BackgroundThe field of epigenomics holds great promise in understanding and treating disease with advances in machine learning (ML) and artificial intelligence being vitally important in this pursuit. Increasingly, research now utilises DNA methylation measures at cytosine-guanine dinucleotides (CpG) to detect disease and estimate biological traits such as aging. Given the challenge of high dimensionality of DNA methylation data, feature-selection techniques are commonly employed to reduce dimensionality and identify the most important subset of features. In this study, our aim was to test and compare a range of feature-selection methods and ML algorithms in the development of a novel DNA methylation-based telomere length (TL) estimator. We utilised both nested cross-validation and two independent test sets for the comparisons.ResultsWe found that principal component analysis in advance of elastic net regression led to the overall best performing estimator when evaluated using a nested cross-validation analysis and two independent test cohorts. This approach achieved a correlation between estimated and actual TL of 0.295 (83.4% CI [0.201, 0.384]) on the EXTEND test data set. Contrastingly, the baseline model of elastic net regression with no prior feature reduction stage performed less well in general-suggesting a prior feature-selection stage may have important utility. A previously developed TL estimator, DNAmTL, achieved a correlation of 0.216 (83.4% CI [0.118, 0.310]) on the EXTEND data. Additionally, we observed that different DNA methylation-based TL estimators, which have few common CpGs, are associated with many of the same biological entities.ConclusionsThe variance in performance across tested approaches shows that estimators are sensitive to data set heterogeneity and the development of an optimal DNA methylation-based estimator should benefit from the robust methodological approach used in this study. Moreover, our methodology which utilises a range of feature-selection approaches and ML algorithms could be applied to other biological markers and disease phenotypes, to examine their relationship with DNA methylation and predictive value.

Background Macular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife - a sign of the earliest stages of age-related macular degeneration (AMD) - are associated with accelerated biological ageing more generally. Methods Members of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing defined from a combination of clinical and serum biomarkers obtained at ages 26, 32, 38, and 45 years and (ii) Facial Ageing, defined from photographs obtained at age 38 and 45 years. Results Of the 938 participants who participated at the age 45 assessments, 834 had gradable retinal photographs, and of these 165 (19.8%) had macular drusen. There was no significant difference in Pace of Ageing (p = .743) or Facial Ageing (p = .945) among participants with and without macular drusen. Conclusions In this representative general population sample, macular drusen in midlife were not associated with accelerated ageing. Future studies tracking longitudinal changes in drusen number and severity at older ages may reveal whether drusen are a biomarker of accelerated ageing.

Stressful life events have been linked to declining health, and inflammation has been proposed as a physiological mechanism that might explain this association. Using 828 participants from the Dunedin Longitudinal Study, we tested whether people who experienced more stressful life events during adulthood would show elevated systemic inflammation when followed up in midlife, at age 45. We studied three inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. Stressful life events were not associated with CRP or IL-6. However, people who experienced more stressful life events from age 38 to 44 had elevated suPAR at age 45, and had significantly greater increases in suPAR from baseline to follow-up across the same period. When examining stressful life events across the lifespan, both adverse childhood experiences (ACEs) and adult stressful life events were independently associated with suPAR at age 45. ACEs moderated the association of adult stressful life events and suPAR at age 45—children with more ACEs showed higher suPAR levels after experiencing stressful life events as adults. The results suggest systemic chronic inflammation is one physiological mechanism that could link stressful life events and health, and support the use of suPAR as a useful biomarker for such research.

Importance DNA methylation has been proposed as an epigenetic mechanism by which the childhood neighborhood environment may have implications for the genome that compromise adult health. Objective To ascertain whether childhood neighborhood socioeconomic disadvantage is associated with differences in DNA methylation by age 18 years. Design, Setting, and Participants This longitudinal cohort study analyzed data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of children born between 1994 and 1995 in England and Wales and followed up from age 5 to 18 years. Data analysis was performed from March 15, 2019, to June 30, 2019. Exposures High-resolution neighborhood data (indexing deprivation, dilapidation, disconnection, and dangerousness) collected across childhood. Main Outcomes and Measures DNA methylation in whole blood was drawn at age 18 years. Associations between neighborhood socioeconomic disadvantage and methylation were tested using 3 prespecified approaches: (1) testing probes annotated to candidate genes involved in biological responses to growing up in socioeconomically disadvantaged neighborhoods and investigated in previous epigenetic research (stress reactivity-related and inflammation-related genes), (2) polyepigenetic scores indexing differential methylation in phenotypes associated with growing up in disadvantaged neighborhoods (obesity, inflammation, and smoking), and (3) a theory-free epigenome-wide association study. Results A total of 1619 participants (806 female individuals [50%]) had complete neighborhood and DNA methylation data. Children raised in socioeconomically disadvantaged neighborhoods exhibited differential DNA methylation in genes involved in inflammation (beta = 0.12; 95% CI, 0.06-0.19; P < .001) and smoking (beta = 0.18; 95% CI, 0.11-0.25; P < .001) but not obesity (beta = 0.05; 95% CI, -0.01 to 0.11; P = .12). An epigenome-wide association study identified multiple CpG sites at an arraywide significance level of P < 1.16 x 10(-7) in genes involved in the metabolism of hydrocarbons. Associations between neighborhood disadvantage and methylation were small but robust to family-level socioeconomic factors and to individual-level tobacco smoking. Conclusions and Relevance Children raised in more socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their less disadvantaged peers. This finding suggests that epigenetic regulation may be a mechanism by which the childhood neighborhood environment alters adult health. Question Is childhood neighborhood disadvantage associated with differential DNA methylation? Findings In this cohort study of 1619 children in Great Britain, exposure to neighborhood socioeconomic disadvantage during childhood was associated with differential DNA methylation at age 18 years in genes involved in inflammation, exposure to tobacco smoke, and metabolism of toxic air pollutants. Meaning The study found that children who were raised in socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their more advantaged peers. This cohort study traces the biological responses and associated phenotypes of an upbringing in a socially and economically disadvantaged environment.

Exploring new material as adsorbent for the efficient enrichment of pollutants is always of great significance in analytical chemistry. In this work, a magnetic azobenzene framework (labeled as MAzo) was constructed as a magnetic solid phase extraction (MSPE) adsorbent by a simple and environmentally benign strategy. The MAzo exhibited the attractive features of strong magnetism, outstanding adsorption performance, as well as good reusability. Combining MAzo-based MSPE with high performance liquid-phase chromatography, a simple and effective method was developed for simultaneous determination of four phenylurea herbicides in pear juice and apple juice samples. Under optimized experimental conditions, the method offered low limits of detection of 0.05-0.15 ng mL−1, high recoveries of 86.7-109.2% with RSD less than 7%. Density functional theory calculation indicated that the good adsorption performance of MAzo for PUHs can be ascribed to the strong H-bonding forces and weak π-π interactions. The facile, green, low-cost synthesis method together with the excellent adsorption performance endows the MAzo great application prospect in sample preparation.

Across Europe, hedgehogs ( Erinaceus europaeus ) appear to be in decline in both urban and rural landscapes. Current methods used to monitor urban populations are, however, associated with several potential limitations. In this study, we conducted hedgehog footprint-tunnel surveys in 219 residential gardens across Reading, UK between May–September in 2013 and/or 2014; gardens were surveyed for five continuous days. Single-species occupancy models were used to investigate factors influencing hedgehog occupancy and two-species occupancy models were used to estimate a species interaction factor (SIF) between hedgehogs and (a) badgers ( Meles meles ), (b) foxes ( Vulpes vulpes ) and (c) dogs ( Canis familiaris ). The five-day survey protocol was associated with a false-absence error rate of 0.1–0.4%, indicating that it was a reliable method for determining hedgehog presence; conversely, 34.7% of householders were not able to correctly predict hedgehog presence or absence. Hedgehogs were widely distributed across Reading, but detected in only 32–40% of gardens. None of the within-garden or outside-garden factors investigated significantly affected hedgehog occupancy in the single-species models, but the two-species models indicated that badgers (SIF = 0.471 ± 0.188), but not foxes (SIF = 0.954 ± 0.048) or dogs (SIF = 0.780 ± 0.228), negatively affected the presence of hedgehogs in gardens, although not significantly. Overall, footprint-tunnels represent a viable field method for monitoring urban hedgehog populations, however, other approaches are required to identify factors that make gardens “hedgehog friendly”.

Agricultural landscapes have become increasingly intensively managed resulting in population declines across a broad range of taxa, including insectivores such as the hedgehog (Erinaceus europaeus). Hedgehog declines have also been attributed to an increase in the abundance of badgers (Meles meles), an intra-guild predator. The status of hedgehogs across the rural landscape at large spatial scales is, however, unknown. In this study, we used footprint tracking tunnels to conduct the first national survey of rural hedgehog populations in England and Wales. Single and two-species occupancy modelling was used to quantify hedgehog occupancy in relation to habitat and predator covariates. Hedgehog occupancy was low (22% nationally), and significantly negatively related to badger sett density and positively related to the built environment. Hedgehogs were also absent from 71% of sites that had no badger setts, indicating that large areas of the rural landscape are not occupied by hedgehogs. Our results provide the first field based national survey of hedgehogs, providing a robust baseline for future monitoring. Furthermore, the combined effects of increasing badger abundance and intensive agriculture may have provided a perfect storm for hedgehogs in rural Britain, leading to worryingly low levels of occupancy over large spatial scales.

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their "biological aging" (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

Indirect survey methods are often used in studies of mammals, but are susceptible to biases caused by failure to detect species where they are present. Occupancy analysis is an analytical technique which enables non-detection rates to be estimated and which can be used to develop and refine novel survey methods. In this study, we investigated the use of footprint tunnels by volunteers as a method for surveying occupancy of sites by hedgehogs Erinaceus europaeus. The survey protocol led to a very low non-detection rate and could reasonably be used to detect occupancy changes of 25% with statistical power of 0.95 in a national survey.

The apparent age and mass of a stellar cluster can be strongly affected by stochastic sampling of the stellar initial mass function, when inferred from the integrated color of low mass clusters (less than 10^4 solar masses). We use simulated star clusters to show that these effects are minimized when the brightest, rapidly evolving stars in a cluster can be resolved, and the light of the fainter, more numerous unresolved stars can be analyzed separately. When comparing the light from the less luminous cluster members to models of unresolved light, more accurate age estimates can be obtained than when analyzing the integrated light from the entire cluster under the assumption that the initial mass function is fully populated. We show the success of this technique first using simulated clusters, and then with a stellar cluster in M31. This method represents one way of accounting for the discrete, stochastic sampling of the stellar initial mass function in less massive clusters and can be leveraged in studies of clusters throughout the Local Group and other nearby galaxies.

We confirm our earlier tentative detection of M31* in X-rays and measure its light-curve and spectrum. Observations in 2004-2005 find M31* rather quiescent in the X-ray and radio. However, X-ray observations in 2006-2007 and radio observations in 2002 show M31* to be highly variable at times. A separate variable X-ray source is found near P1, the brighter of the two optical nuclei. The apparent angular Bondi radius of M31* is the largest of any black hole, and large enough to be well resolved with Chandra. The diffuse emission within this Bondi radius is found to have an X-ray temperature ~0.3 keV and density 0.1 cm-3, indistinguishable from the hot gas in the surrounding regions of the bulge given the statistics allowed by the current observations. The X-ray source at the location of M31* is consistent with a point source and a power law spectrum with energy slope 0.9+/-0.2. Our identification of this X-ray source with M31* is based solely on positional coincidence.

We present the first X-ray analysis of the diffuse hot ionized gas and the point sources in IC131, after NGC604 the second most X-ray luminous giant H II region (GHR) in M33. The X-ray emission is detected only in the south eastern part of IC131 (named IC131-se) and is limited to an elliptical region of similar to 200 pc in extent. This region appears to be confined toward the west by a hemispherical shell of warm ionized gas and only fills about half that volume. Although the corresponding X-ray spectrum has 1215 counts, it cannot conclusively be told whether the extended X-ray emission is thermal, non-thermal, or a combination of both. A thermal plasma model of kT(e) = 4.3 keV or a single power law of Gamma similar or equal to 2.1 fit the spectrum equally well. If the spectrum is purely thermal (non-thermal), the total unabsorbed X-ray luminosity in the 0.35-8 keV energy band amounts to L-X = 6.8 (8.7) x 10(35) erg s(-1). Among other known H II regions IC131-se seems to be extreme regarding the combination of its large extent of the X-ray plasma, the lack of massive O stars, its unusually high electron temperature (if thermal), and the large fraction of L-X emitted above 2 keV (similar to 40%-53%). A thermal plasma of similar to 4 keV poses serious challenges to theoretical models, as it is not clear how high electron temperatures can be produced in H II regions in view of mass-proportional and collisionless heating. If the gas is non-thermal or has non-thermal contributions, synchrotron emission would clearly dominate over inverse Compton emission. It is not clear if the same mechanisms which create non-thermal X-rays or accelerate cosmic rays in supernova remnants can be applied to much larger scales of 200 pc. In both cases the existing theoretical models for GHRs and superbubbles do not explain the hardness and extent of the X-ray emission in IC131-se. We also detect a variable source candidate in IC131. It seems that this object (CXO J013315.10+304453.0) is a high mass X-ray binary whose optical counterpart is a B2-type star with a mass of similar to 9 M-circle dot.

In this paper, we conduct the window design for single-input single-output (SISO) and multiple-input multiple- output (MIMO) OFDM systems. The key value of this paper is to optimize the receiver SINR when carrier frequency offset (CFO) and phase noise both affecting an OFDM system. To our best knowledge, this is the first research to design window coefficients through leveraging the CFO and phase noise statistics for SISO and MIMO OFDM systems over frequency-selective channels. CFO and phase noise will destroy the orthogonality of OFDM system and lead to inter-carrier interference (ICI). Simulation results show that our proposed method can improve the system performance.

Objective: Existing research suggests that the rate of depressive illness and depressive symptoms are high in people living with HIV/AIDS, but investigations on the causes of depression provide conflicting results. Social, psychological and biological factors have all been suggested as possible causes of depression in people living with HIV/AIDS. The suggestion that depression may be the result of the neurotropic effects of the virus on the central nervous system leading to an ‘organic’ or secondary depression has major implications in the treatment of HIV/AIDS. The aim of the current study was to further investigate the nature and underlying aetiology of depression in people living with HIV/AIDS. Method: One hundred and twenty-nine people living with HIV/AIDS recruited for the study from outpatients clinics and primary care settings completed a range of self-report symptom measures including the Beck Depression Inventory (BDI), SF-36, SPHERE and a personality measure, the NEO Personality Inventory (NEO-PI). They also completed a battery of neuropsychological tests (CANTAB) and a structured clinical interview (SCID-DSM-IV). Medical and sociodemographic data were also recorded. Results: Approximately one-third scored ≥14 on the BDI and 27% met criteria for a current ‘mood disorder’ on the SCID. Depressive symptoms were strongly related to personality style, having a past psychiatric history and current stressful psychosocial situation. There was no association between depression and HIV disease status. There was no evidence in this study cohort of a distinct subtype of ‘organic’ or secondary depression. Conclusions: These results suggest that at least for ‘well’ people living with HIV/AIDS, there is no distinct subtype of depression and early treatment approaches can be modelled on those used for other non-HIV groups. Further longitudinal studies will be required to dissect out the multiple factors underlying depression in HIV/AIDS.

ackground: Recent evidence documents that cannabis use by young people is a modest statistical risk factor for psychotic symptoms n adulthood, such as hallucinations and delusions, as well as clinically significant schizophrenia. The vast majority of cannabis users o not develop psychosis, however, prompting us to hypothesize that some people are genetically vulnerable to the deleterious effects of annabis. ethods: In a longitudinal study of a representative birth cohort followed to adulthood, we tested why cannabis use is associated with he emergence of psychosis in a minority of users, but not in others. esults: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent annabis use on developing adult psychosis. Carriers of the COMT valine allele were most likely to exhibit psychotic symptoms and o develop schizophreniform disorder if they used cannabis. Cannabis use had no such adverse influence on individuals with two opies of the methionine allele. onclusions: These findings provide evidence of a gene environment interaction and suggest that a role of some susceptibility genes s to influence vulnerability to environmental pathogens.

Objective: Our aim was to gain an estimate of the rate of depressive disorder in patients with HIV/AIDS attending general practice and to investigate factors associated with depression. A further objective was to determine the ability of non-mental health medical practitioners to detect depressive symptoms in their patients with HIV/AIDS. Method: Participants comprised 322 persons living with HIV/AIDS ((PLWHA); 13 females, 309 males; mean age 41.4, SD = 8.9) who were recruited from four general practice clinics specializing in HIV medicine and from an infectious diseases clinic. Medical, psychiatric and sociodemographic data were obtained. In addition, participants completed the Inventory to Diagnose Depression (IDD), a self-report measure to detect depression. Results: Twenty-two per cent of the sample met criteria for a current Major Depressive Episode (DSM-IV defined) on the IDD. Overall, there was moderate agreement between treating doctors’ diagnosis of depression and patients’ self-report of depressive symptoms. A multivariate model indicated that being in a current relationship was associated with lowered odds of depression (OR = 0.43; CI = 0.23–0.81). The factors strongly associated with increased odds of depression were a past history of illicit drug use (OR = 2.98; CI = 1.60–5.54) and a diagnosis of ‘stress’ by treating doctors (OR = 5.65; CI = 2.50–12.77). HIV-related medical variables such as immune function, use of antiretroviral medication and duration of HIV infection were not associated with depression. Conclusions: There was a high rate of self-reported depression in this group of PLWHA which was also recognized by treating clinicians. Being in a relationship appeared to afford protection against depression while having a history of illicit drug use and current ‘stress’ were highly associated with depression. Interestingly, HIV-related medical variables including laboratory markers of HIV disease, duration of illness and antiretroviral medication regimen were not related to depression.