Social isolation, loneliness, and inflammation: a multi-cohort investigation in early and mid-adulthood

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N=6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N=881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N=1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation in childhood was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers

Extragalactic Peaked-Spectrum Radio Sources at Low Frequencies

This document is the Accepted Manuscript of the following article: J.R. Callingham, et al, 'Extragalactic Peaked-Spectrum Radio Sources at Low Frequencies', The Astrophysical Journal, 836 (2), (28pp), first published online 17 February 2017. DOI: https://doi.org/10.3847/1538-4357-836/2/174. © 2017, The American Astronomical Society. All rights reserved. Data tables, and the appendix containing all of the SEDs, are available from the journal and on request to the authorWe present a sample of 1,483 sources that display spectral peaks between 72 MHz and 1.4 GHz, selected from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. The GLEAM survey is the widest fractional bandwidth all-sky survey to date, ideal for identifying peaked-spectrum sources at low radio frequencies. Our peaked-spectrum sources are the low frequency analogues of gigahertz-peaked spectrum (GPS) and compact-steep spectrum (CSS) sources, which have been hypothesized to be the precursors to massive radio galaxies. Our sample more than doubles the number of known peaked-spectrum candidates, and 95% of our sample have a newly characterized spectral peak. We highlight that some GPS sources peaking above 5 GHz have had multiple epochs of nuclear activity, and demonstrate the possibility of identifying high redshift ($z > 2$) galaxies via steep optically thin spectral indices and low observed peak frequencies. The distribution of the optically thick spectral indices of our sample is consistent with past GPS/CSS samples but with a large dispersion, suggesting that the spectral peak is a product of an inhomogeneous environment that is individualistic. We find no dependence of observed peak frequency with redshift, consistent with the peaked-spectrum sample comprising both local CSS sources and high-redshift GPS sources. The 5 GHz luminosity distribution lacks the brightest GPS and CSS sources of previous samples, implying that a convolution of source evolution and redshift influences the type of peaked-spectrum sources identified below 1 GHz. Finally, we discuss sources with optically thick spectral indices that exceed the synchrotron self-absorption limit.Peer reviewedFinal Accepted Versio

Risk of Myocardial Infarction in Parents of HIV-infected Individuals: a population-based Cohort Study

<p>Abstract</p> <p>Background</p> <p>Previous studies have indicated an increased risk of myocardial infarction (MI) in HIV infected individuals especially after start of highly active antiretroviral therapy (HAART). It is however controversial whether the increased risk of atherosclerotic disease is exclusively associated with the HIV disease and HAART or whether life-style related or genetic factors also increase the risk in this population. To establish whether the increased risk of myocardial infarction in HIV patients partly reflects an increased risk of MI in their families, we estimated the relative risk of MI in parents of HIV-infected individuals.</p> <p>Methods</p> <p>From the Danish HIV Cohort Study and the Danish Civil Registration System we identified the parents of all HIV-infected patients born in Denmark after 1952 in whom a Danish born mother was identifiable. For each HIV patient, 4 matched population controls and their parents were identified. Cumulative incidence functions were constructed to illustrate time to first MI of the parents as registered in the Danish National Hospital Registry. Incidence rate ratios (IRR) were estimated by Cox's regression analyses. Due to the confidential type of the analysed data the study was approved by the Danish Data Protection Agency.</p> <p>Results</p> <p>2,269 mothers and 2,022 fathers of HIV patients as well as 9,076 mothers and 8,460 fathers of control subjects were identified. We observed an increased risk of MI in mothers of HIV patients (adjusted IRR, 1.31; 95% CI: 1.08-1.60). The strongest association was seen in case the offspring was infected heterosexually (adjusted IRR, 1.59; 95% CI: 1.07-2.35) or by IV drug abuse (IVD) (adjusted IRR, 1.63; 95% CI: 1.02-2.60). In fathers of HIV patients the risk of MI was only increased if the offspring was infected by IVD (adjusted IRR, 1.42; 95% CI: 1.01-2.00).</p> <p>Conclusion</p> <p>Mothers of HIV-infected patients have an increased risk of MI. We presume that this stems from family related life style risk factors, some of which may also influence the risk of MI in HIV-infected patients.</p

Perioperative oxygen fraction – effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial

<p>Abstract</p> <p>Background</p> <p>A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (Fi<smcaps>O</smcaps>₂= 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving Fi<smcaps>O</smcaps>₂= 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery.</p> <p>Methods and design</p> <p>The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (Fi<smcaps>O</smcaps>₂= 0.80) or 30% oxygen (Fi<smcaps>O</smcaps>₂= 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power.</p> <p>Discussion</p> <p>This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT00364741.</p

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe