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BackgroundAlthough new approaches for data collection, such as mobile technology and teleresearch, have demonstrated new opportunities for the conduct of more timely and less costly surveys in community-based studies, literature on the feasibility of conducing cardiovascular disease research using mobile health (mHealth) platforms among middle-aged and older African Americans has been limited. ObjectiveThe purpose of this study was to contribute to the knowledge regarding the penetrance of internet and mobile technologies, such as cellphones or smartphones in existing large cohort studies of cardiovascular disease. MethodsA digital connectedness survey was conducted in the Jackson Heart Study (JHS), a Mississippi-based African American cohort study, as part of the annual follow-up calls with participants from July 2017 to February 2019. ResultsOf the 4024 participants contacted, 2564 (63.7%) completed the survey. Among survey respondents, 2262 (88.2%) reported use of internet or cellphone, and 1593 (62.1%) had a smartphone. Compared to nonusers (n=302), internet or cellphone users (n=2262) were younger (mean age 80.1, SD 8.0 vs 68.2, SD 11.3 years), more likely to be affluent (n=778, 40.1% vs n=39, 15.4%), and had greater than high school education (n=1636, 72.5% vs n=85, 28.1%). Internet or cellphone users were less likely to have cardiovascular disease history compared to nonusers (136/2262, 6.6% vs 41/302, 15.8%). The prevalence of current smoking and average BMI were similar between internet or cellphone users and nonusers. Among internet or cellphone users, 1316 (58.3%) reported use of email, 504 (22.3%) reported use of apps to track or manage health, and 1269 (56.1%) expressed interest in using JHS-developed apps. ConclusionsOur findings suggest that it is feasible to use mHealth technologies to collect survey data among African Americans already enrolled in a longitudinal study. Our findings also highlight the need for more efforts to reduce the age and education divide in access and use of internet and smartphones for tracking health and research in African American communities.

Abstract Background All-cause mortality following atrial fibrillation (AF) has decreased over time. Data regarding temporal trends in causes of death among individuals with AF are scarce. The aim of our study was to analyze temporal trends in cause-specific mortality and predictors for cardiovascular (CVD) and non-CVD deaths among participants with incident AF in the Framingham Heart Study. Methods We categorized all newly diagnosed AF cases according to age at AF diagnosis (

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P

Background: The electronic Framingham Heart Study (eFHS) is an ongoing nested study, which includes FHS study participants, examining associations between health data from mobile devices with cardiovascular risk factors and disease. Objective: To describe application (app) design, report user characteristics, and describe usability and survey response rates. Methods: Eligible FHS participants were consented and offered a smartwatch (Apple Watch), a digital blood pressure (BP) cuff, and the eFHS smartphone app for administering surveys remotely. We assessed usability of the new app using 2 domains (functionality, aesthetics) of the Mobile App Rating Scale (MARS) and assessed survey completion rates at baseline and 3 months. Results: A total of 196 participants were recruited using the enhanced eFHS app. Of these, 97 (49.5%) completed the MARS instrument. Average age of participants was 53 ± 9 years, 51.5% were women, and 93.8% were white. Eighty-six percent of participants completed at least 1 measure on the baseline survey, and 50% completed the 3-month assessment. Overall subjective score of the app was 4.2 ± 0.7 on a scale from 1 to 5 stars. Of those who shared their health data with others, 46% shared their BP and 7.7% shared their physical activity with a health care provider. Conclusion: Participants rated the new, enhanced eFHS app positively overall. Mobile app survey completion rates were high, consistent with positive in-app ratings from participants. These mobile data collection modalities offer clinicians new opportunities to engage in conversations about health behaviors.

Abstract Background Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. Methods This single-centre, pilot randomized clinical trial was conducted at the University Hospital “Maggiore della Carità” (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6–8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. Results A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. Conclusions LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. Trial registration registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Context. Solar active regions (ARs) are often surrounded by dark large areas of reduced emission compared to the quiet Sun, observed at various wavelengths corresponding to the chromosphere, transition region (TR), and corona, known as dark halos (DHs). The mechanisms behind the darker emission of DHs remain unclear and merit a wider scope of study. Aims. This study aims to investigate for the first time the fine structure of a DH observed by the EUV High Resolution Imager (HRIEUV) on board the ESA's Solar Orbiter (SO) mission and its appearance in the TR. Aims. We utilized the extensive 1 hour dataset from SO on 19 March 2022, which includes high-resolution observations of NOAA 12967 and part of the surrounding DH. We analyzed the dynamics of the HRIEUV DH fine structure and its appearance in the HRILyα image. We also analyzed the Spectral Imaging of the Coronal Environment (SPICE) Lyβ, C III, N VI, O VI, and Ne VIII lines, which sample the TR in the log T(K) ∼ 4.0–5.8 range. This analysis was complemented with a simultaneous BLOS magnetogram taken by the High Resolution Telescope (HRT). Methods. We report the presence of a peculiar fine structure that has not been observed for the quiet Sun. It is characterized by combined bright EUV bundles and dark regions, arranged and interconnected in such a way that they cannot be clearly separated. They form a spatial continuum extending approximately radially from the AR core, suggesting a deep connection between the DH and the AR. Additionally, we find that the bright EUV bundles are observed in all the SPICE TR lines and the HRILyα band and present photospheric BLOS footprints in the HRT magnetogram. This spatial correlation indicates that the origin of the 174 Å DH may lie in the low atmosphere: the photosphere and chromosphere. [ABSTRACT FROM AUTHOR]

Abstract Background Inappropriate authors’ self-citation (A-SC) is a growing mal-practice possibly boosted by the raising importance given to author’s metrics. Similarly, also excessive journals’ self-citation (J-SC) practice may factitiously influence journal’s metrics (impact factor, IF). Evaluating the appropriateness of each self-citation remains challenging. Main body We evaluated the presence of policies discouraging A-SC in Critical Care Medicine (CCM) journals with IF. We also calculated the J-SC rate of these journals. In order to evaluate if J-SC rates are influenced by the focus of interest of CCM journals, we separated them in three sub-categories (“multidisciplinary”, “broad” or “topic-specific” CCM journals). We analyzed 35 CCM journals and only 5 (14.3%) discouraged excessive and inappropriate A-SC. The median IF was higher in CCM journals with A-SC policies [4.1 (3–12)] as compared to those without [2.5 (2–3.5); p = 0.02]. The J-SC rate was highly variable (0–35.4%), and not influenced by the presence of A-SC policies (p = 0.32). However, J-SC rate was different according to the focus of interest (p = 0.01): in particular, it was higher in “topic-specific” CCM journals [15.3 (8.8–23.3%)], followed by “broad” CCM [11.8 (4.8–17.9%)] and “multidisciplinary” journals [6.1 (3.6–9.1%)]. Conclusions A limited number of CCM journals have policies for limiting A-SC, and these have higher IF. The J-SC rate among CCM journals is highly variable and higher in “topic-specific” interest CCM journals. Excluding self-referencing practice from scientific metrics calculation could be valuable to tackle this scientific malpractice.

Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.

BackgroundThe prevalence of obesity is rising. Most previous studies that examined the relations between BMI and physical activity (PA) measured BMI at a single timepoint. The association between BMI trajectories and habitual PA remains unclear. ObjectiveThis study assesses the relations between BMI trajectories and habitual step-based PA among participants enrolled in the electronic cohort of the Framingham Heart Study (eFHS). MethodsWe used a semiparametric group-based modeling to identify BMI trajectories from eFHS participants who attended research examinations at the Framingham Research Center over 14 years. Daily steps were recorded from the smartwatch provided at examination 3. We excluded participants with

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10(-8) ) and 39 suggestive (P-value< 5 × 10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.

Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10-9), independent of chronological age, even after adjusting for additional risk factors (p

IntroductionThis study examined whether interarm differences in systolic blood pressure (IDSBP) ≥10 mm Hg were associated with the risk of incident dementia and subclinical brain injury.MethodsBetween 1992 and 1998, 2063 participants of the Framingham Heart Study underwent assessment of IDSBP with results related to the 10-year risk of incident dementia including clinically characterized Alzheimer's disease. Secondary outcomes included markers of subclinical brain injury on magnetic resonance imaging.ResultsHigh IDSBP were associated with a greater risk of incident dementia (hazard ratio [HR] 1.92; 95% confidence interval [CI], 1.09-3.40) and Alzheimer's disease (HR, 2.32; 95% CI, 1.29-4.18), but only in those who carried an apolipoprotein E (APOE) ε4 allele. IDSBP also predicted lower total brain volumes and more prevalent silent brain infarcts in those who were APOE ε4 positive.DiscussionHigh IDSBP were associated with an increased risk of dementia, including clinical Alzheimer's disease, and subclinical brain injury in those who were APOE ε4 positive.

RESUMO Objetivo: Realizar uma revisão sistemática para sumarizar o conhecimento relativo à prevalência de burnout entre médicos atuantes na unidade de terapia intensiva. Métodos: Conduzimos uma revisão sistemática nas bases de dados MEDLINE e PubMed® (última atualização em 4 de fevereiro de 2019), com o objetivo de resumir a evidência a respeito de burnout entre médicos atuantes em unidades de terapia intensiva. Incluímos todos os estudos que relatavam burnout em trabalhadores na unidade de terapia intensiva, segundo o Inventário de Burnout de Maslach e, a seguir, triamos os estudos quanto a dados relativos a burnout especificamente em médicos atuantes na unidade de terapia intensiva. Resultados: Encontramos 31 estudos que descreviam burnout em membros da equipe da unidade de terapia intensiva e incluíam diferentes perfis de profissionais de saúde. Dentre estes, cinco estudos se focalizavam apenas em médicos, e 12 outros investigavam burnout em uma mescla de profissionais atuantes na unidade de terapia intensiva, mas forneciam dados à parte relativos aos médicos. A prevalência de burnout teve grande variação entre os estudos (variando entre 18% e 49%), porém diversas discrepâncias metodológicas, dentre elas os critérios de corte para definição de burnout e variabilidade da escala de Likert, impediram uma análise agrupada significativa. Conclusão: A prevalência da síndrome de burnout entre médicos atuantes na unidade de terapia intensiva é relativamente alta, porém heterogeneidades metodológicas significantes exigem precauções na interpretação de nossos resultados. Os níveis mais baixos de burnout relatados parecem mais elevados do que os identificados em estudos que investigaram uma mescla de profissionais da unidade de terapia intensiva. Há uma necessidade urgente de consenso que recomende o uso consistente do Inventário de Burnout de Maslach para triar a presença de burnout a fim de fornecer dados precisos a respeito de burnout entre médicos atuantes na unidade de terapia intensiva.

DNA methylation (DNAm) has a well-established association with age in many tissues, including peripheral blood mononuclear cells (PBMCs). Compared to DNAm, the closely related epigenetic modification known as DNA hydroxymethylation (DNAhm) was much more recently discovered in mammals. Preliminary investigations have observed a positive correlation between gene body DNAhm and cis-gene expression. While some of these studies have observed an association between age and global DNAhm, none have investigated region-specific age-related DNAhm in human blood samples. In this study, we investigated DNAhm and gene expression in PBMCs of 10 young and 10 old, healthy female volunteers. Thousands of regions were differentially hydroxymethylated in the old vs. young individuals in gene bodies, exonic regions, enhancers, and promoters. Consistent with previous work, we observed directional consistency between age-related differences in DNAhm and gene expression. Further, age-related DNAhm and genes with high levels of DNAhm were enriched for immune system processes which may support a role of age-related DNAhm in immunosenescence.

DNA methylation (DNAm) and microRNAs (miRNAs) have been implicated in a wide-range of human diseases. While often studied in isolation, DNAm and miRNAs are not independent. We analyzed associations of expression of 283 miRNAs with DNAm at >400K CpG sites in whole blood obtained from 3565 individuals and identified 227 CpGs at which differential methylation was associated with the expression of 40 nearby miRNAs (cis-miR-eQTMs) at FDR

BackgroundDaily routines (eg, physical activity and sleep patterns) are important for diabetes self-management. Traditional research methods are not optimal for documenting long-term daily routine patterns in participants with glycemic conditions. Mobile health offers an effective approach for collecting users’ long-term daily activities and analyzing their daily routine patterns in relation to diabetes status. ObjectiveThis study aims to understand how routines function in diabetes self-management. We evaluate the associations of daily routine variables derived from a smartwatch with diabetes status in the electronic Framingham Heart Study (eFHS). MethodsThe eFHS enrolled the Framingham Heart Study participants at health examination 3 between 2016 and 2019. At baseline, diabetes was defined as fasting blood glucose level ≥126 mg/dL or as a self-report of taking a glucose-lowering medication; prediabetes was defined as fasting blood glucose level of 100-125 mg/dL. Using smartwatch data, we calculated the average daily step counts and estimated the wake-up times and bedtimes for the eFHS participants on a given day. We compared the average daily step counts and the intraindividual variability of the wake-up times and bedtimes of the participants with diabetes and prediabetes with those of the referents who were neither diabetic nor prediabetic, adjusting for age, sex, and race or ethnicity. ResultsWe included 796 participants (494/796, 62.1% women; mean age 52.8, SD 8.7 years) who wore a smartwatch for at least 10 hours/day and remained in the study for at least 30 days after enrollment. On average, participants with diabetes (41/796, 5.2%) took 1611 fewer daily steps (95% CI 863-2360; P

Inflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer's Disease, dementia, and cognitive disorders. We examined the association of 11 plasma proteins (CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO) related to immune and inflammatory responses with measures of cognitive function, brain MRI and dementia risk. We identified Framingham Heart Study Offspring participants who underwent neuropsychological testing (n = 2358) or brain MRI (n = 2100) within five years of the seventh examination where a blood sample for quantifying the protein biomarkers was obtained; and who were followed for 10 years for incident all-cause dementia (n = 1616). We investigated the association of inflammatory biomarkers with neuropsychological test performance and brain MRI volumes using linear mixed effect models accounting for family relationships. We further used Cox proportional hazards models to examine the association with incident dementia. False discovery rate p-values were used to account for multiple testing. Participants included in the neuropsychological test and MRI samples were on average 61 years old and 54% female. Participants from the incident dementia sample (average 68 years old at baseline) included 124 participants with incident dementia. In addition to CD14, which has an established association, we found significant associations between higher levels of CD40L and myeloperoxidase (MPO) with executive dysfunction. Higher CD5L levels were significantly associated with smaller total brain volumes (TCBV), whereas higher levels of sRAGE were associated with larger TCBV. Associations persisted after adjustment for APOE ε4 carrier status and additional cardiovascular risk factors. None of the studied inflammatory biomarkers were significantly associated with risk of incident all-cause dementia. Higher circulating levels of soluble CD40L and MPO, markers of immune cell activation, were associated with poorer performance on neuropsychological tests, while higher CD5L, a key regulator of inflammation, was associated with smaller total brain volumes. Higher circulating soluble RAGE, a decoy receptor for the proinflammatory RAGE/AGE pathway, was associated with larger total brain volume. If confirmed in other studies, this data indicates the involvement of an activated immune system in abnormal brain aging.

Cities must address many challenges including air quality, climate change and the health and wellbeing of communities. Public authorities and developers increasingly look to improve these through the implementation of interventions and innovations, such as low traffic neighbourhoods, deep housing retrofits and green infrastructure. Monitoring the impacts of interventions is essential to determine the success of such projects and to build evidence for broader urban transformation. In this paper we present a mixed-method cross-disciplinary approach that brings together cutting edge atmospheric and data science, measurements of activity in public spaces and novel methods to assess wellbeing-promoting behaviours. The Manchester Urban Observatory focuses on living areas that have a high density of inter-related systems, which require observation, understanding and intervention at multiple levels. This must be completed in line with urban planning goals as well as a clear and succinct data solution that allows robust scientific conclusions to be made and viewed in real time. Delivery of such a monitoring strategy is not trivial and is time, resource and expertise heavy. This paper discusses the methods employed by the Manchester Urban Observatory to monitor the effectiveness off interventions implemented within cities and effective communication strategies with local communities.

We analyzed state-of-the-art observations of the solar atmosphere to investigate the dependence of the Ca ii K brightness of several solar features on spectral bandwidth and spatial resolution of the data. In particular, we study data obtained at the Swedish Solar Telescope with the Crisp Imaging Spectropolarimeter and Chromospheric Imaging Spectrometer instruments. The analyzed data, which are characterized by a spectral bandwidth of 0.12 Å and a spatial resolution of 0.″078, were acquired close to the disk center by targeting a quiet-Sun area and an active region. We convolved the original observations with Gaussian kernels to degrade their spectral bandwidth and spatial resolution to the instrumental characteristics of the most prominent series of Ca ii K observations available to date. We then studied the effect of data degradation on the observed regions and on parameters derived from Ca ii K line measurements that are largely employed as diagnostics of the solar and stellar chromospheres. We find that the effect of degrading the spectral resolution of Ca ii K observations and line profiles depends on both the employed bandwidth and observed solar region. Besides, we found that the spatial degradation impacts the data characterized by a broad bandwidth to a larger extent compared to those acquired with a narrow band. However, the appearance of the observed solar regions is only slightly affected by the spatial resolution of data with bandwidths up to 1 Å and in the range [3,10] Å. Finally, we derived relationships that can be used to intercalibrate results from observations taken with different instruments in diverse regions of the solar atmosphere.

BackgroundDNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age.ResultsHere we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43.ConclusionsDNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

BackgroundThe genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.MethodsWe conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.ResultsIn our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).ConclusionsWe did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

The increasing amount of data collected about the environment brings tremendous potential to create digital systems that can predict the impact of intended and unintended changes. With growing interest in the construction of Digital Twins across multiple sectors, combined with rapid changes to where we spend our time and the nature of pollutants we are exposed to, we find ourselves at a crossroads of opportunity with regards to air quality mitigation in cities. With this in mind, we briefly discuss the interplay between available data and state of the science on air quality, infrastructure needs and areas of opportunities that should drive subsequent planning of the digital twin ecosystem and associated components. Data driven modeling and digital twins are promoted as the most efficient route to decision making in an evolving atmosphere. However, following the diverse data streams on which these frameworks are built, they must be supported by a diverse community. This is an opportunity to build a collaborative space to facilitate closer working between instrument manufacturers, data scientists, atmospheric scientists, and user groups including but not limited to regional and national policy makers.