Oligocene-Miocene burial and exhumation of the Southern Pyrenean foreland quantified by low-temperature thermochronology

International audienceThe central Pyrenees experienced an episode of rapid exhumation in Late Eocene-Early Oligocene times. Erosional products shed from the range during this time were deposited in large palaeovalleys of the southern flank of the Axial Zone, leading to significant sediment accumulation. A recent numerical modelling study of the post-orogenic exhumation and relief history of the central Axial Zone allowed us to constrain this valley-filling episode in terms of timing and thickness of conglomeratic deposits. This paper aims to test these results for the southern fold-and-thrust belt using apatite fission-track and (U-Th)/He analysis on detrital samples from the Tremp-Graus and Ager basins. inverse thermal-history modelling of the low-temperature thermochronology data indicates that the fold-and-thrust belt was covered during the Late Eocene to Miocene by 0.7-1.6 km of sediments and confirms the timing of re-excavation of the valleys during the Miocene. A detailed analysis of the apatite (U-Th)/He results shows that the significant scatter in grain ages can be explained by the influence of alpha-recoil damage with varying effective uranium content together with distinct pre-depositional thermal histories; the age scatter is consistent with initial exhumation of the sediment sources during the Triassic and Early Cretaceous

Strong tectonic and weak climatic control on exhumation rates in the Venezuelan Andes

International audienceWe studied the relationships among present-day relief, precipitation, stream power, seismic energy, seismic strain rate, and long-term exhumation rates for the Venezuelan Andes. Average long-term exhumation rates were determined for seven large catchments in the Venezuelan Andes from fi ssion-track analysis of detrital apatite. A quantitative comparison between eight new detrital apatite fi ssion-track (AFT) age distributions presented here and previously published bedrock AFT age patterns shows that detrital AFT ages can be used for predicting exhumation patterns across the mountain belt. Catchment-averaged exhumation rates estimated from the raw data range from 0.48 ± 0.02 km m.y.-1 to 0.80 ± 0.26 km m.y.-1 Accounting for variable sediment yield and assuming that short-term sediment production rates scale with long-term exhumation rates, these rates vary from 0.33 ± 0.07 km m.y.-1 to 0.48 ± 0.08 km m.y.-1 No variation in rates is observed between the northwestern and southeastern fl anks of the mountain belt, despite a threefold increase in precipitation from the northwest to the southeast. Long-term exhumation rates are strongly correlated with relief in the different catchments, weak or negative correlations exist with precipitation data or present-day erosion indexes, while the correlation with seismic energy released by earthquakes is weak to moderate. This lack of correlation may be caused by the insuffi cient temporal range of the available precipitation and seismicity data, and the different time scales involved in the comparison. Long-term exhumation rates are, however, strongly correlated with seismic strain rates (which take the temporal earthquake magnitude-frequency scaling into account), suggesting that the moderate correlation with seismic energy is indeed related to the different time scales and that tectonic control on exhumation is signifi cant. In contrast, given that precipitation patterns in the Venezuelan Andes should have been installed during Miocene times, we suggest that decoupling of relief and exhumation from present-day climate explains the lack of correlation between exhumation and precipitation

Increase in late Neogene denudation of the European Alps confirmed by analysis of a fission-track thermochronology database

International audienceA sharp increase in deposited sediment volume since Pliocene times has been observed worldwide and in particular around the European Alps. This phenomenon has been linked to a rise in denudation rates controlled by an increase of either climatic or tectonic forcing. Observation of in-situ cooling histories for orogens is critical to assess the reality of the inferred increase in denudation rates, and to determine whether this phenomenon is widespread or localized at active tectonic structures. We exploit the unique density of fission-track ages in the Western European Alps to reconstruct cooling isoage surfaces and to estimate exhumation rates on the orogen scale between 13.5 and 2.5 Ma. Our novel technique is based on the association of isoage contours with age–elevation relationships. It uses map-view interpolation, enabling a spatio-temporal analysis of exhumation rates over the entire Western Alps. The resulting exhumation histories reconstructed for eight areas of the Western Alps display strong similarities in timing and rates with orogen-wide average denudation rates inferred from sediment volumes. This consistency validates the use of both techniques for the study of an orogen characterized by strong relief and high recent exhumation rates. We conclude that exhumation rates in the Western Alps have increased more than twofold since Late Miocene times. This increase may have been locally modulated by the distinct response of different tectonic units

Flexural isostatic response of the Alps to increased Quaternary erosion recorded by foreland basin remnants, SE France

International audienceWe test the hypothesis that flexural isostatic compensation of the mass removed by enhanced Quaternary erosion is responsible for uplift of the Western European Alps and their forelands. We use two well-preserved and well-dated (1.8 Ma) abandonment surfaces of foreland basin remnants in SE France (the Chambaran and Valensole plateaux) as passive benchmarks for tilting of the foreland. Estimating their initial slope from morphometric scaling relationships, we determine bulk post-depositional tilting of 0.5–0.8% for these surfaces. The calculated isostatic response of the Alpine lithosphere to erosional unloading, using the method recently proposed by Champagnac et al. [Geology 35 (2007) 195–198], yields a predicted tilting of 0.3–0.4% in the considered areas, explaining approximately half of the determined post-depositional tilting. Such long-term deformation being insensitive to cyclic loading/unloading because of glaciations, we suspect the other half to be related to as yet undetermined long-wavelength and long-lived tectonic process(es)

The Rasch-built Pompe-specific activity (R-PAct) scale.

We constructed a patient-based interval scale using Rasch analysis, specifically suited to quantify the effects of Pompe disease on patient's ability to carry out daily life activities and their social participation: Rasch-built Pompe-specific Activity scale. Between July 2005 and April 2011, 186 patients aged 16 or older, participated to develop this scale. External construct validity was determined through correlations with the MRC sumscore and Rotterdam Handicap Scale. Furthermore, test-retest reliability was determined in a subgroup of 44 patients. Finally, individual person-level responsiveness was used to determine the proportion of patients demonstrating significant improvement or deterioration during their natural disease course, or during treatment with enzyme replacement therapy. Of the original 49 items, 31 were removed after investigation of model fit, internal reliability, threshold examination, item bias, and local dependency. The remaining 18 items were ordered on a linearly weighted scale and demonstrated good discriminative ability (Person Separation Index 0.96), external construct validity (intraclass correlation coefficient (ICC) for MRC sumscore 0.82, and for the Rotterdam handicap scale 0.86), reliability of person's location (ability comparison: ICC 0.95), and responsiveness. We therefore conclude that the R-PAct scale enables us to accurately detect limitations in activities and social participation throughout the entire disease spectrum in patients with Pompe disease. Copyrigh

Late Miocene – Recent exhumation of the central Himalaya and recycling in the foreland basin assessed by apatite fission-track thermochronology of Siwalik sediments, Nepal

International audienceThermochronological analysis of detrital sediments derived from the erosion of mountain belts and contained in the sedimentary basins surrounding them allows reconstructing the long-term exhumation history of the sediment source areas. The effective closure temperature of the thermochronological system analysed determines the spatial and temporal resolution of the analysis through the duration of the lag time between closure of the system during exhumation and its deposition in the sedimentary basin. Here we report apatite fission-track (AFT) data from 31 detrital samples collected from Miocene to Pliocene stratigraphic sections of the Siwalik Group in western and central Nepal, as well as three samples from modern river sediments from the same area, that complement detrital zircon fission-track (ZFT) and U-Pb data from the same samples presented in a companion paper. Samples from the upper part of the stratigraphic sections are unreset and retain a signal of source-area exhumation; they show spatial variations in source-area exhumation rates that are not picked up by the higher-temperature systems. More deeply buried samples have been partially reset within the Siwalik basin and provide constraints on the thermal and kinematic history of the fold-and-thrust belt itself. The results suggest that peak source-area exhumation rates have been constant at ~1.8 km Myr-1 over the last ~7 Ma in central Nepal, whereas they ranged between 1 and ~1.5 km Myr-1 in western Nepal over the same time interval; these spatial variations may be explained by either a tectonic or climatic control on exhumation rates, or possibly a combination of the two. Increasing lag times within the uppermost part of the sections suggest an increasing component of apatites that have been recycled within the Siwalik belt and are corroborated by AFT ages of modern river sediment downstream as well as the record of the distal Bengal Fan. The most deeply buried and most strongly annealed samples record onset of exhumation of the frontal Siwaliks along the Himalayan frontal thrust at ~2 Ma and continuous shortening at rates comparable to the present-day shortening rates from at least 0.3 Ma onward

Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria

Enzyme replacement therapy for Pompe disease received market authorization in 2006. To implement this costly treatment in the Netherlands in the most sensible way, a multidisciplinary expert committee was installed. We evaluated decision making in adult patients in relation to the European POmpe Consortium stop criteria. Of 125 adult Pompe patients, 111 started treatment; subsequently treatment stopped in 24 patients (21%). In 10 patients, treatment was discontinued for medical or personal reasons, as defined in the six stop criteria (median treatment duration: 2.1 years, range: 0.3–14.6 years). Three of these patients continued follow-up (follow-up: 1.3–8.0 years), these patients did not display a more rapid decline after discontinuation. In 14 of 24 patients, therapy ended at time of death. In 10 patients death was related to Pompe disease (median treatment duration: 7.2 years, range: 0.4–10.3 years). All 10 patients were severely affected at start of treatment, treatment had elicited positive effects in eight. The European POmpe Consortium guidelines worked well in decision making on stopping treatment. However, (re)evaluation of the rationale for continuation of treatment in advanced disease stage is not addressed. We suggest to add this to the treatment evaluation and to handle treatment decisions in a multidisciplinary expert team

Miocene to Recent exhumation of the central Himalaya determined from combined detrital zircon fission-track and U/Pb analysis of Siwalik sediments, western Nepal

International audienceFission-track (FT) analysis of detrital zircon from synorogenic sediment is a well established tool to examine the cooling and exhumation history of convergent mountain belts, but has so far not been used to determine the long-term evolution of the central Himalaya. This study presents FT analysis of detrital zircon from 22 sandstone and modern sediment samples that were collected along three stratigraphic sections within the Miocene to Pliocene Siwalik Group, and from modern rivers, in western and central Nepal. The results provide evidence for widespread cooling in the Nepalese Himalaya at about 16.0 ± 1.4 Ma, and continuous exhumation at a rate of about 1.4 ± 0.2 km/Myr thereafter. The ~16 Ma cooling is likely related to a combination of tectonic and erosional activity, including movement on the Main Central thrust and Southern Tibetan Detachment system, as well as emplacement of the Ramgarh thrust on Lesser Himalayan sedimentary and meta-sedimentary units. The continuous exhumation signal following the ~16 Ma cooling event is seen in connection with ongoing tectonic uplift, river incision, and erosion of lower Lesser Himalayan rocks exposed below the MCT and Higher Himalayan rocks in the hanging wall of the MCT, controlled by orographic precipitation and crustal extrusion. Provenance analysis, to distinguish between Higher Himalayan and Lesser Himalayan zircon sources, is based on double dating of individual zircons with the FT and U/Pb methods. Zircons with pre-Himalayan FT cooling ages may be derived from either non-metamorphic parts of the Tethyan sedimentary succession or Higher Himalayan protolith that formerly covered the Dadeldhura and Ramgarh thrust sheets, but that have been removed by erosion. Both the Higher and Lesser Himalaya appear to be sources for the zircons that record either ~16 Ma cooling or the continuous exhumation afterwards

The impact of COVID-19 infection, the pandemic and its associated control measures on patients with Pompe disease

Background: Patients with Pompe disease, a rare metabolic myopathy, were thought to be at increased risk of severe COVID-19 disease during the pandemic. In addition, the lockdown may have affected their regular treatment. Objective: To assess the perceived effect of COVID-19 infection and of the pandemic on the treatment, and physical and mental health of patients with Pompe disease. Methods: Patients with Pompe disease over 16 years of age participated in an international, cross-sectional, online survey (September 20, 2022–November 7, 2022). The questionnaire, available in eight languages, consisted of 89 questions divided into 3 parts: (A) severity of Pompe disease, (B) COVID-19 precautions and infection(s) and (C) effects of the COVID-19 pandemic. Results: Among 342 respondents, originating from 25 different countries, 47.6% experienced one or more COVID-19 infections. While most recovered within 4 weeks (69.7%) and only eight patients needed to be admitted to the hospital, 42.2% of patients experienced an impact of the infection on their overall condition, respiratory status and/or mobility status. More severely affected patients took more stringent control measures. The pandemic additionally caused interruptions in medical care in many patients (56.0%) and 17.2% of patients experienced interruptions of enzyme replacement therapy. The pandemic also affected many patients’ disease severity (27.7%), mental health (55.4%) and feeling of loneliness (43.4%). Conclusion: COVID-19 infection(s) and the pandemic affected the treatment, physical health and mental health of patients with Pompe disease, emphasizing the importance of continued patient centered care during a difficult time such as the COVID-19 pandemic.</p

Supporting participation in paid work of cancer survivors and their partners in the Netherlands:protocol of the SusTained Employability in cancer Patients and their partnerS (STEPS) multi-centre randomized controlled trial and cohort study

BACKGROUND: Many cancer survivors experience physical and/or psychosocial problems affecting return to work (RTW) and work retention. Current interventions on RTW lack evidence regarding effectiveness, while interventions for work retention are missing. Partners of cancer survivors may also experience work- and health-related outcomes; yet, these consequences are not well understood. Here, the protocol of the STEPS study is described. The study aims are to: 1) evaluate the (cost-)effectiveness of a rehabilitation program for RTW and work retention in cancer survivors, and 2) assess health- and work-related outcomes among cancer survivors' partners. METHODS: In a multicentre Randomized Controlled Trial (RCT), 236 working-age cancer survivors with an employment contract will be randomly allocated to a usual care group or an intervention group receiving a multidisciplinary rehabilitation program, combining occupational therapy facilitating work retention (e.g., energy management and self-efficacy training) and reintegration consultation addressing work-related issues (e.g., RTW planning and discussing workplace or task modifications with the supervisor). Alongside the RCT, a prospective cohort study will be conducted among cancer survivors' partners (n = 267). Participants in the RCT and cohort study will be asked to complete questionnaires at baseline, and after six and 12 months, assessing work- and health-related outcomes. Generalized estimating equations will be used to assess intervention's effectiveness, compared to usual care, regarding primary (i.e., working hours per week) and secondary outcomes. Also economic and process evaluations will be performed. For the cohort study, logistic or linear regression modelling will be applied assessing work- and health-related outcomes (primary outcome: working hours) of cancer survivors' partners, and what factors predict these outcomes. RESULTS: The study is planned to start in September 2021; results are expected in 2023. CONCLUSION: Compared to usual care, the STEPS intervention is hypothesized to be (cost-)effective and the intervention could be a valuable addition to standard care helping cancer survivors to sustain employment. Further, it is expected that living with a cancer survivor has a substantial impact on work and health of partners, while specific groups of partners that are at particular risk for this impact are likely to be identified. TRIAL REGISTRATION: Dutch Trial Register ( NTR;NL9094 ; 15-12-2020)