Exhumation of the Sierra de Cameros (Iberian Range, Spain): constraints from low-temperature thermochronology

We present new fission-track and (U–Th)/He data from apatite and zircon in order to reconstruct the exhumation of the Sierra de Cameros, in the northwestern part of Iberian Range, Spain. Zircon fission-track ages from samples from the depocentre of the basin were reset during the metamorphic peak at approximately 100 Ma. Detrital apatites from the uppermost sediments retain fission-track age information that is older than the sediment deposition age, indicating that these rocks have not exceeded 110 8C. Apatites from deeper in the stratigraphic sequence of the central part of the basin have fission-track ages of around 40 Ma, significantly younger than the stratigraphic age, recording the time of cooling after peak metamorphic conditions. Apatite (U–Th)/He ages in samples from these sediments are 31–40 Ma and record the last period of cooling during Alpine compression. The modelled thermal history derived from the uppermost sediments indicates that the thermal pulse associated with peak metamorphism was rapid, and that the region has cooled continuously to the present. The estimated palaeogeothermal gradient is around 86 8C km21 and supports a tectonic model with a thick sedimentary fill (c. 8 km) and explains the origin of the low-grade metamorphism observed in the oldest sediments

Characters of the Stephanian-Permian Bronchales basin and the tourmalinization associated to calc-alkaline rhyolites (Teruel Province)

[Resumen] La turmalinización que afecta a riolitas calco-alcalinas presentes en la fosa transtensional de Bronchales, con edad Autuniense, destaca por el elevado contenido en B (0.87 O/o de promedio). Esta mineralización muestra un enriqueciIl\iento de HREE y un empobrecimiento en LREE debido a que el fluido mineralizante (rico en F) pudo ejercer una función acomplejante para estos elementos y, también, con carácter selectivo, para As, Sn, Sb y Bi.[Abstract] Calc-alkaline rhyolites of Bronchales transtensional basin (Autunian age) are affected by a tourmalinization process. Tourmalinized rhyolites with 0.87 O/o ofboron as average value show As, Sb, Sn and Bi increments over nontourmalinized ones, as well as important enrichments of HREE over LREE possibly because tourmalinization fluids were enriched in complexing agents (i.e .F)

Bounds on lepton non-unitarity and heavy neutrino mixing

We present an updated and improved global fit analysis of current flavour and electroweak precision observables to derive bounds on unitarity deviations of the leptonic mixing matrix and on the mixing of heavy neutrinos with the active flavours. This new analysis is motivated by new and updated experimental results on key observables such as Vud, the invisible decay width of the Z boson and the W boson mass. It also improves upon previous studies by considering the full correlations among the different observables and explicitly calibrating the test statistic, which may present significant deviations from a χ 2 distribution. The results are provided for three different Type-I seesaw scenarios: the minimal scenario with only two additional right-handed neutrinos, the next to minimal one with three extra neutrinos, and the most general one with an arbitrary number of heavy neutrinos that we parametrise via a generic deviation from a unitary leptonic mixing matrix. Additionally, we also analyze the case of generic deviations from unitarity of the leptonic mixing matrix, not necessarily induced by the presence of additional neutrinos. This last case relaxes some correlations among the parameters and is able to provide a better fit to the data. Nevertheless, inducing only leptonic unitarity deviations avoiding both the correlations implied by the right-handed neutrino extension as well as more strongly constrained operators is challenging and would imply significantly more complex UV completionsThis project has received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860881-HIDDeN and No 101086085 - ASYMMETRY, and from the Spanish Research Agency (Agencia Estatal de Investigación) through the Grant IFT Centro de Excelencia Severo Ochoa No CEX2020-001007-S and Grant PID2019-108892RB-I00 funded by MCIN/AEI/10.13039/501100011033. EFM, XM and DNT acknowledge support from the HPC-Hydra cluster at IFT. XM acknowledges funding from the European Union’s Horizon Europe Programme under the Marie Skłodowska-Curie grant agreement no. 101066105-PheNUmenal. The work of DNT was supported by the Spanish MIU through the National Program FPU (grant number FPU20/05333). JLP also acknowledges support from Generalitat Valenciana through the plan GenT program (CIDEGENT/2018/019) and from the Spanish Ministerio de Ciencia e Innovacion through the project PID2020-113644GB-I0

El clima de la transición Oligoceno-Mioceno registrado en una secuencia lacustre de la cuenca del Ebro: resultados preliminares

The climate evolution across the Oligocene–Miocene transition has been studied through a 23.5 to 22 Ma succession in the eastern Ebro Basin, dated by magnetostratigraphy. The study is based on the δ13C and δ18O composition coupled with sedimentological analysis of a dominantly lacustrine and palustrine carbonate succession, focusing on the limestone facies. The deposits formed in alluvial plain, saline mud flat, and carbonate lacustrine and palustrine depositional environments. Changes in lake water level and hydrodynamics, and biological processes triggered the formation of distinct carbonate facies, causing isotopic differences among them. The isotopic variations likely reflect changes in the precipitation/evaporation ratio and temperature in the Ebro Basin that might be the regional record of the Mi-1 Glaciation. A change in variability in δ13C and δ18O and an inflection in δ13C mark the Oligocene–Miocene boundary (23.03 Ma). The decrease in δ13C and δ18O variability may correspond to steadier depositional, climatic and hydrological conditions through timeSe estudia la evolución climática de la transición Oligoceno-Mioceno en una sucesión lacustre de la parte oriental de la cuenca del Ebro, de 23,5 a 22 Ma, según la magnetoestratigrafía. Se basa en la composición de δ13C y δ18O, junto con el análisis sedimentológico, de materiales mayoritariamente carbonatados, lacustres y palustres, centrado en las facies de caliza. Los depósitos se formaron en ambientes de llanuras aluviales y fangosas evaporíticas, lacustres y palustres. Los cambios en el nivel de agua del lago y la hidrodinámica, así como los procesos biológicos, ocasionaron la formación de facies carbonatadas distintas e isotópicamente diferentes. Probablemente estas diferencias isotópicas reflejan cambios en la relación precipitación/evaporación y en la temperatura en la cuenca del Ebro, que podrían ser la expresión regional de la Glaciación Mi-1. El límite Oligoceno-Mioceno (23,03 Ma) se manifiesta por un cambio en la variabilidad de δ13C y δ18O, junto con una inflexión en δ13C. La disminución en la variabilidad de δ13C y δ18O puede corresponder a una tendencia hacia condiciones de depósito, climáticas e hidrológicas más estable

The HepHIV 2023 Madrid conference: A call to action for political leadership in reaching the sustainable development goals on earlier testing and linkage to care for HIV, viral hepatitis, and sexually transmitted infections

Introduction and Objectives: The HepHIV 2023 Conference, held in Madrid in November 2023, highlighted how Europe is not on track to meet the United Nations (UN) sustainable development goals and Joint UN Programme on HIV/AIDS (UNAIDS) targets. This article presents the outcomes of the conference, which focus on ways to improve testing and linkage to care for HIV, viral hepatitis, and other sexually transmitted infections. HIV-related stigma and discrimination, a major barrier to progress, was a key concept of the conference and on the agenda of the Spanish Presidency of the European Union. Methods: The HepHIV 2023 organizing committee, alongside the Spanish Ministry of Health, oversaw the conference organization and prepared the scientific programme based on abstract rankings. Key outcomes are derived from conference presentations and discussions. Results: Conference presentations covered the obstacles that HIV-related stigma and discrimination continue to pose to access to services, models for data collection to better monitor progress in the future, and examples of legislative action that can be taken at national levels. Diversification of testing approaches was also highlighted, to reach key populations, (e.g. migrant populations), to increase testing offered in healthcare settings (e.g. emergency departments), and to account for different stages of epidemics across the region. Conclusion: With a strong call for intensified action to address the impact of HIV-related stigma and discrimination on testing uptake, the conference concluded that strengthened collaboration is required between governments and implementers around testing and linkage to care. There is also an ongoing need to ensure sustainable political commitment and appropriate resource allocation to address gaps and inequalities in access for key populations and to focus on the implementation of integrated responses to HIV, viral hepatitis, and sexually transmitted infections. © 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies

Background Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. Methods In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART -naive at the start of each period. Findings Among 189 301 people with HIV included in this study, 16 832 (8 center dot 9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78 center dot 3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25 center dot 0%), non-AIDS non -hepatitis malignancy (2311; 13 center dot 7%), and cardiovascular or heart-related (1403; 8 center dot 3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16 center dot 8 deaths (95% CI 15 center dot 4-18 center dot 4) during 1996-99 to 7 center dot 9 deaths (7 center dot 6-8 center dot 2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0 center dot 85 (95% CI 0 center dot 84-0 center dot 86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0 center dot 81; 0 center dot 79-0 center dot 83). There were also reductions in rates of cardiovascular-related (0 center dot 83, 0 center dot 79-0 center dot 87), liver-related (0 center dot 88, 0 center dot 84-0 center dot 93), non-AIDS infectionrelated (0 center dot 91, 0 center dot 86-0 center dot 96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0 center dot 94, 0 center dot 90-0 center dot 97), and suicide or accident-related mortality (0 center dot 89, 0 center dot 82-0 center dot 95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1 center dot 07, 1 center dot 00-1 center dot 14) and decreased slightly in men (0 center dot 96, 0 center dot 93-0 center dot 99). Interpretation Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. Funding US National Institute on Alcohol Abuse and Alcoholism. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Multi-omics profiling of mouse gastrulation at single-cell resolution.

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes1-5. Global epigenetic reprogramming accompanies these changes6-8, but the role of the epigenome in regulating early cell-fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe a single-cell multi-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by ten-eleven translocation (TET)-mediated demethylation and a concomitant increase of accessibility. By contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled before cell-fate decisions, providing the molecular framework for a hierarchical emergence of the primary germ layers.CRUK, Wellcome Trust, MRC, BBSRC, EMBL, E

Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk

Intra-gastric balloon as an adjunct to lifestyle support in severely obese adolescents; Impact on weight, physical activity, cardio-respiratory fitness and psychosocial wellbeing.

BACKGROUND: Severe adolescent obesity (BMI>99.6th centile) is a significant public health challenge. Current non-invasive treatments, including community-based lifestyle interventions, are often of limited effectiveness in this population, with NICE guidelines suggesting the use of bariatric surgery as the last line of treatment (NICE, 2013). Health professionals are understandably reluctant to commission bariatric surgery and as an alternative, the use of an intra-gastric balloon as an adjunct to a lifestyle programme might offer a reversible, potentially safer and less invasive option. OBJECTIVES: Explore the use of an intra-gastric balloon as an adjunct to a lifestyle support programme, to promote weight loss in severely obese adolescents. Outcomes included Weight loss, Waist and Hip measurements, psychosocial outcomes including health related quality of life and physical self-perceptions, physical activity and cardiorespiratory fitness. METHOD: Non-randomised pilot study. Results: 12 severely obese adolescents (5 males, 7 females; mean age 15yrs; BMI >3.5 s.d.; puberty stage 4 or more) and their families were recruited. Mean weight loss at 12 months (n=9) was 3.05 kg±14.69; d=0.002, P=0.550, and a BMI Z-score (n=12) change of 0.2 s.d.; d=0.7, P=0.002 was observed at 6 months with a large effect, but was not sustained at 12 months (mean change 0.1 s.d.; d=0.3, P=0.146 ) At 24 months (n=10) there was a weight gain from baseline of +9.9 kg±1.21 (d=0.4; P=0.433). Adolescent and parent HRQoL scores exceeded the minimal clinical important difference between baseline and 12 months for all domains but showed some decline at 24 months. CONCLUSION: An intra-gastric balloon as an adjunct to a lifestyle support programme represents a safe and well tolerated treatment approach in severely obese adolescents, with short-term effects on weight change. Improvements in psychosocial health, physical activity and cardiorespiratory fitness were maintained at 12 months, with varying results at 24 months