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The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Bipolar disorder and alcohol use disorder (AUD) have a high rate of comorbidity, more than 50% of individuals with bipolar disorder also receive a diagnosis of AUD in their lifetimes. Although both disorders are heritable, it is unclear if the same genetic factors mediate risk for bipolar disorder and AUD. We examined 733 Costa Rican individuals from 61 bipolar pedigrees. Based on a best estimate process, 32% of the sample met criteria for bipolar disorder, 17% had a lifetime AUD diagnosis, 32% met criteria for lifetime nicotine dependence, and 21% had an anxiety disorder. AUD, nicotine dependence and anxiety disorders were relatively more common among individuals with bipolar disorder than in their non-bipolar relatives. All illnesses were shown to be heritable and bipolar disorder was genetically correlated with AUD, nicotine dependence and anxiety disorders. The genetic correlation between bipolar and AUD remained when controlling for anxiety, suggesting that unique genetic factors influence the risk for comorbid bipolar and AUD independent of anxiety. Our findings provide evidence for shared genetic effects on bipolar disorder and AUD risk. Demonstrating that common genetic factors influence these independent diagnostic constructs could help to refine our diagnostic nosology.
The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular, there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated.
In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range = 3–80), we used mass spectrometry lipidomic measures to evaluate the genetic overlap between twenty-three biologically distinct lipid classes and a dimensional scale of MDD.
We found that the lipid class with the largest endophenotype ranking value (ERV, a standardized parametric measure of pleiotropy) were ether-phosphodatidylcholines (alkylphosphatidylcholine, PC(O) and alkenylphosphatidylcholine, PC(P) subclasses). Furthermore, we examined the cluster structure of the twenty-five species within the top-ranked lipid class, and the relationship of those clusters with MDD. This analysis revealed that species containing arachidonic acid generally exhibited the greatest degree of genetic overlap with MDD.
This study is the first to demonstrate a shared genetic etiology between MDD and ether-phosphatidylcholine species containing arachidonic acid, an omega-6 fatty acid that is a precursor to inflammatory mediators, such as prostaglandins. The study highlights the potential utility of the well-characterized linoleic/arachidonic acid inflammation pathway as a diagnostic marker and/or treatment target for MDD.
Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology.
Here we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing these traits.
Addiction phenotypes and anxiety were shown to be heritable and univariate genome-wide linkage scans revealed significant quantitative trait loci for drug dependence (14q13.2-q21.2, LOD = 3.322) and a broad anxiety phenotype (12q24.32-q24.33, LOD = 2.918). Significant positive genetic correlations were observed between anxiety and each of the addiction subtypes (ρg = 0.550–0.655) and further investigation with bivariate linkage analyses identified significant pleiotropic signals for alcohol dependence-anxiety (9q33.1-q33.2, LOD = 3.054) and drug dependence-anxiety (18p11.23-p11.22, LOD = 3.425).
This study confirms the shared genetic underpinnings of addiction and anxiety and identifies genomic loci involved in the etiology of these comorbid disorders. The linkage signal for anxiety on 12q24 spans the location of TMEM132D, an emerging gene of interest from previous GWAS of anxiety traits, whilst the bivariate linkage signal identified for anxiety-alcohol on 9q33 peak coincides with a region where rare CNVs have been associated with psychiatric disorders. Other signals identified implicate novel regions of the genome in addiction genetics.
At archaeological sites located on islands or near the coast, the potential exists for lipid extracts of potsherds to contain fatty acids (FA) from both aquatic and terrestrial organisms, meaning that consideration must be given to marine reservoir effects (MRE) in radiocarbon (14C) analyses. Here we studied the site of Bornais (Outer Hebrides, UK) where a local MRE, ΔR of –65 ± 45 yr was determined through the paired 14C determinations of terrestrial and marine faunal bones. Lipid analysis of 49 potsherds, revealed aquatic biomarkers in 45% of the vessels, and δ13C values of C16:0 and C18:0 FAs revealed ruminant and marine product mixing for 71% of the vessels. Compound-specific 14C analysis (CSRA) of FAs yielded intermediate 14C ages between those of terrestrial and marine bones from the same contexts, confirming an MRE existed. A database containing δ13C values for FAs from reference terrestrial and marine organisms provided endmembers for calculating the percentage marine-derived C (%marine) in FAs. We show that lipid 14C dates can be corrected using determined %marine and ΔR values, such that pottery vessels from coastal locations can be 14C dated by CSRA of FAs.
In this paper, we present the first data from an alternative extraction method for atmospheric 14CO2 analysis, based on the direct trapping of whole air samples onto a molecular sieve zeolite (13X) trap, incorporated into a commercially available automated graphitization system. Results are presented for both inter-laboratory comparison samples and an in-house reference standard. The in-house reference was used to calculate the standard deviation of measurements (2.0‰). This newly developed method will facilitate faster sample processing and therefore lower cost per analysis, critical for scaling up such studies.
The Bristol Radiocarbon Accelerator Mass Spectrometry (BRAMS) Facility was established at the University of Bristol after the commissioning of our dedicated sample preparation laboratories and the installation and acceptance of the BrisMICADAS AMS in 2016. Routine measurements commenced in mid-2016, once validation was completed for each sample type. Herein, we give an overview of the standard pretreatment methods currently employed in the Facility and the results of radiocarbon (14C) determinations on a wide range of standards, blank materials, and intercomparison samples which have been measured during our extensive pretreatment method validation program and during our routine 14C analyses.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The purpose of this formative study was to explore current knowledge and attitudes towards physical activity, as well as perceived barriers, facilitators and opportunities for physical activity participation among older adults living in the community. The findings have subsequently informed the design, delivery and recruitment strategies of a local community physical activity intervention programme which forms part of Sport England’s national Get Healthy, Get Active initiative.
There is a growing public health concern regarding the amount of time spent in sedentary and physical activity behaviours within the older adult population.
Between March and June 2016, 34 participants took part in one of six focus groups as part of a descriptive formative study. A homogenous purposive sample of 28 community dwelling white, British older adults (six male), aged 65–90 years (M=78, SD=7 years) participated in one of five focus group sessions. An additional convenience pragmatic sub-sample of six participants (three male), aged 65–90 years (M=75, SD=4 years), recruited from an assisted living retirement home participated in a sixth focus group. Questions for focus groups were structured around the PRECEDE stage of the PRECEDE–PROCEDE model of health programme design, implementation and evaluation. Questions addressed knowledge, attitudes and beliefs towards physical activity, as well as views on barriers and opportunities for physical activity participation. All data were transcribed verbatim. Thematic analysis was then conducted with outcomes represented as pen profiles.
Consistent views regarding both the potential physical and psychosocial benefits of physical activity were noted regardless of living status. The themes of, opportunities and awareness for physical activity participation, cost, transport, location and season/weather varied between participants living in an assisted living retirement home and community dwelling older adults. Further comparative research on the physical activity requirements of older adults living in assisted living versus community settings are warranted.
Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
We present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interest
The authors have declared that no competing interests exist.
Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.
At the centre of the Parkes 64—m radio telescope a region of diameter 17 m has recently been resurfaced to improve its efficiency at high frequencies. The first measurements using this section have been made at 22 GHz, in observations of both continuum sources and water tfapour masers. For these observations the receiver front-end used a mixer cooled in liquid nitrogen, followed by a 5 GHz cryogenic parametric amplifier as a second stage. The option of switching against an offset horn was available and the total system
noise temperature was ∽ 750 K.
The 6 GHz transitions of the 2π3/2, J = 5/2 excited state of OH are present in emission in the direction of several OH-emission regions (Rickard et al. 1975; Knowles et al. 1976), and in absorption in compact thermal sources (Gardner and Whiteoak 1975). This has suggested that transitions in the next highest state near 13 GHz (J = 7/2) might also be widely observable. A single detection has already been reported in W3OH by Turner et al. (1970). In this paper we report the observation of narrow-band emission in several other sources.
The objective of this study was to evaluate the impact and efficacy of pulse oximetry screening for CHD in a level-two neonatal unit without on-site access to paediatric echocardiography.
All neonatal unit admissions between 1 September, 2011 and 31 August, 2013 were reviewed to determine the outcomes of newborns identified by pulse oximetry screening. Record linkage with the National Congenital Heart Disease Audit allowed follow-up of newborns with a negative screening result.
There were 11,233 live births during the study period, with 973 neonatal unit admissions unrelated to pulse oximetry screening. From the remaining screening population of 10,260 newborns, 23 were admitted on the basis of a screen-positive result; three of the 23 patients went on to have urgent echocardiograms, and two were found to have critical CHD. In the 21 newborns without critical CHD, an alternative diagnosis was made in 16 cases. Record linkage with the National Congenital Heart Disease Audit indicated that no newborns born in the hospital during the study period received surgery for critical CHD following negative screening. The estimated sensitivity of screening was 100% (95% confidence interval 15.81–100%) and specificity was 99.80% (95% confidence interval 99.69–99.87%), with a false-positive rate of 0.20% (95% confidence interval 0.13–0.31%).
The introduction of pulse oximetry screening to a hospital where paediatric echocardiography services are not available is practical, results in very few referrals to the regional paediatric cardiology centre, and detects cases of CHD that would otherwise go undiagnosed. Record linkage with a national CHD database provides a straightforward method for tracking cases of CHD that may have been missed by screening.
To develop a regime of care for patients with head and neck cancers undergoing intensity-modulated radiotherapy (IMRT), with the support of a health advisor (HA) and temporary access to the mouth care product Caphosol™.
Materials and methods
A HA was temporarily employed to assess, monitor and refer patients as appropriate and ensure patients received and utilised supplies of Caphosol™. A retrospective audit was undertaken to provide a gap analysis of current service. The data were used to develop a pro forma for documenting assessments and monitoring lifestyle factors for IMRT patients. Assessments referrals and compliance, plus hospital admissions owing to treatment-related issues, were documented during the baseline audit and the temporary HA service and provision of Caphosol™.
The presence of a HA facilitated 100% compliance with appropriate assessments, referrals and adherence to treatment. The data suggests that the additional provision of Caphosol™ may have reduced levels of mucositis and associated pain.
It is recommended that a HA role be established within radiotherapy departments to facilitate lifestyle assessments, referrals and compliance with positive behaviour changes (e.g., stopping smoking). The use of Caphosol™ as a routine part of mouth care regime for IMRT patients also warrants further investigation.