Alpine Glaciology: An Historical Collaboration between Volunteers and Scientists and the Challenge Presented by an Integrated Approach

European Alpine glaciology has a long tradition of studies and activities, in which researchers have often relied on the field work of some specialized volunteer operators. Despite the remarkable results of this cooperation, some problems in field data harmonization and in covering the whole range of monitored glaciers are still present. Moreover, dynamics of reduction, fragmentation and decline, which in recent decades characterize Alpine glaciers, make more urgent the need to improve spatial and temporal monitoring, still maintaining adequate quality standards. Scientific field monitoring activities on Alpine glaciers run parallel to a number of initiatives by individuals and amateur associations, keepers of alternative, experiential and para-scientific knowledge of the glacial environment. Problems of harmonization, coordination, recruitment and updating can be addressed with the help of a collaborative approach—citizen science-like—in which the scientific coordination guarantees information quality and web 2.0 tools operate as mediators between expert glaciologists and non-expert contributors. This paper gives an overview of glaciological information currently produced in the European Alpine region, representing it in an organized structure, functional to the discussion. An empowering solution is then proposed, both methodological and technological, for the integration of multisource data. Its characteristics, potentials and problems are discussed

The Ortles ice cores: uncovering an extended climate archive from the Eastern Alps

During the last half century, oxygen and hydrogen stable isotope content of ice cores has been extensively used for air temperature reconstructions. The most suitable glaciers of the Alpine area, most exclusively in the Western Alps, havebeen utilizedfor icecoring formore thanfour decades.The paleoclimatic potential of theEastern Alps isstilllargelyunexploitedandwasscarcelyutilizedinthepastmainlybecauseofthelowerelevation(comparedto Western Alps) and hence the difficulty to find glaciers in cold conditions. The warming temperature trend appears to be particularly pronounced in the Alps, threatening the preservation of the glaciated areas and creating a sense of urgency in retrieving climatic archives before it is too late. In autumn 2011, four deep cores were drilled on Mt Ortles, South Tyrol, Italy, at 3859 m a.s.l. An extensive reconstructed temperature record for the Ortles summit, based on the surrounding meteorological station data, is available for the last 150 years, while an automatic weather station had been operating from 2011 to 2015 in proximity of the drilling site. The new ice core chronology, based on 210Pb, tritium, beta emissions analysis and 14C measurements of the particulate organic carbon, indicates that the bottom ice is 7000 years old, making it the second most extended glaciological archive ever retrieved in the Alps. The three equally long ice cores have been analyzed for oxygen and hydrogen stable isotopes throughout their length, and the goal is to create an Ortles stacked record for d18O and dD and compare the isotopic data to instrumental temperatures and to other Alpine records. Since 2008, several snow pits were dug in proximity of the drilling site during summer, when the temperature can oftenexceedthemeltingpoint.Theisotopicprofilesofthe2015snowpit,dugattheendofanexceptionallywarm summer,showhowtheisotopesignalisnowaffectedbythepost-depositionalprocessesthathaveoccurredduring that summer

Age of the Mt. Ortles ice cores, the Tyrolean Iceman and glaciation of the highest summit of South Tyrol since the Northern Hemisphere Climatic Optimum

In 2011 four ice cores were extracted from the summit of Alto dell'Ortles (3859 m), the highest glacier of South Tyrol in the Italian Alps. This drilling site is located only 37 km southwest from where the Tyrolean Iceman, similar to 5.3 kyrs old, was discovered emerging from the ablating ice field of Tisenjoch (3210 m, near the Italian-Austrian border) in 1991. The excellent preservation of this mummy suggested that the Tyrolean Iceman was continuously embedded in prehistoric ice and that additional ancient ice was likely preserved elsewhere in South Tyrol. Dating of the ice cores from Alto dell'Ortles based on Pb-210, tritium, beta activity and C-14 determinations, combined with an empirical model (COPRA), provides evidence for a chronologically ordered ice stratigraphy from the modern glacier surface down to the bottom ice layers with an age of similar to 7 kyrs, which confirms the hypothesis. Our results indicate that the drilling site has continuously been glaciated on frozen bedrock since similar to 7 kyrs BP. Absence of older ice on the highest glacier of South Tyrol is consistent with the removal of basal ice from bedrock during the Northern Hemisphere Climatic Optimum (6-9 kyrs BP), the warmest interval in the European Alps during the Holocene. Borehole inclinometric measurements of the current glacier flow combined with surface ground penetration radar (GPR) measurements indicate that, due to the sustained atmospheric warming since the 1980s, an acceleration of the glacier Alto dell'Ortles flow has just recently begun. Given the stratigraphic-chronological continuity of the Mt. Ortles cores over millennia, it can be argued that this behaviour has been unprecedented at this location since the Northern Hemisphere Climatic Optimum

Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System.

INTRODUCTION: Therapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders. METHODS: To promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies. RESULTS: As a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression). DISCUSSION: We suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials

Neuroimaging biomarkers for clinical trials in atypical parkinsonian disorders: Proposal for a Neuroimaging Biomarker Utility System

IntroductionTherapeutic strategies targeting protein aggregations are ready for clinical trials in atypical parkinsonian disorders. Therefore, there is an urgent need for neuroimaging biomarkers to help with the early detection of neurodegenerative processes, the early differentiation of the underlying pathology, and the objective assessment of disease progression. However, there currently is not yet a consensus in the field on how to describe utility of biomarkers for clinical trials in atypical parkinsonian disorders.MethodsTo promote standardized use of neuroimaging biomarkers for clinical trials, we aimed to develop a conceptual framework to characterize in more detail the kind of neuroimaging biomarkers needed in atypical parkinsonian disorders, identify the current challenges in ascribing utility of these biomarkers, and propose criteria for a system that may guide future studies.ResultsAs a consensus outcome, we describe the main challenges in ascribing utility of neuroimaging biomarkers in atypical parkinsonian disorders, and we propose a conceptual framework that includes a graded system for the description of utility of a specific neuroimaging measure. We included separate categories for the ability to accurately identify an intention-to-treat patient population early in the disease (Early), to accurately detect a specific underlying pathology (Specific), and the ability to monitor disease progression (Progression).DiscussionWe suggest that the advancement of standardized neuroimaging in the field of atypical parkinsonian disorders will be furthered by a well-defined reference frame for the utility of biomarkers. The proposed utility system allows a detailed and graded description of the respective strengths of neuroimaging biomarkers in the currently most relevant areas of application in clinical trials.</p

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation