Sentinel lymph node biopsy in squamous cell carcinoma of the head and neck: 10 years of experience

Sentinel node (SN) biopsy of head and neck cancer is still considered investigational, and agreement on the width of the surgical sampling has not yet been reached. From May 1999 to Dec 2009, 209 consecutive patients entered a prospective study: 61.7% had primary tumour of the oral cavity and 23.9% of the oropharynx. SN was not found in 26 patients. Based on these data and definitive histopathological analysis, we proposed six hypothetic scenarios to understand the percentage of neck recurrences following different treatments Among patients with identified SN, 54 cases were pN+: 47 in SN and 7 in a different node. Considering the six hypothetic scenarios: "only SN removal", "SN level dissection", "neck dissection from the tumour site to SN level", "selective neck dissection of three levels (SND)", "dissection from level I to IV" and "comprehensive I-V dissection", neck recurrences could be expected in 6.5%, 3.8%, 2.18%, 2.73%, 1.09% and 1.09% of cases, respectively. SN biopsy can be considered a useful tool to personalize the surgical approach to a N0 carcinoma. The minimum treatment of the neck is probably dissection of the levels between the primary tumour and the level containing the SN(s). Outside the framework of a clinical study, the best treatment can still be considered SND

Non-expanding universe: a cosmological system of units

The product of two empirical constants, the dimensionless fine structure constant and the von Klitzing constant (an electrical resistance), turns out to be an exact dimensionless number. Then the accuracy and cosmological time variation (if any) of these two constants are tied. Also this product defines a natural unit of electrical resistance, the inverse of a quantum of conductance. When the speed of light c is taken away from the fine structure constant, as has been shown elsewhere, its constancy implies the constancy of the ratio e2/h (the inverse of the von Klitzing constant), e the charge of the electron and h Planck constant. This forces the charge of the electron e to be constant as long as the action h (an angular momentum) is a true constant too. From the constancy of the Rydberg constant the Compton wavelength, h/mc, is then a true constant and consequently there is no expansion at the quantum mechanical level. The momentum mc is also a true constant and then general relativity predicts that the universe is not expanding, as shown elsewhere. The time variation of the speed of light explains the observed Hubble red shift. And there is a mass-boom effect. From this a coherent cosmological system of constant units can be defined.Comment: 8 page

Assessment of the suitability of chitosan/polybutylene succinate scaffolds seeded with mouse mesenchymal progenitor cells for a cartilage tissue engineering approach

In this work, scaffolds derived from a new biomaterial originated from the combination of a natural material and a synthetic material were tested for assessing their suitability for cartilage tissue engineering applications. In order to obtain a better outcome result in terms of scaffolds’ overall properties, different blends of natural and synthetic materials were created. Chitosan and polybutylene succinate (CPBS) 50/50 (wt%) were melt blended using a twin-screw extruder and processed into 5 5 5mm scaffolds by compression moulding with salt leaching. Micro-computed tomography analysis calculated an average of 66.29% porosity and 92.78% interconnectivity degree for the presented scaffolds. The salt particles used ranged in size between 63 and 125 lm, retrieving an average pore size of 251.28 lm. Regarding the mechanical properties, the compressive modulus was of 1.73 ± 0.4MPa (Esec 1%). Cytotoxicity evaluation revealed that the leachables released by the developed porous structures were not harmful to the cells and hence were noncytotoxic. Direct contact assays were carried out using a mouse bone marrow–derived mesenchymal progenitor cell line (BMC9). Cells were seeded at a density of 5 105 cells/scaffold and allowed to grow for periods up to 3 weeks under chondrogenic differentiating conditions. Scanning electron microscopy analysis revealed that the cells were able to proliferate and colonize the scaffold structure, and MTS test demonstrated cell viability during the time of the experiment. Finally, Western blot performed for collagen type II, a natural cartilage extracellular matrix component, showed that this protein was being expressed by the end of 3 weeks, which seems to indicate that the BMC9 cells were being differentiated toward the chondrogenic pathway. These results indicate the adequacy of these newly developed C-PBS scaffolds for supporting cell growth and differentiation toward the chondrogenic pathway, suggesting that they should be considered for further studies in the cartilage tissue engineering field.J. T. Oliveira would like to acknowledge the grant (SFRH/ BD17135/2004) from Portuguese Foundation for Science and Technology (FCT). The authors would like to thank Fernanda Marques, at the Institute for Health and Life Sciences (ICVS), University of Minho, Braga, Portugal, for her help with the Western blot analysis, as well as the staff at ICVS for allowing to use their facilities. The monoclonal antibody for collagen type II was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the Department of Biological Sciences, University of Iowa (Iowa City, IA). This work was carried out under the scope of the European NoE EXPERTISSUES (NMP3-CT-2004-500283), and partially supported by the European Project GENOSTEM (LSHB-CT-2003-503161) and the FCT Project CartiScaff (POCTI/SAU-BMA/58991/2004)

Effect modification of greenness on the association between heat and mortality: A multi-city multi-country study

Background: Identifying how greenspace impacts the temperature-mortality relationship in urban environments is crucial, especially given climate change and rapid urbanization. However, the effect modification of greenspace on heat-related mortality has been typically focused on a localized area or single country. This study examined the heat-mortality relationship among different greenspace levels in a global setting. Methods: We collected daily ambient temperature and mortality data for 452 locations in 24 countries and used Enhanced Vegetation Index (EVI) as the greenspace measurement. We used distributed lag non-linear model to estimate the heat-mortality relationship in each city and the estimates were pooled adjusting for city-specific average temperature, city-specific temperature range, city-specific population density, and gross domestic product (GDP). The effect modification of greenspace was evaluated by comparing the heat-related mortality risk for different greenspace groups (low, medium, and high), which were divided into terciles among 452 locations. Findings: Cities with high greenspace value had the lowest heat-mortality relative risk of 1·19 (95% CI: 1·13, 1·25), while the heat-related relative risk was 1·46 (95% CI: 1·31, 1·62) for cities with low greenspace when comparing the 99th temperature and the minimum mortality temperature. A 20% increase of greenspace is associated with a 9·02% (95% CI: 8·88, 9·16) decrease in the heat-related attributable fraction, and if this association is causal (which is not within the scope of this study to assess), such a reduction could save approximately 933 excess deaths per year in 24 countries. Interpretation: Our findings can inform communities on the potential health benefits of greenspaces in the urban environment and mitigation measures regarding the impacts of climate change.Research in context - I-Evidence before this study: Urbanization and climate change have resulted in changes to the urban environment, including the urban heat island effect and contributions to other extreme weather events. Recently, as metropolitan areas have become denser due to rapid urbanization, environmental problems such as high temperatures are also worsening. Many studies showed that high temperatures increase health risks, including mortality. Therefore, identifying factors that could mitigate the high-temperature conditions in urban environments are a crucial part of climate change mitigation strategies. Many studies found that urban green spaces may play an important role in mitigating heat. Specifically, large green spaces have shown a significant and positive cooling effect. Vegetation can promote air convection through shading and evapotranspiration, which indicates that dense vegetation can lower air temperature. Therefore, more greenspace could result in lower temperatures during the warm season, which would lower exposure to high temperatures that impact human health. Importantly, while greenspace can lower exposure to heat, this study examined how greenspace modifies the heat-health relationship. Some studies have investigated this issue. For example, studies found that heat-related mortality and ambulance calls are negatively correlated with the amount of greenspace coverage. However, most previous work on how greenspace modifies the heat-health relationship was based on one country or region. Research is needed on a global scale to understand how greenspace in urban areas among different countries, with different populations, levels of urbanization, and types of greenspace, can modify the relationship between extreme temperatures and health. As climate change is anticipated to increase temperatures and the associated health consequences worldwide, greenspace may be a plausible mitigation strategy for cities in order to address heat-related health impacts at present and in the future. II-Added value of this study: In this study, we explored the effect modification of greenspace on the heat-mortality relationship on a global scale. With a dataset of 452 locations from 24 countries located in various climate zones and continents, this study incorporated variability in greenspace, temperature, and population characteristics. We found that, based on 452 locations, the heat-mortality risks differed with greenspace category and the cities with higher greenspace values had lower heat-mortality risk than those with lower greenspace values. III-Implications of all the available evidence: Our findings provide evidence that higher greenspace reduces the heat-related mortality, which is similar to other previous smaller studies, and our study results were consistent in different countries around various climate zones. These findings indicate that disparate greenspace levels, temperature, and environment settings should be considered when developing policies and strategies in climate change mitigation and public health adaptation. This study adds to the existing literature that greenspace can reduce the urban heat island effect, by providing evidence for the theory that greenspace can also lower the heat-mortality association, and documents such impacts on a global scale.This publication was developed under Assistance Agreement No. RD83587101 awarded by the U.S. Environmental Protection Agency to Yale University. Research reported in this publication was also supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Number R01MD012769. Also, this work has been supported by the National Research Foundation of Korea (2021R1A6A3A03038675), Medical Research Council-UK (MR/V034162/1 and MR/R013349/1), Natural Environment Research Council UK (Grant ID: NE/R009384/1), Academy of Finland (Grant ID: 310372), European Union's Horizon 2020 Project Exhaustion (Grant ID: 820655 and 874990), Czech Science Foundation (22-24920S), Emory University's NIEHS-funded HERCULES Center (Grant ID: P30ES019776), and Grant CEX2018-000794-S funded by MCIN/AEI/ 10.13039/501100011033.info:eu-repo/semantics/publishedVersio

Excess mortality attributed to heat and cold: a health impact assessment study in 854 cities in Europe

MCC Collaborative Research Network: Souzana Achilleos (Department of Primary Care and Population Health, University of Nicosia Medical School, Nicosia, Cyprus), Jan Kyselý (Institute of Atmospheric Physics, Academy of Sciences of the Czech Republic, Prague, Czech Republic), Ene Indermitte (Department of Family Medicine and Public Health, University of Tartu, Tartu, Estonia), Jouni J K Jaakkola and Niilo Ryti (Center for Environmental and Respiratory Health Research, and Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland), Mathilde Pascal (Santé Publique France, Department of Environmental Health, French National Public Health Agency, Saint Maurice, France), Antonis Analitis (Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, Athens, Greece), Klea Katsouyanni (School of Population Health and Environmental Sciences, King’s College, London, UK), Patrick Goodman (Technological University Dublin, Dublin, Ireland), Ariana Zeka (Institute for the Environment, Brunel University London, London, UK), Paola Michelozzi (Department of Epidemiology, Lazio Regional Health Service, Rome, Italy), Danny Houthuijs and Caroline Ameling (National Institute for Public Health and the Environment, Centre for Sustainability and Environmental Health, Bilthoven, Netherlands), Shilpa Rao (Norwegian institute of Public Health, Oslo, Norway), Susana das Neves Pereira da Silva and Joana Madureira (Department of Epidemiology, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisbon, Portugal), Iulian-Horia Holobaca (Faculty of Geography, Babes-Bolay University, Cluj-Napoca, Romania), Aurelio Tobias (Institute of Environmental Assessment and Water Research, Spanish Council for Scientific Research, Barcelona, Spain), Carmen Íñiguez (Department of Statistics and Computational Research, Universitat de València, València, Spain), Bertil Forsberg (Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden), and Martina S Ragettli (Swiss Tropical and Public Health Institute, Basel, Switzerland).Online publication has been corrected. Correction available online 2 July 2024 https://doi.org/10.1016/S2542-5196(23)00171-7Background: Heat and cold are established environmental risk factors for human health. However, mapping the related health burden is a difficult task due to the complexity of the associations and the differences in vulnerability and demographic distributions. In this study, we did a comprehensive mortality impact assessment due to heat and cold in European urban areas, considering geographical differences and age-specific risks. Methods: We included urban areas across Europe between Jan 1, 2000, and Dec 12, 2019, using the Urban Audit dataset of Eurostat and adults aged 20 years and older living in these areas. Data were extracted from Eurostat, the Multi-country Multi-city Collaborative Research Network, Moderate Resolution Imaging Spectroradiometer, and Copernicus. We applied a three-stage method to estimate risks of temperature continuously across the age and space dimensions, identifying patterns of vulnerability on the basis of city-specific characteristics and demographic structures. These risks were used to derive minimum mortality temperatures and related percentiles and raw and standardised excess mortality rates for heat and cold aggregated at various geographical levels. Findings: Across the 854 urban areas in Europe, we estimated an annual excess of 203 620 (empirical 95% CI 180 882-224 613) deaths attributed to cold and 20 173 (17 261-22 934) attributed to heat. These corresponded to age-standardised rates of 129 (empirical 95% CI 114-142) and 13 (11-14) deaths per 100 000 person-years. Results differed across Europe and age groups, with the highest effects in eastern European cities for both cold and heat. Interpretation: Maps of mortality risks and excess deaths indicate geographical differences, such as a north-south gradient and increased vulnerability in eastern Europe, as well as local variations due to urban characteristics. The modelling framework and results are crucial for the design of national and local health and climate policies and for projecting the effects of cold and heat under future climatic and socioeconomic scenarios.Funding: The study was funded by Medical Research Council of the UK (MR/V034162/1 and MR/R013349/1), the Natural Environment Research Council UK (NE/R009384/1), the EU’s Horizon 2020 (820655), and the EU’s Joint Research Center (JRC/SVQ/2020/MVP/1654). AU and JK were supported by the Czech Science Foundation (22–24920S). VH has received funding from the EU’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (101032087).info:eu-repo/semantics/publishedVersio

Quantifying Excess Deaths Related to Heatwaves under Climate Change Scenarios: A multicountry time series modelling study

Background: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of climate change on heatwave-related mortality at a global scale is limited. Methods and findings: We collected historical daily time series of mean temperature and mortality for all causes or nonexternal causes, in periods ranging from January 1, 1984, to December 31, 2015, in 412 communities within 20 countries/regions. We estimated heatwave–mortality associations through a two-stage time series design. Current and future daily mean temperature series were projected under four scenarios of greenhouse gas emissions from 1971–2099, with five general circulation models. We projected excess mortality in relation to heatwaves in the future under each scenario of greenhouse gas emissions, with two assumptions for adaptation (no adaptation and hypothetical adaptation) and three scenarios of population change (high variant, median variant, and low variant). Results show that, if there is no adaptation, heatwave-related excess mortality is expected to increase the most in tropical and subtropical countries/regions (close to the equator), while European countries and the United States will have smaller percent increases in heatwave-related excess mortality. The higher the population variant and the greenhouse gas emissions, the higher the increase of heatwave-related excess mortality in the future. The changes in 2031–2080 compared with 1971–2020 range from approximately 2,000% in Colombia to 150% in Moldova under the highest emission scenario and high-variant population scenario, without any adaptation. If we considered hypothetical adaptation to future climate, under high-variant population scenario and all scenarios of greenhouse gas emissions, the heatwave-related excess mortality is expected to still increase across all the countries/regions except Moldova and Japan. However, the increase would be much smaller than the no adaptation scenario. The simple assumptions with respect to adaptation as follows: no adaptation and hypothetical adaptation results in some uncertainties of projections. Conclusions: This study provides a comprehensive characterisation of future heatwave-related excess mortality across various regions and under alternative scenarios of greenhouse gas emissions, different assumptions of adaptation, and different scenarios of population change. The projections can help decision makers in planning adaptation and mitigation strategies for climate change. © 2018 Guo et al. http://creativecommons.org/licenses/by/4.0/

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries

Background: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. Methods: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. Results: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1–2.3) and 9.1 (95% eCI, 8.9–9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4–2.8) and 12.8 (95% eCI, 12.2–13.1) for every 1000 heart failure deaths, respectively. Conclusions: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day—and especially under a changing climate.Clinical Perspective_ What Is New?: This study provided evidence from what we believe is the largest multinational dataset ever assembled on cardiovascular outcomes and environmental exposures; Extreme hot and cold temperatures were associated with increased risk of death from any cardiovascular cause, ischemic heart disease, stroke, and heart failure; For every 1000 cardiovascular deaths, 2 and 9 excess deaths were attributed to extreme hot and cold days, respectively. _ What Are the Clinical Implications?: Extreme temperatures from a warming planet may become emerging priorities for public health and preventative cardiology; The findings of this study should prompt professional cardiology societies to commission scientific statements on the intersections of extreme temperature exposure and cardiovascular health.This study was supported by the Kuwait Foundation for the Advancement of Science (CB21-63BO-01); the US Environmental Protection Agency (RD-835872); Harvard Chan National Institute of Environmental Health Sciences Center for Environmental Health (P01ES009825); the UK Medical Research Council (MR/R013349/1); the UK Natural Environment Research Council (NE/R009384/1); the European Union’s Horizon 2020 Project Exhaustion (820655); the Australian National Health and Medical Research Council (APP 2000581, APP 1109193, APP 1163693); the National Institute of Environmental Health Sciences–funded HERCULES Center (P30ES019776); the MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S); the Taiwanese Ministry of Science and Technology (MOST 109–2621-M-002–021); the Environmental Restoration and Conservation Agency, Environment Research and Technology Development Fund (JPMEERF15S11412); the São Paulo Research Foundation; and Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016)info:eu-repo/semantics/publishedVersio