Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis

Background: Understanding the true prevalence of lymphangioleiomyomatosis (LAM) is important in estimating disease burden and targeting specific interventions. As with all rare diseases, obtaining reliable epidemiological data is difficult and requires innovative approaches. Aim: To determine the prevalence and incidence of LAM using data from patient organizations in seven countries, and to use the extent to which the prevalence of LAM varies regionally and nationally to determine whether prevalence estimates are related to health-care provision. Methods: Numbers of women with LAM were obtained from patient groups and national databases from seven countries (n = 1001). Prevalence was calculated for regions within countries using female population figures from census data. Incidence estimates were calculated for the USA, UK and Switzerland. Regional variation in prevalence and changes in incidence over time were analysed using Poisson regression and linear regression. Results: Prevalence of LAM in the seven countries ranged from 3.4 to 7.8/million women with significant variation, both between countries and between states in the USA. This variation did not relate to the number of pulmonary specialists in the region nor the percentage of population with health insurance, but suggests a large number of patients remain undiagnosed. The incidence of LAM from 2004 to 2008 ranged from 0.23 to 0.31/million women/per year in the USA, UK and Switzerland. Conclusions: Using this method, we have found that the prevalence of LAM is higher than that previously recorded and that many patients with LAM are undiagnose

Late Pleistocene Neanderthal exploitation of stable and mosaic ecosystems in northern Iberia shown by multi-isotope evidence

The carbon, nitrogen and sulphur stable isotope analyses and the stable isotope analyses of bioapatite carbonates were funded as part of the ABRUPT project (HAR2017-84997-P) funded by the Ministry of Science, Innovation and Universities and the SUBSILIENCE project funded by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 818299—ERC-2018-Consolidator), both awarded to ABM-A. SP was supported by the Max Planck Society and the University of Aberdeen during the time of this project, and the oxygen isotope analysis of bioapatite phosphates was funded by the Max Planck Society. Access to the archaeological collections was granted by the Museo de Arqueología de Bizkaia (Basque Government), and initial sampling for carbon and nitrogen isotope analysis was achieved by Hazel Reade funded by the FP7-PEOPLE-2012-CIG- 322112 project) and ABM-A. We appreciate Joseba Rios-Garaizar's advice about Axlor stratigraphy during the sampling process. We thank Ignacio Valera (IBBTEC, University of Cantabria) for kindly allowing the use of his laboratory facilities for collagen extraction. We thank Carlos Revilla Gómez (IBBTEC, University of Cantabria) for laboratory assistance during collagen extraction. Thanks are also due to Manuel Trost (MPI-EVA) for assistance during silver phosphate preparation and to Sven Steinbrenner for assistance with TC/EA-IRMS. KB is supported by a Philip Leverhulme Prize from the Leverhulme Trust (PLP-2019-284).Peer reviewedPublisher PD

Palaeoecology of ungulates in northern Iberia during the Late Pleistocene through isotopic analysis of teeth

We acknowledge the Museo de Arqueología y Prehistoria de Cantabria (MUPAC); the Consejería de Educación, Cultura y Deporte del Gobierno de Cantabria; the Museo de Arqueología de Bizkaia (Arkeologi Museoa); and the Centro de Colecciones Patrimoniales de la Diputación Foral de Gipuzkoa (Gordailua) – Provincial Government of Guipuzkoa's Heritage Collection Centre for access to their archaeological collections. We appreciate the work of Hazel Reade during the initial sampling, pretreatment, and sample analysis undertaken at the University of Cantabria and the University of Cambridge. We want to thank the two anonymous referees for their valuable comments, which significantly improved the quality of the paper.Peer reviewe

High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany

Abstract Background and aims Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. Methods Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. Results Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). Conclusion In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy. Graphical abstrac

A Spatial Distribution Study of Faunal Remains from Two Lower Magdalenian Occupation Levels in El Mirón Cave, Cantabria, Spain

Abstract: Human behaviour can be reconstructed by analysing specific activities and campsite organization using spatial analysis. The dense occupation layers of the Lower Cantabrian Magdalenian in the Northern Spain reveal varied aspects of Upper Palaeolithic lifeways, including evidence of specific localized activities. The outer vestibule of El Mirón cave has a particularly rich and intact Lower Magdalenian occupation horizon, Levels 15–17. The excavations in the outer vestibule “Cabin” area of the site revealed excellent bone preservation. Artefacts and faunal remains were individually recorded and sediments water-screened to yield a large sample of archaeological finds and spatial data. Zooarchaeological analysis provided the taxonomic, anatomic and taphonomic determination of the faunal individual finds. Smaller animal remains were categorized and counted; special attention was given to the identification of anthropogenic modifications such as burnt bones or bone flakes. These small refuse items are considered to be useful, in situ indicators of localized activities. The spatial distribution analysis of this dense and complex palimpsest of El Mirón Lower Cantabrian Magdalenian layers required GIS based methods including density analysis, heatmaps and cluster analysis. Based on the spatial distribution of Level 15 and 16 faunal remains, different activity areas were identified comprising hearth, working and dropping zones. These results imply the deliberately segregated use of space within the Lower Cantabrian Magdalenian site area, in which bone-processing activities played a central rol