Showing papers by "University of Florence published in 2016"
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.
For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.
Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.
5,187 citations
Mariachiara Di Cesare1, Mariachiara Di Cesare2, James Bentham2, Gretchen A Stevens3 +738 more•Institutions (60)
TL;DR: The posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue, is calculated.
3,766 citations
TL;DR: In this article, the authors used a Bayesian hierarchical model to estimate trends in diabetes prevalence, defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs in 200 countries and territories in 21 regions, by sex and from 1980 to 2014.
2,782 citations
West Virginia University1, Yale University2, Food and Agriculture Organization3, Landcare Research4, University of Udine5, Max Planck Society6, University of Alaska Fairbanks7, Technische Universität München8, Université du Québec à Montréal9, University of the French West Indies and Guiana10, University of Freiburg Faculty of Biology11, Cornell University12, Wageningen University and Research Centre13, University of Sydney14, Polytechnic Institute of Viseu15, University of Trás-os-Montes and Alto Douro16, University of Göttingen17, Russian Academy of Sciences18, Oeschger Centre for Climate Change Research19, Lakehead University20, University of La Frontera21, Seoul National University22, Martin Luther University of Halle-Wittenberg23, University of Cambridge24, Center for International Forestry Research25, James Cook University26, University of Zurich27, University of Yaoundé I28, University of Wisconsin-Madison29, Queensland Government30, Institut national de la recherche agronomique31, Florida International University32, Forest Research Institute33, Polish Academy of Sciences34, University of Minnesota35, Warsaw University of Life Sciences36, Ştefan cel Mare University of Suceava37, University of Florence38, University of Warsaw39, King Juan Carlos University40, Spanish National Research Council41, International Trademark Association42, National University of Austral Patagonia43, National Scientific and Technical Research Council44, Wildlife Conservation Society45, College of African Wildlife Management46, University of York47, Durham University48, Ontario Ministry of Natural Resources49, Pontificia Universidad Católica del Ecuador50, Centre national de la recherche scientifique51, Museu Paraense Emílio Goeldi52, University College London53, University of Leeds54
TL;DR: A consistent positive concave-down effect of biodiversity on forest productivity across the world is revealed, showing that a continued biodiversity loss would result in an accelerating decline in forest productivity worldwide.
Abstract: The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone-US$166 billion to 490 billion per year according to our estimation-is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities.
889 citations
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
Max Planck Society1, University of Tübingen2, Broad Institute3, Harvard University4, Howard Hughes Medical Institute5, University College Dublin6, University of Coimbra7, University of Adelaide8, Russian Academy of Sciences9, Altai State University10, University of Pisa11, University of Bari12, University of Cantabria13, University of New Mexico14, Austrian Academy of Sciences15, Naturhistorisches Museum16, University of Vienna17, University of Ferrara18, University of Florence19, University of Siena20, Centre national de la recherche scientifique21, University of Bucharest22, California State University, Northridge23, University of Bordeaux24, University of Toulouse25, Royal Belgian Institute of Natural Sciences26, Masaryk University27, Academy of Sciences of the Czech Republic28
TL;DR: In this article, the authors analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago and find that the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans.
Abstract: Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.
702 citations
TL;DR: In this paper, the authors explored the relationship between social media marketing activities and consumers' behavior towards a brand and found that SMMEs have a significant positive effect on brand equity and on the two main dimensions of brand awareness and brand image.
698 citations
Vardan Khachatryan1, Albert M. Sirunyan1, Armen Tumasyan1, Wolfgang Adam +2283 more•Institutions (141)
TL;DR: Combined fits to CMS UE proton–proton data at 7TeV and to UEProton–antiproton data from the CDF experiment at lower s, are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13.
Abstract: New sets of parameters ("tunes") for the underlying-event (UE) modeling of the PYTHIA8, PYTHIA6 and HERWIG++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE data at sqrt(s) = 7 TeV and to UE data from the CDF experiment at lower sqrt(s), are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13 TeV. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan (q q-bar to Z / gamma* to lepton-antilepton + jets) observables at 7 and 8 TeV are presented, as well as predictions of MB and UE observables at 13 TeV.
686 citations
TL;DR: Structural-based drug design campaigns allowed the discovery of highly isoform selective CA inhibitors (CAIs), which may lead to a new generation of drugs targeting these widespread enzymes, and the use of CAs in CO2 capture processes for mitigating the global temperature rise has also been investigated more recently.
Abstract: Carbonic anhydrases (CAs, EC 4.2.1.1) catalyse the interconversion between CO2 and bicarbonate as well as other hydrolytic reactions. Among the six genetic families known to date, the α-, β-, γ-, δ-, ζ- and η-CAs, detailed kinetic and X-ray crystallographic studies have allowed a deep understanding of the structure-function relationship in this superfamily of proteins. A metal hydroxide nucleophilic species of the enzyme, and a unique active site architecture, with half of it hydrophilic and the opposing part hydrophobic, allow these enzymes to act as some of the most effective catalysts known in Nature. The CA activation and inhibition mechanisms are also known in detail, with a large number of new inhibitor classes being described in the last years. Apart from the zinc binders, some classes of inhibitors anchor to the metal ion coordinated nucleophile, others occlude the entrance of the active site cavity and more recently, compounds binding outside the active site were described. CA inhibition has therapeutic applications for drugs acting as diuretics, antiepileptics, antiglaucoma, antiobesity and antitumour agents. Targeting such enzymes from pathogens may lead to novel anti-infectives. Successful structure-based drug design campaigns allowed the discovery of highly isoform selective CA inhibitors (CAIs), which may lead to a new generation of drugs targeting these widespread enzymes. The use of CAs in CO2 capture processes for mitigating the global temperature rise has also been investigated more recently.
633 citations
TL;DR: This work provides for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105-109 years old, in comparison to adults, elderly, and centenarian, thus reconstructing the longest available human microbiota trajectory along aging.
579 citations
TL;DR: Recent findings in the field of CA inhibition may be useful for a structure-based drug design approach of more selective/potent modulators of the activity of these enzymes.
Abstract: Six genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) were described to date. Inhibition of CAs has pharmacologic applications in the field of antiglaucoma, anticonvulsant, anticancer, and anti-infective agents. New classes of CA inhibitors (CAIs) were described in the last decade with enzyme inhibition mechanisms differing considerably from the classical inhibitors of the sulfonamide or anion type. Five different CA inhibition mechanisms are known: (i) the zinc binders coordinate to the catalytically crucial Zn(II) ion from the enzyme active site, with the metal in tetrahedral or trigonal bipyramidal geometries. Sulfonamides and their isosters, most anions, dithiocarbamates and their isosters, carboxylates, and hydroxamates bind in this way; (ii) inhibitors that anchor to the zinc-coordinated water molecule/hydroxide ion (phenols, carboxylates, polyamines, 2-thioxocoumarins, sulfocoumarins); (iii) inhibitors which occlude the entrance to the active site cavity (coumarins and their isosters), this binding site coinciding with that where CA activators bind; (iv) compounds which bind out of the active site cavity (a carboxylic acid derivative was seen to inhibit CA in this manner), and (v) compounds for which the inhibition mechanism is not known, among which the secondary/tertiary sulfonamides as well as imatinib/nilotinib are the most investigated examples. As CAIs are used clinically in many pathologies, with a sulfonamide inhibitor (SLC-0111) in Phase I clinical trials for the management of metastatic solid tumors, this review updates the recent findings in the field which may be useful for a structure-based drug design approach of more selective/potent modulators of the activity of these enzymes.
European Space Agency1, Leibniz University of Hanover2, Paris Diderot University3, Imperial College London4, University of Rome Tor Vergata5, University of Trento6, Airbus Defence and Space7, fondazione bruno kessler8, University of Birmingham9, Institut de Ciències de l'Espai10, ETH Zurich11, UK Astronomy Technology Centre12, INAF13, University of Urbino14, European Space Operations Centre15, University of Zurich16, University of Glasgow17, Polytechnic University of Catalonia18, Goddard Space Flight Center19, University of Florence20
TL;DR: The first results of the LISA Pathfinder in-flight experiment demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density.
Abstract: We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2 +/- 0.1 fm s(exp -2)/square root of Hz, or (0.54 +/- 0.01) x 10(exp -15) g/square root of Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8 +/- 0.3) fm square root of Hz, about 2 orders of magnitude better than requirements. At f less than or equal to 0.5 mHz we observe a low-frequency tail that stays below 12 fm s(exp -2)/square root of Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.
University of Maryland, Baltimore1, Harvard University2, University of Florence3, University of Toulouse4, Catholic University of the Sacred Heart5, Université catholique de Louvain6, Katholieke Universiteit Leuven7, Yeshiva University8, University of Turku9, Memorial Hospital of South Bend10, University of California, San Francisco11, University of Barcelona12, Group Health Cooperative13, Seoul National University14, University of Minnesota15, California Pacific Medical Center16, French Institute of Health and Medical Research17, Johns Hopkins University18, University of Ferrara19
TL;DR: The association between poor performance on SPPB and all-cause mortality remained highly consistent independent of follow-up length, subsets of participants, geographic area, and age of the population.
Abstract: The Short Physical Performance Battery (SPPB) is a well-established tool to assess lower extremity physical performance status. Its predictive ability for all-cause mortality has been sparsely reported, but with conflicting results in different subsets of participants. The aim of this study was to perform a meta-analysis investigating the relationship between SPPB score and all-cause mortality. Articles were searched in MEDLINE, the Cochrane Library, Google Scholar, and BioMed Central between July and September 2015 and updated in January 2016. Inclusion criteria were observational studies; >50 participants; stratification of population according to SPPB value; data on all-cause mortality; English language publications. Twenty-four articles were selected from available evidence. Data of interest (i.e., clinical characteristics, information after stratification of the sample into four SPPB groups [0–3, 4–6, 7–9, 10–12]) were retrieved from the articles and/or obtained by the study authors. The odds ratio (OR) and/or hazard ratio (HR) was obtained for all-cause mortality according to SPPB category (with SPPB scores 10–12 considered as reference) with adjustment for age, sex, and body mass index. Standardized data were obtained for 17 studies (n = 16,534, mean age 76 ± 3 years). As compared to SPPB scores 10–12, values of 0–3 (OR 3.25, 95%CI 2.86–3.79), 4–6 (OR 2.14, 95%CI 1.92–2.39), and 7–9 (OR 1.50, 95%CI 1.32–1.71) were each associated with an increased risk of all-cause mortality. The association between poor performance on SPPB and all-cause mortality remained highly consistent independent of follow-up length, subsets of participants, geographic area, and age of the population. Random effects meta-regression showed that OR for all-cause mortality with SPPB values 7–9 was higher in the younger population, diabetics, and men. An SPPB score lower than 10 is predictive of all-cause mortality. The systematic implementation of the SPPB in clinical practice settings may provide useful prognostic information about the risk of all-cause mortality. Moreover, the SPPB could be used as a surrogate endpoint of all-cause mortality in trials needing to quantify benefit and health improvements of specific treatments or rehabilitation programs. The study protocol was published on PROSPERO (CRD42015024916).
University of Queensland1, University of Adelaide2, Griffith University3, University Medical Center Groningen4, University of Utah5, National Institute for Health Research6, University of London7, Hannover Medical School8, Zürcher Fachhochschule9, La Trobe University10, University of British Columbia11, University of Melbourne12, French Institute of Health and Medical Research13, University of Florence14, University of Auckland15, Monash University16, University of Bristol17, Southmead Hospital18, Central Manchester University Hospitals NHS Foundation Trust19, University of Manchester20, Mater Health Services21, Columbia University22
TL;DR: In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts and programs at community and country level need to improve health in disadvantaged families.
TL;DR: The aim was to characterize the VOC’s profile of the wholemeal flour and of the kernel to find out if any VOCs were specific to varieties and sample matrices, and the results show that it is possible describe samples using VOC profiles and protein data.
Abstract: In this paper volatile organic compounds (VOCs) from durum wheat cultivars and landraces were analyzed using PTR-TOF-MS. The aim was to characterize the VOC’s profile of the wholemeal flour and of the kernel to find out if any VOCs were specific to varieties and sample matrices. The VOC data is accompanied by SDS-PAGE analyses of the storage proteins (gliadins and glutenins). Statistical analyses was carried out both on the signals obtained by MS and on the protein profiles. The difference between the VOC profile of two cultivars or two preparations of the same sample - matrices, in this case kernel vs wholemeal flour - can be very subtle; the high resolution of PTR-TOF-MS - down to levels as low as pptv - made it possible to recognize these differences. The effects of grinding on the VOC profiles were analyzed using SIMPER and Tanglegram statistical methods. Our results show that it is possible describe samples using VOC profiles and protein data.
University of Liège1, Arthritis Research UK2, University of Sheffield3, University of Toulouse4, Geneva College5, World Health Organization6, Vrije Universiteit Brussel7, University of Florence8, King Saud University9, Tufts University10, Katholieke Universiteit Leuven11, Catholic University of the Sacred Heart12, VU University Medical Center13, VU University Amsterdam14, Australian National University15, University of Southampton16, University of Oxford17
TL;DR: Assessment of sarcopenia in individuals with risk factors, symptoms and/or conditions exposing them to the risk of disability will become particularly important in the near future.
Abstract: Sarcopenia is increasingly recognized as a correlate of ageing and is associated with increased likelihood of adverse outcomes including falls, fractures, frailty and mortality. Several tools have been recommended to assess muscle mass, muscle strength and physical performance in clinical trials. Whilst these tools have proven to be accurate and reliable in investigational settings, many are not easily applied to daily practice. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were afterwards organized for the whole group to make amendments and discuss further recommendations. This paper proposes some user-friendly and inexpensive methods that can be used to assess sarcopenia in real-life settings. Healthcare providers, particularly in primary care, should consider an assessment of sarcopenia in individuals at increased risk; suggested tools for assessing risk include the Red Flag Method, the SARC-F questionnaire, the SMI method or different prediction equations. Management of sarcopenia should primarily be patient centered and involve the combination of both resistance and endurance based activity programmes with or without dietary interventions. Development of a number of pharmacological interventions is also in progress. Assessment of sarcopenia in individuals with risk factors, symptoms and/or conditions exposing them to the risk of disability will become particularly important in the near future.
TL;DR: It was shown that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits and there was no unexpected increased incidence of adverse events with longer exposure.
Abstract: Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35-0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44-1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18-1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.
TL;DR: The results show that Social Media use is still rather limited and restricted and that academics are not much inclined to integrate these devices into their practices for several reasons, such as cultural resistance, pedagogical issues or institutional constraints.
Abstract: Social Media tools are seen by many authors as powerful drivers of change for teaching and learning practices, in terms of openness, interactivity and sociability. However, extensive surveys about actual use that are carried out with large samples at a national level are rare. This study reports the results of a survey addressed to the Italian academic staff, with the aim of identifying the uses of Social Media in the field of university teaching practices. The response rate was 10.5%, corresponding to 6139. The respondents were asked to identify frequency of use, motivations, teaching practices and obstacles related to the use of a number of tools: generic social network sites (Twitter, Facebook), professional and academic networking services (LinkedIn, ResearchGate and Academia.edu), tools to write and comment (blogs, wikis) and to archive and retrieve content material for lectures and group work (podcasts, YouTube and Vimeo, SlideShare). Analyses of data tested which socio-demographic variables mostly affected frequency of use, and the relationships between motivations, ways of use, barriers to use and the scientific discipline. The results show that Social Media use is still rather limited and restricted and that academics are not much inclined to integrate these devices into their practices for several reasons, such as cultural resistance, pedagogical issues or institutional constraints. However, there are differences among academics in the ways they use Social Media or perceive them, mostly depending on the scientific discipline of teaching. Overall, the results emphasise ambivalent attitudes towards the benefits and challenges of Social Media in the context of higher education with obstacles prevailing over advantages. We examine the frequency of use of Social Media for teaching purposes.The variable most associated with frequency of use is scientific discipline.We present motivations and ways to use Social Media tools in teaching.A principal component analysis reveals three main factors as obstacles to use.Results show a complex scenario where potentials and barriers are intertwined.
TL;DR: Results from randomized clinical trials on MM showed that PD-L1 expression is significantly associated with mortality and clinical response to anti-PD-1/PD-L 1 antibodies in MM patients and with clinical response in patients with non-squamous NSCLC.
Abstract: Background Despite the success of immunotherapy directed at inhibiting of programmed death-1 (PD-1)/PD-ligand (L)1 signaling, it is not established whether PD-L1 expression correlates with the clinical response and outcome in different tumors. The present meta-analysis investigates whether the PD-L1 status, detected by immunohistochemistry, is associated with clinical response and mortality in patients treated with anti-PD-1/PD-L1 therapy. Methods A systematic literature search and quantitative analysis were planned, conducted and reported following CONSORT and QUORUM checklists, up to December 2015, to identify clinical trials with information on cancer outcome by PD-L1 immunohistochemical expression in tumor tissues. We used random effects models to estimate Summary Objective Response Rates (SORRs) and Summary Odd Ratio (SOR) for the comparison of PD-L1 positive and negative patients. Results We summarized 20 trials carried out in metastatic melanoma (MM), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) patients receiving anti-PD-1/PD-L1 antibodies (4230 MM, 1417 NSCLC and 312 RCC patients). Positive PD-L1 MM patients showed a significant decrease (53%) in the risk of mortality vs. negative cases with no heterogeneity. Furthermore, SORRs were 45% and 27% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference in term of responses: 2.14 (95% CI: 1.65, 2.77), with low between-study heterogeneity (I 2 = 35%). Furthermore, results from randomized clinical trials on MM showed that PD-L1 expression is significantly associated with greater clinical response rates to anti-PD1 treatments (SOR 1.89; 95%CI: 1.35, 2.64) but not to other treatments (SOR 0.96; 95%CI: 0.5, 1.87). In non-squamous NSCLC SORRs were 29% and 11% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference between responses: 3.78 (1.54, 9.24), with no between-study heterogeneity. Squamous NSCLC and RCC did not show any significant difference in response according to the PD-L1 status. Conclusion PD-L1 expression is significantly associated with mortality and clinical response to anti-PD-1/PD-L1 antibodies in MM patients and with clinical response in patients with non-squamous NSCLC.
TL;DR: An overview of recent static and time-resolved vibrational spectroscopic studies of liquid water from ambient conditions to the supercooled state, as well as of crystalline and amorphous ice forms, reveals a coherent picture of water dynamics and energetics.
Abstract: We present an overview of recent static and time-resolved vibrational spectroscopic studies of liquid water from ambient conditions to the supercooled state, as well as of crystalline and amorphous ice forms. The structure and dynamics of the complex hydrogen-bond network formed by water molecules in the bulk and interphases are discussed, as well as the dissipation mechanism of vibrational energy throughout this network. A broad range of water investigations are addressed, from conventional infrared and Raman spectroscopy to femtosecond pump–probe, photon-echo, optical Kerr effect, sum-frequency generation, and two-dimensional infrared spectroscopic studies. Additionally, we discuss novel approaches, such as two-dimensional sum-frequency generation, three-dimensional infrared, and two-dimensional Raman terahertz spectroscopy. By comparison of the complementary aspects probed by various linear and nonlinear spectroscopic techniques, a coherent picture of water dynamics and energetics emerges. Furthermore,...
TL;DR: In this article, an extended analysis is presented which has been carried out with the final aim of identifying the most effective simulation settings to ensure a reliable fully-unsteady, two-dimensional simulation of an H-type Darrieus turbine.
TL;DR: Rabi oscillations are observed in this nuclear spin-active environment ((1)H and (14)N nuclei) at room temperature also for 2, indicating an outstanding robustness of the quantum coherence in this molecular semiconductor exploitable in spintronic devices.
Abstract: Here we report the investigation of the magnetic relaxation and the quantum coherence of vanadyl phthalocyanine, VOPc, a multifunctional and easy-processable potential molecular spin qubit. VOPc in its pure form (1) and its crystalline dispersions in the isostructural diamagnetic host TiOPc in different stoichiometric ratios, namely VOPc:TiOPc 1:10 (2) and 1:1000 (3), were investigated via a multitechnique approach based on the combination of alternate current (AC) susceptometry, continuous wave, and pulsed electron paramagnetic resonance (EPR) spectroscopy. AC susceptibility measurements revealed a linear increase of the relaxation rate with temperature up to 20 K, as expected for a direct mechanism, but τ remains slow over a very wide range of applied static field values (up to ∼5 T). Pulsed EPR spectroscopy experiments on 3 revealed quantum coherence up to room temperature with Tm ∼1 μs at 300 K, representing the highest value obtained to date for molecular electronic spin qubits. Rabi oscillations are...
University of the Algarve1, Royal Horticultural Society2, Polytechnic University of Valencia3, Süleyman Demirel University4, Hungarian Academy of Sciences5, University of Catania6, University of Aberdeen7, University of Extremadura8, Institut national de la recherche agronomique9, Forest Research Institute10, University of Sassari11, University of Florence12, University of Belgrade13, Finnish Forest Research Institute14, Instituto Nacional dos Recursos Biológicos15, Nancy-Université16, Swedish University of Agricultural Sciences17, Agricultural University of Athens18, Swiss Federal Institute for Forest, Snow and Landscape Research19, University of Córdoba (Spain)20, Scottish Government21, Tuscia University22, Wageningen University and Research Centre23
TL;DR: At least 47 of the 68 Phytophthora species/taxa detected in nurseries and plantings were exotic species several of which are considered well established in both nurseries or plantings in Europe.
Abstract: An analysis of incidence of Phytophthora spp. in 732 European nurseries producing forest transplants, larger specimen trees, landscape plants and ornamentals, plus 2525 areas in which trees and shrubs were planted, is presented based on work conducted by 37 research groups in 23 European countries between 1972 and 2013. Forty-nine Phytophthora taxa were recorded in 670 nurseries (91.5%); within these nurseries, 1614 of 1992 nursery stands (81.0%) were infested, although most affected plants appeared healthy. In forest and landscape plantings, 56 Phytophthora taxa were recovered from 1667 of 2525 tested sites (66.0%). Affected plants frequently showed symptoms such as crown thinning, chlorosis and dieback caused by extensive fine root losses and/or collar rot. Many well-known highly damaging host-Phytophthora combinations were frequently detected but 297 and 407 new Phytophthora-host associations were also observed in nurseries and plantings, respectively. On average, 1.3 Phytophthora species/taxa per infested nursery stand and planting site were isolated. At least 47 of the 68 Phytophthora species/taxa detected in nurseries and plantings were exotic species several of which are considered well established in both nurseries and plantings in Europe. Seven known Phytophthora species/taxa were found for the first time in Europe, while 10 taxa had not been previously recorded from nurseries or plantings; in addition, 5 taxa were first detections on woody plant species. Seven Phytophthora taxa were previously unknown to science. The reasons for these failures of plant biosecurity in Europe, implications for forest and semi-natural ecosystems and possible ways to improve biosecurity are discussed.
TL;DR: This work has engineered fermionic ladders with synthetic magnetic flux in an experimental configuration that has allowed them to achieve uniform fluxes on a lattice with minimal requirements and unprecedented tunability and opens new directions for the investigation of topological states of matter with ultracold atomic gases.
Abstract: Spin-orbit interactions in ultracold quantum gases are synthesized via clock transitions between two energy levels, which act like pseudospin states.
TL;DR: A systematic review of the principal studies that analyze the impact of the economic crisis on the health of workers found that a rise in unemployment, increased workload, staff reduction, and wages reduction were linked to an increased rate of mood disorders, anxiety, depression, dysthymia, and suicide.
Abstract: In 2008 a deep economic crisis started in the US and rapidly spread around the world. The crisis severely affected the labor market and employees' well-being. Hence, the aim of this work is to implement a systematic review of the principal studies that analyze the impact of the economic crisis on the health of workers. We conducted our search on the PubMed database, and a total of 19 articles were selected for review. All studies showed that the economic crisis was an important stressor that had a negative impact on workers' mental health. Most of the studies documented that a rise in unemployment, increased workload, staff reduction, and wages reduction were linked to an increased rate of mood disorders, anxiety, depression, dysthymia, and suicide. Some studies showed that problems related to the crisis may have also affected the general health of workers by increasing the risk of such health problems as cardiovascular and respiratory diseases. Finally, some studies looked at the impact of the crisis on health care services. These studies demonstrated that the reduction in public expenditure on health care services, and the reduction of public hospital budgets due to the recession, led to organizational problems (eg, medical supply shortages).
TL;DR: The AIRUSE-LIFE+ project aims at characterizing similarities and heterogeneities in particulate matter (PM) sources and contributions in urban areas from southern Europe as mentioned in this paper, where the main PMx sources are identified and tested the efficiency of specific and non-specific measures to improve urban air quality.
Abstract: . The AIRUSE-LIFE+ project aims at characterizing similarities and heterogeneities in particulate matter (PM) sources and contributions in urban areas from southern Europe. Once the main PMx sources are identified, AIRUSE aims at developing and testing the efficiency of specific and non-specific measures to improve urban air quality. This article reports the results of the source apportionment of PM10 and PM2.5 conducted at three urban background sites (Barcelona, Florence and Milan, BCN-UB, FI-UB and MLN-UB), one suburban background site (Athens, ATH-SUB) and one traffic site (Porto, POR-TR). After collecting 1047 PM10 and 1116 PM2.5 24 h samples during 12 months (from January 2013 on) simultaneously at the five cities, these were analysed for the contents of OC, EC, anions, cations, major and trace elements and levoglucosan. The USEPA PMF5 receptor model was applied to these data sets in a harmonized way for each city. The sum of vehicle exhaust (VEX) and non-exhaust (NEX) contributes between 3.9 and 10.8 µg m−3 (16–32 %) to PM10 and 2.3 and 9.4 µg m−3 (15–36 %) to PM2.5, although a fraction of secondary nitrate is also traffic-related but could not be estimated. Important contributions arise from secondary particles (nitrate, sulfate and organics) in PM2.5 (37–82 %) but also in PM10 (40–71 %), mostly at background sites, revealing the importance of abating gaseous precursors in designing air quality plans. Biomass burning (BB) contributions vary widely, from 14–24 % of PM10 in POR-TR, MLN-UB and FI-UB, 7 % in ATH-SUB, to – Local dust, 7–12 % of PM10 at SUB and UB sites and 19 % at the TR site, revealing a contribution from road dust resuspension. In PM2.5 percentages decrease to 2–7 % at SUB-UB sites and 15 % at the TR site. – Industry, mainly metallurgy, contributing 4–11 % of PM10 (5–12 % in PM2.5), but only at BCN-UB, POR-TR and MLN-UB. No clear impact of industrial emissions was found in FI-UB and ATH-SUB. – Natural contributions from sea salt (13 % of PM10 in POR-TR, but only 2–7 % in the other cities) and Saharan dust (14 % in ATH-SUB, but less than 4 % in the other cities). During high pollution days, the largest sources (i.e. excluding secondary aerosol factors) of PM10 and PM2.5 are VEX + NEX in BCN-UB (27–22 %) and POR-TR (31–33 %), BB in FI-UB (30–33 %) and MLN-UB (35–26 %) and Saharan dust in ATH-SUB (52–45 %). During those days, there are also quite important industrial contributions in BCN-UB (17–18 %) and local dust in POR-TR (28–20 %).
University of Melbourne1, Royal Melbourne Hospital2, Monash University3, Charles University in Prague4, University of Bari5, University of Bologna6, Amiri Hospital7, Karadeniz Technical University8, John Hunter Hospital9, University of Newcastle10, Cliniques Universitaires Saint-Luc11, University of Parma12, Flinders Medical Centre13, University of Florence14, University of Queensland15, Westmead Hospital16, University of Sydney17, Liverpool Hospital18, Geelong Hospital19, Jewish General Hospital20
TL;DR: In this article, the authors evaluated the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies, using MSBase, a large, prospectively acquired, global cohort study, and analyzed the accuracy of 576 data-derived onset definitions for SPM and compared these to a consensus opinion of three neurologists.
Abstract: A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis.
University of Tübingen1, Max Planck Society2, California State University, Northridge3, Centre national de la recherche scientifique4, University of Florence5, University of Siena6, University of Bordeaux7, University of Toulouse8, Royal Belgian Institute of Natural Sciences9, Leiden University10, University of Groningen11, University of Bucharest12, Academy of Sciences of the Czech Republic13, Masaryk University14, University of Adelaide15
TL;DR: Demographic modeling not only indicates an LGM genetic bottleneck, but also provides surprising evidence of a major population turnover in Europe around 14,500 years ago during the Late Glacial, a period of climatic instability at the end of the Pleistocene.
TL;DR: G6PD deficiency, one of the commonest inherited enzyme abnormalities in humans, arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age.
Abstract: G6PD is a housekeeping gene expressed in all cells. Glucose-6-phosphate dehydrogenase (G6PD) is part of the pentose phosphate pathway, and its main physiologic role is to provide NADPH. G6PD deficiency, one of the commonest inherited enzyme abnormalities in humans, arises through one of many possible mutations, most of which reduce the stability of the enzyme and its level as red cells age. G6PD-deficient persons are mostly asymptomatic, but they can develop severe jaundice during the neonatal period and acute hemolytic anemia when they ingest fava beans or when they are exposed to certain infections or drugs. G6PD deficiency is a global health issue.
TL;DR: A deeper functional, biochemical and molecular characterization of the various EV classes might identify more selective clinical markers, and significantly advance the knowledge of the pathogenesis and disease progression of many cancer types.
Abstract: Extracellular Vesicles (EVs) have received considerable attention in recent years, both as mediators of intercellular communication pathways that lead to tumor progression, and as potential sources for discovery of novel cancer biomarkers. For many years, research on EVs has mainly investigated either the mechanism of biogenesis and cargo selection and incorporation, or the methods of EV isolation from available body fluids for biomarker discovery. Recent studies have highlighted the existence of different populations of cancer-derived EVs, with distinct molecular cargo, thus pointing to the possibility that the various EV populations might play diverse roles in cancer and that this does not happen randomly. However, data attributing cancer specific intercellular functions to given populations of EVs are still limited. A deeper functional, biochemical and molecular characterization of the various EV classes might identify more selective clinical markers, and significantly advance our knowledge of the pathogenesis and disease progression of many cancer types.