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1.
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2.
  • Broman, K. K., et al. (författare)
  • Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis
  • 2021
  • Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515. ; 232:4, s. 424-431
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown. STUDY DESIGN: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma specific mortality were compared. RESULTS: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86). CONCLUSIONS: SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN. Crown Copyright (C) 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons. All rights reserved.
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3.
  • Broman, K. K., et al. (författare)
  • Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy trial II (MSLT-2)
  • 2021
  • Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:13, s. 2251-2261
  • Tidskriftsartikel (refereegranskat)abstract
    • Background For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. Methods In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. Results Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. Conclusions Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.
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4.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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5.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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6.
  • Calvert, Clara, et al. (författare)
  • Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries
  • 2023
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:4, s. 529-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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7.
  • KC, Ashish, 1982-, et al. (författare)
  • Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.
  • 2023
  • Ingår i: Nature human behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:4, s. 529-544
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.
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8.
  • Stock, SJ, et al. (författare)
  • The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol
  • 2021
  • Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 6, s. 21-
  • Tidskriftsartikel (refereegranskat)abstract
    • Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.
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9.
  • Frier, Emily M, et al. (författare)
  • Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
  • 2023
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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10.
  • Lemmen, P., et al. (författare)
  • Development of an advanced frontal dummy thorax demonstrator
  • 2012
  • Ingår i: 2012 IRCOBI Conference Proceedings - International Research Council on the Biomechanics of Injury, Dublin:12 September through14 September 2012. ; :IRC-12-87, s. 828-842
  • Konferensbidrag (refereegranskat)
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11.
  • Lundy, Lian, et al. (författare)
  • Making Waves : Collaboration in the time of SARS-CoV-2 - rapid development of an international co-operation and wastewater surveillance database to support public health decision-making
  • 2021
  • Ingår i: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 199
  • Tidskriftsartikel (refereegranskat)abstract
    • The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE “SARS-CoV-2 in sewage” database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice.
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12.
  • Rado, Marta, et al. (författare)
  • Effect of comprehensive smoke-free legislation on neonatal mortality and infant mortality across 106 middle-income countries : a synthetic control study
  • 2022
  • Ingår i: The Lancet Public Health. - : Elsevier Science Ltd. - 2468-2667. ; 7:7, s. E616-E625
  • Tidskriftsartikel (refereegranskat)abstract
    • Background There are few quantitative studies into the effect of comprehensive smoke-free legislation on neonatal and infant mortality in middle-income countries. We aimed to estimate the effects of implementing comprehensive smoke-free legislation on neonatal mortality and infant mortality across all middle-income countries. Methods We applied the synthetic control method using 1990-2018 country-level panel data for 106 middle-income countries from the WHO, World Bank, and Penn World datasets. Outcome variables were neonatal (age 0-28 days) mortality and infant (age 0-12 months) mortality rates per 1000 livebirths per year. For each middle-income country with comprehensive smoke-free legislation, a synthetic control country was constructed from middle-income countries without comprehensive smoke-free legislation, but with similar prelegislation trends in the outcome and predictor variables. Overall legislation effect was the mean average of country-specific effects weighted by the number of livebirths. We compared the distribution of the legislation effects with that of the placebo effects to assess the likelihood that the observed effect was related to the implementation of smoke-free legislation and not merely influenced by other processes. Findings 31 (29%) of 106 middle-income countries introduced comprehensive smoke-free legislation and had outcome data for at least 3 years after the intervention. We were able to construct a synthetic control country for 18 countries for neonatal mortality and for 15 countries for infant mortality. Comprehensive smoke-free legislation was followed by a mean yearly decrease of 1.63% in neonatal mortality and a mean yearly decrease of 1.33% in infant mortality. An estimated 12 392 neonatal deaths in 18 countries and 8932 infant deaths in 15 countries were avoided over 3 years following the implementation of comprehensive smoke-free legislation. We estimated that an additional 104 063 infant deaths (including 95 850 neonatal deaths) could have been avoided over 3 years if the 72 control middle-income countries had introduced this legislation in 2015. 220 (43%) of 514 placebo effects for neonatal mortality and 112 (39%) of 289 for infant mortality were larger than the estimated aggregated legislation effect, indicating a degree of uncertainty around our estimates. Sensitivity analyses showed results that were consistent with the main analysis and suggested a dose-response association related to comprehensiveness of the legislation. Interpretation Implementing comprehensive smoke-free legislation in middle-income countries could substantially reduce preventable deaths in neonates and infants. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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13.
  • Rado, Marta, et al. (författare)
  • Socio-economic inequalities in smoking and drinking in adolescence: Assessment of social network dynamics
  • 2024
  • Ingår i: Addiction. - : WILEY. - 0965-2140 .- 1360-0443. ; 119:3, s. 488-498
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: We investigated whether (1) adolescents selected friends with a similar socio-economic status (SES), (2) smoking and alcohol consumption spread in networks and (3) the exclusion of non-smokers or non-drinkers differed between SES groups. Design: This was a longitudinal study using stochastic actor-oriented models to analyze complete social network data over three waves. Setting: Eight Hungarian secondary schools with socio-economically diverse classes took part. Participants: This study comprised 232 adolescents aged between 14 and 15 years in the first wave. Measurements: Self-reported smoking behavior, alcohol consumption behavior and friendship ties were measured. SES was measured based upon entitlement to an income-tested regular child protection benefit. Findings: Non-low-SES adolescents were most likely to form friendships with peers from their own SES group [odds ratio (OR) = 1.07, 95% confidence interval (CI) = 1.02-1.11]. Adolescents adjusted their smoking behavior (OR = 24.05, 95% CI = 1.27-454.86) but not their alcohol consumption (OR = 1.65, 95% CI = 0.62-4.39) to follow the behavior of their friends. Smokers did not differ from non-smokers in the likelihood of receiving a friendship nomination (OR = 0.98, 95% CI = 0.87-1.10), regardless of their SES. Alcohol consumers received significantly more friendship nominations than non-consumers (OR = 1.16, 95% CI = 1.01-1.33), but this association was not significantly different according to SES. Conclusions: Hungarian adolescents appear to prefer friendships within their own socio-economic status group, and smoking and alcohol consumption spread within those friendship networks. Socio-economic groups do not differ in the extent to which they encourage smoking or alcohol consumption.
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14.
  • Soliveres, S., et al. (författare)
  • Low frequency noise in contacted single-wall carbon nanotube
  • 2005
  • Ingår i: AIP Conference Proceedings. - 0094-243X. ; 780, s. 462-465
  • Konferensbidrag (refereegranskat)abstract
    • Since their discovery, carbon nanotubes present many interesting electrical properties and can be candidates for future shrinking devices. Electrode realization on nanotubes remains a challenge. The deposited contacts must present interesting electrical parameters: low contact resistance, low series resistance, low parasitic capacity and low excess noise. The understanding of conduction phenomena induced into or near the metal/nanotube contact is necessary to improve the device. In this paper we present characterization of a Au-Ti deposited contact on a single-wall carbon nanotube. Steady-state current-voltage measurements, impedance and noise measurements lead to the frequency device characteristic. From this study a low frequency noise electrical model is presented. Using this model and the low frequency noise measurements, we show that the measured thermal noise has its origin in the electrode/nanotube contacts.
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