconstruction using bone-patellar tendon-bone graft. Synovial fluid was collected within 24–72 hours of ACL rupture (acute), 1 month after injury immediately prior to surgery (presurgery), and 1 month thereafter (postsurgery). For comparison, a “control” group consisted of individuals presenting chronic ACL tears. Our results indicate that levels of IL-6, IL-8, and IL-10 vary significantly over time in reconstruction patients. In the acute phase, the levels of these cytokines in reconstruction patients were significantly greater than those in controls. In the presurgery phase, cytokine levels in reconstruction patients were reduced and comparable with those in controls. Finally, cytokine levels increased again with respect to control group in the postsurgery phase. The levels of IL-1β and TNF-α showed no temporal variation. Our data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α and IL-1β.
422 citations
TL;DR: In this paper, the MAGIC-I camera and its trigger system were replaced with a new one for low and medium zenith angles to assess the key performance parameters of MAGIC stereo system for point-like sources with Crab Nebula-like spectrum.
421 citations
TL;DR: In this paper, the counting of the micro states of supersymmetric asymptotically AdS black holes in terms of a holographically dual eld theory is addressed.
Abstract: This paper addresses a long standing problem, the counting of the microstates of supersymmetric asymptotically AdS black holes in terms of a holographically dual eld theory. We focus on a class of asymptotically AdS4 static black holes preserving two real supercharges which are dual to a topologically twisted deformation of the ABJM theory. We evaluate in the large N limit the topologically twisted index of the ABJM theory and we show that it correctly reproduces the entropy of the AdS4 black holes. An extremization of the index with respect to a set of chemical potentials is required. We interpret it as the selection of the exact R-symmetry of the superconformal quantum mechanics describing the horizon of the black hole.
396 citations
TL;DR: It is reported that encounters with microbial products and self-encoded oxidized phospholipids (oxPAPC) induce an enhanced DC activation state, which is called “hyperactive” and induce potent adaptive immune responses and are elicited by caspase-11, an enzyme that binds oxP APC and bacterial lipopolysaccharide (LPS).
Abstract: Dendritic cells (DCs) use pattern recognition receptors to detect microorganisms and activate protective immunity. These cells and receptors are thought to operate in an all-or-nothing manner, existing in an immunologically active or inactive state. Here, we report that encounters with microbial products and self-encoded oxidized phospholipids (oxPAPC) induce an enhanced DC activation state, which we call "hyperactive." Hyperactive DCs induce potent adaptive immune responses and are elicited by caspase-11, an enzyme that binds oxPAPC and bacterial lipopolysaccharide (LPS). oxPAPC and LPS bind caspase-11 via distinct domains and elicit different inflammasome-dependent activities. Both lipids induce caspase-11-dependent interleukin-1 release, but only LPS induces pyroptosis. The cells and receptors of the innate immune system can therefore achieve different activation states, which may permit context-dependent responses to infection.
389 citations
TL;DR: An angular analysis of the B0 → K*0(→ K+π−)μ+μ− decay is presented in this paper, where the angular observables and their correlations are reported in bins of q2, the invariant mass squared of the dimuon system.
Abstract: An angular analysis of the B0 → K*0(→ K+π−)μ+μ− decay is presented. The dataset corresponds to an integrated luminosity of 3.0 fb−1 of pp collision data collected at the LHCb experiment. The complete angular information from the decay is used to determine CP-averaged observables and CP asymmetries, taking account of possible contamination from decays with the K+π− system in an S-wave configuration. The angular observables and their correlations are reported in bins of q2, the invariant mass squared of the dimuon system. The observables are determined both from an unbinned maximum likelihood fit and by using the principal moments of the angular distribution. In addition, by fitting for q2-dependent decay amplitudes in the region 1.1 < q2 < 6.0 GeV2/c4, the zero-crossing points of several angular observables are computed. A global fit is performed to the complete set of CP-averaged observables obtained from the maximum likelihood fit. This fit indicates differences with predictions based on the Standard Model at the level of 3.4 standard deviations. These differences could be explained by contributions from physics beyond the Standard Model, or by an unexpectedly large hadronic effect that is not accounted for in the Standard Model predictions.[Figure not available: see fulltext.]
376 citations
TL;DR: It is argued that a valid update of a prior belief distribution to a posterior can be made for parameters which are connected to observations through a loss function rather than the traditional likelihood function, which is recovered as a special case.
Abstract: We propose a framework for general Bayesian inference. We argue that a valid update of a prior belief distribution to a posterior can be made for parameters which are connected to observations through a loss function rather than the traditional likelihood function, which is recovered as a special case. Modern application areas make it increasingly challenging for Bayesians to attempt to model the true data-generating mechanism. For instance, when the object of interest is low dimensional, such as a mean or median, it is cumbersome to have to achieve this via a complete model for the whole data distribution. More importantly, there are settings where the parameter of interest does not directly index a family of density functions and thus the Bayesian approach to learning about such parameters is currently regarded as problematic. Our framework uses loss functions to connect information in the data to functionals of interest. The updating of beliefs then follows from a decision theoretic approach involving cumulative loss functions. Importantly, the procedure coincides with Bayesian updating when a true likelihood is known yet provides coherent subjective inference in much more general settings. Connections to other inference frameworks are highlighted.
TL;DR: It is shown that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells, and the data support the view that different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin.
Abstract: A widely shared view reads that mesenchymal stem/stromal cells (“MSCs”) are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with ubiquitous pericytes. Using stringent in vivo differentiation assays and transcriptome analysis, we show that human cell populations from different anatomical sources, regarded as “MSCs” based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis reveals that muscle pericytes, which are not spontaneously osteochondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called “MSCs,” with important applicative implications. The data also support the view that rather than a uniform class of “MSCs,” different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, possibly of different developmental origin.
TL;DR: Procedure as discussed by the authors is a software package within the statistical programming environment R, which aims to facilitate the visualisation and interpretation of large amounts of sedimentary provenance data, including mineralogical, petrographic, chemical and isotopic provenance proxies, or any combination of these.
TL;DR: It is shown how the photon parton distribution function (PDF) can be determined in a model-independent manner, using electron-proton scattering data, in effect viewing the ep→e+X process as an electron scattering off the photon field of the proton.
Abstract: It has become apparent in recent years that it is important, notably for a range of physics studies at the Large Hadron Collider, to have accurate knowledge on the distribution of photons in the proton. We show how the photon parton distribution function (PDF) can be determined in a model-independent manner, using electron-proton (ep) scattering data, in effect viewing the ep→e+X process as an electron scattering off the photon field of the proton. To this end, we consider an imaginary, beyond the Standard Model process with a flavor changing photon-lepton vertex. We write its cross section in two ways: one in terms of proton structure functions, the other in terms of a photon distribution. Requiring their equivalence yields the photon distribution as an integral over proton structure functions. As a result of the good precision of ep data, we constrain the photon PDF at the level of 1%-2% over a wide range of momentum fractions.
TL;DR: In this paper, the rigidity dependence of the boron to carbon flux ratio (B/C) is studied and a detailed variation with rigidity of the B=C spectral index is reported for the first time.
Abstract: Knowledge of the rigidity dependence of the boron to carbon flux ratio (B/C) is important in
understanding the propagation of cosmic rays. The precise measurement of the B=C ratio from 1.9 GV to
2.6 TV, based on 2.3 million boron and 8.3 million carbon nuclei collected by AMS during the first 5 years
of operation, is presented. The detailed variation with rigidity of the B=C spectral index is reported for the
first time. The B=C ratio does not show any significant structures in contrast to many cosmic ray models
that require such structures at high rigidities. Remarkably, above 65 GV, the B=C ratio is well described by
a single power law RΔ with index Δ ¼ −0.333 + 0.014ðfitÞ + 0.005ðsystÞ, in good agreement with the
Kolmogorov theory of turbulence which predicts Δ ¼ −1=3 asymptotically.
TL;DR: A detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties are provided.
Abstract: Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors.
TL;DR: The largest experiment of applying machine learning algorithms to code smells to the best of the authors' knowledge concludes that the application of machine learning to the detection of these code smells can provide high accuracy (>96 %), and only a hundred training examples are needed to reach at least 95 % accuracy.
Abstract: Several code smell detection tools have been developed providing different results, because smells can be subjectively interpreted, and hence detected, in different ways. In this paper, we perform the largest experiment of applying machine learning algorithms to code smells to the best of our knowledge. We experiment 16 different machine-learning algorithms on four code smells (Data Class, Large Class, Feature Envy, Long Method) and 74 software systems, with 1986 manually validated code smell samples. We found that all algorithms achieved high performances in the cross-validation data set, yet the highest performances were obtained by J48 and Random Forest, while the worst performance were achieved by support vector machines. However, the lower prevalence of code smells, i.e., imbalanced data, in the entire data set caused varying performances that need to be addressed in the future studies. We conclude that the application of machine learning to the detection of these code smells can provide high accuracy (>96 %), and only a hundred training examples are needed to reach at least 95 % accuracy.
TL;DR: This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5 in 60weeks, respectively.
TL;DR: Updating of previous meta-analyses indicates that more vs. less intense BP lowering can reduce not only stroke and coronary events, but also cardiovascular mortality.
Abstract: Background and objectives:Previous meta-analyses of our group have investigated the cardiovascular effects of more vs. less intense blood pressure (BP) treatment and the BP levels to be achieved by treatment. A few additional trials have been completed recently, particularly the large SPRINT study.
TL;DR: In this paper, the authors discuss new N-body simulations of massive (6.5x10^4 ) star clusters, in which they added upgraded recipes for stellar winds and supernova explosion at different metallicity.
Abstract: The runaway collision scenario is one of the most promising mechanisms to explain the formation of intermediate-mass black holes (IMBHs) in young dense star clusters. On the other hand, the massive stars that participate in the runaway collisions lose mass by stellar winds. In this paper, we discuss new N-body simulations of massive (6.5x10^4 Msun) star clusters, in which we added upgraded recipes for stellar winds and supernova explosion at different metallicity. We follow the evolution of the principal collision product (PCP), through dynamics and stellar evolution, till it forms a stellar remnant. At solar metallicity, the mass of the final merger product spans from few solar masses up to ~30 Msun. At low metallicity (0.01-0.1 Zsun) the maximum remnant mass is ~250 Msun, in the range of IMBHs. A large fraction (~0.6) of the PCPs are not ejected from the parent star cluster and acquire stellar or black hole (BH) companions. Most of the long-lived binaries hosting a PCP are BH-BH binaries. We discuss the importance of this result for gravitational wave detection.
Research Triangle Park1, Umeå University2, Mario Negri Institute for Pharmacological Research3, University of North Carolina at Chapel Hill4, University of Strasbourg5, National Institutes of Health6, United States Environmental Protection Agency7, University of Bari8, Technical University of Denmark9, University of Milano-Bicocca10, Food and Drug Administration11, Lockheed Martin Corporation12, Research Institute for Fragrance Materials13, University of Milan14, United States Department of Agriculture15
TL;DR: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches and the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing.
Abstract: BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most ...
TL;DR: The paper focuses on the two leading virtual technologies – augmented reality (AR) and virtual reality (VR) – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses.
Abstract: During our life we undergo many personal changes: we change our house, our school, our work and even our friends and partners. However, our daily experience shows clearly that in some situations subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: a) the focus of personal change is reducing the distance between self and reality (conflict); b) this reduction is achieved through (1) an intense focus on the particular experience creating the conflict or (2) an internal or external reorganization of this experience; c) personal change requires a progression through a series of different stages; d) clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper will focus on the two leading virtual technologies – Augmented Reality (AR) and Virtual Reality (VR) – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience, by focusing on the high level of self-reflectiveness and personal efficacy induced by their emotional engagement and sense of presence. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual’s worldview.
University of Toronto1, St. Michael's Hospital2, University of Milan3, Paris Diderot University4, University of Paris5, Mount Sinai Hospital, Toronto6, University of Milano-Bicocca7, Harvard University8, National University of Ireland, Galway9, University of Göttingen10, Australian National University11, Yokohama City University Medical Center12, Oslo University Hospital13, Uppsala University14, Queen's University Belfast15, Southeast University16, Sapienza University of Rome17, Sunnybrook Health Sciences Centre18, Leipzig University19, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico20
TL;DR: Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS, compared with older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.
Abstract: PURPOSE: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.METHODS: The large observational st ...
TL;DR: Dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL and monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy.
TL;DR: Entrectinib is a novel, potent inhibitor of ALK, ROS1, and TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins, and is potentially suited to the therapy of several molecularly defined cancer settings, especially that of TRK-dependent tumors, for which no approved drugs are currently available.
Abstract: Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non–small cell lung cancers (NSCLC) as well as other tumor types and their oncogenic relevance as actionable targets has been demonstrated by the efficacy of selective kinase inhibitors such as crizotinib, ceritinib, and alectinib. More recently, low-frequency rearrangements of TRK kinases have been described in NSCLC, colorectal carcinoma, glioblastoma, and Spitzoid melanoma. Entrectinib, whose discovery and preclinical characterization are reported herein, is a novel, potent inhibitor of ALK, ROS1, and, importantly, of TRK family kinases, which shows promise for therapy of tumors bearing oncogenic forms of these proteins. Proliferation profiling against over 200 human tumor cell lines revealed that entrectinib is exquisitely potent in vitro against lines that are dependent on the drug's pharmacologic targets. Oral administration of entrectinib to tumor-bearing mice induced regression in relevant human xenograft tumors, including the TRKA-dependent colorectal carcinoma KM12, ROS1-driven tumors, and several ALK-dependent models of different tissue origins, including a model of brain-localized lung cancer metastasis. Entrectinib is currently showing great promise in phase I/II clinical trials, including the first documented objective responses to a TRK inhibitor in colorectal carcinoma and in NSCLC. The drug is, thus, potentially suited to the therapy of several molecularly defined cancer settings, especially that of TRK-dependent tumors, for which no approved drugs are currently available. Mol Cancer Ther; 15(4); 628–39. ©2016 AACR .
TL;DR: The MAGIC telescopes as mentioned in this paper are two Imaging Atmospheric Cherenkov Telescopes (IACTs) located on the Canary island of La Palma, Spain, which are designed to measure Cherennikov light from air showers initiated by gamma rays in the energy regime from around 50GeV to more than 50TeV.
St George's, University of London1, University of Birmingham2, University of Edinburgh3, Brigham and Women's Hospital4, Tokai University5, Technische Universität München6, Heidelberg University7, University of Milano-Bicocca8, Bayer HealthCare Pharmaceuticals9, Maastricht University10, McMaster University11, University College London12
TL;DR: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation, suggesting that a more comprehensive approach to the management of NVAF may be needed to improve outcome.
Abstract: Aims The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year.
Methods and results GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death.
Conclusion The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death.
Clinical Trial Registration . Unique identifier: [NCT01090362][1].
[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01090362&atom=%2Fehj%2F37%2F38%2F2882.atom
TL;DR: BN and BED are associated with childhood abuse, whereas AN shows mixed results, and individuals with similar trauma should be monitored for early recognition of EDs.
Abstract: OBJECTIVES: The aim of this systematic review and meta-analysis was to estimate the association between distinct types of child abuse-sexual (CSA), physical (CPA), and emotional (CEA)-and different eating disorders (EDs). METHODS: Electronic databases were searched through January 2014. Studies reporting rates of CSA, CPA, and CEA in people with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), as compared with individuals without EDs, were included. Pooled analyses were based on odds ratios (ORs), with relevant 95% confidence intervals (CIs), weighting each study with inverse variance models with random effects. Risk of publication bias was estimated. RESULTS: Thirty-two of 1714 studies assessed for eligibility met the inclusion criteria, involving more than 14,000 individuals. The association between EDs and any child abuse showed a random-effects pooled OR of 3.21 (95% CI = 2.29-4.51, p CONCLUSIONS: BN and BED are associated with childhood abuse, whereas AN shows mixed results. Individuals with similar trauma should be monitored for early recognition of EDs. TRIAL REGISTRATION: The protocol was registered in PROSPERO (an international prospective register of systematic reviews) with the reference number CRD42014007360. Language: en
TL;DR: It is concluded that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse.
TL;DR: The data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and magnetic resonance imaging information alone, with good sensitivity and excellent specificity.
Abstract: Importance Cerebral amyloid angiopathy–related inflammation (CAA-ri) is an important diagnosis to reach in clinical practice because many patients with the disease respond to immunosuppressive therapy. Reliable noninvasive diagnostic criteria for CAA-ri would allow some patients to avoid the risk of brain biopsy. Objective To test the sensitivity and specificity of clinical and neuroimaging-based criteria for CAA-ri. Design, Setting, and Participants We modified the previously proposed clinicoradiological criteria and retrospectively analyzed clinical medical records and magnetic resonance imaging fluid-attenuated inversion recovery and gradient-echo scans obtained from individuals with CAA-ri and noninflammatory CAA. At 2 referral centers between October 1, 1995, and May 31, 2013, and between January 1, 2009, and December 31, 2011, participants included 17 individuals with pathologically confirmed CAA-ri and 37 control group members with pathologically confirmed noninflammatory CAA. The control group was further divided into those with past lobar intracerebral hemorrhage (ICH) (n = 21) and those with cerebral microbleeds only and no history of ICH (n = 16). The dates of our analysis were September 1, 2012, to August 31, 2015. Main Outcomes and Measures The sensitivity and specificity of prespecified criteria for probable CAA-ri (requiring asymmetric white matter hyperintensities extending to the subcortical white matter) and possible CAA-ri (not requiring the white matter hyperintensities to be asymmetric). Results The 17 patients in the CAA-ri group were a mean (SD) of 68 (8) years and 8 (47%) were women. In the CAA-ri group, 14 of 17 (82%) met the criteria for both probable and possible CAA-ri. In the control group having noninflammatory CAA with lobar ICH, 1 of 21 (5%) met the criteria for possible CAA-ri, and none met the criteria for probable CAA-ri. In the control group having noninflammatory CAA with no ICH, 11 of 16 (69%) met the criteria for possible CAA-ri, and 1 of 16 (6%) met the criteria for probable CAA-ri. These findings yielded a sensitivity and specificity of 82% and 97%, respectively, for the probable criteria and a sensitivity and specificity of 82% and 68%, respectively, for the possible criteria. Conclusions and Relevance Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and magnetic resonance imaging information alone, with good sensitivity and excellent specificity.