Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Diverse values of nature for sustainability

Data availability: All the data are freely available online. The supplementary information provides links to Zenodo with specific DOIs where the data are stored for free use.Supplementary information is available online at https://static-content.springer.com/esm/art%3A10.1038%2Fs41586-023-06406-9/MediaObjects/41586_2023_6406_MOESM1_ESM.docx . The Supplementary Information includes three parts. Part A explains how the paper is associated with the IPBES Values Assessment. Part B provides details about each of the 29 review protocols. Part C offers information about the case study of Chilika Lagoon, India, that is used in the main paper.Copyright © The Author(s) 2023. Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature’s diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature’s values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a ‘values crisis’ underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature’s diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.We received no specific funding for this work; all authors involved in IPBES do so on a voluntary basis. The IPBES Values Assessment was made possible thanks to many generous contributions, including non-earmarked contributions to the IPBES trust fund from governments. All donors are listed on the IPBES website www.ipbes.net/donors. U.P. acknowledges BC3’s Maria de Maeztu excellence accreditation 2023–2026 (reference no. CEX2021-001201-M) provided by grant no. MCIN/AEI/10.13039/501100011033

Solidarity : A Plan to Restore the Chiquito River and Reclaim Public Space in Morelia, Mexico

El río Chiquito ha tenido un papel central en la historia de Morelia. El primer asentimiento registrado de Valladolid se ubicó en lo que hoy se conoce como los Filtros Viejos. El río fue la principal fuente de abastecimiento de agua potable durante los primeros siglos de la ciudad, y el génesis del icónico acueducto en Morelia. Hoy, sin embargo, la parte urbana del río es símbolo de polución, congestión, e inundaciones para la mayoría de los ciudadanos. Aun así, el río Chiquito es un espacio verde que atraviesa una gran parte de la ciudad, pasando cerca del centro histórico, y cruzando límites demográficos. El río se cuida por algunos residentes, se atraviesa por muchos diariamente, y su potencial es para todos. | The Río Chiquito has played a central role in Morelia’s history. The first registered settlement of pre-Morelia Valladolid was in present-day Filtros Viejos. The river was the city’s primary source of water for centuries, and the genesis of Morelia’s iconic aqueduct. Today, however, the urban part of the river is, for most residents, a symbol of pollution, traffic, and flooding. Nevertheless, the Río Chiquito is a green space that passes through most of the city, near the historic center, and across demographic lines; it is tended by some residents, crossed daily by many, and holds potential for all. La meta de nuestro proyecto es desarrollar—a través de colaboraciones interdisciplinarias y multilaterales—un plan conceptual para alcanzar el potencial del río. Con el amplio apoyo de IMPLAN, CIGA, UBC, entre otros, preparamos este informe de conceptos claves para la restauración ecológica y prosperidad social del río. Esperamos que pueda motivar el dialogo entre los los ciudadanos e instituciones de Morelia, para que en última instancia, el río Chiquito sea tan clave para el futuro de la ciudad como lo fue en su pasado. | The intent of our project is to develop—through cross-disciplinary, multi-stakeholder collaboration—a conceptual plan to help realize the river’s potential. With extensive support from IMPLAN, CIGA, UBC, and others, we have prepared this report to capture key conceptual ideas for the river’s ecological restoration and social flourishing. We hope it will serve to spark the conversation between Morelia’s citizens and its institutions so that the Río Chiquito will ultimately be as central to the city’s future as it has been to its past.Applied Science, Faculty ofNon UBCArchitecture and Landscape Architecture (SALA), School ofCivil Engineering, Department ofCommunity and Regional Planning (SCARP), School ofUnreviewedFacultyGraduat

Using Geographical Information Systems to Identify Populations in Need of Improved Accessibility to Antivenom Treatment for Snakebite Envenoming in Costa Rica

INTRODUCTION: Snakebite accidents are an important health problem in rural areas of tropical countries worldwide, including Costa Rica, where most bites are caused by the pit-viper Bothrops asper. The treatment of these potentially fatal accidents is based on the timely administration of specific antivenom. In many regions of the world, insufficient health care systems and lack of antivenom in remote and poor areas where snakebites are common, means that efficient treatment is unavailable for many snakebite victims, leading to unnecessary mortality and morbidity. In this study, geographical information systems (GIS) were used to identify populations in Costa Rica with a need of improved access to antivenom treatment: those living in areas with a high risk of snakebites and long time to reach antivenom treatment. METHOD/PRINCIPAL FINDINGS: Populations living in areas with high risk of snakebites were identified using two approaches: one based on the district-level reported incidence, and another based on mapping environmental factors favoring B. asper presence. Time to reach treatment using ambulance was estimated using cost surface analysis, thereby enabling adjustment of transportation speed by road availability and quality, topography and land use. By mapping populations in high risk of snakebites and the estimated time to treatment, populations with need of improved treatment access were identified. CONCLUSION/SIGNIFICANCE: This study demonstrates the usefulness of GIS for improving treatment of snakebites. By mapping reported incidence, risk factors, location of existing treatment resources, and the time estimated to reach these for at-risk populations, rational allocation of treatment resources is facilitated.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP