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Background: Some individuals who receive long-acting reversible contraception (LARC) face barriers to discontinuation. The inability to discontinue a contraceptive method when desired negatively impacts a person's reproductive autonomy. Persons impacted by social determinants of health (SDH) may be disproportionately affected. The objective of this study is to evaluate the association of SDH with patient-reported difficult LARC discontinuation. Methods: A retrospective cross-sectional analysis of data from the 2017-2019 cycle of the National Survey of Family Growth was conducted. The main outcome was patient-reported difficulty discontinuing a LARC method (intrauterine device or implant) in the last 10 years. Descriptive statistics were used to identify demographic characteristics and SDH domains. Multivariable logistic regression models were used to estimate associations across SDH domains with difficult LARC removal. Results: A total of 754 respondents reported wanting to have their LARC removed, and 105 (11%) reported difficulty discontinuing LARC methods. One-third of respondents experienced one or more SDH, notably food insecurity (26%) or transportation barriers (30%). After adjusting for age, race, education, geographic location, parity, and body mass index (BMI), persons with one or more SDH had an increased adjusted odds ratio (aOR) for difficultly discontinuing LARCs compared with respondents without any SDH (2.11; 95% confidence interval [CI]: 1.21, 3.69). Transportation barriers demonstrated the largest aOR of 2.90 (95% CI: 1.07, 7.87). Conclusions: SDH are associated with challenges to LARC discontinuation. SDH are unique risk factors that can impact one's entire contraceptive experience. A nuanced discussion of SDH at the time of contraceptive counseling may be a critical step in addressing the intersectionality of method selection and reproductive agency.
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There are varying data concerning the effect of prior anti-vector immunity on the T-cell response induced by immunisation with an identical vectored vaccine containing a heterologous antigen insert. To determine whether prior exposure to ChAdOx1-SARS-CoV2 immunisation (Vaxzevria®) impacts magnitudes of antigen-specific T-cell responses elicited by subsequent administration of the same viral vector (encoding HBV antigens, ChAdOx1-HBV), healthy volunteers that had received Vaxzevria® (n = 15) or the Pfizer or Moderna mRNA COVID-19 vaccine (n = 11) between 10 and 18 weeks prior were recruited to receive a single intramuscular injection of ChAdOx1-HBV. Anti-ChAdOx1-neutralising antibody titers were determined, and vector or insert-specific T-cell responses were measured by a gamma-interferon ELISpot and intracellular cytokine staining (ICS) assay using multiparameter flow cytometry. Participants were followed for three months after the ChAdOx1-HBV injection, which was well-tolerated, and no dropouts occurred. The baseline ChAdOx1 neutralisation titers were higher in the Vaxzevria® cohort (median of 848) than in the mRNA cohort (median of 25). T-cell responses to HBV antigens, measured by ELISpot, were higher on day 28 in the mRNA group (p = 0.013) but were similar between groups on day 84 (p = 0.441). By ICS, these differences persisted at the last time point. There was no clear correlation between the baseline responses to the adenoviral hexon and the subsequent ELISpot responses. As vaccination within 3 months using the same viral vector backbone affected the insert-specific T-cell responses, a greater interval after prior adenoviral immunisation using heterologous antigens may be warranted in settings in which these cells play critical roles.
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BACKGROUND: Protection afforded by inactivated influenza vaccines can theoretically be improved by inducing T-cell responses to conserved internal influenza A antigens. We assessed whether, in an influenza controlled human infection challenge, susceptible individuals receiving a vaccine boosting T-cell responses would exhibit lower viral load and decreased symptoms compared with placebo recipients. METHODS: In this single centre, randomised, double-blind phase 2 study, healthy adult (aged 18-55 years) volunteers with microneutralisation titres of less than 20 to the influenza A(H3N2) challenge strain were enrolled at an SGS quarantine facility in Antwerp, Belgium. Participants were randomly assigned double-blind using a permuted-block list with a 3:2 allocation ratio to receive 0·5 mL intramuscular injections of modified vaccinia Ankara (MVA) expressing H3N2 nucleoprotein (NP) and matrix protein 1 (M1) at 1·5 × 108 plaque forming units (4·3 × 108 50% tissue culture infectious dose [TCID50]; MVA-NP+M1 group) or saline placebo (placebo group). At least 6 weeks later, participants were challenged intranasally with 0·5 mL of a 1 × 106 TCID50/mL dose of influenza A/Belgium/4217/2015 (H3N2). Nasal swabs were collected twice daily from day 2 until day 11 for viral PCR, and symptoms of influenza were recorded from day 2 until day 11. The primary outcome was to determine the efficacy of MVA-NP+M1 vaccine to reduce the degree of nasopharyngeal viral shedding as measured by the cumulative viral area under the curve using a log-transformed quantitative PCR. This study is registered with ClinicalTrials.gov, NCT03883113. FINDINGS: Between May 2 and Oct 24, 2019, 145 volunteers were enrolled and randomly assigned to the MVA-NP+M1 group (n=87) or the placebo group (n=58). Of these, 118 volunteers entered the challenge period (71 in the MVA-NP+M1 group and 47 in the placebo group) and 117 participants completed the study (71 in the MVA-NP+M1 group and 46 in the placebo group). 78 (54%) of the 145 volunteers were female and 67 (46%) were male. The primary outcome, overall viral load as determined by quantitative PCR, did not show a statistically significant difference between the MVA-NP+M1 (mean 649·7 [95% CI 552·7-746·7) and placebo groups (mean 726·1 [604·0-848·2]; p=0·17). All reported treatment emergent adverse events (TEAEs; 11 in the vaccination phase and 51 in the challenge phase) were grade 1 and 2, except for two grade 3 TEAEs in the placebo group in the challenge phase. A grade 4 second trimester fetal death, considered possibly related to the MVA-NP+M1 vaccination, and an acute psychosis reported in a placebo participant during the challenge phase were reported. INTERPRETATION: The use of an MVA vaccine to expand CD4+ or CD8+ T cells to conserved influenza A antigens in peripheral blood did not affect nasopharyngeal viral load in an influenza H3N2 challenge model in seronegative, healthy adults. FUNDING: Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; and Barinthus Biotherapeutics.
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Linfócitos T CD8-Positivos , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Influenza Humana , Carga Viral , Humanos , Adulto , Bélgica/epidemiologia , Método Duplo-Cego , Vírus da Influenza A Subtipo H3N2/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Feminino , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Linfócitos T CD8-Positivos/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Adolescente , Proteínas da Matriz Viral/imunologia , Proteínas do Core Viral/imunologia , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/genética , Vacinas de DNA/imunologia , Vacinas de DNA/administração & dosagem , Proteínas do Nucleocapsídeo/imunologia , Anticorpos Antivirais/sangue , Imunidade CelularRESUMO
PURPOSE: 5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU. PATIENTS AND METHODS: NUC-3373 was administered as monotherapy to patients with advanced solid tumors refractory to standard therapy via intravenous infusion either on Days 1, 8, 15 and 22 (Part 1) or on Days 1 and 15 (Part 2) of 28-day cycles until disease progression or unacceptable toxicity. Primary objectives were maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) and schedule of NUC-3373. Secondary objectives included pharmacokinetics (PK), and anti-tumor activity. RESULTS: Fifty-nine patients received weekly NUC-3373 in 9 cohorts in Part 1 (n = 43) and 3 alternate-weekly dosing cohorts in Part 2 (n = 16). They had received a median of 3 prior lines of treatment (range: 0-11) and 74% were exposed to prior fluoropyrimidines. Four experienced dose-limiting toxicities: two Grade (G) 3 transaminitis; one G2 headache; and one G3 transient hypotension. Commonest treatment-related G3 adverse event of raised transaminases occurred in < 10% of patients. NUC-3373 showed a favorable PK profile, with dose-proportionality and a prolonged half-life compared to 5-FU. A best overall response of stable disease was observed, with prolonged progression-free survival. CONCLUSION: NUC-3373 was well-tolerated in a heavily pre-treated solid tumor patient population, including those who had relapsed on prior 5-FU. The MTD and RP2D was defined as 2500 mg/m2 NUC-3373 weekly. NUC-3373 is currently in combination treatment studies. TRIAL REGISTRATION: Clinicaltrials.gov registry number NCT02723240. Trial registered on 8th December 2015. https://clinicaltrials.gov/study/NCT02723240 .
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Floxuridina , Neoplasias , Humanos , Floxuridina/uso terapêutico , Timidilato Sintase/uso terapêutico , Neoplasias/patologia , Fluoruracila/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive and limited therapeutic options lead to poor prognosis for patients. HPN328 is a tri-specific T cell activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro concomitant with T cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T cell engagers. HPN328 exhibited linear pharmacokinetic in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3 expressing malignancies.
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Freshwater megafish species, such as sturgeons, salmonids, carps, and catfishes, have a maximum reported weight ≥30 kg. Due to their charisma and economic value, they have been widely introduced outside of their native ranges. Here, we provide a comprehensive overview of the introduction of freshwater megafish and an assessment of their environmental impacts. Of the 134 extant freshwater megafish species, 46% have been introduced to new environments, and of these, 69% have established self-sustaining alien populations. These introductions affect 59% of the world's main basins, with the USA and western Europe being particular hotspots of megafish introductions. The common carp (Cyprinus carpio) is the most widely introduced species. Using the Environmental Impact Classification for Alien Taxa (EICAT and EICAT+) frameworks, we assessed the severity and type of negative and positive impacts posed by alien megafish on native species. Alien megafish caused negative impacts through nine different mechanisms, with predation being the most frequently reported mechanism, followed by herbivory and competition. Moreover, 58% of the alien megafish species with sufficient data to evaluate the severity of their impacts caused declining populations of native species, or worse, extirpations of native species populations. The positive environmental impacts of alien megafish were far less frequently documented. They include biotic interactions that benefit native species, and the provision of trophic resources or habitats. Widely introduced or extensively studied species are more likely to have documented severe impacts on native species. There is a clear trade-off between the economic benefits associated with megafish introductions and the severe adverse impacts they have on native biodiversity. Our study highlights the need for comprehensive risk assessments to evaluate the potential environmental impacts of megafish. More research and long-term monitoring schemes are required to inform management actions to protect biodiversity, particularly in the Global South.
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Peixes , Água Doce , Espécies Introduzidas , Animais , Meio AmbienteRESUMO
Corruption represents a complex problem firmly embedded within our societal structures, governments, and organizations. The current study aimed to build a clearer consensus on the extent to which perceptions of organizational corruption are associated with organizational hierarchy. Two high-powered close replications of studies 1c and 6 by Fath and Kay provide further evidence for the claim that taller organizational structures are associated with greater perceived potential for corruption, and that these perceptions may compromise subsequent trust-related outcomes. Our results reinforce the importance of organizational design and aim to inspire future works to consider the ways in which researchers and organizations can minimize corruption. Preregistration, data and materials can be found on the OSF: https://osf.io/zb5j2.
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Journal editors have a large amount of power to advance open science in their respective fields by incentivising and mandating open policies and practices at their journals. The Data PASS Journal Editors Discussion Interface (JEDI, an online community for social science journal editors: www.dpjedi.org ) has collated several resources on embedding open science in journal editing ( www.dpjedi.org/resources ). However, it can be overwhelming as an editor new to open science practices to know where to start. For this reason, we created a guide for journal editors on how to get started with open science. The guide outlines steps that editors can take to implement open policies and practices within their journal, and goes through the what, why, how, and worries of each policy and practice. This manuscript introduces and summarizes the guide (full guide: https://doi.org/10.31219/osf.io/hstcx ).
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Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49).
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Antineoplásicos , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Antineoplásicos/efeitos adversos , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Pirimidinas/efeitos adversosRESUMO
BACKGROUND: WGS is increasingly being applied to healthcare-associated vancomycin-resistant Enterococcus faecium (VREfm) outbreaks. Within-patient diversity could complicate transmission resolution if single colonies are sequenced from identified cases. OBJECTIVES: Determine the impact of within-patient diversity on transmission resolution of VREfm. MATERIALS AND METHODS: Fourteen colonies were collected from VREfm positive rectal screens, single colonies were collected from clinical samples and Illumina WGS was performed. Two isolates were selected for Oxford Nanopore sequencing and hybrid genome assembly to generate lineage-specific reference genomes. Mapping to closely related references was used to identify genetic variations and closely related genomes. A transmission network was inferred for the entire genome set using Phyloscanner. RESULTS AND DISCUSSION: In total, 229 isolates from 11 patients were sequenced. Carriage of two or three sequence types was detected in 27% of patients. Presence of antimicrobial resistance genes and plasmids was variable within genomes from the same patient and sequence type. We identified two dominant sequence types (ST80 and ST1424), with two putative transmission clusters of two patients within ST80, and a single cluster of six patients within ST1424. We found transmission resolution was impaired using fewer than 14 colonies. CONCLUSIONS: Patients can carry multiple sequence types of VREfm, and even within related lineages the presence of mobile genetic elements and antimicrobial resistance genes can vary. VREfm within-patient diversity could be considered in future to aid accurate resolution of transmission networks.
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Anti-Infecciosos , Enterococcus faecium , Humanos , Antibacterianos/farmacologia , Enterococcus faecium/genética , Vancomicina , Farmacorresistência BacterianaRESUMO
Polypharmacotherapy is an ever-increasing issue with an ageing patient population. Anticholinergic medications make up a large proportion of patient medication but cause significant side effects, contributing to well-documented issues within the older population and in hospital medicine. This review explores the documented impact of anticholinergic burden in older surgical patients on postoperative delirium, infection, length of stay and readmission, urinary retention, ileus and mortality. It also highlights the need for further high-quality research into anticholinergic burden management among older surgical patients to further impact practice and policy in the area.
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Medicina Hospitalar , Obstrução Intestinal , Retenção Urinária , Humanos , Idoso , Envelhecimento , Antagonistas Colinérgicos/efeitos adversosRESUMO
Stable isotope ratios in organisms can be used to estimate dietary source contributions, but lipids must first be accounted for to interpret values meaningfully. Lipids are depleted in heavy isotopes because during lipid synthesis light isotopes of carbon (12C) and hydrogen (1H) are preferentially incorporated. Prior work in larval lampreys has noted unusual lipid effects, which suggest lipids are enriched in the heavy isotope of carbon (13C), but still depleted in the heavy isotope of hydrogen (deuterium; 2H); nitrogen, a relatively rare element in lipids, has not been identified as being as sensitive to lipid content. Our objective was to determine if stable isotope ratios of hydrogen, carbon, and nitrogen behaved as expected in larval lampreys, or if their lipids presented different isotopic behavior. The δ2H, δ13C, and δ15N were measured from the muscle of four lamprey species before and after lipid extraction. In addition, muscle of least brook lamprey (Lampetra aepyptera) was collected every three months for a year from two streams in Maryland. Isotopic ratios were measured in bulk and lipid-extracted muscles, as well as in extracted lipids. The difference between muscle samples before and after lipid extraction (Δδ2H, Δδ13C, Δδ15N) was positively related to lipid proxy (%H or C:N ratio) and were fit best by linear models for Δδ2H and Δδ15N, and by a non-linear model for Δδ13C. The difference between lipid-extracted muscle and lipid δ13C (ΔMLδ13C) was negative and varied between months (ANOVA, F3,53 = 5.05, p < 0.005). Our work suggests that while lipids are often depleted in 13C, this is not a universal rule; however, the depletion of 2H in lipid synthesis appears broadly true.
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Carbono , Lampreias , Animais , Isótopos de Nitrogênio , Isótopos de Carbono , Larva , Hidrogênio , Lipídeos , Nitrogênio , MúsculosRESUMO
We created a database of lost and rediscovered tetrapod species, identified patterns in their distribution and factors influencing rediscovery. Tetrapod species are being lost at a faster rate than they are being rediscovered, due to slowing rates of rediscovery for amphibians, birds and mammals, and rapid rates of loss for reptiles. Finding lost species and preventing future losses should therefore be a conservation priority. By comparing the taxonomic and spatial distribution of lost and rediscovered tetrapod species, we have identified regions and taxa with many lost species in comparison to those that have been rediscovered-our results may help to prioritise search effort to find them. By identifying factors that influence rediscovery, we have improved our ability to broadly distinguish the types of species that are likely to be found from those that are not (because they are likely to be extinct). Some lost species, particularly those that are small and perceived to be uncharismatic, may have been neglected in terms of conservation effort, and other lost species may be hard to find due to their intrinsic characteristics and the characteristics of the environments they occupy (e.g. nocturnal species, fossorial species and species occupying habitats that are more difficult to survey such as wetlands). These lost species may genuinely await rediscovery. However, other lost species that possess characteristics associated with rediscovery (e.g. large species) and that are also associated with factors that negatively influence rediscovery (e.g. those occupying small islands) are more likely to be extinct. Our results may foster pragmatic search protocols that prioritise lost species likely to still exist.
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Ecossistema , Extinção Biológica , Animais , Anfíbios , Áreas Alagadas , Mamíferos , Conservação dos Recursos Naturais/métodos , Espécies em Perigo de Extinção , BiodiversidadeRESUMO
BACKGROUND: Hypertension is a leading cause of adverse pregnancy outcomes. These outcomes disproportionately affect Black individuals. Reproductive life planning that includes patient-centered contraception counseling could mitigate the impact of unintended pregnancy. OBJECTIVE: The primary objective of the study is to compare contraception counseling and use between hypertensive and nonhypertensive individuals at risk for unintended pregnancy. Our secondary objectives are the following: (1) to evaluate the effect of race on the probability of counseling and the use of contraception, and (2) to evaluate the methods used by individuals with hypertension. METHODS: Data from the 2015-2017 and 2017-2019 National Survey of Family Growth Female Respondent Files were used to analyze whether individuals who reported being informed of having high blood pressure within the previous 12 months received counseling about contraception or received a contraceptive method. Covariates considered in the analysis included age, race, parity, educational attainment, body mass index, smoking, diabetes, and experience with social determinants of health. The social determinants of health covariate was based on reported experiences within 5 social determinants of health domains: food security, housing stability, financial security, transportation access, and childcare needs. Linear probability models were used to estimate the adjusted probability of receiving counseling and the use of a contraceptive. Using difference-in-difference analyses, we compared the change in counseling and use between hypertensive and nonhypertensive respondents by race, relative to White respondents. RESULTS: Of the 8625 participants analyzed, 771 (9%) were hypertensive. Contraception counseling was received by 26.2% (95% confidence interval, 20.4-31.9) of hypertensive individuals and 20.7% (95% confidence interval, 19.3-22.2) of nonhypertensive individuals. Contraception use was reported by 39.8% (95% confidence interval, 33.2-46.5) of hypertensive and 35.3% (95% confidence interval, 33.3-37.2) of nonhypertensive individuals. The linear probability model adjusting for age, parity, education attainment, body mass index, smoking, diabetes, and social determinants of health indicated that hypertensive individuals were 8 percentage points (95% confidence interval, 3-18 percentage points) more likely to receive counseling and 9 percentage points (95% confidence interval, 3-16 percentage points) more likely to use contraception. Hypertensive Black individuals did not receive more counseling or use more contraceptives compared with nonhypertensive Black individuals. The difference in counseling when hypertension was present was 13 percentage points lower than the difference observed for White respondents when hypertension was present (P=.01). The most frequently used contraceptive method among hypertensive individuals was combined oral contraceptive pills (54.0%; 95% confidence interval, 44.3%-63.5%). CONCLUSION: Despite the higher likelihood of receiving contraception counseling and using contraception among hypertensive individuals at risk for unintended pregnancy, two-thirds of this population did not receive contraception counseling, and <40% used any contraceptive method. Furthermore, unlike White individuals, Black individuals with hypertension did not receive more contraception care than nonhypertensive Black individuals. Of all those who used contraception, half relied on a method classified as Centers for Disease Control and Prevention Medical Eligibility Criteria Category 3. These findings highlight a substantial unmet need for safe and accessible contraception options for hypertensive individuals at risk for unintended pregnancy, emphasizing the importance of targeted interventions to improve contraceptive care and counseling in this population.
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Diabetes Mellitus , Hipertensão , Gravidez , Feminino , Humanos , Gravidez não Planejada , Anticoncepção/métodos , Anticoncepcionais , Hipertensão/epidemiologia , Aconselhamento , Comportamento Contraceptivo , Serviços de Planejamento FamiliarRESUMO
The Environmental Impact Classification for Alien Taxa (EICAT) is an important tool for biological invasion policy and management and has been adopted as an International Union for Conservation of Nature (IUCN) standard to measure the severity of environmental impacts caused by organisms living outside their native ranges. EICAT has already been incorporated into some national and local decision-making procedures, making it a particularly relevant resource for addressing the impact of non-native species. Recently, some of the underlying conceptual principles of EICAT, particularly those related to the use of the precautionary approach, have been challenged. Although still relatively new, guidelines for the application and interpretation of EICAT will be periodically revisited by the IUCN community, based on scientific evidence, to improve the process. Some of the criticisms recently raised are based on subjectively selected assumptions that cannot be generalized and may harm global efforts to manage biological invasions. EICAT adopts a precautionary principle by considering a species' impact history elsewhere because some taxa have traits that can make them inherently more harmful. Furthermore, non-native species are often important drivers of biodiversity loss even in the presence of other pressures. Ignoring the precautionary principle when tackling the impacts of non-native species has led to devastating consequences for human well-being, biodiversity, and ecosystems, as well as poor management outcomes, and thus to significant economic costs. EICAT is a relevant tool because it supports prioritization and management of non-native species and meeting and monitoring progress toward the Kunming-Montreal Global Biodiversity Framework (GBF) Target 6.
Uso de la Clasificación de Impacto Ambiental de los Taxones Exóticos de la UICN para la toma de decisiones Resumen La Clasificación de Impacto Ambiental de los Taxones Exóticos (EICAT, en inglés) es una herramienta importante para las políticas y manejo de las invasiones biológicas y ha sido adoptada como un estándar de la Unión Internacional para la Conservación de la Naturaleza (UICN) para medir la seriedad del impacto ambiental causado por los organismos que viven fuera de su extensión nativa. La EICAT ya ha sido incorporada a algunos procedimientos locales y nacionales de toma de decisiones, lo que la vuelve un recurso particularmente relevante para abordar el impacto de las especies no nativas. Algunos principios conceptuales subyacentes de la EICAT han sido cuestionados recientemente, en particular aquellos relacionados con el uso del principio de precaución. Aunque todavía son relativamente nuevas, las directrices para la aplicación e interpretación de la EICAT tendrán una revisión periódica, basada en evidencia científica, por parte de la comunidad de la UICN para mejorar el proceso. Algunas de las críticas recientes están basadas en suposiciones seleccionadas subjetivamente que no pueden generalizarse y podrían perjudicar los esfuerzos globales para manejar las invasiones biológicas. La EICAT adopta un principio de precaución cuando considera el historial de impacto de una especie en cualquier otro lugar ya que algunos taxones tienen características que podrían volverlos más dañinos. Además, las especies no nativas suelen ser factores de pérdida de bidiversidad, incluso bajo otras presiones. Cuando ignoramos el principio de precaución al abordar el impacto de las especies no nativas, hay consecuencias devastadoras para el bienestar humano, la biodiversidad y los ecosistemas, así como resultados pobres de conservación, y por lo tanto con costos económicos importantes. La EICAT es una herramienta relevante porque respalda la priorización y el manejo de las especies no nativas y ayuda con el cumplimiento y monitoreo del progreso para llegar al objetivo 6 del Marco Mundial de Biodiversidad KunmingMontreal.
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Ecossistema , Espécies Introduzidas , Humanos , Conservação dos Recursos Naturais , BiodiversidadeRESUMO
Respiratory syncytial virus (RSV) infection and shingles are two viral diseases that affect older adults, and a combined vaccine to protect against both could be beneficial. RSV infection causes hospitalisations and significant morbidity in both children and adults and can be fatal in the elderly. The RSV fusion (F) envelope glycoprotein induces a strong RSV-neutralising antibody response and is the target of protective immunity in the first RSV vaccine for older adults, recently approved by the FDA. An initial childhood infection with the varicella zoster virus (VZV) results in chickenpox disease, but reactivation in older adults can cause shingles. This reactivation in sensory and autonomic neurons is characterized by a skin-blistering rash that can be accompanied by prolonged pain. The approved protein-in-adjuvant shingles vaccine induces VZV glycoprotein E (gE)-fspecific antibody and CD4+ T cell responses and is highly effective. Here we report the evaluation of RSV/shingles combination vaccine candidates based on non-replicating chimpanzee adenovirus (ChAd) vectors. We confirmed the cellular and humoral immunogenicity of the vaccine vectors in mice using T cell and antibody assays. We also carried out an RSV challenge study in cotton rats which demonstrated protective efficacy following a homologous prime-boost regimen with our preferred vaccine candidate.
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OBJECTIVE: The COVID-19 pandemic had an undoubted impact on the provision of elective and emergency cancer care, including the diagnosis and management of patients with hepatocellular carcinoma (HCC). Our aim was to determine the effects of the COVID-19 pandemic on patients with HCC in the West of Scotland. DESIGN: This was a retrospective audit of a prospectively collated database of patients presented to the West of Scotland Multidisciplinary Team (MDT) between April and October 2020 (during the pandemic), comparing baseline demographics, characteristics of disease at presentation, diagnostic workup, treatment and outcomes with patients from April to October 2019 (pre pandemic). RESULTS: There was a 36.5% reduction in new cases referred to the MDT during the pandemic. Patients presented at a significantly later Barcelona Cancer Liver Clinic stage (24% stage D during the pandemic, 9.5% pre pandemic, p<0.001) and with a significantly higher Child-Pugh Score (46% Child-Pugh B/C during the pandemic vs 27% pre pandemic, p<0.001). We observed a reduction in overall survival (OS) among all patients with a median OS during the pandemic of 6 months versus 17 months pre pandemic (p=0.048). CONCLUSION: The impact of the COVID-19 pandemic is likely to have contributed to a reduction in the presentation of new cases and survival among patients with HCC in the West of Scotland. The reason for this is likely multifactorial, but disruption of standard care is likely to have played a significant role. Resources should be provided to address the backlog and ensure there are robust investigation and management pathways going forward.
Assuntos
COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Pandemias , Estudos de Coortes , Estudos Retrospectivos , COVID-19/epidemiologiaRESUMO
Background & Aims: Millions of people worldwide are infected chronically with HBV, which results in significant morbidity and mortality. Therapeutic vaccination is a strategy that aims to induce functional cure by restoring cellular immunity to HBV. Previously we have shown the candidate HBV immunotherapeutic vaccine ChAdOx1-HBV, encoding all major HBV antigens and a genetic adjuvant (shark invariant chain), is highly immunogenic in mice. Methods: Here we report the results of HBV001, a first-in-human, phase I, non-randomised, dose-escalation trial of ChAdOx1-HBV assessed in healthy volunteers and patients with chronic HBV (CHB). Results: Vaccination with a single dose of ChAdOx1-HBV was safe and well tolerated in both healthy and CHB cohorts. Vaccination induced high magnitude HBV-specific T cell responses against all major HBV antigens (core, polymerase, and surface) in healthy volunteers. Responses were detected but lower in patients with CHB. T cells generated by vaccination were cross-reactive between HBV C and D genotypes. Conclusions: ChAdOx1-HBV is safe and immunogenic in healthy volunteers and patients with CHB. In further studies, ChAdOx1-HBV will be used in combination with other therapeutic strategies with an aim to overcome the attenuated immunogenicity in patients with CHB. Impact and implications: Therapeutic vaccine ChAdOx1-HBV, a novel treatment for chronic hepatitis B infection (CHB), has been shown to be immunogenic in preclinical studies. In HBV001, a first-in-human phase I study, we show vaccination with ChAdOx1-HBV is safe and generates high magnitude T cell responses in healthy volunteers and lower levels of responses in patients with CHB. This is an important first step in the development of ChAdOx1-HBV as part of a wider therapeutic strategy to induce hepatitis B functional cure, and is of great interest to patients CHB and clinicians treating the condition. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT04297917).